CRITICAL REVIEW EVIDENCE BASED

PEMENUHAN KEBUTUHAN PENGONTROLAN INFEKSI

PADA PASIEN HIPERTENSI DENGAN RISIKO COVID-19

Diajukan untuk Memenuhi Tugas pada Stase Keperawatan Dasar Profesi

Program Profesi Ners XLI

Dosen Pembimbing:
Kurniawan Yudianto, S.Kp., M., Kep
Dikumpulkan pada 25 Februari 2021

Disusun oleh:
Kelompok 10

Leni Restiyanti 220110166018

Jihan Salimah Aribah 220110160092
Selly Amalia Nurhasanah 220110166053
Trisna Rosanti 220110166120

UNIVERSITAS PADJADJARAN
FAKULTAS KEPERAWATAN
BANDUNG
2021
 DAFTAR ISI

DAFTAR ISI ....................................................................................................................i

DAFTAR TABEL............................................................................................................ii
DAFTAR GAMBAR......................................................................................................iii
BAB I PENDAHULUAN................................................................................................1
BAB II TINJAUAN TEORITIS.....................................................................................3
2.1 Perspektif Teoritis Kebutuhan Dasar Manusia......................................................3
2.1.1 Definisi Kebutuhan dasar manusia............................................................4
2.1.2 Jenis kebutuhan dasar manusia..................................................................5
2.1.3 Karakteristik kebutuhan dasar manusia.....................................................5
2.1.4 Faktor-faktor yang mempengaruhi kebutuhan dasar manusia...................6
2.2 Perspektif Teori Pemenuhan Kebutuhan Pengontrolan Infeksi.............................7
2.2.1 Definisi Infeksi...........................................................................................7
2.2.2 Jenis-Jenis infeksi.......................................................................................7
2.2.3 faktor-faktor yang mempengaruhi onfeksi.................................................7
2.2.4 Dampak perubahan kebutuhan pengelolaan infeksi terhadap
homeostatis tubuh.......................................................................................8
2.2.5 Masalah keperawatan yang berhubungan dengan
pemenuhan kebutuhan pengontrolan infeksi..............................................9
2.3 Intervensi Pemenuhan Kebutuhan Infeksi.............................................................9
BAB III INTERVENSI KEPERAWATAN PEMENUHAN KEBUTUHAN..........15
3.1 Pencarian Literatur..............................................................................................15
3.2 Metode Pendidikan Kesehatan dengan Infografis...............................................15
3.3 Metode Pendidikan Kesehatan dengan Ekie........................................................16
3.4 Topik Pendidikan Kesehatan...............................................................................16
BAB IV PEMBAHASAN..............................................................................................19
BAB V SIMPULAN DAN SARAN..............................................................................27
5.1 Simpulan..............................................................................................................27
5.2 Saran....................................................................................................................27

DAFTAR PUSTAKA....................................................................................................28
LAMPIRAN ..................................................................................................................31

i
 DAFTAR TABEL

Tabel 2.1 Analisis Jurnal ................................................................................................10

ii
 DAFTAR GAMBAR

Gambar 2.1 Kebutuhan Dasar Manusia Menurut Maslow................................................4

iii
 BAB I
PENDAHULUAN

Hipertensi merupakan penyakit tidak menular serta menjadi faktor utama

permasalahan kesehatan di dunia karena prevalensinya yang masih tinggi. Hipertensi juga
menjadi tantangan besar di Indonesia, hal ini dikarenakan banyaknya penderita hipertensi
yang sering ditemukan pada pelayanan kesehatan tingkat primer atau di puskesmas (Eriana,
2017). Hipertensi adalah kondisi saat penderita mengalami tekanan darah sistolik lebih dari
130 mmHg dan tekanan diastolik lebih dari 80 mmHg. Hipertensi juga diartikan sebagai
kondisi seseorang yang mengalami peningkatan tekanan darah diatas normal yang dapat
berakibat pada angka kesakitan serta angka kematian (American Heart Association, 2017).
Hipertensi dikatakan sebagai The Silent Killer karena dapat membunuh penderitanya secara
diam-diam tanpa gejala serta penderitanya tidak menyadari dan tidak mengetahui
penyebabnya (Suprayitno, 2019).

Penyebab terjadinya hipertensi dapat diakibatkan oleh beberapa faktor risiko

diantaranya adalah umur, jenis kelamin, riwayat keluarga, serta genetik (Manuntung, 2018).
Faktor resiko terjadinya hipertensi juga dapat diakibatkan oleh gaya hidup seseorang seperti
tidak mengontrol makanan, berat badan berlebih, konsumsi minuman beralkohol, perilaku
merokok, kejadian stress, dan jarang melakukan aktivitas fisik. Gaya hidup yang kurang sehat
tersebut dapat mengakibatkan angka hipertensi yang semakin tinggi (Hanafi, 2016). Tekanan
darah yang tinggi dapat berbahaya jika bersifat persisten karena membuat sistem sirkulasi dan
organ yang mendapatkan suplai darah (termasuk jantung dan otak) menjadi tegang sehingga
dikhawatirkan dapat berkembang menjadi komplikasi (Triyanto, 2014).

Coronavirus 2019 (COVID-19) adalah penyakit yang disebabkan oleh virus corona
baru yang disebut SARS-CoV-2 meliputi gejala pernafasan ringan hingga berat. Wabah ini
terjadi secara cepat akibat perjalanan internasional dan globalisasi sehingga pada tanggal 11
Maret 2020 World Health Organization (WHO) menetapkan COVID-19 sebagai pandemi
yang terjadi pertama kali di Wuhan, Provinsi Hubei, China yang terjadi mulai tanggal 31
Desember 2019. Gejala biasanya mulai antara 2 sampai 14 hari setelah seseorang terinfeksi
terutama setelah demam, batuk dan sesak napas (Cheng dan Shan, 2020). Kelompok rentan
memiliki risiko yang tinggi terhadap infeksi COVID-19. Menurut WHO, yang termasuk ke
dalam kelompok rentan adalah lansia dan orang yang memiliki penyakit penyerta (komorbid)
diantaranya hipertensi, diabetes, masalah jantung dan paru-paru, obesitas, asma, dan kanker.

1
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Hasil penelitian menyatakan bahwa komorbid utama COVID-19 adalah Hipertensi.

Pernyataan tersebut disebabkan karena orang dengan riwayat hipertensi memiliki jumlah
limfosit yang rendah dan memiliki faktor risiko prognosis yang buruk pada pasien dengan
COVID-19 (Zhou, Zhu and Xu, 2020). Berdasarkan data per tanggal 13 Oktober 2020 yang
dihimpun oleh Satuan Tugas Penanganan COVID-19, dari total kasus yang terkonfirmasi
positif COVID-19, terdapat 1.488 kasus pasien yang memiliki penyakit penyerta dengan
presentase terbanyak yaitu penyakit hipertensi sebesar 50,5% dan kasus pasien COVID-19
dengan hipertensi yang meninggal sebesar 13,2% (Kementerian Kesehatan Republik
Indonesia, 2020).

Berdasarkan penjelasan berikut, penderita hipertensi dapat dikatakan memiliki risiko

yang tinggi terhadap infeksi COVID-19 karena memiliki imunitas yang cenderung rendah
sehingga lebih mudah untuk terinfeksi. Selain itu, mereka juga tidak dapat menerima vaksin
(WHO, 2021). Tetapi saat ini di Indonesia sendiri telah diberlakukan aturan dengan surat
edaran HK.02.02/I/368/2021 tentang Pelaksanaan Vaksinasi COVID-19 pada Kelompok
Sasaran Lansia, Komorbid dan Penyintas COVID-19, serta Sasaran Tunda, yang mencakup
salah satunya bahwa penderita hipertensi bisa untuk diberikan vaksin covid 19 dengan
ketentuan tekanan darah tidak boleh lebih dari 180/110 mmHg serta dilakukan pemeriksaan
tekanan darah di meja skrinning sebelum dilakukan vaksinasi (Kementerian Kesehatan
Republik Indonesia, 2020). Orang dengan hipertensi akan menunjukkan gejala yang lebih
berat, bahkan hingga terjadi kerusakan pada organ tubuhnya jika terinfeksi (Bahtiar dan
Ariyanti, 2021). Oleh karena itu, maka diperlukan upaya pengelolaan infeksi pada pasien
dengan hipertensi di masa pandemi COVID-19 ini.
 BAB II
TINJAUAN TEORITIS

2.1 Perspektif Teoritis Kebutuhan Dasar Manusia

1.1 Definisi Kebutuhan Dasar Manusia

Saat ini perawat menghadapi suatu tantangan baru dalam upaya memberikan
perawatan yang berkualitas pada klien. Keperawatan merupakan ilmu pengetahuan dan seni
yang dapat memenuhi kebutuhan klien (Patrisia, etc., 2020). Menurut DeLaune & Ladner
(2011), kebutuhan merupakan segala sesuatu yang penting dan mutlak bagi seseorang
terutama klien. Kebutuhan dasar manusia adalah kebutuhan yang diperlukan dalam
kelangsungan hidup dan kesehatan manusia. Jika kebutuhan dasar manusia seperti psikologis,
fisiologis, sosial budaya, spiritual, dan intelektualnya terpenuhi, maka di dalam dirinya akan
merasakan kepuasan. Selama sehat, manusia dapat memenuhi kebutuhan dirinya sendiri.
Namun, jika sedang sakit maka manusia membutuhkan bantuan dalam memenuhi kebutuhan
dasarnya (Rosdahl & Kowalski, 2012). Adapun teori-teori kebutuhan dasar manusia menurut
para ahli:

1.1.1 Abraham Maslow (1970)

Abraham Maslow membagi kebutuhan dasar manusia menjadi lima tingkatan.

Kebutuhan tingkat paling dasar yaitu kebutuhan fisiologis. Kebutuhan fisiologis harus
dipenuhi sebelum mempengaruhi kebutuhan yang lebih tinggi. Kebutuhan tingkat kedua yaitu
kebutuhan keamanan dan keselamatan, merupakan kebutuhan untuk melindungi diri dari
berbagai bahaya yang mengancam (Asmadi, 2008).

Kebutuhan dasar tingkat ketiga yaitu kebutuhan akan cinta dan dicintai, seperti
persahabatan, hubungan sosial dan cinta. Kebutuhan tingkat keempat mencakup kebutuhan
harga diri yang termasuk kepercayaan diri, kegunaan, prestasi, dan harga diri (Potter & Perry,
2013). Kebutuhan dasar tingkat terakhir yaitu aktualisasi diri, merupakan keadaan mencapai
kondisi yang optimal dan memiliki kemampuan untuk memecahkan dan mengatasi masalah
secara realistis (Potter & Perry, 2013).

3
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Gambar 2.1 Kebutuhan dasar manusia menurut Maslow

1.1.2 Virginia Henderson (1966)

Henderson membagi kebutuhan dasar manusia menjadi 14 tipologi, diantaranya

kebutuhan bernafas secara normal, kebutuhan makan dan minum secara adekuat, kebutuhan
eliminasi (BAB dan BAK), kebutuhan bergerak dan mempertahankan posisi, kebutuhan
istirahat dan tidur, kebutuhan memilih pakaian yang tepat, kebutuhan mempertahankan
temperatur tubuh, kebutuhan untuk menjadikan tubuh bersih dan baik, kebutuhan
menghindari kerusakan lingkungan atau injuri, kebutuhan berkomunikasi, emosi, kebutuhan
kepercayaan, kebutuhan kerja, dan kebutuhan bermain (Hidayat & Uliyah, 2018).

1.1.3 Jean Watson

Jean Watson membagi kebutuhan dasar manusia menjadi empat cabang, diantaranya
kebutuhan dasar biofisikal (kebutuhan untuk hidup) meliputi kebutuhan makan dan cairan,
kebutuhan psikofisikal (kebutuhan fungsional) meliputi kebutuhan aktifitas dan istirahat,
kebutuhan psikososial (kebutuhan untuk integrasi) meliputi kebutuhan berprestasi dan
berorganisasi, kebutuhan intra dan interpersonal (kebutuhan untuk pengembangan) termasuk
kebutuhan aktualisasi diri (Hidayat & Uliyah, 2018).

1.2 Jenis Kebutuhan Dasar Manusia

Kebutuhan dasar manusia dibagi ke dalam beberapa bentuk. Jenis-jenis kebutuhan

dasar manusia menurut Abraham Maslow diantaranya:

1. Kebutuhan Fisiologis merupakan kebutuhan dasar manusia yang paling dasar,

mencakup oksigen / udara, cairan, nutrisi, tidur dan istirahat, suhu tubuh,
eliminasi, dan seksual (Rosdahl & Kowalski, 2012). Pemenuhan kebutuhan
 5

fisiologis bersifat lebih mendesak untuk didahulukan daripada kebutuhan-

kebutuhan yang lainnya.

2. Kebutuhan Rasa Aman (perlindungan dari cedera tubuh) serta kebutuhan akan
tempat tinggal dan bebas dari bahaya (Rosdahl & Kowalski, 2012).

3. Kebutuhan Cinta dan Dicintai, manusia memiliki kebutuhan bawaan dalam

menjadi bagian dari kelompok dan merasa diterima oleh orang lain (DeLaune &
Ladner, 2011). Setiap klien yang dirawat, memerlukan terpenuhinya kebutuhan
mencintai dan dicintai karena klien berada dalam kondisi ketidakberdayaan yang
disebabkan oleh penyakitnya (Asmadi, 2008).

4. Kebutuhan Harga Diri, seseorang dapat mencapai kebutuhan harga diri bila
kebutuhan dasar terhadap cinta dan dicintainya terpenuhi (Asmadi, 2008).

5. Kebutuhan Aktualisasi Diri, dibagi menjadi hambatan internal dan eksternal.

Hambatan internal adalah hambatan yang berasal dari dalam diri seseorang,
sedangkan hambatan eksternal adalah hambatan yang berasal dari luar diri
seseorang (Asmadi, 2008).

1.3 Karakteristik Kebutuhan Dasar Manusia

Untuk mengetahui kebutuhan dasar manusia, terdapat hal yang perlu diperhatikan
oleh perawat terkait dengan karakteristik kebutuhan dasar manusia. Karakteristik tersebut
adalah:

1. Manusia mempunyai kebutuhan dasr yang sama, walaupun setiap orang memiliki
latar belakang social, budaya, persepsi, dan pengetahuan yang berbeda.

2. Umumnya pemenuhan kebutuhan dasar setiap manusia sesuai dengan tingkat

prioritasnya.

3. Sebagian pemenuhan kebutuhan dasar dapat ditunda walaupun umumnya harus

dipenuhi.

4. Kegagalan pemenuhan salah satu kebutuhan dasar dapat mengakibatkan kondisi

yang tidak seimbang sehingga menyebabkan sakit.

5. Munculnya keinginan pemenuhan kebutuhan dasar dipengaruhi oleh stimulus

internal maupun eksternal.
 6

6. Berbagai kebutuhan dasar akan saling berhubungan dan berpengaruh pada

manusia.

7. Ketika timbul keinginan terhadap suatu kebutuhan, maka individu akan berusaha
untuk memenuhinya (Asmadi, 2008).

1.4 Faktor-Faktor yang Mempengaruhi Kebutuhan Dasar Manusia

Pemenuhan kebutuhan dasar pada manusia dipengaruhi oleh berbagai faktor, dari
internal maupun eksternal. Faktor-faktor tersebut adalah sebagai berikut.

1. Penyakit: Adanya penyakit dalam tubuh dapat menyebabkan perubahan

pemenuhan kebutuhan, baik secara fisiologis maupun psikologis, karena beberapa
fungsi organ tubuh memerlukan pemenuhan kebutuhan yang lebih besar dari
biasanya.

2. Hubungan keluarga: Hubungan keluarga yang baik dapat meningkatkan

pemenuhan kebutuhan dasar karena adanya saling percaya, merasakan
ketenangan hidup, tidak ada rasa curiga, dan lain-lain.

3. Konsep: Konsep diri manusia memiliki peran dalam pemenuhan kebutuhan dasar.
Konsep diri yang positif memberikan makna dan keutuhan bagi seseorang.
Konsep diri yang sehat menghasilkan diri yang positif terhadap diri. Orang yang
merasa positif tentang dirinya akan mudah berubah, mudah mengenali
kebutuhan, dan mengembangkan cara hidup yang sehat sehingga mudah
memenuhi kebutuhan dasarnya.

4. Tahap perkembangan:

a. Sejalan dengan meningkatnya usia, manusia mengalami perkembangan.

b. Berbagai fungsi organ tubuh mengalami proses kematangan dengan aktivitas

yang berbeda pada setiap tahap perkembangan.

c. Setiap tahap tersebut memiliki pemenuhan kebutuhan yang berbeda, baik

kebutuhan biologis, psikologis, social, maupun spiritual (Ardhiyanti, Pitriani,
& Damayanti. 2012)
 7

2.2 Perspektif Teori Pemenuhan Kebutuhan Pengontrolan Infeksi

2.1 Definisi Infeksi

Infeksi merupakan invasi tubuh oleh patogen atau mikroorganisme yang mampu
menyebabkan sakit. Penyakit akan timbul jika patogen berbiak dan menyebabkan perubahan
pada jaringan normal (Potter & Perry, 2005). Menurut Kurniati, Trisyani, & Theresia (2013),
infeksi merupakan mikroba dalam tubuh yang ditandai dengan respons inflamasi terhadap
keberadaan mikroorganisme atau invasi organisme terhadap jaringan host. Penuaan
menyebabkan banyak perubahan dalam proses biologis yang ditandai dengan penurunan
fungsi organ dan daya tahan tubuh yang terkait dengan peningkatan kerentanan seseorang
terhadap berbagai penyakit. Seseorang dengan lanjut usia memiliki resiko yang lebih besar
terinfeksi suatu penyakit. Banyak dari lansia yang mengeluhkan hipertensi, karena tingkat
kejadiannya masih dalam keadaan yang sangat tinggi serta tanda gejalanya dapat
membahayakan.

2.2 Jenis-Jenis Infeksi

1. Infeksi lokal, infeksi yang spesifik dan terbatas pada bagian tubuh dimana
mikroorganisme tinggal.

2. Infeksi sistemik, terjadi bila mikroorganisme menyebar ke bagian tubuh yang lain
dan menimbulkan kerusakan

3. Infeksi akut, infeksi yang muncul dalam waktu singkat

4. Infeksi kronik, infeksi yang terjadi secara lambat dalam periode yang lama (bulan
sampai tahun)

5. Bakteremia, terjadi apabila dalam darah ditemukan bakteri

6. Septicemia, multiplikasi bakteri dalam darah sebagai hasil dan infeksi sistemik

7. Kolonisasi, merupakan suatu proses dimana benih mikroorganisme menjadi flora

yang menetap. Mikroorganisme tersebut bisa tumbuh dan berkembang biak tetapi
tidak menimbulkan penyakit (Azis & Alimul, 2006)

2.3 Faktor-Faktor yang mempengaruhi Infeksi

Beberapa faktor mempengaruhi kerentanan seseorang terhadap infeksi. Berikut ini

adalah faktor-faktor yang mempengaruhi infeksi.
 8

1. Usia

Sepanjang hidup kerentanan seseorang terhadap infeksi berubah. Pertahanan

terhadap infeksi berubah seiring penuaan karena adanya perubahan respon imun.

2. Status Nutrisi

Kesehatan nutrisi pasien secara langsung memengaruhi kerentanan terhadap

infeksi. Penurunan asupan protein dan nutrisi lain seperti karbohidrat dan lemak
mengurangi pertahanan tubuh terhadap infeksi.

3. Stres

Tubuh merespon terhadap stress emosional atau fisik sesuai dengan sindrom
adaptasi umum. Jika seseorang sedang stress, kadar kortisol yang tinggi
mengakibatkan penurunan resistensi terhadap infeksi. Stress yang berlanjut
menyebabkan kelelahan, yang menyebabkan pengurangan energy yang
tersimpan, dan tubuh tidak memiliki ketahanan terhadap nutrisi seperti operasi
atau trauma juga meningkatkan tekanan fisiologis.

4. Proses Penyakit

Pasien dengan penyakit terkait sistem kekebalan tubuh memiliki risiko khusus
untuk infeksi. Pasien dengan penyakit kronis seperti diabetes melitus dan multiple
sclerosis juga lebih rentan terhadap infeksi karena kelemahan umum dan
gangguan nutrisi. Penyakit yang merusak pertahanan sistem tubuh seperti
emfisema dan bronkitis (yang menghambat aksi siliaris dan memperkental
lender), kanker (yang mengubah respons imun), dan penyakit vaskular perifer
(yang mengurangi aliran darah ke jaringan yang cedera) meningkatkan
kerentanan terhadap infeksi.

2.4 Dampak Perubahan Kebutuhan Pengelolaan Infeksi terhadap Homeostasis

Tubuh

Homeostasis merupakan mekanisme tubuh untuk mempertahankan keseimbangan

dalam menghadapi berbagai kondisi yang dialaminya. Proses homeostatis ini dapat terjadi
secara alamiah apabila tubuh sedang mengalami stres (Hidayat, 2008). Dampak apabila
infeksi tidak terkelola bagi tubuh adalah akan menimbulkan keadaan tubuh memburuk dari
yang biasanya (Alfhad, Saftarina, & Kurniawan, 2020).
 9

2.5 Masalah Keperawatan yang Berhubungan dengan Pemenuhan Kebutuhan

Pengontrolan Infeksi

1. Risiko infeksi

2. Risiko intoleransi aktivitas

3. Defisien pengetahuan

4. Perilaku kesehatan cenderung berisiko (NANDA, 2018-2020)

2.3 Analisis Hubungan Hipertensi, Pengontrolan Infeksi, dan COVID-19

Terpaparnya infeksi COVID-19 pada kelompok yang rentan memiliki risiko tinggi,
yang termasuk kelompok retan adalah lansia dan orang yang memiliki penyakit penyerta
(komorbid) salah satunya adalah hipertensi. Hasil penelitian Zou, Zhu, & Xu (2020),
menunjukan bahwa komorbid utama COVID-19 adalah hipertensi. Orang yang terpapar
infeksi COVID-19 dengan riwayat hipertensi memiliki jumlah limfosit yang rendah dan
memiliki faktor risiko prognosis yang buruk. Menurut WHO (2021), penderita hipertensi
memiliki risiko tinggi terhadap infeksi COVID-19 karena memiliki imunitas yang cenderung
rendah sehingga lebih mudah untuk terinfeksi.

Hasilnya membuktikan berdasarkan data per 13 Oktober 2020, dari total 1.488 kasus
COVID-19, sebanyak 50,5% memiliki penyakit penyerta yaitu hipertensi, dan kasus pasien
dengan penyakit penyerta hipertensi sebanyak 13,2% meninggal dunia (Kemenkes RI, 2020).
Seseorang yang terpapar infeksi COVID-19 dengan penyakit penyerta akan menunjukan
gejala yang lebih berat, bahkan hingga terjadi kerusakan pada organ tubuhnya (Bahtiar &
Ariyanti, 2021). Oleh karena itu, maka diperlukan upaya pengelolaan infeksi pada pasien
dengan hipertensi di masa pandemi COVID-19 ini.

2.4 Intervensi Pemenuhan Kebutuhan Infeksi

Pencarian literatur dilakukan dengan menggunakan tiga search engine yaitu Google
Scholar, EBSCO CINAHL Plus, dan PubMed. Untuk menjawab latar belakang yang telah
ditetapkan, dibutuhkan literatur yang sesuai dengan topik bahasan. Maka, digunakan kata
kunci dalam bahasa inggris “hypertension” OR “high blood pressure” AND “infection
control” OR “infection prevention” AND “pandemic” OR “COVID-19”. Sementara untuk
mencari literatur berbahasa Indonesia, kata kunci yang digunakan adalah “hipertensi” ATAU
“darah tinggi” DAN “pencegahan infeksi” DAN “COVID-19”.
 10

Tabel 2.1 Analisis Jurnal

No. Judul Artikel Penulis dan Tujuan Artikel Jenis Hasil Analisis
Tahun Artikel

1. Recommendation Ja Young Kim, Untuk memberi Guidelines Selain melakukan karantina di rumah, terdapat lima
for Response to Jin-Ok Han1, rekomendasi cara kunci aturan pengendalian infeksi individu sebagai
The COVID-19 and Heeyoung agar masyarakat berikut:
Pandemic: Lee. dapat mendukung a. Tetap di rumah selama 3-4 hari jika merasa
Korean Context dan melindungi tidak enak badan karena pasien dengan COVID-
of “Distancing in (2020) populasi yang 19 gejala ringan dapat menyebarkan virus pada
Daily Life” rentan agar dapat tahap awal.
Considering memperkuat b. Jaga jarak sejauh 1 meter (atau panjang dua
Vulnerable struktur sosial lengan) dari yang lain karena COVID-19
Population secara menular lewat droplets.
keseluruhan. c. Mencuci tangan selama 30 detik dan batuk atau
bersin ke lengan baju, hal tersebut juga dapat
didukung dengan penggunaan masker.
d. Membuka ventilasi setidaknya dua kali sehari
dan melakukan desinfeksi secara teratur,
terutama di ruang publik.
e. Tetap terhubung sambil menjaga jarak secara
fisik, hal ini diperlukan untuk mengurangi
kecemasan dan rasa takut dalam menghadapi
pandemi.

2. Olahraga Rutin Badai Bhatara Untuk melihat Literatur Salah satu upaya pencegahan primer dari hipertensi
untuk Tiksnadi, Nova pengaruh Review ialah dengan olahraga rutin. Manfaat olahraga tidak
Meningkatkan Sylviana, olahraga rutin hanya bertujuan untuk pengendalian tekanan darah,
Imunitas Adi Imam dalam dan mengurangi risiko kardiovaskular namun juga
Pasien Hipertensi Cahyadi, meningkatkan dalam meningkatkan
Selama Masa Alberta Claudia imunitas tubuh Imunitas. Aktivitas fisik teratur dengan intensitas
 11

Pandemi COVID- Undarsa. pada pasien sedang telah banyak dibuktikan berhubungan dengan
19. dengan hipertensi penurunan mortalitas, serta insiden pneumonia dan
(2020) pada masa Influenza. Olahraga jenis aerobik dengan intensitas
pandemi COVID- sedang dalam waktu 30-60 menit, menunjukkan peran
19. yang penting dalam menstimulasi sistem imun.

Dalam masa pembatasan sosial, maka olahraga

tersebut dilakukan dengan pembatasan jarak, atau
dengan teknik home-exercise, secara virtual atau
dengan daring.

3. Pengaruh Anung Ahadi Untuk Literatur Tenaga kesehatan wajib mengedepankan pengkajian
Kebijakan Social Pradana, memberikan Review terhadap kelompok rentan dalam hal pemahaman
Distancing Ppda Casman, gambaran efek terkait COVID-19, bagaimana upaya pencegahan,
Wabah Nur’aini. social distancing hambatan yang mungkin terjadi dalam melaksanakan
COVID-19 pada upaya pencegahan, serta modifikasi apa yang bisa
Terhadap (2020) kelompok rentan dilakukan kelompok rentan untuk mendukung upaya
Kelompok Rentan di negara social distancing.
di Indonesia. Indonesia.
Hal-hal yang penting menjadi perhatian tenaga
kesehatan selama pandemi COVID-19 antara lain:
melanjutkan pencegahan utama melalui skrining dan
isolasi rutin untuk mengurangi penyebaran penyakit,
menggunakan teknik Konseling, Informasi, dan
Edukasi (KIE) berbasis internet bagi masyarakat
dengan tujuan untuk mengurangi ketergantungan
masyarakat pada pelayanan kesehatan primer dan
sekunder, menciptakan program untuk melindungi
kelompok rentan dari infeksi yang terjadi, serta
memastikan respon pelayanan cepat dan alat-alat
pendukung di RS khususnya pelayanan bagi
kelompok rentan.
 12

4. State-of-The-Art Keith C. Untuk Guidelines Beberapa metode non-farmakologi yang

Review: Ferdinand, merangkum direkomendasikan untuk mengontrol darah tinggi
Hypertension Thanh N. Vo, konsep dan data pada masa pandemi COVID-19 adalah sebagai
Practice Melvin R. terkait diagnosis, berikut:
Guidelines in The Echols. pemantauan, a. Monitoring tekanan darah rutin dengan
Era of penaganan, dan pemeriksaan secara mandiri di rumah.
COVID-19. (2020) perawatan b. Targetkan penurunan berat badan minimal 1 kg
sebagai pedoman untuk orang dewasa yang kelebihan berat badan.
penangan pasien Hal ini diharapkan dapat menurunkan tekanan
dengan hipertensi darah sebesar ~ 1 mmHg untuk setiap 1 kg berat
di tengah badan.
pandemi COVID- c. Melakukan Pola diet DASH. Diet kaya buah-
19. buahan, sayuran, biji-bijian, produk susu rendah
lemak, dengan pengurangan kandungan lemak
jenuh.
d. Diet sodium (<1500 mg/hari) dan diet potasium
(3500–5000 mg/hari).
e. Melakukan olahraga aerobik sebanyak 90-150
menit/minggu pada 65–75% dari denyut jantung
maksimal.
f. Kurangi minum alkohol jadi hanya 1 gelas/hari
(~ 12 ons bir atau 5 ons wine)

5. Can Optimum Joji Abraham, Untuk Literatur Vitamin D terbukti berperan dalam menghambat
Solar Radiation Kim Dowling, menganalisis Review berbagai infeksi dan peradangan sehingga perannya
Exposure or Singarayer hasil penelitian sangat penting dalam kesehatan tubuh secara umum.
Supplemented Florentine. yang Terutama dalam konteks COVID-19, vitamin D
Vitamin D Intake dipublikasikan berkorelasi dengan dampak positif dalam mengurangi
Reduce the (2021) dan menunjukkan infeksi dan gejala. Faktor yang terkait dengan
Severity of pengaruh kematian COVID-19, seperti usia tua, etnis, obesitas,
COVID-19 peningkatan hipertensi, penyakit kardiovaskular, dan diabetes,
Symptoms? kadar vitamin D semuanya ditemukan berhubungan dengan kurangnya
 13

dalam meredakan vitamin D.

gejala yang mirip
dengan COVID- Oleh karena itu, paparan sinar matahari yang tepat
19, terutama dan aman serta konsumsi makanan dan suplemen
ARDS dan ARTI. yang diperkaya vitamin D harus dipertimbangkan.
Vitamin D juga dapat mengurangi dampak penyakit
lain, sehingga dapat membantu menjaga kesejahteraan
manusia secara umum.

6. Nutrients In Fatemeh Untuk Literature Kandungan nutrisi pada makanan seperti protein,
Prevention, BourBour, menganalisis Riview asam lemak omega-3, vitamin A D E B1 B12 C, zat
Treatment, And Samaneh nutrisi yang besi, seng dan selenium memiliki efek penting untuk
Management Of Mirzae Dahka, efektif pada meningkatkan kekebalan tubuh sehingga
Viral Infection; Maryam sistem kekebalan meningkatkan kemampuan tubuh dalam mencegah
Special Focus On Gholamalizadeh terhadap infeksi dan mengatasi infeksi virus. Selain itu, Vitamin C
Coronavirus ,Mohammad virus dan nutrisi dosis tinggi intravena dan D dapat menjadi pilihan
Esmail Akbar, yang berpotensi pengobatan yang efektif untuk COVID-19 tahap awal.
Mahdi efektif dalam
Shadnoush, pencegahan,
Mohammad pengobatan dan
Haghighi, pengelolaan
Hamidreza COVID-19.
Taghvaye-
Masoumi,
Narjes Ashoori
and Saied Doaei
(2020)
 BAB III
INTERVENSI KEPERAWATAN PEMENUHAN KEBUTUHAN

2.1 Pencarian Literatur

Pencarian literatur dilakukan dengan menggunakan Google Scholar dengan kata kunci
berbahasa Indonesia, yaitu “pendidikan” ATAU “edukasi” DAN “pencegahan” DAN
“COVID-19”.

2.2 Metode Pendidikan Kesehatan dengan Infografis

Salah satu intervensi yang dapat dilakukan pada kelompok yang beresiko (hipertensi)
berdasarkan sumber yang dibuat oleh Kementrian Kesehatan Republik Indonesia tahun 2020
yang berjudul “Strategi Komunikasi Perubahan Perilaku (KPP) dalam Pencegahan COVID-
19” yaitu pendidikan kesehatan melalui infografis. Infografis dipilih karena masyarakat
Indonesia lebih menyukai visual dan dapat memberikan informasi yang memadai untuk
sebuah pesan tertentu dalam sebuah frame dan mudah disebarkan melalui media sosial seperti
Facebook, Instagram, Line, termasuk melalui grup-grup Whatsapp. Hal ini juga dilakukan
untuk mengakomodasi kebutuhan masyarakat akan informasi yang akurat dan cepat melalui
handphone, tanpa harus keluar rumah.

Dalam membagikan infografis ada dua opsi, yang pertama meminta kader untuk
membagikan infografis kedalam grup whatsapp yang telah dibuat oleh kader dan opsi yang
kedua adalah kelompok kami yang akan membuat grup whatsapp khusus untuk masyarakat
yang berisiko dalam penularan COVID-19. Adapun infografis yang akan diberikan adalah
mengenai topik berikut:

1. Disiplin di Rumah Saja

2. Cara Batuk dan Bersin yang benar

3. Disiplin Jaga Jarak

4. Mencuci Tangan yang benar (Kim, Han, & Lee, 2020)

5. Olahraga rutin (Tiksnadi, Sylviana, Cahyadi, & Undarsa, 2020)

14
 15

3 Metode Pendidikan Kesehatan eKIE (Komunikasi, Informasi dan Edukasi

Elektronik)

Promosi kesehatan melalui komunikasi, informasi, dan edukasi merupakan pilihan yang
baik (Nuraeni, Mirwanti & Anna, 2017). Pemberian informasi dan edukasi pada masyarakat
dapat melalui berbagai cara, salah satunya adalah penyampaian informasi dan edukasi
kesehatan melalui media sosial seperti whattsapp yang sekarang banyak digunakan di
masyarakat. Metode yang digunakan dalam kegiatan ini yaitu promosi kesehatan eKIE
(komunikasi, informasi dan edukasi elektronik) berupa pemberian materi dan diskusi
interaktif secara online. Pemberian materi dilakukan dengan mem-posting materi dalam
bentuk gambar, kemudian dijelaskan dengan tulisan dan atau pesan suara (voice note). Sesi
pertama eKIE mengenai penyakit hipertensi, dan sesi kedua membahas mengenai perawatan
diri pasien hipertensi secara mandiri di rumah. Kemudian di evaluasi menggunakan pre test
dan post test.

Metode ini terbukti dapat meningkatkan pengetahuan penderita hipertensi, hal ini
menunjukkan bahwa pengetahuan mengenai penyakit hipertensi, motivasi diri, diet
hipertensi, aktifitas fisik/olahraga yang sesuai, perawatan diri dan meningkatkan imunitas
tubuh, pencegahan dan perilaku pengobatan hipertensi di rumah di masa pandemik COVID-
19 atau era new normal bertambah setelah dilakukan eKIE (Angeraina, et al. 2020).

4 Topik Pendidikan Kesehatan

Intervensi yang akan dilakukan pada kelompok yang beresiko khususnya hipertensi di
masa pandemi COVID-19 ini berdasarkan sumber yang dibuat oleh Kementrian Kesehatan
Republik Indonesia tahun 2020 dengan judul “Panduan Gizi Seimbang Pada Masa Pandemi
COVID-19 (Lindungi Keluarga)” yaitu mencuci tangan dengan sabun, rutin berolahraga dan
makan makanan bergizi. Pada masa pandemi ini, kita harus meningkatkan kekebalan tubuh
sebagai kekuatan pertahanan tubuh untuk melawan bakteri, virus, dan organisme penyebab
penyakit melalui sentuhan, konsumsi maupun udara. Meningkatkan daya tahan tubuh
merupakan salah satu kunci supaya tidak tertular virus COVID-19 ini.

Hal yang dapat mencegah tertularnya COVID-19 yaitu dengan makanan yang bergizi
dan seimbang sehingga dapat meningkatkan sistem kekebalan tubuh dan menurunkan risiko
pada penyakit kronis khususnya hipertensi dan infeksi, dengan memperhatikan asupan nutrisi
pada makanan dan gaya hidup yaitu:
 16

1. Konsumsi makanan bergizi seimbang (isi piringku). Mengkonsumsi makanan sebaiknya

bergizi dan seimbang serta perbanyak konsumsi buah dan sayur. Buah sayuran segar
merupakan sumber vitamin dan mineral serta serat yang dibutuhkan. Pilih buah yang
mengandung vitamin khususnya vit A dan C, mineral dan antioksidan yang sangat
potensial melawan oksidasi yang menurunkan kondisi tubuh sehingga tubuh tetap sehat.

2. Batasi pemakaian gula, garam, dan lemak

3. Hindari rokok dan minuman beralkohol

4. Istirahat atau tidur yang cukup, sekitar 6-8 jam sehari

5. Rileks dan mengendalikan emosi

6. Beraktivitas fisik. Berolahraga dan terpapar cukup sinar matahari selama 30 menit setiap
hari atau minimal 3-5 hari seminggu. Selain itu, usahakan cukup mendapatkan sinar
matahari dengan membuka jendela rumah atau berjemur setiap pagi selama 15 menit.

7. Mengkonsumsi vitamin jika diperlukan

8. Berperilaku hidup bersih dan sehat (PHBS). Budaya perilaku hidup bersih dan sehat akan
menyebabkan seseorang terhindar dari paparan sumber infeksi, contohnya:

a. Mencuci tangan dengan sabun dan air mengalir selama 40-60 detik atau
menggunakan hand sanitizer.

b. Menerapkan etika batuk dan bersin dengan cara menggunakan masker,

menggunakan tisu lalu membuang ke tempat sampah tertutup, lalu segera mencuci
tangan dengan sabun dan air mengalir.

c. Tidak meludah di sembarang tempat.

d. Tidak merokok dan mengkonsumsi narkoba.

e. Menghindari menyentuh area wajah (mata, hidung, mulu) dengan tangan yang
belum dicuci

f. Mengganti baju dan mandi segera setelah bepergian

g. Membersihkan dengan desinfektan secara rutin benda-benda yang sering disentuh

dirumah seperti meja dan lainnya
9. Menjaga jarak fisik dari orang lain. Pembatasan jarak yang benar yaitu:

a. Menjaga jarak dengan orang lain minimal 1 meter.

 17

b. Selalu menggunakan masker ketika keluar rumah

c. Menghindari kerumunan

d. Menghindari bepergian ke tempat umum dan makan diluar.

e. Tidak pergi ke luar kota atau luar negeri

f. Menunda mudik

g. Tidak bersalaman atau berjabat tangan, cium pipi, berpelukan, dan lain-lain

h. Bekerja, belajar, beribadah dan bermain di rumah

i. Jika ada yang sakit, lakukan isolasi mandiri di rumah dan mencari pengobatan

segera apabila ada gejala berat atau memburuk.

 BAB IV

PEMBAHASAN

Penderita hipertensi memiliki resiko terkena covid-19 karena memiliki imunitas yang
rendah dan akan menjadi lebih berat sampai kepada kerusakan pada organ. Berdasarkan
penelitian beberapa ahli  orang yang lebih  beresiko terkena virus covid yaitu seseorang
dengan usia 60 tahun keatas dan yang memiliki masalah kesehatan diantaranya hipertensi,
diabetes, masalah jantung dan paru-paru, obesitas dan kanker. Hasil penelitian menyatakan
bahwa komorbid utama covid 19 adalah Hipertensi. Pernyataan tersebut disebabkan karena
orang dengan riwayat hipertensi memiliki jumlah limfosit yang rendah dan memiliki faktor
risiko prognosis yang buruk pada pasien dengan covid 19.

Kebutuhan dasar manusia sangat di perlukan baik dalam keadaan sehat yang dapat
memenuhi kebutuhan dirinya sendiri, maupun keadaan sakit membutuhkan bantuan dalam
memenuhi kebutuhan dasarnya. menurut teori jean Watson kebutuhan dasar manusia dibagi
menjadi empat cabang, diantaranya kebutuhan dasar biofisikal (kebutuhan untuk hidup)
meliputi kebutuhan makan dan cairan, kebutuhan psikofisikal (kebutuhan fungsional)
meliputi kebutuhan aktifitas dan istirahat, kebutuhan psikososial (kebutuhan untuk integrasi)
meliputi kebutuhan berprestasi dan berorganisasi, kebutuhan intra dan interpersonal
(kebutuhan untuk pengembangan) termasuk kebutuhan aktualisasi diri. Teori ini sejalan
dengan teori dari Henderson yang salah satunya adalah kebutuhan makan dan minum secara
adekuat, kebutuhan eliminasi (BAB dan BAK), kebutuhan bergerak dan mempertahankan
posisi. Pasien dengan penyakit terkait sistem kekebalan tubuh dengan kdm yang kurang baik
memiliki risiko khusus untuk infeksi dampaknya apabila infeksi tidak terkelola bagi tubuh
adalah akan menimbulkan keadaan tubuh memburuk dari yang biasanya salah satunya infeksi
Covid-19.

Corona virus 2019 (Covid-19) adalah penyakit yang disebabkan oleh virus baru yang
disebut dengan SARS-CoV-2 yang memiliki gejala  pada sistem pernafasan. Berbagai cara
telah dilakukan baik farmasi di rumah sakit maupun non farmasi seperti karantina,
pembatasan jarak sosial, memeriksa setiap orang yang melakukan perjalanan yang berasal
dari daerah yang berbeda serta sering mencuci tangan tetapi semua itu belum cukup karena
ternyata dengan tingginya resiko penderita hipertensi terinfeksi covid 19 yang kemudian
dapat memperburuk keadaan kesehatannya akibat komorbid tersebut, maka diperlukan

18
 19

pendidikan kesehatan sebagai upaya pengelolaan infeksi pada pasien dengan hipertensi di
masa pandemi covid 19 ini.

Hal yang dapat dijadikan sebagai topik pendidikan kesehatan yaitu pengetahuan
mengenai yaitu mencuci tangan dengan sabun dengan air mengalir atau menggunakan
handsanitizer, rutin berolahraga salah satunya lakukan olahraga dengan intensitas ringan,
seperti jogging, jalan cepat, bersepeda, maupun berenang dan makan makanan bergizi yaitu
perbanyak konsumsi makanan yang kaya akan oksidan, mineral, dan vitamin yang bisa kamu
temui pada sayur-sayuran, buah, biji-bijian, serta beragam jenis kacang. Selain itu, makanan
yang kaya akan lemak sehat, seperti salmon dan minyak zaitun – juga dianjurkan untuk
dikonsumsi. Dalam mengurangi resiko infeksi maka perlu dilakukan intervensi yang sesuai
dengan evidence based practice sebagai berikut:

4.1 Karantina Di Rumah

Tetap dirumah selama 3-4 hari jika badan terasa tidak enak merupakan salah satu
pencegahan yang baik dilakukan individu dalam mengurangi resiko terjadinya Covid-19
karena pasien COVID-19 dengan gejala ringan dapat menyebarkan virus pada tahap awal.
Untuk mengikuti aturan penting pertama untuk pengendalian infeksi individu, ketika mereka
mengalami demam atau gejala pernapasan terkait dengan COVID-19. Dalam kasus diagnosis
yang dikonfirmasi atau kontak dekat dengan pasien COVID-19, pemerintah Korea mencoba
untuk mendukung pembayaran sakit selama periode isolasi (Kim, 2020). Salah satu hal yang
bisa dilakukan untuk mencegah penularan virus Covid 19 adalah dengan tidak melakukan
aktivitas di luar rumah. Dengan tidak beraktivitas di luar rumah, seseorang dapat menekan
angka penyebaran virus Covid 19. mengurang kegiatan aktivitas di luar rumah dapat menjadi
salah satu cara untuk menjaga seseorang dari kontang langsung dan fisik terhadap orang yang
positif virus Covid 19 (Karuniawan, 2020)

4.2 Jaga Jarak/Social Distancing

Menjaga jarak 1 meter kebijakan jaga jarak yang dipilih pemerintah bukanlah tanpa
resiko. Perintah kebijakan jaga jarak dalam jangka panjang dapat memperlambat kegiatan
produksi ekonomi (supply shock). Pembatasan interaksi sosial dapat mengurangi jumlah
produksi barang yang krusial. Hal ini berlaku untuk produksi baik didalam maupun luar

19
 20

negeri. Akibatnya, tingkat kegiatan dan permintaan ekonomi secara keseluruhan juga akan
terganggu. Terlepas efektif atau tidak, yang jelas jaga jarak adalah tindakan menghindari
yang paling mungkin dilakukan oleh setiap orang guna terhindar dari penularan virus tersebut
(Khaeruman, 2020).

4.3 Mencuci Tangan

Mencuci tangan selama 30 detik adalah salah satu cara yang mudah dipraktikkan oleh
semua orang merupakan metode paling dasar untuk meminimalkan penularan COVID-19
melalui tangan yang terkontaminasi atau tetesan air liur (Kim, 2020). Cuci tangan secara
teratur dan menyeluruh dengan sabun dibawah air mengalir dengan 7 langkah yang
dianjurkan oleh WHO karena dapat membunuh virus yang mungkin ada di tangan seperti
virus corona (Covid-19) yang bisa menempel di berbagai permukaan secara tak langsung
dipegang dan mencuci tangan dibawah air mengalir menjaga kita tetap sehat dan mencegah
penyebaran infeksi pernapasan dan diare dari satu orang ke orang lain. Cara mencuci tangan
yang baik yaitu

1. Telapak Tangan Gunakan sabun dan ditaruh di telapak tangan. Basahi tangan dan
gosokkan telapak tangan yang sudah diberi sabun tersebut.
2. Telapak Punggung Tangan Gosok juga punggung tangan bagian kanan dan kiri.
Pastikan seluruh permukaan terkena sabun.
3. Sela-sela Jari Kemudian gosokkan sabun ke sela-sela jari. Sela-sela jari menjadi
salah satu tempat bersembunyinya kuman.
4. Punggung Tangan Bersihkan juga punggung tangan dengan gerakan saling
mengunci.
5. Jempol Bersihkan jempol bagian kanan dan kiri secara bergantian dengan gerakan
memutar. Jempol menjadi salah satu bagian jari tangan yang paling aktif
beraktivitas.
6. Ujung Jari Bersihkan bagian ujung jari dengan gerakan menguncup. Tujuannya
untuk membebaskan kuku dari kuman-kuman.
7. Bersihkan Tangan Bersihkan tangan yang sudah disabunkan dengan air mengalir
selama 20 detik dan keringkan (WHO, 2020)

Mencuci tangan dengan sabun sebelum makan juga perlu dilakukan. Salah satu langkah
untuk mencegah penyebaran virus COVID-19 adalah dengan cuci tangan sebelum makan

20
 21

maupun melakukan aktivitas apapun menggunakan sabun dan air mengalir selama 20 detik.
Pilih sabun maupun cairan pencuci tangan yang mengandung alkohol sebesar 60%.Cara
mencuci tangannya pun harus tepat agar Anda terhindar dari virus Corona, kuman dan
bakteri. Tujuan cuci tangan adalah menghilangkan kotoran dan debu secara mekanis dari per-
mukaan kulit dan secara bermakna mengurangi jumlah mikroorganisme penyebab penyakit
seperti virus, bakteri dan parasit lainnya pada kedua tangan. Mencuci tangandengan
menggunakan air dan sabun dapat lebih efektif membersihkan kotoran dan telur cacing yang
menempelpada permukaan kulit, kuku dan jari-jari (Karuniawan, 2020).

4.4 Rutin Membuka Ventilasi Dan Desinfeksi

Pengelolaan lingkungan hunian dan tempat kerja perlu dikelola secara optimal, tidak
hanya di tingkat pribadi tetapi juga di tingkat masyarakat. Informasi mengenai potensi virus
penyebab COVID-19 bisa bertahan di udara atau menyebar secara aerosol. Oleh karena itu,
menjaga sirkulasi udara yang baik dan melakukan desinfeksi di rumah merupakan salah satu
bentuk upaya penyebaran virus COVID-19 di rumah. Setidaknya ventilasi rumah harus
dibuka dua kali sehari untuk mengurangi virus COVID-19. Hasil penelitian Karuniawan
(2020), menunjukkan bahwa responden sudah menjaga sirkulasi udara di rumah masing-
masing dengan selalu membuka jendela dan ventilasi. Hal ini tentu menjadi salah satu upaya
perwujudan pencegahan penyebaran virus Covid 19. Kesadaran ini tentu juga menjadi sebuah
hal yang menggembirakan di tengah pandemi virus ini. Hal Ini menunjukkan bahwa
masyarakat sudah sangat sadar untuk melakukan beberapa hal dalam menanggulani
penyebaran virus Covid 19 (Karuniawan, 2020).

4.5 Tetap Melakukan Interaksi Sosial

4.6 Meningkatkan Asupan Vitamin D

Asupan vitamin dan pengoptimallam paparan radiasi terbukti sangat berperan dalam
menghambat berbagai infeksi yang masuk kedalam tubuh. Vitamin D memiliki peranan yang
sangat penting untuk meningkatkan sistem kekebalan tubuh. Vitamin D bersifat larut dalam
lemak dan memiliki manfaat yang sangat besar dalam hal kemampuan melawan peradangan
dalam tubuh. Vitamin D juga berperan dalam regulasi imun, serta membantu mengaktifkan

21
 22

pertahanan sistem imun dengan cara mendorong fungsi sel-sel imun seperti sel T dan
makrofag. Cara yang dapat dilakukan untuk memenuhi kebutuhan vitamin D adalah dengan
mendapatkan sinar matahari pada pagi hari sekitar 10-15 menit serta mengkonsumsi makanan
sehat antara lain  kuning telur, jamur shitake, hati sapi, keju, udang, ikan terutama ikan yang
berlemak seperti salmon dan tuna. Faktanya, untuk mendapatkan vitamin D sesuai kebutuhan
tubuh paparan sinar matahari dan makanan saja tidak cukup. Berdasarkan penelitian
meskipun Indonesia termasuk negara tropis yang kaya sinar matahari, sebanyak 80 % orang
indonesia dari berbagai usia bahkan ibu hamil masih mengalami defisiensi vitamin D.
Meskipun hingga saat ini masih belum ada bukti kuat bahwa vitamin D dapat membantu
melindungi tubuh dari virus covid-19 tetapi ada cukup bukti ilmiah yang menunjukkan bahwa
kadar vitamin D yang rendah dalam tubuh dapat membuat tubuh lebih rentan terhadap infeksi
dan penyakit pernapasan, seperti Covid-19. Kebutuhan vitamin D dapat dipenuhi dengan
mengkonsumsi tambahan suplemen Vitamin D.

4.7 Olahraga Rutin

Berdasarkan penelitian penderita hipertensi dan penyakit kardiovaskular rentan

mengalami sakit berat dan kematian bila terinveksi Covid-19, oleh karena itu kelompok
pasien hipertensi memerlukan strategi penguatan imunitas tubuh agar terhindar dari infeksi
Covid-19. Maka dari itu olahraga rutin sangat diperlukan dan secara umum dapat diterapkan
di masyarakat indonesia maupun luar. Salah satunya dengan cara senam aerobik regular
(minimal 30 menit, latihan dinamik dengan intensitas sedang, 5-7 hari perminggu) untuk
pasien hipertensi berdasarkan meta analisis penurunan tekanan darah sekitar 3,5-20 mmHg
dan tekanan diastolik 2,5-6,2 mmHg tergantung jenis dan rutinnya dalam berolahraga
(Bhatara, 2020). Olahraga sangat disarankan untuk seseorang yang sehat maupun sakit
teritama hipertensi dan penderita Covid sekalipun. Manfaaat olahraga tidak hanya untuk
pengendalian tekanan darandan mengurangi resiko penyakit kardiovaskular tetapi juga unuk
meingkatkan imunitas. Dengan olahraga 30-60 menit olahraga menunjukan hasul yang bak
dan dapat menstimulasi sistem imun dengan catatan tetap menjaga jarak 1 dengan lainnya
atau dengan cara home-exercise, virtual atau daring (Bhatara, 2020).

4.8 Monitoring Tekanan Darah Rutin

Seseorang dengan riwayat hipertensi sangat penting dilakukannya monitoring tekanan

darah rutin yang bisa dilakukan dengan kontrol rutin ke puskesmas atau petugas kesehatan.

22
 23

Dampak yang ditimbulkan pada seseorang dengan riwayat hipertensi ini cukup berat
sehingga membutuhkan penanganan yang baik serta deteksi dini yang tepat oleh tenaga
kesehatan. Kegiatan skrining hipertensi pada lansia yang belum mengetahui mempunyai
hipertensi sangat perlu dilakukan baik itu skrining berbasis rumah, Puskesmas dan
komunitas untuk menemukan kasus baru dan melakukan manajemen hipertensi dari mulai
edukasi, perawatan dan pengobatanya (Kemenkes, 2018). Hasil penelitian didukung oleh
penelitian Suparti dan Handayani (2018) yang menyatakan bahwa Skrining hipertensi
responden yang berisiko menderita hipertensi sebanyak 107 (52,2%) dan yang tidak berisiko
menderita hipertensi dan sebanyak 98 (47,8) (Susanti, 2021).

4.9 Menurunkan Berat Badan

Targetkan penurunan berat badan minimal 1 kg pada orang dewasa yang memiliki
kelebihan berat badan, hal ini diharapkan dapat menurunkan tekanan darah sebesar ~ 1
mmHg untuk setiap 1 kg berat badan. Berat badan yang berlebih (obesitas) mempunyai kaitan
erat dengan terjadinya hipertensi dikemudian hari. Obesitas terjadi akibat mengonsumsi
kalori lebih banyak daripada yang dibutuhkan oleh tubuh. Ada kecenderungan lansia memilih
makanan lunak yang seringkali mempunyai kandungan energi tinggi, misalnya jenis
karbohidrat atau lemak. Lingkungan juga memegang peranan penting dalam kasus obesitas,
misalnya apa yang dimakan dan berapa kali makan dalam sehari, serta bagaimana
aktivitasnya. Hampir semua lansia mengonsumsi kalori lebih dari angka kecukupan gizi
(AKG). Pada kondisi obesitas, terjadi peningkatan jumlah asam lemak bebas yang akan
mempersempit pembuluh darah sehingga tekanan darah meningkat. Daya pompa jantung dan
sirkulasi volume darah penderita obesitas dengan hipertensi menjadi lebih tinggi dibanding
dengan yang berat badannya normal. Hasil analisis membuktikan adanya pengaruh antara
obesitas terhadap hipertensi. Penelitian lain yang menggunakan RLPP sebagai indikator
obesitas, membuktikan bahwa perempuan dengan RLPP lebih dari atau sama dengan 0,8
mempunyai risiko 11,5 kali untuk menderita hipertensi (Malonda, 2012).

4.10 Diet Sodium(Garam) dan Potassium

Pola makan dengan diet rendah garam dapat mengurangi asupan garam kedalam
tubuh. Perilaku diet rendah garam merupakan hasil keputusan berdasarkan niat individu yang
dibentuk melalui sikap terhadap perilaku diet rendah garam dan control perilaku yang
dirasakan.Melaksanakan diet rendah garam dibangun oleh sikap terhadap perilaku lansia

23
 24

penderita hipertensi. Niat melaksanakan diet rendah garam didukung oleh norma subyektif
lansia penderita hipertensi. Hasil penelitian Alberta, Proboningsih dan Almahmudah (2014),
menyatakan bahwa sikap yang baik terhadap niat melaksanakan diet rendah garam sebesar
93,75%. Penelitian yang dilakukan oleh Indriyawati (2018), menyatakan bahwa pendidikan
kesehatan tentang diet efektif mencegah terjadinya hipertensi. Penelitian yang dilakukan oleh
Saraswati dan Novianti (2019), menyatakan bahwa pelatihan diet sehat gizi seimbang efektif
untuk mencegah hipertensi. Penelitian Trisnowati (2018), menyatakan bahwa program
promosi kesehatan tentang diet seimbang efektif untuk mencegah hipertensi di masa pandemi
Covid saat ini (Susanti, 2021).

4.11 Mengatur Asupan Nutrisi

Pola konsumsi makanan sebaiknya mengandung zat gizi dalam jenis dan jumlah yang
sesuai dengan kebutuhan tubuh sebagai upaya diet sehat dan seimbang. Zat gizi yang
dibutuhkan untuk sehat adalah karbohidrat, protein, lemak, vitamin dan mineral (Thasim
2013). Konsumsi makanan juga sebaiknya memperbanyak konsumsi buah dan sayur. Buah
dan sayuran segar merupakan sumber vitamin dan mineral serta serat yang dibutuhkan.
Pilihlah buah yang mengandung vitamin khususnya vit A dan C, mineral dan antioksidan
yang sangat baik untuk melawan oksidasi yang menurunkan kondisi tubuh sehingga kondisi
tubuh tetap sehat (Kementrian Kesehatan Republik Indonesia, 2020). Faktor yang
menyebabkan kurangnya gizi pada lansia adalah keterbatasan ekonomi keluarga, penyakit
kronis, pengaruh psikologis, hilangnya gigi, kesalahan dalam pola makan, kurangnya
pengetahuan tentang gizi dan cara pengolahannya serta menurunya energi (Susanti, 2021).

4.12 Kurangi Minum Alkohol

Kurangi minum alkohol jadi hanya 1 gelas/hari (~ 12 ons bir atau 5 ons wine).
Minuman beralkohol adalah semua jenis minuman yang mengandung etanol, termasuk Cap
Tikus, anggur, bir, dan saguer. Peminum alkohol harian ternyata mempunyai tingkat tekanan
darah yang lebih tinggi dibandingkan dengan peminum sekali seminggu, berapapun jumlah
total yang diminum setiap minggunya. Mengkonsumsi alkohol sebanyak 1-2 sloki oleh lansia
mempengaruhi terjadinya hipertensi. Begitu juga dengan penelitian di Amerika yang
menyimpulkan bahwa wanita peminum alkohol yang tergolong ringan dan sedang potensi
risiko hipertensinya rendah, sedangkan pada pria risiko terjadinya hipertensi lebih tinggi. Hal
ini dapat dipengaruhi oleh perbedaan pola minum, pilihan minuman, dan gaya hidup, yang

24
 25

dihubungkan dengan kebiasaan konsumsi alkohol pada pria maupun wanita (Malonda, 2012).

Berdasarkan hasil analisis berbagai artikel telah terbukti bahwa upaya pengelolaan
infeksi pada pasien hipertensi pada masa pandemi COVID-19 sangat berpengaruh, maka dari
itu intervensi sangat penting dalam mengurangi berkembangnya infeksi COVID-19
khususnya di Indonesia, karena angka kasusnya terus mengalami peningkatan setiap harinya.
Beberapa metode yang dapat dilakukan atau digunakan pada saat pendidikan kesehatan
kepada pasien yaitu dengan cara:

a. Infografik
Suatu cara penkes yang biasanya digunakan untuk mengedukasi atau
menambah pengetahuan masyarakat melalui media visual berbentuk frame yang
kemudian kan disebarkan melalui media sosial seperti instagram, whatsapp dan
facebook sehingga masyarakat tidak perlu keluar rumah
b. Komunikasi Informasi dan Edukasi Elektronik (eKIE)
Sama halnya dengan infografik tetapi eKIE ini bertujuan untuk mengedukasi
masyarakat melalui promosi kesehatan memalui online oleh petugas dengan membuat
gambar kemudian diberikan penjelasan melalui tulisan atau pesan suara

25
 BAB V

KESIMPULAN DAN SARAN

5. 1 Kesimpulan

Dari 5 artikel pengelolaan infeksi pada pasien hipertensi pada masa pandemi Covid-19
intervensi yang dapat dilakukan yaitu dengan cara karantina secara mandiri dirumah, jaga
jarak/social distancing, cuci tangan 30 detik dengan sabun dan air atau menggunakan
antiseptik berbasis alkohol, rutin membuka ventilasi selama 2 kali sehari dan desinfeksi, tetap
melakukan interaksi sosial, meningkatkan asupan vitamin D yaitu mendapatkan sinar
matahari pada pagi hari sekitar 10-15 menit serta mengkonsumsi makanan sehat antara lain 
kuning telur, jamur shitake, hati sapi, keju, udang, ikan terutama ikan yang berlemak seperti
salmon dan tuna, olahraga rutin yaitu dengan cara olahraga aerobic 30-60 menit setiap hari,
monitoring tekanan darah rutin, menurunkan bb, diet sodium dan potassium diet sehat gizi
seimbang efektif untuk mencegah hipertensi, melakukan diet dan kurangi minum alcohol
Konsumsi alkohol sebanyak 1-2 sloki dalam penelitian ternyata mempengaruhi terjadinya
hipertensi . Hasil analisis berbagai artikel telah terbukti bahwa upaya pengelolaan infeksi
pada pasien hipertensi pada masa pandemi Covid-19 sangat berpengaruh

5. 2 Saran

Untuk mengurangi bertambahnya dan berkembangnya covid 19 terutama pada pasien

hipertensi dalam mengelola resiko terjadinya hipertensi intervensi-intervensi dari sumber
yang relevan sangat diperlukan dalam meningkatkan pengetahuan masyarakat juga peran
petugas kesehatan sangat diperlukan dalalm mengedukasi dan melakukan intervensi dalam
mengelola infeksi pada pasien hipertensi pada masa pandemi Covid-19.

26
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LAMPIRAN
Kim et al. International Journal for Equity in Health (2020) 19:198
https://doi.org/10.1186/s12939-020-01309-x

COMMENTARY Open Access

Recommendation for response to the

COVID-19 pandemic: Korean context of
“distancing in daily life,” considering
vulnerable population
Ja Young Kim1†, Jin-Ok Han1† and Heeyoung Lee1,2*

Abstract
While the coronavirus disease 2019 (COVID-19) pandemic is an ongoing worldwide, including South Korea
(hereinafter Korea), it is impossible to predict the duration of the pandemic. To stop the spread of COVID-19,
“social distancing,” which included mandatory lockdown, and attention to personal hygiene are being adopted
globally as non-pharmaceutical preventive strategies. In Korea, after maintaining strong social distancing rules for
a while, the government transitioned to implementing “distancing in daily life” since May 6, 2020. The distancing
in daily life was combined with infection prevention activities to stop the COVID-19 pandemic, while
guaranteeing one’s daily life and economic activities.
In this regard, the Ministry of Health and Welfare in Korea disclosed key rules for personal quarantine. The five
key rules for individual infection control are as follows: to stay at home for 3–4 days if you feel unwell, keep a
distance of two arms’ length from others, to wash your hands for 30 s and cough or sneeze into your sleeves,
ventilate at least twice a day and disinfect regularly, and stay connected while physically distancing. However, for
vulnerable populations, it is very difficult to follow such rules.
Thus, we attempted to recommend how the society could support such vulnerable populations who may face
difficulties in following these individual infection control rules. Through our recommendations for the weakest
part of our society, we expect to strengthen the overall social structure.
Keywords: Vulnerable population, Vulnerable group, COVID-19, Personal quarantine

* Correspondence: lhy0313@gmail.com
†
Ja Young Kim and Jin-Ok Han contributed equally to this work.
1
Gyeonggi Public Health Policy Institute, 7th Floor, 172, Dolma-
ro, Seongnam-si, Gyeonggi-do 13605, Republic of Korea
2
Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-
gil, Seongnam-si, Gyeonggi-do 13620, Republic of Korea

© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if
changes were made. The images or other third party material in this article are included in the article's Creative Commons
licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons
licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the
data made available in this article, unless otherwise stated in a credit line to the data.
Kim et al. International Journal for Equity in (2020) 19:198
Health
요약
전세계적으로 코로나 19 관련 상황🕔 장기화되고 있고 , 우리나라 역시 종식 시점에 대한 전망🕔 어렵다 . 그
럼에도 강력한 사회적 거리두기를 지속하기에는 어려움🕔 있기 때문에 국내에서는 5 월 6 일부터 생활 속 거
리두기 단계로 전환하였다 . 🕔 러한 생활 속 거리두기는 일상생활과 경제활동을 보장하면서 , 코로나 19 유
행 차단을 위한 감염예방 활동🕔 조화되는 방향으로 전개 중🕔♘다 . 보건복지부에서는 🕔와 관련하여 개인
방역 핵심 수칙 등을 공개하였다 .
발표된 개인방역 핵심 수칙은 ‘아프면 3~ 4 일 집에 머물기’ , ‘ 사람과 사람 사🕔 , 두 팔 간격 거리두기’ , ‘30
초 손씻기 , 기침은 옷소매에’ , ‘ 매일 2 번 🕔상 환기 , 주기적 소독’ , ‘ 거리는 멀어져도 마음은 가까🕔’ 🕔렇
게 5 가 지로 구성되♘다 . 하지만 , 우리 주변의 취약계층에 속한 대상자들은 🕔러한 생활수칙을 준수하는데
어려움
🕔 따를 수밖에 없다 .
🕔 에 생활 속 거리두기 실천을 위한 개인방역 핵심 수칙을 바탕으로 우리 사회의 취약계층별로 직면하게 되
는 어려움과 🕔들을 위한 지원방안을 제시하고자 하였다 . 🕔 러한 노력을 통해 우리 사회의 가장 약한 부 분
을 돌아보게 되어 사회 구조 전반을 강화할 수 있을 것으로 기대되는 바🕔다 .
Background
On March 11, 2020, the World Health Organization
(WHO) officially declared that the outbreak caused by
coronavirus disease 2019 (COVID-19) as a pandemic
[1], and since then, the situation has been prolonged,
with the overall number of confirmed cases increasing
con- tinuously. In Korea, the total cumulative number
of con- firmed cases is 24,988 as of October 15, 2020,
and of which 23,082 cases have been discharged from
isolation, and 52 cases has increased compared to the
previous day [2]. To date, various efforts have been
made to de- velop vaccines/therapeutic drugs, and it is
still difficult to predict the end of COVID-19.
As a response to the COVID-19 pandemic, “social dis-
tancing” is one of the non-pharmaceutical preventive
strategies for slowing down the spread of the virus
effectively; thus, it is a vital long-term approach. In
addition, various ways of “social distancing” have been
implemented worldwide, including mandatory lock-
downs and paying attention to personal hygiene [3, 4].
Even though Korea did not employ the lockdown strat-
egy, the government had required people to keep strong
social distances for about a month (from March 22 to
April 19). After that, the government has implemented
“Distancing in daily life” since May 06, 2020 [5].
In Korea, a “distancing in daily life” strategy has been
used for curbing the spread of COVID-19 in the
long- term while maintaining social interaction. The
strategy is based on the values that all members of the
society are responsible for overcoming the COVID-19
pandemic and protecting their own health. The main
goals of ‘dis- tancing in daily life’ are as follows:
prevent virus infiltra- tion into living spaces, minimize
conditions that are favorable for pathogen transmission
and survival, minimize discharge of the virus outside
the body, and trace and block the virus transmission
path.
The infection control strategy consists of five key
rules and four supplementary actions for individuals
[5].
Page 2 of 5
● Five key rules for individual infection control
– Rule 1: “Stay home for 3 to 4 days if you
feel unwell.”
– Rule 2: “Keep a distance of two arms’ length
from others.”
– Rule 3: “Wash your hands for 30 seconds.
Cough or sneeze into your sleeve.”
– Rule 4: “Ventilate at least twice a day
and disinfect regularly.”
– Rule 5: “Stay connected while
physically distancing.”
● Four Supplementary Actions for Individuals
– Use of Masks
– Disinfection of Environments
– Guidelines for the Elderly and High-risk Groups
– Healthy Lifestyle
Even though the strategy of “social distancing” was
possible of making people feel exhausted and could
lead to unavoidable economic recession in Korea, it was
con- sidered a successful model of “citizen participation
in quarantine” due to voluntary actions of the public.
Nevertheless, it was difficult for people to follow the
rules. According to an online survey on the prevention
of COVID-19 in daily life conducted by the Ministry
of Health and Welfare in Korea, many concerns have
been raised regarding the situation of vulnerable
groups in the COVID-19 pandemic in keeping social
distancing in daily life [2]. The Korean government is
making efforts and taking actions, such as providing
emergency relief funds and urgent support programs
for unpaid leaves [6, 7]. Nevertheless, the vulnerable
population is in need for further support.
The purpose of this article was to introduce the “dis-
tancing in daily life” strategy in Korea, provide tangible
evidence for other countries facing the pandemic, and
propose important considerations for the vulnerable
population.
Main text during the COVID-19 pandemic than they did prior to it
As COVID-19 is a novel virus, we cannot understand because the support services have been discontinued and
fully the characteristics of the virus causing it and its
impact on our health, but it is assumed that a specific
population is more vulnerable to this pandemic than
others [8]. It is difficult to define the term “vulnerable
population” [9], but it generally includes foreign workers,
homeless/poor urban residents, people with disabilities,
older people, and so on.

Foreign workers
Although the number of foreign workers, including
illegal workers, is not known, the number of regular
for- eign workers under the Employment Permit System
was reported to be 51,365 in 2019 [10], and over 70%
of for- eign workers in the Employment Permit System
have been working in the manufacturing industry,
which is known for its risky physical work environments.
Usually, foreign workers perceive themselves to be
legally un- stable, and since they tend to share a single
living space/ residence with many people, they tend to
live in poor conditions. Furthermore, their working
environment is likely to be poor because over 70% of
the foreign workers who work under the Employment
Permit Sys- tem in Korea [10] are engaged in the
manufacturing in- dustry, which is known to have a
poor working environment. They also have limitations
in accessing useful information due to language
differences and can be excluded from the government’s
public resource pro- curement system and benefit
distribution.

Homeless/poor urban residents

These people tend to have no place to live or live in
an environment with a high risk of infection [11]. For
example, homeless people often stay in shelters that
are crowded and poor urban residents live in highly
popu- lated areas; thus, these groups are highly
susceptible to the viral infection. Another serious
problem is that the public hospitals they used to visit
have been converted into public relief hospitals
designated for handling COVID-19 cases; thus, their
medical accessibility has reduced since the COVID-19
outbreak.

People with disabilities

People with disabilities have limited physical or mental
ability, depending on the disease severity. In-person
services including community-based rehabilitation pro-
vided to them may have been stopped or limited during
the COVID-19 pandemic. As they require continuous
medical services, these combined problems could worsen
their health status [12]. For instance, people with mental
disabilities would feel more isolated and depressed
contact with people has reduced. In addition, they
have underlying medical conditions, such as high
blood pres- sure and diabetes, and the pandemic may
have worsened these problems.

Older people
Older people aged over 60 years old have more under-
lying diseases than other age groups and have limited
physical abilities [12]. In addition, the services
provided to them by the public health center have been
suspended or limited since the outbreak of COVID-
19.
During the COVID-19 pandemic, it is crucial to take
additional measures for vulnerable populations in
terms of support provision and policy design.
However, so far, the basic guidelines for distancing in
daily life by the KDCA are mostly geared toward the
general population and some high-risk populations with
underlying diseases such as high blood pressure and
diabetes. Therefore, in this commentary, we are going
to examine the popula- tions that would be at high
risk of COVID-19 infection and what kind of support
would be necessary for pro- tecting them.

Rule 1: “Stay home for 3-4 days if you feel unwell”

The KDCA recommends those feeling unwell to stay
home for 3–4 days because COVID-19 patients with
mild symptoms can spread the virus at an early stage
[5]. To follow the first essential rule for individual
infec- tion control, it is necessary to let people use
their sick leave when they have a fever or respiratory
symptoms related to COVID-19. In the cases of
confirmed diagno- sis or close contact with COVID-19
patients, the Korean government tries to support sick
pay for the isolation period. However, most people
with fever or respiratory symptoms cannot receive
this kind of support from the government.
Considering the unstable legal status of foreign
workers, it is difficult for them to take days off or a
sick leave in case of fever or respiratory symptoms
before they receive a definitive diagnosis of COVID-19.
There- fore, to help them adhere to the first key
rule, the government should recommend companies
to check the body temperature of the workers before
they enter the workspace and provide support to the
companies that provide preventive measures such as
days off or sick leaves for those with fever or
respiratory symptoms.
In addition, homeless people/poor urban residents
often have unstable working conditions and thus
resting itself can pose a threat to their survival. Thus,
support may be needed in terms of special relief funds
to main- tain income during unemployment. In
addition, it may be necessary to provide a
thermometer to help them check their temperatures
regularly and to provide a service they can visit only
if they have difficulties in
checking their own body temperature (people with such as public restrooms and community centers. Since
disability, elderly people, etc.). the risk

Rule 2: “Keep a distance of two arms’ length from others”

According to government guidelines [5], COVID-19 is
mainly transmitted through saliva droplets; thus, it is
important to maintain 1 meter (or 2 arms’ length) gap
between people. It is better to eat at home than
going outside. However, in some cases, such as in the
work environment, it would be very difficult to keep
distance despite personal efforts. For example, in
Korea, there was a COVID-19 outbreak among call
center workers, and the number of cases rapidly
increased due to the close distance working situation
(call center cluster; [13]). Since then, Korea has
recommended telecommut- ing (working from home),
flexible work hours, etc. It may be necessary to
control the population density or the number of people
in a shared space to maintain proper distance. This
change is only possible through cooperation between
public and business sectors, rather than through
individual efforts.
Foreign workers are more likely to work or live in
population-dense environments, such as dormitories.
Homeless or poor urban residents are likely to reside in
crowded shelters or poor urban areas, and these envi-
ronments make them vulnerable to the virus.
Therefore, efforts to improve the residential
environment are urgently needed, such as providing
safe shelter.

Rule 3: “Wash your hands for 30 seconds. Cough or

sneeze into your sleeve”
This rule is relatively easier than other rules for everyone
to practice and is the most basic method for minimizing
COVID-19 transmission through contaminated hands or
saliva droplets. However, it may not be easy for vulner-
able populations to do this because their activities may
be limited, but wearing masks can be helpful in follow-
ing the rule. Thus, providing protective items, including
masks, can be helpful.
In Korea, the government attempted to control the
supply of masks, and for Korean residents, it was not
challenging to buy masks. However, it was only
recently that foreigners, including foreign workers, were
able to get access to the public supply of masks. Those
who do not have a foreigner registration card will not be
able to buy masks through public supply systems.
Thus, it would be imperative to implement a new policy
to allow all foreign workers regardless of their legal status
to have access to masks and quarantine items. In addition,
basic preventive guidelines need to be offered in
various languages. To help the homeless people or poor
urban residents who do not have stable places to stay,
hand sanitizers can be distributed in public places
of COVID-19 infection may be relatively high in these
environments, masks and quarantine items need to
be provided through various methods. For the
disabled and older populations, the provision of
masks and protective supplies is necessary because
physical constraints can make it difficult for them to
follow the rules and lead to poor access to relevant
information. All provided infor- mation should be
translated into sign language and braille to help
those with low access to information about
individual infection control. In fact, some local
governments (Seoul Metropolitan Government) have
set up a task force for supplying quarantine goods
and implemented a project to visit vulnerable people and
dis- tribute masks and quarantine items such as hand
saniti- zers. This action should be followed by other
local governments.

Rule 4: “Ventilate at least twice a day and disinfect

regularly”
The KDCA guidelines recommend ventilating at least
twice a day to reduce the concentration of droplets
con- taining COVID-19 virus and to disinfect surfaces
on which infectious droplets could have landed [5]. It
is im- portant to manage the residential and
workplace envi- ronments to the optimal, not only at
the personal but also at the community level. In order
to adhere to these rules, the ventilation system
should be well maintained for regular ventilation
(more than twice a day), and it is important to have
relevant supplies for regular disinfec- tion, which
may be difficult to manage in some work and
residential environments.
Foreign workers in crowded environments may find
it difficult to change their situation by themselves.
There- fore, disinfection of public spaces, such as
foreign workers’ dormitories, may be crucial. For
homeless people who do not have housing or
residents of urban slums living in crowded
environments, special services may be required, such
as providing temporary shelter capable of quarantine
management or visiting the areas to carry out
disinfection/cleaning process. These visiting services
may be equally necessary for the disabled and older
people who are restricted in their daily life
activities.

Rule 5: “Stay connected while physically distancing”

Most vulnerable people could have been feeling
isolated from society, and the COVID-19 pandemic
must have made things worse for them. When “social
distancing” is encouraged to curb the spread of the
infection, it may be difficult to deal with mental
problems alone given that direct support/service/visit
is restricted. In particu- lar, it may be difficult for
them to cope with anxiety when exposed to
sensational media reports about the
COVID-19 pandemic situation coupled with no social
interaction.
In Korea, so-called “psychological quarantine” is
being primarily offered via psychological counseling for
those in self-quarantine. However, psychological
counseling services should also be provided to
vulnerable popula- tions who are socially isolated due
to the COVID-19 pandemic. In fact, some local bodies
are providing con- sultation services to older people by
making regular phone calls and checking on their
mental health.
Conclusions
In this commentary, we examined the difficult condi-
tions of vulnerable populations in implementing key
rules of “distancing in daily life.” Vulnerable people are
more likely to suffer from the COVID-19 pandemic than
others. According to the WHO Regional Office for
Europe report [14], strengthening social structures is
essential for reducing socioeconomic damage. A strong
social structure can help enhance social cohesion and
participation and help prevent vulnerable people from
falling behind. Therefore, effective protection/support
policies are needed for vulnerable populations.
In particular, efforts should be made to provide an
appropriate environment and educate on adequate pre-
ventive measures by organizing campaigns for individ-
uals to follow the rules to prevent COVID-19
regardless of their social status. In fact, a budget of 15
billion Korea won was allocated to support unpaid
workers, special employment, and freelancers. In
addition to financial support, social support policies
should be enacted for isolated vulnerable populations.
Abbreviations
COVID-19: Coronavirus disease 2019; KDCA: Korea Disease Control and
Prevention Agency; WHO: World Health Organization
Acknowledgments
We would like to thank Editage (www.editage.co.kr) for English
language editing.
Authors’ contributions
HL provided guidance in preparation of the manuscript. JYK and JOH
reviewed guidelines and literatures, and drafted the manuscript. All authors
read and approved the final manuscript.
Funding
All of works done by Gyeonggi Public Health Policy Institute are
supported by Gyeonggi province. This article is the result of the research
project in Gyeonggi Health Public Policy Institute in 2020.
Availability of data and materials
Not applicable.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
Not applicable.
Received: 30 September 2020 Accepted: 22 October 2020
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Hanvoravongchai P, Obando C, Petrosyan V, Rao KD. Health equity and
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Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
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 3 Indonesian Journal of
Cardiology
Indonesian J Cardiol 2020:41:112-119
Tinjauan Pustaka pISSN: 0126-3773 / eISSN: 2620-4762
doi: 10.30701/ijc.1016

Olahraga Rutin untuk Meningkatkan Imunitas

Pasien Hipertensi Selama Masa Pandemi COVID-19

Badai Bhatara Tiksnadi1, Nova Sylviana2,

Adi Imam Cahyadi3, Alberta Claudia Undarsa1

3.1 Abstrak
Hipertensi merupakan salah satu komorbid yang paling banyak ditemukan pada Coronavirus disease-19
(COVID-19) dan berasosiasi dengan prognostik buruk dari infeksi tersebut. Olahraga rutin ternyata dapat
meningkatkan imunitas tubuh, sehingga dapat berperan dalam pencegahan infeksi COVID-19 selain efeknya
terhadap penurunan tekanan darah. Olahraga tipe aerobik dengan intensitas sedang 30-60 menit, dengan cara
tetap melakukan pembatasan jarak, ataupun dengan teknik home exercise dan virtual dengan daring, dapat
dilakukan oleh penderita hipertensi dalam meningkatkan imunitas selama masa pandemi COVID-19.

(Indonesian J Cardiol. 2020;41:112-119)

Kata Kunci: Aerobik, COVID-19, hipertensi, imunitas, olahraga

1 Departemen Kardiologi dan Kedokteran Vaskular, Universitas Pendahuluan

C
Padjadjaran, Bandung
2 Divisi Fisiologi, Departemen Ilmu Kedokteran
Dasar, Universitas Padjajaran, Bandung
3 Divisi Mikrobiologi, Departemen Ilmu Kedokteran
Dasar, Universitas Padjajaran, Bandung
Koresponden:
Badai Bhatara Tiksnadi
Universitas Padjadjaran, Jl. Raya Bandung Sumedang No.KM
21, Hegarmanah, Kec. Jatinangor, Kabupaten Sumedang, Jawa
Barat 45363
E-mail: badai.bhatara.tiksnadi@unpad.ac.id
oronavirus disease-19 (COVID-19) adalah
penyakit yang disebabkan oleh virus novel
Corona 2019-nCoV dan telah ditetapkan
oleh WHO sebagai global pandemi karena
penyakit ini telah mewabah, terjadi bersamaan
hampir diseluruh negara didunia.1 Kebijakan “social
distancing” dan “work from home” dilakukan
pemerintah di berbagai negara untuk mengurangi
risiko transmisi virus antar manusia. Namun
kebijakan ini berpotensi meningkatkan pola hidup
sedenter akibat menurunnya aktivitas fisik dan
kebiasaan berolahraga.1 Padahal, selain untuk
mencegah penyakit kronis, berolahraga rutin dapat
berperan meningkatkan sistem imun tubuh sehingga
secara tidak langsung dapat meningkatkan
Indonesian J Cardiol ● Vol. 41, Issue 2 ● April - June 2020 113
 Indonesian Journal of
Cardiology
pertahanan tubuh terhadap COVID-19.
Penderita hipertensi, yang jumlahnya sangat
banyak di Indonesia (prevalensi 34,1% berdasarkan
RISKESDAS 2018), termasuk salah satu kelompok
yang rentan untuk terinfeksi COVID-19.2, 3 Beberapa
studi menyatakan bahwa kelompok pasien dengan
hipertensi dan penyakit kardiovaskular mempunyai
kecenderungan mengalami sakit berat dan kematian
bila terinfeksi COVID-19.3-6 Oleh karena itu pada
kelompok pasien hipertensi diperlukan strategi
penguatan imunitas tubuh agar terhindar dari infeksi
COVID-19, salah satunya adalah dengan olahraga
secara rutin dan dengan panduan yang spesifik.
Perubahan Gaya Hidup dan Aktivitas Fisik Mas-
yarakat pada Masa Pandemi COVID-19
Penerapan kebijakan untuk tetap di rumah saja serta
peningkatan komunikasi virtual merupakan perubahan
gaya hidup yang menjadi trend dalam pencegahan
penularan infeksi COVID-19. Akibatnya, gaya hidup
sedenter tidak dapat dihindari, padahal inaktivitas
fisik merupakan faktor risiko keempat dari mortalitas
global, mencakup 5.5% kematian di dunia.7 Inaktivitas
fisik juga telah diketahui sebagai faktor risiko utama
dari hipertensi, baik pada pria maupun wanita segala
usia.7, 8 Penelitian telah membuktikan bahwa intervensi
terhadap aktivitas fisik merupakan cara pencegahan dan
kontrol terhadap penyakit tidak menular yang efektif
dan hemat biaya.9
3.1 Pandemi COVID-19: Morbiditas,
Mortalitas dan Peranan Komorbid, Terutama
Hipertensi. 3.2
Hingga awal Mei 2020, angka kasus COVID-19 di
dunia mencapai 3.4 juta kasus dengan laju mortalitas
dunia sebesar 3.4%, dimana kasus positif di
Indonesia mencapai lebih dari 10 ribu kasus.10
Sekitar 2% pasien yang terinfeksi mengalami kondisi
yang kritis, dan umumnya berhubungan dengan
kondisi komorbid yang menyertai.10, 11 Beberapa studi
di Cina melaporkan bahwa COVID-19 berasosiasi
dengan hipertensi dengan rerata 21%. Beberapa studi
juga menunjukkan bahwa pasien COVID-19 dengan
komorbid tersebut berhubungan dengan peningkatan
kasus keparahan dan bahkan risiko kematian.11
Studi pada 1099 pasien yang terkonfirmasi
COVID-19, sebanyak 173 pasien tersebut mengalami
114
sakit berat karena mempunyai penyakit komorbid
hipertensi (23,7%). Sebanyak 30% dari 140 pasien yang
diharus di rawat di rumah sakit, memiliki komorbid
hipertensi. Pasien dengan hipertensi serta penyakit
kardiovaskular juga mempunyai kecenderungan
mengalami sakit berat dan kematian bila terinfeksi
COVID-19.3 Sebuah metaanalisis yang dilakukan
menunjukkan bahwa hipertensi merupakan komorbid
kardiovaskular yang paling banyak ditemui dan secara
signifikan meningkatkan risiko mortalitas pada pasien
dengan COVID-19.4 Sejalan dengan temuan tersebut,
hasil meta-analisis terhadap delapan studi yang
melibatkan 46.248 pasien yang terinfeksi di Cina,
jika dibandingkan dengan kasus yang ringan, maka
odds ratio dari hipertensi, pada pasien dengan infeksi
COVID-19 berat adalah 2,36 (95% CI: 1,46-3,83).5 Di
Italia, yaitu salah satu negara yang paling terdampak
dari penyakit COVID-19 ini, hipertensi juga
meningkatkan risiko 2,5 kali lipat (OR:2,49 [95%CI:
1,98-3,12]) untuk terjadinya keparahan penyakit dan
mortalitas dari infeksi virus ini.6
Meskipun hipertensi diketahui sebagai salah satu
komorbid yang memberikan luaran buruk pada kasus
COVID-19, namun belum jelas apakah tekanan
darah tak terkontrol merupakan faktor risiko untuk
terinfeksi COVID-19 atau apakah tekanan darah
yang terkontrol pada pasien dengan hipertensi berisiko
lebih rendah untuk terinfeksi. Walaupun demikian,
beberapa organisasi tetap menitikberatkan pada fakta
bahwa pencegahan ataupun pengendalian hipertensi
tetap menjadi fokus dalam menurunkan beban
penyakit.12
Olahraga Sebagai Tatalaksana Hipertensi
Penanganan hipertensi tidak hanya menitikberatkan
pada medikamentosa, namun juga pada gaya hidup
dalam meningkatkan kebugaran kardiorespiratori yang
memiliki properti preventif, prognostik dan
terapeutik baik pada prehipertensi maupun
hipertensi.13 Dengan demikian, intervensi gaya hidup
yaitu olahraga rutin, direkomendasikan dalam
berbagai panduan dan konsensus hipertensi baik di
dalam maupun luar negeri.13-15 Latihan fisik aerobik
regular (minimal 30 menit, latihan dinamik dengan
intensitas sedang, 5-7 hari per minggu)
merupakan rekomendasi level IA sebagai intervensi
gaya hidup pada pasien hipertensi.14 Hal ini didukung
oleh hasil metaanalisis yang dilakukan terhadap
5223 subjek, yaitu terjadi
 Indonesian Journal of
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penurunan tekanan darah sistolik dengan kisaran 3,5-
10 mmHg dan tekanan darah diastolik 2,5-6,2 mmHg
bergantung dari jenis olahraga yang dilakukan, baik
latihan endurance, latihan resistensi dinamik,
ataupun resistensi isometrik.16 Rendahnya latihan fisik
aerobik telah dibuktikan sebagai prediktor kuat untuk
penyakit kardiovaskular dan kematian pada pasien
hipertensi.17 Dengan demikian banyak konsensus yang
menetapkan latihan fisik aerobik sebagai pilihan
utama untuk pencegahan, tatalaksana dan mengontrol
hipertensi.18
Tabel 1. Rekomendasi Latihan Fisik Pada Pasien Hipertensi
Secara Umum8
Risk factors Rekomendasi
Frekuensi • Latihan fisik aerobik dianjurkan dilakukan
setiap hari
• Latihan fisik tipe resistensi dapat dilakukan
sebagai tambahan 2-3x/minggu secara selang-
seling.
Intensitas • Latihan aerobik dilakukan dengan intensitas
sedang (misalnya jalan cepat), hingga
mencapai 50-70% dari denyut jantung
maksimal
• Latihan tipe resistensi dilakukan dengan
intensitas sedang, yaitu 50-70% dari berat
maksimal yang dapat diangkat pada satu kali
repetisi latihan.
Waktu • 30-60 menit per hari untuk latihan aerobik
tanpa henti, atau secara berselang sekitar 10
menit dengan total 30 menit per hari.
• Latihan tipe resistensi minimal mencakup
8-10 sesi, dimana per latihan setidaknya
terdiri dari 8-12 repetisi.
Tipe • Penekanan pada latihan aerobik, misalnya
jalan, jogging, bersepeda, dan berenang.
Aktivitas yang menggunakan banyak otot
secara terus-menerus, ritmikal dan aerobik
merupakan rekomendasi utama untuk
pasien dengan hipertensi
• Latihan tipe resistensi sebaiknya meliputi
kaki, panggul, dada, punggung, perut, bahu
dan lengan. Latihan angkat beban baik
dengan atau mesin dapat menjadi pilihan.
Mekanisme pengaruh olahraga dalam menurunkan
tekanan darah masih belum diketahui secara jelas,
namun mungkin disebabkan adanya keterlibatan (1)
penurunan respon vasokonstriksi akibat simpatis dan
penurunan segregasi katekolamin, (2) peningkatan
sensitivitas insulin, (3) efek anti-inflamasi, dan (4)
adaptasi struktur pembuluh darah pada individu yang
melakukan latihan fisik reguler.18
3.3 Pengaruh Olahraga Dalam Meningkatkan
Imu- nitas
Manfaat olahraga teratur, terjadwal, tepat intensitas
dan tipenya, tidak hanya ditujukan sebagai tatalaksana
hipertensi yang merupakan salah satu komorbid
utama pada kasus COVID-19, melainkan juga untuk
meningkatkan imunitas tubuh. Banyak studi telah
membuktikan bahwa olahraga dapat meningkatkan
fungsi imun tubuh.19, 20 Mekanisme yang mendukung
peningkatan imunitas dengan latihan fisik intensitas
sedang antara lain berhubungan dengan stimulasi
pertukaran sel sistem imun bawaan dan komponen
antara jaringan limfoid dan darah, yang akan
meningkatkan immunosurveillance terhadap patogen
disertai dengan penurunan inflamasi sistemik seperti
IL-6, komplemen dan immunoglobulin.21
Respon imun terhadap latihan fisik dependen
terhadap intensitas dan durasi olahraga. Pada olahraga
intensitas sedang, dengan durasi kurang dari 60
menit, terjadi peningkatan immunosurveillance dari
subtipe sel imun yang memiliki efek terapeutik dan
preventif. Respon akut dari latihan fisik sedang ialah
peningkatan aktivitas antipatogen dari makrofag yang
timbul bersamaan dengan peningkatan resirkulasi
immunoglobulin, sitokin anti-inflamasi, neutrophil, sel
natural-killer (NK), sel T sitotoksik, dan sel B,
dimana seluruhnya berperan penting sebagai imun
pertahanan tubuh. Latihan fisik akut akan
memobilisasi sel NK dan CD8+ Limfosit T, dimana
keduanya memiliki sitotoksisitas yang tinggi.
Hormon stres, yang dapat menekan fungsi sel imun
dan sitokin proinflamasi, tidak meningkat tinggi pada
latihan fisik dengan durasi yang singkat dan intensitas
sedang. Apabila latihan fisik terus dilakukan secara
reguler, maka peningkatan limfosit yang awalnya
bersifat sementara atau transien ini, akan meningkatkan
immunosurveillance dan menurunkan inflamasi
sistemik. Studi lain juga mendukung bahwa latihan
fisik rutin selain mampu memperbaiki regulasi
sistem imun, juga dapat menunda onset dari
immunosenescence.21
Walaupun dapat meningkatkan imunitas tubuh,
perubahan pada pertahanan mekanik dari saluran napas
juga terjadi pada individu yang berolahraga. Olahraga
diduga dapat meningkatkan kerentanan terhadap
infeksi, namun hanya pada olahraga yang berat.19
Indonesian J Cardiol ● Vol. 41, Issue 2 ● April - June
2020 115
 Banyak virus dan patogen pada droplet di udara yang
menyebabkan tubuh menjadi rentan untuk terinfeksi,
salah satunya infeksi saluran napas atas. Kerentanan
ini dipengaruhi oleh pola aliran udara dan pertahanan
mekanik dari saluran napas atas. Silia di trakea akan
mengeluarkan mukus dan partikel-partikel patogen
yang terjerat untuk kembali ke tenggorokan yang
dibantu oleh refleks batuk dan bersin. Ketika
berolahraga, terjadi perubahan pola napas
menggunakan hidung dan mulut secara bergantian
menyebabkan saluran napas menjadi kering dan
mengurangi pergerakan silia serta mengentalkan
mukus. Hal tersebut akan mengganggu proses
pembersihan mikroorganisme dari traktus respiratori
dan individu menjadi rentan terhadap infeksi saluran
napas atas. Namun kerentanan terhadap virus baru
terlihat meningkat pada jarak tempuh lari maraton,
yaitu sekitar 42 km atau latihan fisik dengan
intensitas berat, dan tidak pada jarak tempuh 20-30
km.19
3.4 Kontroversi Pengaruh Intensitas
Olahraga terh- adap Sistem Imunitas
Beberapa studi menemukan bahwa latihan fisik
dengan intensitas terlalu berat dan terlalu lama justru
berpotensi memberikan dampak buruk. Pada studi
terhadap 2311 pelari maraton, 13% mengalami sakit
dalam waktu 1 minggu setelah lari maraton
dibandingkan dengan 2.2% kelompok pelari yang
tidak ikut maraton
Grafik 1. Perbedaan respon imun akut pada olahraga inten-
sitas berat dan sedang. DTH= delayed-typer-
hypertensitivity; IgA: immunoglobulin A; Ne/Ly=
neutrophil/lymphocyte ratio; NK=natural killer; OB:
oxidative burst. Grafik diadaptasi dari Nieman et al21
(OR:5.9; 95% CI: 1.9-18.8).22 Sebuah studi lain juga
menyatakan bahwa risiko infeksi saluran napas atas
tertinggi didapatkan pada atlit yang berpartisipasi
pada perlombaan kompetitif, aktifitas fisik berat dan
dengan beban stres mental.23 Beban olahraga yang berat,
kompetisi, stress fisiologis, psikologis dan metabolik
berhubungan dengan disfungsi imun, inflamasi, stres
oksidatif dan kerusakan otot.21 Terjadi perubahan dari
fungsi sel imun antara lain sel NK, neutrofil, fungsi sel
T dan sel B, produksi IgA saliva, respon
hipersensitivitas, ekspresi MHC-II pada makrofag dan
biomarker sistem imun lainnya pada beberapa jam
hingga hari setelah paparan aktivitas fisik dengan
intensitas berat dan lama.21 Rangkuman perbedaan
respon imun akut antara aktivitas fisik sedang dan
berat terdapat pada grafik 1. Perubahan sistem ini
terjadi pada berbagai kompartemen sistem imun
tubuh antara lain termasuk jaringan mukosa saluran
napas bagian atas dan paru- paru.20
Beberapa studi epidemiologi dan RCT mendukung
adanya hubungan yang berbanding terbalik antara
latihan fisik sedang dan insiden infeksi saluran napas
bagian atas. Hubungan ini digambarkan dengan
kurva model-J antara risiko infeksi saluran napas atas
dengan beban latihan fisik, dimana aktivitas fisik
yang terlalu berat justru bisa meningkatkan risiko
infeksi. Namun aktivitas fisik teratur dengan intensitas
sedang telah banyak dibuktikan berhubungan dengan
Grafik 2. Model Kurva-J Yang Menggambarkan Beban
Latihan Dan Risiko Infeksi Saluran Napas Atas. Grafik
diadaptasi dari Nieman.22
116 Indonesian J Cardiol ● Vol. 41, Issue 2 ● April - June 2020
penurunan mortalitas, serta insiden pneumonia dan
influenza (grafik 2).21 Studi terbaru menyatakan bahwa
justru atlet dengan volume latihan fisik berat secara
reguler menunjukkan insiden sakit yang lebih rendah
dibandingkan populasi umum, dimana pada rerata
jumlah hari sakit pada 1,212 pelari ultramaraton
ialah
1.5 hari pertahun dan 2.8 hari pertahun pada studi
terhadap 489 pelari ultramaraton, jauh lebih rendah
dibandingkan dengan jumlah hari sakit pada populasi
umum di Amerika serikat tahun 2009, yaitu 4.4 hari.24-
26
Dengan demikian konsep baru yang disarankan ialah
dengan memperluas kurva model-J menjadi kurva
model-S, dimana atlet yang terlatih dapat menunjukkan
respon yang adaptif terhadap latihan fisik dalam durasi
yang panjang.26, 27
High-intensity interval training (HIIT), sebuah
protokol latihan fisik dengan komponen intensitas
tinggi (~85% hingga 95% dari denyut jantung maksimal
dan/atau VO2max) dalam waktu sebentar (durasi 1
hingga 4 menit) dan diselingi periode pemulihan
aktif (intensitas sedang / ringan) secara interval /
bergantian.28 Akhir-akhir ini HIIT mulai
dipertimbangkan sebagai alternatif latihan fisik
intensitas sedang dan kontinu tanpa periode istirahat/
continuous moderate-intensity training (CMT).28 Hal
ini disebabkan karena HIIT memiliki manfaat yang
sebanding dalam memperbaiki komposisi tubuh,
VO2max dan nilai kolesterol dengan CMT seperti
yang dianjurkan oleh pedoman, bahkan memiliki
kelebihan yaitu dapat dilakukan dengan waktu yang
lebih singkat.29 Pada populasi hipertensi, HIIT juga
lebih superior dalam meningkatkan kebugaran
kardiorespirasi, fungsi endotel, aktivitas simpatis,
dan kekauan arteri dibandingkan dengan latihan fisik
dengan intensitas sedang.28 Hubungan antara HIIT
dan fungsi sistem imun masih menunjukkan hasil
yang beragam. Walaupun menurut Born et al, HIIT
tidak menyebabkan penurunan fungsi sistem imun jika
dibandingkan dengan latihan berlari lambat dengan
jarak tempuh jauh (70%-75% maksimal denyut
jantung), dan justru menunjukan adaptasi fungsional
oleh sistem imun mukosa terhadap beban latihan dan
stress akibat HIIT,30 namun penelitian yang
dilakukan oleh Khammassi et al, menunjukkan
bahwa CMT lebih menunjukkan peningkatan pada
jumlah sel imun dibandingkan dengan HIIT pada
populasi laki- laki muda yang sehat.31 Sehingga
walaupun HIIT menunjukkan manfaat yang
sebanding atau bahkan
lebih baik dari CMT pada pasien hipertensi namun
kurang menunjukkan manfaat terhadap peningkatan
sistem imun, sehingga kurang disarankan untuk
dilakukan pada masa pandemi ini.
3.5 Panduan Olahraga Sebagai Tatalaksana
Hiper- tensi Di Masa Pandemi COVID-19
Olahraga tetap merupakan hal yang penting dan
dapat dilakukan terutama pada pasien hipertensi pada
era COVID-19 walaupun dengan pembatasan
“physical distancing”. Hal yang dapat dilakukan
misalnya dengan memaksimalkan penggunaan sosial
media untuk pertemuan virtual dengan komunitas
olahraga secara daring. Olahraga dengan intensitas
sedang, di lingkungan dengan ventilasi yang baik dan
sendirian serta menghindari kontak dengan orang lain
(misalnya di rumah), serta mengutamakan
penggunaan barang- barang olahraga pribadi lebih
direkomendasikan. Home exercise program
merupakan salah satu pilihan olahraga karena dalam
pelaksanaannya aman, mudah dan murah. Program
ini termasuk aerobik (misalnya: berjalan di rumah
atau sekitarnya), pelatihan kekuatan otot
(strengthening), latihan peregangan (stretching) dan
keseimbangan (balance) atau kombinasi.32
Aktivitas fisik outdoor pada era COVID-19
masih diperbolehkan di beberapa negara walau
dengan tetap mengutamakan “physical distancing”.
Jarak minimal “physical distancing” pada latihan
fisik outdoor masih menjadi perdebatan. Jarak 1.5
meter banyak direkomendasikan karena umumnya
droplet akan jatuh dan terevaporasi sebelum
mencapai jarak 1.5 meter. Namun yang perlu diingat
ialah jarak ini tidak mempertimbangkan potensi efek
aerodinamik dari pergerakan seorang individu,
misalnya pada saat berjalan cepat, berlari atau
bersepeda.33 Dengan demikian, walaupun dengan
membatasi jarak minimal 1.5 meter dengan individu
lain, masih memungkinan adanya risiko penularan
akibat droplet yang terbawa angin atau udara saat
berlari ataupun bersepeda di outdoor. Hasil analisa
simulasi memberi kesimpulan bahwa pada jarak 5 meter
untuk berjalan dengan kecepatan 4 km/jam dan jarak 10
meter untuk berlari dengan kecepatan 14,4 km/jam,
maka tidak ada droplet yang dapat mencapai bagian
tubuh individu dibelakangnya yang berolahraga dengan
kecepatan yang sama.33
Olahraga disarankan untuk individu yang sehat
atau orang tanpa gejala, begitupula bagi penderita
Indonesian J Cardiol ● Vol. 41, Issue 2 ● April - June
2020 117
 COVID-19 dengan mengalami gejala ringan yang
hanya terbatas sampai ke leher, misalnya hidung berair,
kongesti sinus, dan nyeri tenggorokan ringan.
Namun untuk pasien bergejala ringan tersebut, perlu
dilakukan tes jogging 10 menit sebelumnya, apabila
kondisi umum dan gejala semakin berat maka
olahraga tidak diperbolehkan hingga sembuh total,
sebaliknya apabila bisa tidak ada perburukan gejala,
maka olahraga dengan intensitas ringan sedang (<80%
VO2max) dapat dilakukan. Olahraga tidak
diperbolehkan bagi penderita dengan gejala berat.32
Umumnya, proses penyembuhan dari infeksi virus
respiratori memakan waktu 2-3 minggu, sesuai
dengan waktu sistem imun seseorang untuk
membentuk sel T sitotoksik sebagai pertahanan untuk
melawan virus pada sel yang terinfeksi. Setelah periode
ini jika sudah tidak ada gejala, maka olahraga dapat
kembali dimulai secara bertahap.34
Kesimpulan
Dengan hanya beberapa bulan saja, infeksi
COVID-19 telah menyebar ke seluruh dunia dan
mengubah gaya hidup jutaan manusia menjadi
lebih sedenter. Hipertensi sebagai komorbid yang
paling banyak ditemukan pada kasus berat infeksi
COVID-19, menyebabkan pentingnya penanganan
dan pengendalian tekanan darah juga tidak dapat
dilewatkan dalam penanganan infeksi. Salah satu
upaya pencegahan primer dari hipertensi ialah dengan
olahraga rutin. Manfaat olahraga tidak hanya bertujuan
untuk pengendalian tekanan darah, dan mengurangi
risiko kardiovaskular namun juga dalam meningkatkan
imunitas. Olahraga jenis aerobik dengan intensitas
sedang dalam waktu 30-60 menit, menunjukkan
peran yang penting dalam menstimulasi sistem imun.
Dalam masa pembatasan sosial, maka olahraga tersebut
dilakukan dengan pembatasan jarak, atau dengan teknik
home-exercise, secara virtual atau dengan daring.
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 JURNAL KEBIJAKAN KESEHATAN INDONESIA : JKKI

VOLUME 09 No. 02 Juni • 2020 Halaman 61-67

Artikel Penelitian

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 Pengaruh Kebijakan Social Distancing : Anung Ahadi Pradana, Casman, Nur’aini
usia, individu yang menderita kelemahan, atau
yang memiliki beberapa kondisi kronis. Risiko
kematian meningkat dengan bertambahnya usia,
dan juga lebih tinggi pada mereka yang memiliki
diabetes, penyakit jantung, masalah pembekuan
darah, atau yang telah menunjukkan tanda-tanda
sepsis. Dengan tingkat kematian rata-rata 1%,
tingkat kematian meningkat menjadi 6% pada
orang dengan kanker, menderita hipertensi, atau
penyakit pernapasan kronis, 7% untuk penderita
diabetes, dan 10% pada penderita penyakit
jantung. Sementara tingkat kematian di antara
orang berusia 80 atau lebih berisiko 15% lebih
tinggi (13).
Kelompok rentan adalah kelompok masyarakat
yang mudah terpapar pada kondisi kesehatan
yang rendah, yang termasuk ke dalam kelompok
ini antara lain : kelompok minoritas, masyarakat
yang tidak memiliki asuransi kesehatan,
kelompok masyarakat pengidap HIV / AIDS, anak
– anak, lansia, masyarakat miskin, dan para
gelandangan (14). Menurut UU 39 tahun 1999
tentang Hak Asasi Manusia dalam pasal 5
disebutkan Setiap orang yang termasuk
kelompok masyarakat yang rentan berhak
memperoleh perlakuan dan perlindungan lebih
berkenaan dengan kekhususannya (15).
Karena banyak kelompok yang terpinggirkan
sering tidak mempercayai sistem layanan
kesehatan dan memiliki keengganan untuk
menghubungi tenaga kesehatan. Status sosial
ekonomi rendah (Perbedaan dalam pendapatan
dan pencapaian pendidikan dikaitkan dengan
harapan hidup yang lebih pendek, status
kesehatan yang lebih buruk; Kurangnya asuransi
kesehatan; dan perbedaan ras / etnis) adalah
salah satu penyebab terbesar dari status
kesehatan yang buruk sebagian besar populasi
rentan (16).
Tenaga kesehatan berbasis masyarakat
adalah petugas kesehatan garis depan publik
yang lebih dipercaya oleh anggota komunitas
yang mereka layani. Peran tenaga kesehatan
dalam mempromosikan perilaku sehat dan
informasi kesehatan kepada populasi rentan yang
sering kali menghadapi ketidaksetaraan di bidang
kesehatan menjadi perhatian utama saat ini.
Intervensi yang dilakukan oleh tenaga kesehatan
tampaknya efektif jika dibandingkan dengan
alternatif lain dan juga hemat biaya untuk
beberapa kondisi kesehatan tertentu, terutama
pada masyarakat minoritas berpenghasilan
rendah, termarjinalkan, dan berisiko tinggi.(17).
Kondisi social distancing yang diterapkan
di Indonesia akibat wabah Covid-19 dapat
mempengaruhi status kesehatan kelompok
rentan dalam kesehariannya, tujuan penulisan
manuskrip ini antara lain untuk memahami
pengaruh yang terjadi pada kelompok rentan
akibat social distancing di Indonesia.
3.1 METODE PENELITIAN
Penelitian ini bertujuan untuk menemukan
dampak social distancing selama fase pandemic
terhadap kelompok rentan di Indonesia
menggunakan metode studi literatur sederhana.
Pencarian artikel didapatkan dari beberapa
beberapa database diantaranya Cumulative
Index to Nursing and Allied Health Literature
(CINAHL), ScienceDirect, ProQuest dan PubMed
antara tahun 2015 hingga 2020. Kata kunci yang
dipergunakan merupakan gabungan dan
kombinasi dari beberapa kata, antara lain
“COVID-19”, “Social distancing”, “kelompok
rentan”, “anak”, “ibu hamil”, dan “lansia”. Total
artikel terkait kata kunci yang didapatkan
sebanyak 100 artikel jurnal. Kriteria inklusi yang
dipergunakan antara lain : (1) artikel berbahasa
Indonesia dan inggris, (2) memuat artikel
hubungan COVID-19 dengan kelompok rentan,
(3) memuat artikel hubungan social distancing
dengan kelompok rentan. Dari total 100 artikel
jurnal yang didapat, terdapat 15 artikel yang
memenuhi kriteria inklusi dan lolos proses
skrining menggunakan diagram PRISMA.
3.2 HASIL DAN PEMBAHASAN
Sustainable Development Goals (SDGs) poin
ke – 10 bertujuan untuk mencegah terjadinya
ketidakadilan dan ketidakberpihakan yang dapat
terjadi kepada mereka yang berada dalam
kelompok rentan. Peran serta pemerintah dunia
belum secara penuh menunjukkan hasil yang
signifikan dalam mendukung kesejahteraan
kelompok rentan melalui peraturan dan program
yang pada akhirnya menyebabkan terjadinya
ketidakberpihakan maupun ketidakadilan bagi
mereka, meskipun secara demografi jumlah
kelompok rentan mencapai taraf yang signifikan
jika melihat persentase penduduk.
Gambar 1. Konseptual model kelompok rentan (14)
Menurut UU 39 tahun 1999 tentang Hak Asasi
Manusia dalam pasal 5 disebutkan Setiap orang
yang termasuk kelompok masyarakat yang
rentan
62 • Jurnal Kebijakan Kesehatan Indonesia : JKKI, Vol. 09, No. 02 Juni 2020
 Jurnal Kebijakan Kesehatan Indonesia : JKKI
berhak memperoleh perlakuan dan perlindungan
lebih berkenaan dengan kekhususannya (15).
Dalam paragraf penjelasan disebutkan bahwa
yang dimaksud dengan “kelompok masyarakat
yang rentan” antara lain adalah kelompok
manusia yang memiliki risiko tinggi mengalami
ketidakadilan dalam pemenuhan hak – hak
asasinya sebagai manusia, kelompok rentan
yang dimaksud antara lain : Ibu hamil, anak –
anak, fakir miskin, dan lansia. Kelompok rentan
didefinisikan sebagai kelompok sosial yang
memiliki risiko lebih besar untuk mengalami
perubahan kondisi kesehatan dibanding
masyarakat umum.
Jika kota memberlakukan Lockdown untuk
mencegah penularan COVID-19, ada beberapa
hal yang harus direncanakan terkait
kesiapsiagaan darurat untuk mengangkut dan
menyediakan tempat perlindungan bagi sejumlah
besar populasi rentan. Dalam situasi lockdown,
ruang publik ditutup, pergerakan di luar rumah
dibatasi, dan jalan transportasi utama mungkin
ditutup, yang semuanya dapat berdampak negatif
pada populasi rentan dan termajinalkan.(18).
Dalam pembahasan ini, penulis berfokus kepada
3 kelompok, yakni anak-anak, ibu hamil, dan
lansia berdasarkan 4 dimensi H.L. Blum yang
meliputi lingkungan, perilaku/ gaya hidup,
pelayanan kesehatan, dan genetik dalam
kaitannya dengan social distancing akibat
pandemik.
3.2.1 Kelompok Anak-anak
Data anak dalam perawatan COVID-19 di
Indonesia per 15 April ada sebesar 0,1% dari
total pasien positif, meskipun kasus COVID-19
pada anak di Indonesia masih sedikit, namun
secara aspek sosial hampir seluruh anak
yang berada di Indonesia mengalami dampak
langsung dari social distancing yang diterapkan
pemerintah (2). Covid 19 masih dianggap ringan
menginfeksi anak, sejauh ini belum ada kasus
yang menyatakan anak menularkan virus (19).
Kasus Covid-9 pada bayi telah dikonfirmasi
terjadi pada bayi baru lahir, namun semua bayi
tertular dari ibu yang semuanya juga dinyatakan
positif Covid-19. Bayi termuda dinyatakan
terinfeksi setelah 30 jam pasca kelahiran (20).
Data tentang covid 19 pada neonatus masih
sangat terbatas karena penularan pada neonatus
masih jarang. Kasus neonatus dengan covid
tidak memiliki gejala, gejala sangat ringan sampai
sedang mungkin ditemui (21). Anak dengan
fibrosis kistik atau asma berat meningkatkan
keparahan jika sudah terpapar Covid-19,
sehingga anak dengan komorbiditas masuk
kedalam kelompok rentan yang perlu
pemantauan khusus (22). Sehingga, dapat
dikatakan sejauh ini gejala COVID-19 pada
anak sangat ringan bahkan hampir tidak
Jurnal Kebijakan Kesehatan Indonesia : JKKI, Vol. 09, No. 02 Juni 2020
ada gejala, anak juga bersifat tertular bukan
menularkan.
Meskipun anak memiliki risiko lebih rendah
dari paparan COVID-19, namun ketidakjelasan
nasib pada keluarga, akan berdampak besar
pada anak. Isolasi membuat anak gagal
memahami, bingung dan ketakutan. Fokus tidak
hanya pada cara orag tua memperhatikan
anaknya lebih dari biasanya, namun anak harus
berkompromi dengan ketidakjelasan disekitar
keluarganya (23). Untuk mengatasi hal tersebut,
penting bagi orang tua memuaskan anak dan
memberi rasa nyaman. Hal ini dapat dihubungkan
dengan teori Sarwono yang menjelaskan teori
Freud tentang tahap perkembangan psikoseksual
anak yang mana memiliki 5 tahap, yaitu oral,
anal, phalik, latens, dan genital(24).
Penelitian terbaru menunjukkan bahwa bayi
selama masa pandemi bahkan yang positif
COVID-19 harus tetap diberikan ASI untuk
meningkatkan kekebalan tubuh, dimana sebelum
menyusui ibu harus mencuci tangan dan
memakai masker saat menyusui(21). Hal ini
sesuai karena pada fase oral, anak disebut juga
bayi akan berfokus pada mulut, dengan cara
menghisap meskipun tidak lapar, sehingga pada
bayi hal terpenting adalah memberinya ASI. Fase
phalik terjadi dimana balita berfokus pada
ketertarikan orang tua lawan jenis, sedangkan
pada fase latens anak akan berfokus pada
kecakapan sosial dan intelektual. Fase genital
sendiri, remaja mulai tertarik dengan lawan jenis.
Pada ketiga fase ini sebaiknya orang tua mulai
mengajarkan bagaimana etika batuk, memakai
masker, dan mencuci tangan. Pengajaran
mencuci tangan pada balita dapat dilakukan oleh
orang tua lawan jenis, dengan modifikasi,
misalnya mencuci tangan sambil bernyanyi.
Pemerintah Republik Indonesia telah
mengumumkan adanya Social distancing
Berskala Besar (PSBB) dimana salah satu
bagiannya adalah tentang penutupan sekolah.
Penutupan sekolah dilakukan di Indonesia sejak
3 April, diganti dengan Pembelajaran Jarak Jauh
(PJJ) sesuai amanat menteri pendidikan.
Komunikasi sangat diperlukan sebelum sekolah
ditutup, bagaimana cara orang tua akan
berkomunikasi dengan perwakilan yang
berwenang dari sekolah. Efek negatif dari
penutupan sekolah juga perlu dipikirkan, orang
tua merasa bahwa anaknya memiliki potensi
stres, depresi, merasa terisolasi, sekolah harus
mampu mencari cara atau program untuk
menjaga emosi anak, terutama anak dengan
kebutuhan khusus(25).
Weaver & Wiener(26) menyatakan belajar dari
rumah memungkinkan anak merasa kebingungan
terhadap perubahan, atau cemas terhadap
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 Pengaruh Kebijakan Social Distancing : Anung Ahadi Pradana, Casman, Nur’aini
infeksi, bahkan takut apa yang akan terjadi jika
anak atau keluarganya positif Covid-19. Hal
penting yang perlu diperhatikan orang tua adalah
mengedepankan kejujuran dan kebenaran. Anak
akan selalu mengobservasi keadaan disekeliling
mereka, dan anak akan mulai banyak bertanya
sementara mayoritas orang tua tidak yakin apa
yang harus dikatakan kepada anaknya. Satu-
satunya cara untuk menenangkan mereka dari
kecemasan, kebingungan dan salah persepsi
adalah dengan menjawab pertanyaannya dengan
jujur dan benar. Anak yang terlalu lama tidak
masuk sekolah juga dapat mengalami
kebosanan, sehingga perlu adanya
keseimbangan dalam hal mengerjakan tugas
dan bersenang-senang. Memberikan internet
salah satu hal yang dibutuhkan anak saat ini,
namun perlu adanya pembatasan penggunaan.
Anak yang terpisah dari orangtua akibat
terkarantina atau orangtuanya mengalami
karantina membutuhkan perhatian khusus,
masalah-masalah psikologis cenderung dialami
lebih tinggi oleh mereka(27). China telah
mengatur kebijakan bagi anak yang positif,
dimana perawat tersedia 24 jam disamping anak,
petugas gizi berkala berdiskusi dengan anak
terkait pemeneuha gizi, anak juga dipersilahkan
melakukan video call dengan orang tua kapan
pun anak inginkan. Anak yang telah sembuh
namun orang tua mereka masih dikarantina
maupun anak yang dari awal terpisah dari orang
tua, selain dipantau oleh dinas sosial setempat,
relawan ibu-ibu sekita tempat tinggal anak juga
membantu mengasuh anak.
3.2.2 Kelompok Ibu Hamil
Kondisi kehamilan menyebabkan penurunan
kekebalan parsial karena perubahan fisiologi
pada saat kehamilan, sehingga mengakibatkan
ibu hamil lebih rentan terhadap infeksi virus. Oleh
karena itu, pandemi COVID-19 sangat mungkin
menyebabkan konsekuensi yang serius bagi ibu
hamil(28–30). Sampai saat ini informasi tentang
COVID-19 pada kehamilan masih terbatas.
Pengumpulan data ibu hamil dengan COVID-19
di Indonesia sendiri juga belum dapat
disimpulkan.
Perubahan fisiologis dan imunologis yang
terjadi sebagai komponen normal kehamilan
dapat memiliki efek sistemik yang meningkatkan
risiko komplikasi obstetrik dari infeksi pernapasan
pada ibu hamil (31). Melalui evaluasi yang
dilakukan dalam wabah koronavirus sebelumnya
(SARS dan MERS), ibu hamil telah terbukti
memiliki risiko kematian yang tinggi, keguguran
spontan, kelahiran prematur, dan IUGR
(intrauterine growth restriction). Tingkat fatalitas
SARS dan MERS di antara pasien hamil adalah
25% dan 40%, masing- masing terdapat
beberapa risiko seperti ketuban
pecah dini, kelahiran prematur, takikardia janin,
dan gawat janin (32). Namun, Apakah COVID-19
meningkatkan risiko keguguran dan kelahiran
mati belum diketahui(33,34).
Dalam pandemi, langkah-langkah social
distancing telah terbukti efektif dalam mengurangi
penularan penyakit (30). Termasuk hal ini juga
berlaku pada ibu hamil, agar membatasi diri
untuk tidak banyak terpapar dengan lingkungan
luar, apalagi melakukan perjalanan ke daerah
pandemi. Risiko ibu hamil bisa tertular COVID-19
salah satunya saat melakukan kunjungan
pemeriksaan kehamilan di klinik kebidanan atau
rumah sakit. Sehingga ibu hamil harus lebih
meningkatkan kewaspadaan dengan terus
disiplin dalam penggunaan APD. Ibu hamil bisa
membatasi kunjungan ke klinik kebidanan atau
rumah sakit dengan melakukan konsultasi via
daring, aktif melakukan pengecekan sendiri tanda
dan bahaya saat kehamilan, dan hanya
melakukan kunjungan saat ditemukan hal-hal
yang mengkhawatirkan.
Dalam analisis laporan yang ditulis oleh (31)
dari 38 ibu hamil dengan COVID-19, dengan usia
kehamilan bervariasi antara 30-40 minggu, 37
orang di antaranya dikonfirmasi melalui tes PCR,
tidak ditemukan adanya pneumonia berat atau
kematian maternal. Di antara 30 neonatus yang
dilahirkan, tidak ditemukan adanya kasus yang
terkonfirmasi dengan COVID-19. Kurangnya
penularan wanita-janin dari COVID-19 ini
konsisten dengan pengalaman ibu hamil dengan
infeksi coronavirus lainnya - SARS dan MERS –
pada masa lampau. Belum ada data pasti yang
menginformasikan apakah kehamilan
meningkatkan kerentanan terhadap COVID-19
(34).
COVID-19 tidak terdeteksi pada Air Susu Ibu
(ASI) yang berstatus pasien Covid-19. Namun,
fokus utama kekhawatiran adalah apakah wanita
yang terinfeksi dapat menularkan virus melalui
tetesan pernapasan selama menyusui(35).
Menyusui selama infeksi COVID-19 tidak
dikontraindikasikan oleh Pusat Pengendalian
dan Pencegahan Penyakit (CDC) dengan syarat
semua tindakan pencegahan harus dilakukan
untuk menghindari penyebaran virus kepada
bayi, termasuk mencuci tangan sebelum
menyentuh bayi dan memakai masker wajah
(36).
Data terbatas yang diperoleh dari kasus ibu
hamil dengan COVID-19 menunjukkan bahwa
penularan vertikal intrauterine tidak terjadi; virus
dalam cairan ketuban, plasenta, ASI dari wanita-
wanita yang terinfeksi atau dalam sekresi hidung
neonatus tidak ditemukan. Namun, infeksi dapat
terjadi pada neonatus melalui kontak jarak dekat
saat postnatal (20,30,35). Pada penelitian yang
dilakukan oleh Liang & Acharya(29) , hasil
analisis cairan ketuban, darah tali pusat, usap
tenggorokan
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 Jurnal Kebijakan Kesehatan Indonesia : JKKI

neonatal, dan sampel ASI yang diambil pada

dan sebagainya), penggunaan atau pemanfaatan
enam dari sembilan pasien ditemukan hasil
layanan kesehatan, dan stresor yang muncul.
COVID-19 negatif. Selama periode ini, menyusui
Sementara status kesehatan menggambarkan
langsung tidak dianjurkan. Pilihan yang
kondisi kesehatan individu pada suatu waktu (14).
memungkinkan bagi wanita untuk memompa
Dalam perjalanan proses penuaan yang dialami
ASInya, yang diberikan kepada bayi oleh perawat
oleh lanjut usia, setidaknya terdapat 3 faktor yang
atau pengasuh yang sehat.
terpengaruhi, yaitu fisik, psikologis, dan sosial (38).
Kebutuhan unik wanita hamil harus
Perubahan tersebut akan menyebabkan terjadinya
dimasukkan dalam rencana kesiapsiagaan di
konsekuensi fungsional pada lansia. Konsekuensi
tengah wabah yang berkembang pesat dan
fungsional adalah suatu efek yang muncul sebagai
memberikan efek yang cukup signifikan pada
akibat dari perubahan fisik, faktor risiko, serta
kesehatan masyarakat serta infrastruktur medis
perilaku kesehatan individu atau lanjut usia yang
ini. Pada wabah sebelumnya, dokter enggan
dapat diobservasi serta mempengaruhi kehidupan
untuk merawat atau memvaksinasi wanita hamil
sehari – hari lanjut usia. Proses penuaan yang
karena kekhawatiran akan keselamatan janin.
dialami lansia menyebabkan kelompok ini menjadi
Seperti halnya semua keputusan mengenai
salah satu kelompok yang mengalami efek paling
perawatan selama kehamilan, penimbangan parah akibat COVID-19.
manfaat intervensi untuk wanita dan janin dengan Pusat Pengendalian dan Pencegahan Penyakit
risiko potensial sangat diperlukan (29). Secara (CDC) Amerika Serikat menyatakan bahwa
khusus, lebih banyak perhatian harus diberikan tidak ada pengobatan antivirus khusus yang
kepada wanita hamil dengan COVID-19 pada direkomendasikan, dan pasien harus menerima
trimester pertama dan kedua. Meskipun tidak ada perawatan suportif untuk membantu meringankan
bukti yang mendukung kemungkinan penularan gejala muncul. Untuk kasus yang lebih parah,
vertikal COVID-19 dari ibu ke bayi, penelitian perawatan harus mencakup mempertahankan
yang ada menunjukkan bahwa meskipun virus fungsi organ vital. Pencegahan sekunder dan
tidak mencapai janin, infeksi ibu dan peradangan perawatan komplikasi umum dapat menjadi
yang terjadi sebagai respons terhadap infeksi masalah utama pada pasien lansia (39).
virus dapat memengaruhi perkembangan Di Indonesia, persentase harian jumlah
janin(27). penderita lansia dalam perawatan mencapai
Perawatan yang aman dan optimal dari ibu
rerata 1,7% dari kasus yang ditemukan,
nifas dalam periode postpartum membutuhkan
meninggal 0,2%, dan sembuh 0,08%. Angka yang
pendekatan tim multidisiplin(30,37). Prinsip-
ditemukan ini tentu bukan merupakan angka final
prinsip umum mengenai manajemen COVID-19
mengingat fenomena gunung es yang terjadi di
selama kehamilan meliputi isolasi awal, prosedur
masyarakat (2). Social distancing yang dilakukan
pengendalian infeksi, pengujian untuk COVID-19,
saat ini diketahui memiliki efek negatif pada
terapi oksigen sesuai kebutuhan, penghindaran
lansia dan dianggap sebagai masalah kesehatan
kelebihan cairan, antibiotik empiris (karena risiko
masyarakat yang serius karena risiko tinggi
infeksi bakteri sekunder), pemantauan kontraksi
masalah kardiovaskular, autoimun, neurokognitif,
janin dan uterus, ventilasi mekanik awal untuk
dan kesehatan mental yang dapat muncul pada
kegagalan pernapasan progresif, perencanaan
lansia (40).
persalinan individual, dan pendekatan berbasis
Mengisolasi lansia mungkin dapat mengurangi
tim dengan konsultasi multispecialty (33).
penularan, dimana tujuan utamanya adalah untuk
Manajemen berbasis tim direkomendasikan untuk
menunda memuncaknya kasus yang ada, dan
kehamilan yang dikelola di fasilitas perawatan
meminimalkan penyebaran ke kelompok berisiko
Kesehatan.
tinggi. Mengisolasi diri tidak cocok dilakukan
3.2.3 Kelompok Lansia lansia yang sangat bergantung pada kontak
sosial di luar rumah, seperti layanan homecare,
Kerangka konseptual atau karakteristik rentan komunitas lansia, dan tempat ibadah. Mereka
yang terjadi pada lansia terdiri atas 3 konsep, yang tidak memiliki keluarga atau teman dekat,
yaitu: ketersediaan sumber daya, faktor risiko, dan bergantung pada dukungan layanan sukarela
dan status kesehatan. Ketersediaan sumber daya atau perawatan sosial, dapat mengalami rasa
mengacu kepada sumber daya sosial – ekonomi kesepian, terisolasi, atau terpencil(41). Banyak
(meliputi pekerjaan, pendapatan, pendidikan, dan lansia memiliki kondisi mental dan fisik yang
tempat tinggal) dan lingkungan (akses kepada menyedihkan dan seringkali tidak memiliki akses
layanan kesehatan dan kualitas pelayanan ke pelayanan kesehatan, yang mana dapat
kesehatan di wilayah). Faktor risiko mangacu mengarah pada masalah potensial. Lansia
kepada aksesibilitas individu kepada faktor – yang mengalami pemisahan dari dunia luar
faktor yang mempengaruhi diantaranya : gaya sering kali tidak diikutsertakan dan dilibatkan
hidup dan perilaku sehari – hari (merokok, pola
diit,

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 Pengaruh Kebijakan Social Distancing : Anung Ahadi Pradana, Casman, Nur’aini

dalam pelayanan kesehatan yang dapat diakses

6. Jiang R. Inside China and COVID-19:
maupun dalam memilih layanan kesehatan
Questions and answers. Travel Med Infect
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Jurnal Kebijakan Kesehatan Indonesia : JKKI, Vol. 09, No. 02 Juni 2020 • 67
 American Journal of Preventive Cardiology 2 (2020) 100038

Contents lists available at ScienceDirect

American Journal of Preventive Cardiology

journal homepage: www.journals.elsevier.com/the-american-journal-of-preventive-cardiology

State-of-the-Art Review

State-of-the-Art review: Hypertension practice guidelines in the era of COVID-

19
Keith C. Ferdinand a,*, Thanh N. Vo b, Melvin R. Echols c
a
Tulane Heart and Vascular Institute, John W. Deming Department of Medicine (KCF), USA
b
Tulane University School of Medicine (TNV), Tulane University, New Orleans, LA, 70112, USA
c
Cardiology Division (MRE), Department of Medicine, Morehouse School of Medicine, Atlanta, GA, 30310, USA

A RTICLEIN FO
A BSTR ACT

Keywords:
Hypertension The global burden of hypertension (HTN) is immense and increasing. In fact, HTN is the leading risk factor for adverse
Prevention cardiovascular disease outcomes. Due to the critical significance and increasing prevalence of the disease, several national and
Public health international societies have recently updated their guidelines for the diagnosis and treatment of HTN. In consideration of the
Guidelines COVID-19 pandemic, this report provides clinicians with the best strategies to prevent HTN, manage the acute and long-term
COVID-19 cardiac complications of HTN, and provide the best evidence-based care to patients in an ever-changing healthcare environment.
The overarching goal of the various HTN guidelines is to provide easily accessible information to healthcare providers and
public health officials, which is key for optimal clinical practice. However, the COVID-19 pandemic has challenged the ability to
provide safe care to the most vulnerable hypertensive populations throughout the world. Therefore, this review compares the most
recent guidelines of the 2017 American College of Cardiology/American Heart Association and multiple U.S. societies, the
2018 European Society of Cardiology/European Society of Hypertension, the 2019 National Institute for Care and Health
EXcellence, and the 2020 International Society of Hypertension. While a partial emphasis is placed on the management of HTN in
the midst of COVID-19, this review will summarize current concepts and emerging data from the listed HTN guidelines on the
diagnosis, monitoring, management, and evidence-based treatments in adults.

1. Introduction
progression in patients with COVID-19 [6]. Other studies have shown similar
findings of the deleterious effects of COVID-19 patients with HTN [7,8]. Yet it
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel
remains unclear how contemporary guideline recommen- dations may be
coronavirus composed of a single stranded positive-sense RNA. The specifics of
impacted in the setting of the COVID-19 pandemic.
the detailed pathobiology and human cellular in- teractions have been described
Moreover, the current public health crisis of COVID-19 has already impacted
previously [1–4]. This virus binds to the angiotensin-converting enzyme 2
patients with HTN from multiple aspects. Appro Ximately 1.5 million people in the
(ACE2), a cellular transmembrane ho- mologue of angiotensin-converting enzyme
U.S. lost their employment-based health insurance coverage, directly affecting
(ACE), in order to enter most human cell lines, including pneumocytes and those
patients with HTN and other chronic condi- tions [9]. Coverage losses are likely
in the cardiovascular system [4]. Consequently, in addition to the eponymous
the steepest in states without Medicaid expansion under the Patient Protection
respiratory complications, COVID-19 is associated with increased vascular
and Affordable Care Act. Unfortunately, access to health coverage is most
throm- bosis, myocardial inflammation, arrhythmia, and potentially increased risk
deficient in states with the largest racial/ethnic disparities in cardiovascular care,
for adverse outcomes in patients with HTN [5]. In a recent meta-analysis of
poten- tially impacting adherence and medication affordability [10,11]. Spe-
6560 patients from 30 studies, HTN was associated with an increased composite poor
cifically, African Americans may suffer worse outcomes related to COVID-19
outcome, which included mortality, acute respiratory disease syndrome, need for
exposure, due to a variety of reasons, including socioeco- nomic factors and
intensive care, and disease
limited health access [12].

* Corresponding author. Tulane Heart and Vascular Institute, John W. Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, #8548, New Orleans,
LA, 70112, USA.
E-mail addresses: kferdina@tulane.edu (K.C. Ferdinand), tvo4@tulane.edu (T.N. Vo), mechols@msm.edu (M.R. Echols).

https://doi.org/10.1016/j.ajpc.2020.100038
Received 9 June 2020; Received in revised form 5 July 2020; Accepted 5 July 2020
2666-6677/© 2020 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
K.C. Ferdinand et
al.
This review will compare and contrast contemporary evidence-based
guidelines for the prevention and treatment of HTN: the 2017 American College
of Cardiology/American Heart Association (ACC/AHA) Guide- line for the
Prevention, Detection, Evaluation, and Management of High Blood Pressure in
Adults; the 2018 European Society of Cardiology/Eu- ropean Society of
Hypertension (ESC/ESH) Guidelines for the Manage- ment of Arterial
Hypertension; the 2019 National Institute for Health and Care EXcellence (NICE)
Hypertension in Adults; and the 2020 Interna- tional Society of Hypertension
(ISH) Global Hypertension Practice Guidelines. Accordingly, this review will
summarize current best prac- tices in HTN management, taken into account the
current COVID-19 pandemic, emerging data on diagnosis and BP monitoring,
and evidence-based treatment of certain special populations, including related to
race/ethnicity. Guidelines-directed medical care will provide best strategies to
battle the acute and long-term cardiac complications of HTN across diverse
populations in the COVID-19 era and beyond.
2. The hypertension pandemic
HTN, the most widely prevalent and potent risk factor for athero- sclerosis
cardiovascular disease (ASCVD) and associated microvascular complications,
affects an estimated 1.4 billion people worldwide, disproportionately so in
low- and middle-income countries. Globally, upwards to 1 in 4 men and 1 in 5
women have the chronic HTN [13,14]. Consequently, HTN is the leading global
cause of mortality, accounting for 10.4 million deaths per year and a major cause
of premature death worldwide [15]. Regarding systolic blood pressures (SBP),
there are over
7.8 million deaths and ~140,000 million disease adjusted life years (DALYs)
attributed to a SBP > 140 mmHg alone [13–15].
As well, there are unique considerations and persistent world-wide
disparities in HTN death and morbidity in specific populations, such as related to
racial/ethnicity, female sex, advanced age, and socioeconomic status. Recent data
from the Centers for Disease Control and Prevention (CDC) noted a significantly
higher prevalence of uncontrolled HTN among U.S. racial/ethnic minority
groups compared with non-Hispanic whites [16]. The prevalence of self-
reported HTN in 2017 ( 140/90 mmHg) was much higher in Non-Hispanic
≥ define Stage I HTN. The 2020 ISH pro- poses HTN guidelines for global use, fit
blacks (African Americans) and American Indians (40% vs. 37%, respectively)
than the self-reported prevalence of HTN in Hispanics and whites (28% vs. 29%,
respectively) [16]. After the introduction of the 2017 ACC/AHA and multi-
society high blood pressure (HBP) guidelines, the prevalence of HTN increased
from 32% in the U.S. to 46% using a BP threshold for HTN 130/80 mmHg,
further disproportionately affecting blacks and older individuals [17]. Due to the
≥
increasing prevalence of HTN in younger patients, the U.S. Preventive Task Force
recommendations now support office BP screening in patients 18 years of age and
older [18]. Therefore, there may be further disparate prevalence among various
groups with HTN as time progresses.
This review evaluates current recommended lifestyle interventions and
pharmacotherapy within the major guidelines, and the ongoing ef- forts to combat
the challenges of HTN management in the setting of COVID-19. Although
recommended in evidence-based guidelines, the COVID-19 pandemic has limited
physical activity secondary to social distancing, home quarantining, and fitness
center shutdowns [19]. Moreover, the COVID-19 pandemic has forced the
practice of medicine into a new paradigm, where telehealth technologies and self-
monitoring techniques have developed more prominent roles for clinical manage-
ment of HTN and ASCVD risk reduction.
3. Recent major guidelines for hypertension: similarities and
differences
Current guidelines, despite major and minor differences, serve as tools for the
advancement of “standard of care” recommendations in clinical practice,
including specific populations, usually with a regional emphasis. The 2017
ACC/AHA recommendations for tighter BP control
2
American Journal of Preventive Cardiology 2 (2020)
100038
were supported by several sources, including several meta-analyses of
observational cohorts associated with a significantly higher range of hazard ratios
(1.1–1.5) for cardiovascular disease (CVD) and stroke with
SBP/DBP ≥ 120–129/80-84 mmHg as compared to <120/80 mmHg [17, 20].
Furthermore, data for the benefit of tighter BP control also emerged
from the Systolic Blood Pressure Intervention Trial (SPRINT). This Na- tional
Institute of Health landmark trial was a large randomized control study which
evaluated the benefits of intensive BP goals (<120 mmHg)
compared with standard treatment goals (<140 mmHg) [21]. As a result
of an overwhelming positive effect, SPRINT was stopped early after
demonstrating a 25% and 27% relative risk reduction (RRR) in the pri- mary
endpoint and all-cause mortality in the intensive BP lowering group compared to
standard treatment (HR 0.75, 95% CI 0.64–0.89, HR 0.73, 95% CI 0.60–0.90,
respectively). Thus, the prospect of encouraging pa- tients and providers in the
U.S. to manage HTN more intensively was recommended to decrease end-organ
damage and mortality.
The 2018 ESC/ESH HTN guidelines reflected a broad scope, intended for the
treatment of hypertensive individuals in countries with various socioeconomic
populations [22]. The prevalence of HTN ( 140/90 mmHg) in central ≥ and
Eastern Europe is approXimately 30–45%, affecting over 150 million adults,
with an increasing prevalence of up to 60% in adults of advanced age. Instead of
focusing on tighter BP control, the ESC/ESH guidelines defined HTN as the level
of BP at which the benefits of treatment, whether lifestyle interventions or
medications, outweighed the risks. Recommendations were based on meta-
analyses of randomized controlled trials (RCTs), in which treatment of stage I BP
values of 140/90 mmHg were considered beneficial [22]. Moreover, utilizing
older and high-risk cohort studies may increase statistical power over a shorter
duration of≥follow-up. These differences in the type of evidence used between
the 2017 ACC/AHA and the 2018 ESC/ESH guidelines may provide clarity as to
why the BP thresholds for HTN vary between the reports.
Most recently published are the NICE’s ‘Hypertension in Adults’ in 2019 and
the 2020 ISH report [23,24]. The NICE guidelines only reviewed evidence
beyond the year 2000, reflecting the current use of electronic BP devices.
However, both guidelines use the SBP/DBP threshold of 140/90 mmHg to
for low and high resource settings by advising essential and optimal standards, in a
concise and easy to use format. Therefore, the overarching goal of contemporary
HTN develop- ment is to reduce the adverse outcomes in the populations of interest
and regional differences often inhibit complete uniformity.
4. Current definitions of Arterial Hypertension in adult
Although the CVD morbidity and mortality of increased BP is linear, direct,
and continuous, the definition of HTN varies among guidelines (Table 1). The
current recommendations, in general, provide BP thresholds based on average
measurements in an office setting. The rationale for these categorizations is
determined primarily by in-office observational data related to the association of
SBP/DBP and CVD risk, randomized-controlled trials (RCTs) of lifestyle
modifications to lower BP, and RCTs of medication therapy to reduce BP [17].
The 2018 ESC/ESH HTN definition characterizes ‘optimal’ BP defined as SBP
<120
mmHg and DBP <80 mmHg. On the other hand, this level of blood
pressure is considered ‘normal’ by the 2017 ACC/AHA definitions [17] (Table 1).
The NICE and ISH publications use similar thresholds for the defini- tions of
HTN ( 140/90 mmHg).
≥ The BP for a visit is determined by the average of at least
two measurements in the clinic setting, at least one minute apart. If the final BP
measurement is between 140/90 and 180/ 120 mmHg, the NICE and ISH
guidelines recommend offering ambula- tory blood pressure monitoring (ABPM)
to confirm the diagnosis [23,24]. Additionally, all of the reviewed guidelines
strongly recommend the utilization of out-of-office BP measurements for
monitoring and/titration antihypertensive therapies. The various reports reviewed
herein support
Table 1
home blood pressure monitoring (HBPM) and provide strong recom- mendations
Guideline Definitions of Hypertension [17,22,24,29].
of these techniques to confirm the diagnosis of HTN and monitor medication
BP Category ACC/AHA ESC/ESH 2018 NICE ISH 2020 adjustments. HBPM is an alternative to confirm the diagnosis of HTN if ABPM is
(mmHg)a 2017 2019
not possible. The technology for ABPM has been available for many years and is
Normal recommended by the ACC/AHA, ESH/ESC, NICE, and ISH guidelines with similar
SBP <120 120–129 <140 <130 protocols suggested for use. ABPM has a stronger association with hypertension-
DBP <80 80–84 <90 <85
related target- organ damage and adverse clinical outcomes [30].
Elevated
SBP 120–129 130–139 * 130–139
The ABPM devices usually measure BP every 15–30 min during the day and
DBP <80 85–89 * 85–89 every 15 min to 1 h during the night over a 24-hour period. There are BP
Hypertension correlate values to in-office setting BP measurements within the guidelines for HTN
Stage I management to assist with HTN management (Table 2). ABPM is also useful to
SBP 130–139 140–159 140–179 140–159 detect certain BP phenotypes of HTN that may confer increased CVD risk. White-
DBP 80–89 90–99 90–119 90–99
coat HTN occurs when in- dividuals demonstrate higher BP measurements in the
Stage II
office setting when compared with measurements outside of the office. The white-
SBP ≥140 160–179 ≥180 ≥160
DBP ≥90 100–109 ≥120 ≥100
coat effect is a term used to describe the same phenomenon in patients having a
Stage III history of HTN and receiving antihypertensive medications [26]. Although the
SBP * ≥180 * * data are limited, there may be a modest increase in CVD risks for patients
DBP ≥110 * * experiencing these conditions. Most studies demon- strating an increased CVD risk
BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; are in patients with other CVD risk factors that could explain the higher risk [31,32].
ACC/AHA, American College of Cardiology/American Heart Association; ESC/ ESH, The guidelines also reference terminology of isolated office HTN and other
European Society of Cardiology, European Society of Hypertension; NICE, National Institute subclasses of HTN, although these conditions are not covered extensively within
for Health and Care EXcellence; ISH, International Society of Hypertension. this review [17,22, 24].
a
Blood pressure is defined as seated clinic BP and by the highest level of ABPM has also been used to detect masked HTN, which refers to in-
measurement, whether systolic or diastolic. dividuals demonstrating a mean out-of-office BP in the hypertensive range and
normal BP measurements in an office setting. The ESC/ESH guidelines suggest
the initial or concomitant use of nonpharmacological interventions for most incorporation of nighttime BP measurements with daytime readings for this
patients, which include lifestyle modifications of dietary and ac- tivity levels, prior diagnosis, although most guidelines use day- time readings of ABPM [22,30].
to medications in most individuals to reduce BP values. Incorporation of nighttime readings also increases the detection and prevalence
rates of masked HTN in blacks, associated with higher rates of declining renal
5. Contemporary recommendation of blood pressure techniques function [33,34].
and devices Despite the evidence supporting the use of ABPM in HTN manage- ment,
several issues limit its use and availability for patients. The monitoring requires
The accurate measurement of in-office and out-of-office BP is crucial in HTN proper training of patients and providers, as well as compliance of use to provide
diagnosis and management. Although the traditional use of de- vices calibrated to accurate and helpful information. The reimbursement rates for the utilization
a column of mercury is still utilized in some regions, most guidelines report of ABPM is historically low,
recommendations from data using electronic de- vices for BP monitoring. All of representing <1% of Medicare beneficiary claims in some studies [35]. There are
the guidelines recommend validated de- vices, whether electronic or manual also only modest data supporting better outcomes with the
[25,26]. The US Blood Pressure Validated Device Listing (VDLTM) was the first treatment of white-coat or masked HTN outside of standard treatment of existing CVD
U.S. list of blood pressure (BP) measurement devices developed to assist physicians risk factors. Further investigations as to whether ABPM can specify individuals
and patients in identifying BP devices that are validated for clinical accuracy. BP requiring additional treatments to reduce CVD risk may be warranted.
devices listed on the VDLTM have specific criteria detailed as determined As recommended in all contemporary guidelines, HBPM and self- monitored
through independent review. Visit ValidateBP.org to view the current device blood pressure (SMBP) outside the office are considered a
listings for more information on the independent review process [27]. The
ESC/ESH guidelines recommend validated devices by the As- sociation of
Medical Instrumentation [26]. Table 2
As errors in BP measurements are common in most settings, the HTN guidelines Hypertension Correlation of Clinic, Home, and Ambulatory Blood Pressure Monitoring
all thoroughly describe protocols to obtain accurate results [28]. BP is measured [17,22,24,29].
in both arms to detect any differences in the first office visit. Most guidelines Guideline Clinic HBPM Daytime Nightime 24-h avg
recommend using the arm with the higher BP reading for a subsequent visit. All of (mmHg) (mmHg) ABPM ABPM ABPM
the reviewed guidelines suggest taking the BP 2–3 times, separated by at least 1 (mmHg) (mmHg) (mmHg)
min apart, averaging at least two of the readings for the final result. The ESC/ESH ACC/ ≥130/80 ≥130/80 ≥130/80 ≥110/65 ≥125/75
and NICE guidelines also suggest measuring the standing BP at least once after AHA
standing for 1 min, to determine the likelihood of orthostatic BP changes [22,29]. All
guidelines also suggest measuring BP in at least two separate office visits to diagnose ESC/ESH ≥140/90 ≥135/85 ≥135/85 ≥120/70 ≥130/80
HTN before any interventions are recommended. EXpert panels of the AHA and ≥ 140/90 ≥ 135/85 ≥ 135/85
NICE⁺ * *
ACC have published recent scientific statements evaluating the accuracy of BP
measurements in further detail, emphasizing the need for proper and ongoing
ISH ≥140/90 ≥135/85 ≥135/85 ≥120/70 ≥130/80
training of technicians and healthcare providers for the use of validated devices
[28,30]. HBPM, home blood pressure monitoring; ABPM, ambulatory blood pressure monitoring;
ACC/AHA, American College of Cardiology/American Heart Asso- ciation; ESC/ESH,
European Society of Cardiology, European Society of Hyper-
6. Guidance for out-of-office and ambulatory BP monitoring

The reviewed HTN guidelines acknowledge the benefits of ABPM and tension; NICE, National Institute for Health and Care International EXcellence; ISH,
Society of Hypertension.

3
more practical alternative to ABPM. The Agency for Healthcare Research and Quality
management, which is ideal at this time. Several barriers to overcome include
(AHRQ) found strong evidence that SMBP plus additional support (defined
payment and regulatory structures, state licensing, and cre- dentialing across
below) was more effective than usual care in lowering blood pressure among
health centers [40]. Yet, the use of remote patient monitoring, patient-initiated
patients with HTN [36,37]. SMBP protocols are likely to become much more
messaging, telephone visits, and video visits are within the reach of telehealth
useful in HTN control as the COVID-19 pandemic continues to direct current day
medicine should be beneficial for BP control in a large population effort. Wosik
medical care (see Fig. 1).
and colleagues suggest the COVID-19 pandemic will stimulate the need for
Public health organizations have recognized the devastating effects of HTN on the
telehealth services in significant shifts or phases of care. Phase I, or the initial
US population and have developed several initiatives to utilize the techniques of
outpatient management of conditions such as HTN with the “stay at home”, order
SMBP to manage CVD outcomes for HTN. The Million Hearts 2022 is a national
has already begun as some health centers have increased the need for telehealth
initiative to prevent 1 million heart attacks and strokes within 5 years through
services to as much as 70% of total outpatient visits. Phase II is described as the
the implementation of evidence-based strategies that can improve cardiovascular
telehealth needs during inpatient related surge, through the use of network care
health for all. This effort recognizes the use of out-of-office BP monitoring
management and e-consultations. Phase III is considered the post-pandemic
and rec- ommends use of these strategies, according to the best evidence [36].
recovery period, which is still unknown at this time. The authors appropriately
The TargetBP national initiative, formed by the AHA and the American Medical
discuss the issues in delayed care for serious non-COVID-19 related medical
Association, also assists health care organizations and care teams, at no cost, in
conditions, such as acute coronary syndromes, which has already occurred in many
improving BP control rates through a quality improvement program [38]. These
communities. A “care debt” is described as well from the first two phases and will
large-scale efforts will provide new insights into the challenges and management
likely require intense sustained telehealth efforts [41].
of adherence with BP rec- ommendations for all populations within the US.
In addition, mobile health services may become a preferred method of HTN
In general, the use of HBPM/SMBP have been recommended by several
management during and post the COVID-19 pandemic, particularly in poorer
societies, and most recently as a potential means to manage HTN during the COVID-
populations with less health care access. Mobile health in- terventions for HTN
19 outbreak in conjunction with the 2020 surge in telehealth [13,18,39]. It is
usually involve the use of a patient’s mobile phone, along with a validated BP
likely these BP measuring methods will become more useful over time as the
measuring device, to track and communicate measurements with providers. A
readings outside of the office may decrease the prevalence of white-coat
recent meta-analysis of eleven ran- domized controlled trials (4271 participants)
hypertension and inconsistent readings within office measurements. These
associated significantly lower systolic and diastolic BP measurements with the use
measures, in conjunction with advancing telehealth services, have the potential to
of mobile health interventions in patients with HTN [42]. These findings were
provide more responsibility for the patient’s HTN management. Thus, the
consistent through study duration and treatment intervention intensity within the
increasing steps to use out of office BP monitoring and telehealth services may
trials. Further investigations, involving nonpharmacologic interventions and
indirectly increase patient engagement and health literacy.
modes of patient engagement, may increase the effectiveness of future mobile
Many health centers and medical practices have quickly introduced more
and telehealth BP interventions.
pronounced telehealth services into the current models of care

Fig. 1. Feedback loop between patients and healthcare providers supporting SMBP [36].

4
7. Evidence-based approaches to
nonpharmacologic management of HTN
Therapeutic lifestyle changes are necessary to prevent poor CVD outcomes
with HTN. All of the major HTN guidelines support in- terventions of weight-
control (weight loss if necessary), sodium restric- tion, smoking cessation, regular
physical activity, healthy diet, and limiting alcohol consumption to reduce blood
pressure in all individuals (Table 3) [17,22,29]. However, the Dietary Approaches
to Stop Hyper- tension (DASH) pattern appears most effective to yield significant
re- ductions in BP for all individuals (blacks with reductions of SBP as high as 20
mmHg) slowing the decline of renal dysfunction and for weight loss with
overweight status [43–45].
Increased potassium intake (3500–5000 mg/day), aside from following the
DASH diet, is recommended by the ACC/AHA to provide further reductions in
BP (2–5 mmHg for hypertensive individuals) [17]. Dietary supplementation of
potassium can help further lower blood pressure by easing tension on blood vessel
walls. Behavioral therapies such as yoga and meditation, effectively reduce
blood pressure [24]. Additionally, the 2019 ACC/AHA Guideline on the Primary
Prevention of Cardiovascular Disease and a report from the American Society of
Pre- ventive Cardiology (ASPC) support the benefits of therapeutic lifestyle
interventions for BP control [13,46].
Additionally, Mediterranean diet (MedDiet) may have a favorable effect on the
risk of HTN in contrast to unfavorable dietary patterns such as red meat, processed
meat, and poultry [47]. The MedDiet or DASH diet are also likely beneficial over
the Western diet (WD) in relation to COVID-19 susceptibility, as the high rate
of consumption of saturated fats, sugars, and refined carbohydrates in the WD
contribute to the prevalence of obesity and type 2 diabetes (T2D) potentially
increasing
Table 3
Blood pressure reductions of nonpharmacological interventions [17].
Nonpharmacological
Dose Reduction in SBP
Intervention
(mmHg)
HTN Normal
BP
the risk for severe COVID-19 pathology and mortality [48].
Patient engagement, in addition to nonpharmacologic interventions, will likely
require more emphasis during and post COVID-19, as the prevalence of HTN
could increase over time with decreased activity and attention to diet. The need for
health coaching by clinicians and members of the community may increase in order to
initiate or maintain adherence to nonpharmacologic BP interventions. A recent
meta-analysis comparing implementation strategies for HTN control evaluated a
total of 55, 920 patients, which included studies evaluating the use of patient-
level health coaching. Health coaching was associated with a significant reduction
in blood pressure over a minimum of 6 months ( 3.9 mmHg, 95% CI -5.4 to 2.3
mmHg) [49]. Thus, multilevel interventions, including patient-level strategies, are
likely to become more important in the treatment of HTN during—and after the
COVID-19 pandemic. —
8. Impact of adherence on blood pressure control and outcomes
Nonadherence, affecting as much as 80% of patients with HTN, in- creases
the associated risk for CVD morbidity and mortality, with approXimately one
of every four patients not filling their initial pre- scription [17,24]. The major
HTN guidelines equally recognize the eco- nomic burden of HTN medications
increasing nonadherence [50]. In a recent study, 67% of patients who do not
experience financial barriers to pharmacotherapy are more likely adherent and
have normal BP within the past 12 months [50–53]. There are promising data
using highly sensitive high-performance liquid chromatography-tandem mass
spec- trometry biochemical measurements of drug levels in the serum or urine as a
surrogate of compliance [54,55]. Although these measurements are now available
for clinical use and covered by some insurance plans, more research is warranted for
determining the effect on large populations and mainstream use.
Guideline-recommended strategies include adherence feedback to the patient,
HBPM/SBPM, linkage of behavior with daily habits, electronic aids, such as
mobile phones and reduction of polypharmacy utilizing a
single pill combination is possible [24,46,56] (Table 4). As most patients will
often require more than one antihypertensive agent to control BP, fiXed-dose
combinations (FDC) pills for HTN are supported by the major guidelines
[17,22,24]. A recent meta-analysis of 62,481 patients with

Weight loss Aim for at least 1-kg reduction in body

weight for most adults who are
overweight. EXpect ~1 mmHg
reduction for every 1-kg reduction in
body weight.
DASH dietary pattern Diet rich in fruits, vegetables,
whole grains, low-fat dairy products,
with reduced content of saturated and
total fat. Available at
https://www.nhlbi.nih.gov/health
/resources/heart/hbp-dash
-how-to.
Dietary sodium Optimal goal <1500 mg/day. Aim
for at least 1000 mg/day reduction in
most adults
Dietary potassium ApproXimately 3500–5000 mg/ day.
For a list of high potassium
foods, visit https://www.drugs.
com/cg/potassium-content-of-
foods-list.html
Physical Activity
Aerobic 90–150 min/week at 65–75% of
max heart rate
Dynamic resistance 90–150 min/week; 6 exercises, 3
sets/exercise, 10 repetitions/set
Isometric resistance 4 × 2 min (hand grip), 1 min rest
between exercises; 3 sessions/week for
8–10 week duration
Alcohol In individuals who drink alcohol,
consumption reduce to: Men ≤ 2 drinks daily,
Women ≤ 1 drink daily (~12 oz.
beer, 5 oz. of wine, or 1.5 oz.
distilled spirits)
5 2–3
HTN reported a mean medication adherence difference of ~15% in pa-
tients receiving FDC medications vs. free separate equivalent dose pills [57].
Many common FDC HTN therapies are included in formularies at reduced co-
pays and may attenuate HTN management costs during the COVID-19 pandemic
and beyond.
11 3
The polypill concept, including HTN and lipid drugs, may help reduce
prescribing complexities for CVD prevention [58–60]. A recent ran- domized,
controlled polypill (atorvastatin 10 mg, amlodipine 2.5 mg, losartan 25 mg, and
hydrochlorothiazide 12.5 mg) trial, involving adults with a CVD risk of >10%
demonstrated significant BP and LDL reduction
5–6 2–3
Table 4
4–5 2 Guideline recommendations for adherence to antihypertensive therapies [17,22, 24].
● Link drug intake with daily habits for patients
● Give adherence feedback
● Use pillboXes or special packaging
5–8 2–4 ● Integrate provider care with pharmacists and nurses (e.g., consider retrieving pharmacy
refill patterns, multidisciplinary approach)
4 2 ● Assess adherence with a “no blame’ approach
● Telemetry transmission of recorded home BP values
5 4 ● Use of long-acting drugs that require once-daily dosing
● Avoid complex dosing schedules
● Use of single-pill combinations when possible
4 3 ● Consider the effects of treatment on patient’s budget
● Use of reminders (e.g., alerts or text messages on mobile devices)
● Assessment and resolution of individual barriers to adherence at every visit.
● Empowerment-based counseling for self-management
● Consider a combination of practical techniques to improve adherence

5
at 12 months versus standard care of participants at a federally qualified community
health center in Alabama [61]. The mean estimated 10-year cardiovascular risk
was 12.7% for the participants, with a mean baseline blood pressure LDL
cholesterol of 140/83 mmHg and 113 mg per deci- liter, respectively. The
monthly cost of the polypill was $26. At 12 months, polypill adherence was
86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill
group, as compared with 2 mmHg
in the usual-care group (difference, —7 mm Hg; 95% confidence interval [CI], —
12 to —2; P ¼ 0.003) [61].
9. Telehealth and hypertension in the COVID-19 era
As previously noted, telehealth, prior to the COVID-19 pandemic, had been
heralded as a potential advancement in successful HTN and CVD risk
management. Moreover, due to safety concerns, the COVID-19 pandemic
required telemedicine for routine outpatient visits, signifi- cantly affecting HTN
and other chronic medical condition management. Initiatives, such as Million
Hearts 2022 and Target BP, have emphasized the importance of SBPM with continual
patient and provider feedback. In addition, the Centers of Medicare and Medicaid
Services (CMS) recently published reimbursement information for telephone and
other moni- toring services [62] (See Table 5). As a significant amount of
time and detail must be devoted to these modes of communication and assessment,
it is important that providers receive adequate compensation. Therefore, CMS
expanded telephone consultation payment on a temporary and emergency basis
under the 1135 waiver authority and Coronavirus Pre- paredness and Response
Supplemental Appropriations Act: particularly for high-risk COVID-19
beneficiaries and with widespread availability of smart phones, telehealth may
become future standard medical practice [62,63].
Nevertheless, the use of digital technology may further increase dis- parities. A
recent study evaluating telehealth in cardiac clinics suggested disparate use of video
encounters in low income and black patients [64]. Of the 2940 patients scheduled
for a telehealth encounter during the study, 1339 (46%) completed telehealth
encounters and 1601 (54%) patients had a canceled/no-show visit. On
unadjusted analysis, patients with a completed telehealth visit were slightly older,
more likely to be male and speak English. However, low income and black
patients were less likely to video visits possibly related to insurance coverage
[64]. More investigation is warranted in the future to understand the risks and
benefits of video telehealth encounters to enhance cardiac care.
10. Special populations: diabetes, race/ethnicity, sex, and older
age
Although each guideline provides specific comments for the man- agement
of special populations, including persons with diabetes (DM) and certain
involving race/ethnicity, sex, and older age, this review will only detail various
aspects of care for certain groups [17,22,24,29,65].
Table 5
Summary of medicare telemedicine services [62].
Type of Service What is the Service?
Medicare
A visit with a provider that uses telecommunication systems between a provider
Telehealth
and a patient
Visits
Virtual Check-
In A brief (5–10 min) check in with a patient via telephone or other
telecommunications device to decide whether an office visit or other service is
needed. A remote evaluation of recorded video and/or images submitted by an
established patient
E-Visits A communication between a patient and their provider through an online
patient portal
HCPCS, The Healthcare Common Procedure Codign System; CPT, Common Procedural Technology; SNFs, Skilled nursing facilities.
6
The vast majority of adults with DM have 10-years ASCVD risk >10% placing
them in a high-risk category. However, in the most recent ADA
recommendations, patients with DM and a 10-year ASCVD risk <15% should
maintain a target of <140/90 mmHg, with <130/80 mmHg for the highest
risk patients [66]. In ACC/AHA 2017 and other major
guidelines, antihypertensive drug treatment with diabetes should be initiated at a
BP of 130/80 mmHg or higher with a treatment goal of
<130/80 mmHg [17,67]. Moreover, major guidelines recommend the addition
of renin-angiotensin modulators, including an angiotensin
converting enzyme inhibitor (ACE-I) or angiotensin receptor blockers (ARB) in
the setting of compelling comorbid issues such as diabetes with albuminuria,
renal dysfunction, or HF [17,22,24,66,67].
The ACC/AHA, ESC/ESH, and ISH guidelines discuss the significance of
race/ethnicity in HTN management. In the U.S., as well as globally, black
ancestry may be associated with a higher prevalence of HTN than that of Hispanic
Americans, whites, Native Americans, and other groups [17,22,24]. In some parts
of the world, HTN prevalence is greater than 60% among blacks [15,68]. In
comparison to the U.S., the prevalence of HTN in the black population in Europe
is higher than the non-black population. The ESC/ESH guidelines emphasize the
data are scarce for the European black populations and extrapolate much of their
recom- mendations from U.S. studies [22]. Non-Hispanic U.S. white adults are
more likely to have a higher prevalence of controlled HTN when compared to
other groups. The lower rates of control in Hispanic Americans are likely
secondary to decreased awareness. However, American blacks have lower
controlled rates due to more severe HTN and possibly to less effective treatments
[17].
Thiazide-type diuretics and calcium channel blockers (CCBs) are most effective
as the first step in lowering BP and stroke in blacks. Although ACE-I and ARB
are less effective in blacks as monotherapy when compared to whites,
combination therapy is equally effective in whites and blacks [51,69,70]. Perhaps
due to suppression of the renin angio- tensin aldosterone system, ACE-I and ARB
may not only lower BP less effectively, but also for the prevention of heart
failure and stroke [69–71]. ACE-I are also associated with a higher incidence of
angioe- dema in blacks, and ARBs are recommended over an ACE-I by the
ESC/ESH and ISH guidelines for HTN treatment, in combination with a diuretic
or CCBs. The ACC/AHA, ESC/ESH, and ISH guidelines recom- mend two or
more antihypertensive medications to achieve adequate BP control in blacks, with
a diuretic or CCBs used as first-line agents. Pa- tients with BP that is 20/10 mmHg
above target may be considered for combination therapy at treatment onset. Given
resistant hypertension (rHTN) is more common in African American patients,
multidrug phar- macological therapy may be often indicated [17,22,24].
The ISH guidelines acknowledge ethnic-specific characteristics for East and
South Asian populations, who have a greater likelihood of salt- sensitivity
accompanied with mild obesity [24]. East Asians also have a higher prevalence of
hemorrhagic stroke and nonischemic heart failure when compared to Western
populations, associated with morning or
HCPCS/CPT Code Type of
Patient
* 99201-99215 (Office or other outpatient visit) New or
* G0425-G0427 (Telehealth consultations, Established
emergency department or initial inpatient) * G0406-G0408
(Follow-up inpatient telehealth consultations furnished to
beneficiaries in hospitals or SNFs)
* HCPCS code G2012 * HCPCS code G2010 Established
* 99241-99243 * G2061-G2063 Established
nighttime HTN. Individuals from the Indian subcontinent have high risks for CVD
and type 2D.
Although of considerable interest, special populations related to sex and older
age are not detailed in this review, although detailed in the ACC/AHA and
ESC/ESH guidelines [17,22]. Furthermore, the ISH guidelines also provide
extensive recommendations for the treatment of HTN in pregnancy, whereas this
area is covered in supplementary doc- uments for the others [24]. Most recently,
Aronow extensively reviewed the management of HTN in the elderly [65].
Overall, recognizing unique aspects in the treatment of various populations,
including regional dif- ferences, is an important component for optimal care.
11. HTN and COVID-19: present and future concepts
According to the most recent data from the World Health Organiza- tion
COVID-19 has infected over 11.1 million people, responsible for over 528,000
deaths worldwide [72]. Further clinical observation may be required to
determine the long-term risk of COVID-19 and HTN. The devastating effects of
COVID-19 have also disproportionately affected several vulnerable populations,
including those with certain comorbid diseases, advanced age, and lower
socioeconomic status. COVID-19 also has the potential to impact CVD outcomes
via a ‘domino effect’, which is initiated by social fears and issues stemming from
social distancing. Due to concerns of visiting hospital facilities, patients may not
present for outpatient and emergent care needed, such as with acute coronary syn-
dromes. Furthermore, physical inactivity and unhealthy eating due to home
quarantine status, along with the social stressors related to increasing
unemployment, may increase the rates of HTN, obesity, and CVD events in
years to come [73].
Despite the early concern that ACEI/ARB therapy would worsen outcomes by
upregulating ACE2, RAS inhibitors may actually improve the clinical status of
COVID-19 patients with hypertension and may even be preferential for
antihypertensive treatment [2,74–76]. In a recent study of 417 COVID-19 patients
with HTN from China, the data suggest ACEI/ARB therapy attenuated the
inflammatory response, potentially through the inhibition of IL-6 levels, which is
consistent with the findings that ACEI and ARB therapy alleviated pneumonic
injury [77]. Perhaps, ACEI/ARB therapy has a beneficial effect on the immune
system by avoiding peripheral T cell depletion, thereby allowing for a better im-
mune response to the virus in these patients.
As the standards of practice, the Heart Failure Society of America, ACC,
AHA, and American Society of Preventive Cardiology currently recommend the
continuation of RAS inhibitors with compelling com- plications such as: heart
failure, hypertension, or ischemic heart disease [39,78]. Moreover, abrupt
withdrawal of RAS inhibitors in high-risk patients, including those who have
heart failure or have had recent myocardial infarction, may result in clinical
instability and adverse health outcomes [79].
On the other hand, dihydropyridines CCBs (nifedipine and amlodi- pine) may
be a benefit for the treatment of hypertensive patients with COVID-19. In a
retrospective analysis, a small cohort of elderly hyper- tensive patients treated
with a CCB during a COVID-19 infection, had a significantly higher survival rate
and were much less likely to require mechanical intubation (50% vs. 14.6%,
respectively) as compare to those not on CCBs [80]. Although further clinical
studies are warranted, the data are promising that treatment of a CCB in hypertensive
patients with COVID-19 may significantly improve outcomes.
12. Conclusion
Current guideline recommendations emphasize the importance of evidence-
based care to curtail the widespread mortality and morbidity related to HTN and
associated ASCVD. Additionally, the acute and long- term effects of COVID-19
may influence treatment in the hypertensive population and require further
investigation. The importance of unifying
7
recommendations that help to curve the burden of HTN may become more
significant in the coming years as we learn more about new treat- ments and the
long-term effects of the current COVID-19 crisis. The COVID-19 associated
morbidity and mortality including patients with underlying HTN and CVD are
likely to have profound impact for several decades due to the worldwide
medical, economic, and psychological effects. However, although contemporary
guidelines suggest benefits of the use of telehealth technologies and out-of-office
medical management, as recently required by the cOVID-19 pandemic, these
evolving tech- niques will be increasingly used for HTN control and CVD risk
control. Ultimately, future HTN guidelines may increasingly reflect the impact of the
COVID-19 pandemic and the utility of measures such as SMBP/HBMP over time.
Declaration of competing interest
The authors declare that they have no known competing financial interests or
personal relationships that could have appeared to influence the work reported in
this paper.
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[80]

9
 International Journal of
Environmental Research
and Public Health
Review
Can Optimum Solar Radiation Exposure or Supplemented
Vitamin D Intake Reduce the Severity of COVID-19
Symptoms?
3.3.1.1 Joji Abraham 1,*, Kim Dowling 1,2 and Singarayer Florentine 3
check ror
updates
Citation: Abraham, J.; Dowling, K.;
Florentine, S. Can Optimum Solar
Radiation Exposure or Supplemented
Vitamin D Intake Reduce the Severity
of COVID-19 Symptoms?. Int. J.
Environ. Res. Public Health 2021,
18,
740. https://doi.org/10.3390/
ijerph18020740
Received: 9 November 2020
Accepted: 12 January 2021
Published: 16 January 2021
Publisher’s Note: MDPI
neutral with regard to jurisdictional
claims in published maps
institutional affil- iations.
Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access
article distributed under the terms
and conditions of the Creative
Commons Attribution (CC BY)
license (https://
creativecommons.org/licenses/by/
4.0/).
1
School of Engineering, Information Technology and Physical Sciences, Mount Helen Campus,
Federation University Australia, Ballarat, VIC 3353, Australia; k.dowling@federation.edu.au
2
Department of Geology, University of Johannesburg, Johannesburg 2006, South Africa
3
School of Science, Psychology, and Sport, Centre for Environmental Management, Mount Helen
Campus, Federation University Australia, Ballarat, VIC 3353, Australia; s.florentine@federation.edu.au
* Correspondence: J.abraham@federation.edu.au; Tel.: +61-412-751-134
Abstract: The foremost mortality-causing symptom associated with COVID-19 is acute respiratory
distress syndrome (ARDS). A significant correlation has been identified between the deficiency in
vitamin D and the risk of developing ARDS. It has been suggested that if we can reduce or modify
ARDS in COVID-19 patients, we may significantly reduce the severity of COVID-19 symptoms and
associated mortality rates. The increased mortality of dark-skinned people, who have a reduced
UV absorption capacity, may be consistent with diminished vitamin D status. The factors
associated with COVID-19 mortality, such as old age, ethnicity, obesity, hypertension,
cardiovascular diseases, and diabetes, are all found to be linked with vitamin D deficiency. Based
on this review and as a precautionary measure, it is suggested that the adoption of appropriate
and safe solar exposure and vitamin D enriched foods and supplements should be considered to
reduce the possible severity of COVID-19 symptoms. Safe sun exposure is deemed beneficial
globally, specifically in low and middle-income countries, as there is no cost involved. It is also
noted that improved solar exposure and vitamin D levels can reduce the impact of other diseases
as well, thus assisting in maintaining general human well-being.
Keywords: acute respiratory distress syndrome (ARDS); acute respiratory tract infection (ARTI);
calcifediol; calcitriol; coronavirus; environment; human health; infectious disease; pandemic;
SARS-CoV-2
1. Introduction
In December 2019, a novel coronavirus (nCoV) strain [1], initially identified as
‘severe acute respiratory syndrome coronavirus’ (SARS-CoV), and later named as SARS-
CoV-2, became the focus of attention all around the world with the resulting disease
named ‘Coronavirus Disease 2019 (COVID-19)’ by the World Health Organisation
stays (WHO) [2]. Despite the continued efforts from governments across the world to slow
down the rates of infection and fatality, the disease has become a pandemic. As of the 26
and December 2020, more than 80 million confirmed cases and more than 1.8 million fatalities
across the world have been reported, with majority of the reported fatalities being in the
United States (330,254), Brazil (190,488), and India (147,092) [3]. This infection rate sharply
contrasts with two previously reported coronavirus exposure events in the last two
decades [4].
The disease is potentially lethal to adults over 60 years of age and is particularly so
for those with comorbidities such as diabetes, hypertension, heart disease, cancer, and
obesity [5]. Even though vaccinations have begun in several countries, it is unclear when
the vaccine will be available more widely, specifically to low-income countries. The most
optimistic current estimates are mid to late 2021, and not much is known concerning
how long the vaccine can protect the individual. This lag of availability and uncertainty
in protection highlight the significance of finding strategies to confront and mitigate
the
Int. J. Environ. Res. Public Health 2021, 18, 740. https://doi.org/10.3390/ijerph18020740 https://www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2021, 18, 2 of 21
740

spread and severity of COVID-19 at least for several more months. A detailed analysis of
the data regarding the clinical problems of COVID-19 across the world has emphasised
that immunity is a significant factor in controlling viral pathogenicity [6]. The mode of
COVID-19 spreading, together with the number of fatalities across the world, has alerted
the researchers to the possibility that location, climate, exposure to solar radiation, and
vitamin D have a link in viral pathogenicity and mortality [7,8]. Moreover, previous studies
conducted across the world have observed a significant association between vitamin
D and immunity, especially in terms of acute respiratory tract infections (ARTI) and
acute respiratory distress syndrome (ARDS), resulting multiple health outcomes and
mortality [9–11].
Vitamin D is recognised as a secosteroid and is synthesised endogenously by the
effect of ultraviolet B (UVB) radiation on the skin. It has well understood substantial
immunomodulatory and anti-inflammatory actions in the human body [12]. Several
stud- ies have emphasized the implications of vitamin D deficiency as a contributing
factor in many diseases such as diabetes mellitus [13], cardiovascular disease [14],
autoimmune liver disease [8], and obesity [15]. Of importance here is that studies have
shown that lung inflammation that leads to ARDS is considered to be the main cause of
the deaths among COVID-19 patients, and it is the renin–angiotensin system which is
very significant in making such an inflammatory response [16]. With direct relevance to
this paper, it has been unequivocally observed that vitamin D substantially influences the
renin–angiotensin system and leads to a reduction in the inflammatory response [17–19].
In a mouse model study, Kong et al. [17] identified that vitamin D could have significant
influence in re- ducing lipopolysaccharide-induced lung injury by blocking the effects
of Ang-2-Tie-2 and renin–angiotensin pathways. In support of this observation, Zhang
et al. [18] and Xu et al. [19] reported that vitamin D acts as a protective substrate in
alleviating the lipopolysaccharide-induced acute lung injury (ALI) by the inhibition of
pro-inflammatory cytokine interleukin-6 (IL-6). Both these studies are of significance to the
welfare of COVID- 19 patients. In parallel with these studies, a recent meta-analysis of
eight observational studies incorporating the details of 21,000 subjects revealed that there
was the potentiality of increased risk of acquiring pneumonia from community sources
among those with low vitamin D (<20 ng/mL) levels [20].
People with common immunodeficiency and adults detected with vitamin D defi-
ciency have been found to be vulnerable to COVID-19 [21,22]. More than 70% of the deaths
recorded in Chicago (USA) are among the African-American population, who are normally
vitamin D deficient communities, specifically during the winter, probably due to skin
pigmentation blocking the UV radiation [23,24]. This finding also supports similar data
from the United Kingdom [25], where according to the 2011 census, only around 14% of
the population in England and Wales are black and minority ethnic, but a third of the
confirmed COVID-19 cases admitted to the critical care in the hospitals belong to these
black minorities [25,26].
Many of the first phase worst-hit coronavirus areas are located in the same
latitudinal temperature region known to have reported vitamin D deficiency. This
emphasises the significance of the lack of serum vitamin D in COVID-19 fatalities [27].
Even though data from large randomised placebo-controlled double-blind, multicentre
studies are lacking, the available data from observational and interventional studies give
strong supportive results to the hypothesised link between vitamin D deficiency and
increased infection rates of COVID-19. Apart from this observation, vitamin D treatment
given to a small cohort of COVID-19 patients in Spain has revealed promising results
[28].
It is already well known that vitamin D has a role in inhibiting a range of infections
and inflammations, including acute respiratory tract infection (ARTI) and acute respiratory
distress syndrome (ARDS). Whilst there are alternative methods of obtaining vitamin D,
acquiring increased levels through solar radiation is considered most convenient and bene-
ficial as it is completely free and natural. Unfortunately, in times of lockdown and social
distancing, those who are most at risk, the elderly, and health compromised individuals
face practical hurdles in obtaining vitamin D via natural means. The objective of this article
is to examine published evidence showing the influence of the increase in vitamin D
levels in relieving symptoms similar to COVID-19, especially ARDS and ARTI. The study has
also reviewed recently published observational studies, including small pilot studies (in
2020), which have shown the association between vitamin D deficiency and COVID-19
positivity or severity. The work concludes with suggestions of various methods to improve
vitamin D sufficiency among the general public to prevent severe COVID-19 symptoms and
mortality.

2. Methodology
Several searches have been conducted in the existing literature using Google
Scholar, PubMed, Scopus, Web of Science, and the preprint database Medrevix to obtain
the most up to date research information regarding vitamin D and human health. The
searches specifically focus on COVID-19 symptoms such as ARTI and ARDS identifying
publica- tions from the last two decades, using the terminologies (i) vitamin D and
human health,
(ii) vitamin D and COVID-19, (iii) vitamin D and ARTI, and (iv) vitamin D and ARDS.
Most of the studies highlighting the relation between vitamin D and ARDS/ARTI were
incorporated, whilst other, only generally related studies were eliminated from the
review. These studies and their influence on ARDS and ARTI have been discussed, and a
summary is prepared as a Table. Recent studies showing a correlation between vitamin D
serum level deficiency and COVID-19 severity conducted in 2020 were also reviewed,
discussed, and prepared as a separate Table. This review includes the following sections:
(i) symptomatic background of COVID-19; (ii) some background information to vitamin
D studies; (iii) influence of vitamin D in reducing ARTI and ARDS; (iv) vitamin D
geographical context, ethnicity and age; (v) vitamin D and COVID-19; (vi) the role of
vitamin D in infection control; and finally (vii) how to acquire a sufficient level of
vitamin D.

3. The Symptomatic Background of COVID-19

Coronaviruses are a large family of single-stranded, enveloped RNA viruses generally
seen in several animal species, with SARS-CoV-2 being the specific pathogen related to
the current pandemic. Symptoms associated with COVID-19 usually appear after an
incubation period of two to twelve days, with the majority of people showing signs
within six days [4]. Apart from fever, fatigue, and myalgia, ARDS is a critical factor in
6% to 16% of COVID-19 patients and is considered the major cause of organ failure and
death [29,30]. It is characterized by the critical progression of respiratory symptoms,
signs including bilateral diffuse infiltrates on chest imaging, and severe hypoxemia
caused by heterogeneous aetiologies [30]. There are many known causes of ARDS
development, but COVID-19 patients suffer from pathogen-caused lung injury [29].
Even though medical science has progressed, the exact mechanisms behind ALI and
ARDS have not yet been fully revealed, and effective pharmacological interventions are
therefore not able to be developed [19]. Once ARDS occurs, effective management is
difficult. As a consequence, any early intervention that can prevent or reduce either viral
replication, ARTI, or ARDS will be worthwhile, and thus vitamin D has a significant
role in this. In this respect, the association between vitamin D and clinical symptoms
similar to COVID-19 has been mentioned in many studies (Table 1).
Table 1. Clinical symptoms similar to COVID-19 and its relationship with vitamin D (from previous
studies).

Symptoms/Characteristics Relation to Vitamin D References

Acute respiratory distress syndrome (ARDS) risk Inverse correlation [10,31]
Severe pneumonia Inverse correlation
[20,32,33]
Sepsis risk inverse correlation [34,35]
Inverse correlation cytokine [36,37]
Pro-inflammatory production
C-Reactive Protein increase Inverse correlation [38]
 4. Some Background to Vitamin D Studies
Vitamin D3 is naturally produced as a result of the action of sunlight (UVB
radiation 290–315 nm) on 7-dehydrocholesterol within the skin [39]. The material
produced from this source, in addition to that absorbed from food, is inert and requires
hydroxylation to circulate in the body. This reaction occurs in the liver, where it forms
calcifediol (25- hydroxyvitamin D) using the enzyme D-25 hydroxylase [40].
Subsequently, this moves to the kidney for further hydroxylation, forming 1 ´α,25
dihydroxy vitamin D (1,25(OH)2D or calcitriol-C27H44O3) using the enzyme 25(OH)D-1
hydroxylase (a mitochondrial oxyge- nase), and this calcitriol is the major active form of
vitamin D [40] (Figure 1). Vitamin D has several biological functions in the body, including
(i) calcium homeostasis; (ii) the regu- lation of up to 1000 genes; (iii) inhibition of cellular
proliferation, angiotensins, and renin production; and (iv) inducing insulin and
macrophage cathelicidin and defensins produc- tions (both have immune-modulatory
effects) [41–43]. Studies have shown that cathelicidin has anti-microbial properties against
several bacteria and viruses (including enveloped viruses) [44,45]. A mouse model study
demonstrated that LL-37 reduced influenza-A virus replication [46], and a pig model
study underlined that vitamin D could reduce the replication of the rotavirus in vitro
and in vivo [47]. Similar studies, including data, and reports have revealed that vitamin
D has a substantial role in inducing innate immunity by maintaining localised the
production of antibacterial CAP (cathelicidin antimicrobial peptide) [47].

Figure 1. Formation of two main forms of vitamin D: the main circulating form, 25 hydroxyvitamin D (25(OH)D), and the
main active form, 1´α,25 dihydroxy vitamin D (1,25(OH)2, D) as well as their interaction with the innate cells. (VDR-vitamin
D receptor) (adapted from [48]).

Many of the immune cells are equipped with vitamin D receptors (VDRs) [49,50].
Antigen-presenting cells such as macrophages and dendritic cells could be influenced by
vitamin D (25 hydroxyvitamin D) as they can synthesize 1,25-dihydroxy vitamin D from
25-hydroxyvitamin D via 1 ´α hydroxylase (CYP27B1) [51]. Many respiratory pathogens,
including SARS-CoV-2, invade the epithelial cells in the lung alveoli, making the epithelial
cells as first responders to recruit neutrophils and T cells to the infection site through the
activation of macrophages and dendritic cells [41]. In the absence or deficiency of vitamin D
(25-hydroxyvitamin D), the first triggering mechanism would be considered to be impaired.
It is hypothesised that this triggering mechanism is like a circuit breaker. In the absence
of 25 hydroxyvitamin D, the circuit cannot be completed, or at best, it will be weak due
to unsatisfied VDR, which may affect the innate immune mechanism of the body.
Researchers were in a debate regarding the cut-off levels of vitamin D serum levels
(25(OH)D) in the body, and most experts in the area suggested that if a level falling
below 20 ng/mL is deficient, 20–30 ng/mL is insufficient and the level above 30 ng/mL
is suffi- cient [52]. However, this notion has developed only by considering calcium
homeostasis and bone health, rather than the immunomodulatory effects of vitamin D.
In this respect, we may require new vitamin D threshold levels, which consider both
bone and immunity health. It is important to note that vitamin D deficiency (where
serum 25-hydroxyvitamin D levels are <20 ng/mL) and insufficiency (25(OH)D between
20 and 29 ng/mL) [52,53] are widespread in the current generation, specifically for
people living away from the equatorial region [24,39,54]. This deficiency is also
commonly observed in hospitalised pa- tients suffering from various infections and is
particularly relevant to those with ARTI and ARDS [10,11,44,55]. Most respiratory tract
infections are spread during winter, strength- ening the hypothesis that vitamin D
deficiency is the main factor in lowering immunity in the absence of sunlight.
Interestingly, the same hypothesis supported the relationship between vitamin D and
rickets in 1897, when Kassowitz identified that the incidence of rickets’ was markedly
increased during the winter season and decreased during the summer [56]. Even though
it is noted that vitamin D deficiency may increase the risk of microbial infections,
adequate supplementation will reduce the risk significantly against many infections,
including dengue viral infection [57].

5. The Influence of Vitamin D in Reducing ARTI and ARDS

Apart from the effects of COVID-19, general respiratory tract infections occur
world- wide, causing millions of fatalities annually (2.8 million in 2010) [58]. There have
been several articles published, which have shown the relationship between vitamin D
levels in the body and the potential occurrence of ARTI and ARDS [10,31,59–62].
In an earlier study, Hansdottir and Monick [63] revealed that vitamin D levels are
associated with the mitigation of viral respiratory tract infections and acute lung injury,
which suggest that vitamin D is efficacious in providing protection against acute lung injury
by modulating the expression of the renin–angiotensin system [19]. A randomized placebo-
controlled trial demonstrated that vitamin D deficiency is a risk factor in developing
acute lung injury [62], whilst a second lung function study demonstrated that vitamin D
deficiency has a strong correlation with more rapid lung function decline [57]. In support
of this link, ARDS development in a cohort of post-esophagectomy patients was found to
be associated with a deficiency of vitamin D (Figures 2 and 3) [10]. A murine model
study also found that dietary-induced vitamin D deficiency contributes to exaggerated
alveolar inflammation, epithelial damage, and hypoxia [10]. Similar results have
emerged from researchers who reported that many esophagectomy patients suffer from
ARTI and ARDS in the post-operative environment, and vitamin D supplementation
during pre-operative days appears to reduce the risk of ARTI and ARDS in those cohorts
[60]. They also found that vitamin D supplementation increased the concentration of
25-hydroxyvitamin D and 1,25 dihydroxy vitamin D in affected patients, which
contributed to reduced lung inflammation [60]. Several studies have also showed a link
between the vitamin D level and influenza infection [32,64–66].
Figure 2. The association between plasma 25(OH)D 3 levels and ARDS. The group with low 25(OH)D 3
has ARDS, the moderate level is at risk, and those who have high vitamin D levels are healthy controls
(adapted from [10]).

Figure 3. Relationship between severe 25(OH)D3 deficiency and risk of ARDS in the post-
esophagectomy environment (adapted from [10]).

A large meta-analysis of 25 eligible randomised controlled trials (11,321

participants, aged 0 to 95 years) demonstrated that vitamin D supplementation reduced
the risk of ARTI among all participants by around 11% [11] and found that the protective
effects were stronger (19%) in those who received daily or weekly supplementation.
When the analysis took place in those groups, who had a vitamin D deficiency, the
protective effects were highest for them, being around 70%. The overall conclusion was
that vitamin
 D is a protectant against ARTI, and daily or weekly supplementation is better than a
single bolus dose [11]. A similar large cross-sectional clinical trial has also shown the
effects of lower vitamin D levels in increasing respiratory infection (n = 18,883) [67]. The
deficiency effects were more pronounced in patients with underlying lung conditions
[67]. Another meta-analysis of a randomised control trial was conducted in 2013, using
data from 5660 patients in 11 placebo-controlled studies [68]. Patients with an average
age of 16 years were provided with a vitamin D oral supplement of 1600 IU per day,
with a daily dosing interval over three months. The results revealed that vitamin D
supplementation is an effective method in limiting respiratory tract infections [68]. A
fourth meta-analysis showed a significant correlation between an increase in vitamin D
levels and a lower risk of respiratory tract infections [69]. In addition, a high dose of
vitamin D administered to ventilated intensive care patients validated that it decreased
the length of stay in the hospital environment [11,70].
Apart from the studies mentioned above, observational reports have shown a
strong association between low ‘vitamin D (25(OH)D) levels and increased risk of respiratory
tract infections (RTI). A large cross-sectional trial of more than 18,883 persons was
conducted, and the results revealed an increase in RTI risk associated with lower
25(OH)vitamin D levels, which was significant in persons with chronic obstructive
pulmonary disease (COPDs) [58]. Correlation between pre-hospital vitamin D status and
the potentiality of incident acute respiratory failure in critically ill patients was studied,
and a correlation was found between both lower vitamin D levels and a patient’s chance
of infection [31]. Although vitamin D deficient patients have higher chances of mortality
[31], it was found that timely vitamin D supplementation can mitigate this potentiality
[70]. All these studies (Table 2) demonstrated that sufficient vitamin D levels in the body
could prevent the occurrence of ARTI and ARDS in four ways: (i) elevating natural
immunity, (ii) enhancing the antimicrobial response, (iii) inhibiting the production of
pro-inflammatory cytokines, and (iv) improving the production of anti-inflammatory
cytokines [41,71], which may act in COVID-19 patients.
Table 2. Selected previous studies show the association between vitamin D and ARDS, including lung injury.

Study Details Results/Conclusion Reference(s)

Determined the relationship between vitamin
D and ARDS.
Investigated the role of supplemented vitamin
D in reducing ARTI in a meta-analysis.
This study used 25 randomised controlled trial
data from to 11,321 participants.
Investigated whether vitamin D alleviates
lipopolysaccharide (LPS)-induced acute lung
injury (ALI).
Vitamin D deficiency was ubiquitous with ARDS patients
and was a risk factor in developing ARDS following the
esophagectomy. It also found that the pharmacological
repletion of vitamin D before esophagectomy reduced
the alveolar–capillary damage compared to the vitamin D [10]
deficient patient.
In a murine model, dietary-induced vitamin D deficiency
generated alveolar inflammation, damage in epithelial
cells, and hypoxemia.
The study found that (i) vitamin D supplementation
reduced the risk of ARTI in all patients (odds
ratio-OR-0.88); (ii) protective effects were higher in
those receiving a daily or weekly dose compared to the
bolus dose (OR-0.81); and (iii) among the second
group, protective effects were more potent in those who [11]
had vitamin D deficiency (<10 ng/mL).
The overall conclusion is that vitamin D supplementation
protected from ARTI.
Vitamin D exhibited positive effects to LPS-induced ALI
in rats by modulating the expression of members of the
renin–angiotensin system (RAS) such as angiotensin
(Ang-1) converting enzyme (ACE and ACE2), renin and [19]
Ang-II.
 Table 2.
Cont.

Study Details Results/Conclusion Reference(s)

Investigated the association between
pre-hospital vitamin D level and acute
respiratory failure.
Investigated the role of vitamin D
supplementation in patients undergoing
esophagectomy.
Investigated the association between vitamin D
and ALI and ARDS through a review.
Investigated the association between vitamin D
and acute respiratory infection (ARI) through
systematic review.
Vitamin D deficiency and ARDS.
Investigated whether exogenous vitamin D
attenuates lipopolysaccharide (LPS)-
induced lung injury via modulating the
epithelial cell proliferation.
Investigated whether the vitamin D or VDR
pathway ameliorates LPS-induced ALI (mice
model).
The study found an association between pre-hospital
vitamin D levels and the risk of incident acute respiratory [31]
failure in critically ill patients, including death.
Vitamin D supplementation 3–14 days prior to the
esophagectomy significantly reduced the potentiality of [60]
ARDS during the post-operative environment.
Reviewers found a profound role of vitamin D in
modulating the immune response and a potential role in
[62]
ALI.
The review identified a consistent association between
[68]
vitamin D deficiency and risk to ARI.
Vitamin D deficiency was found to be prevalent (90%)
among 476 ventilated patients with ARDS, also [72]
associated with a longer duration on mechanical
ventilation
It was found that vitamin D supplementation attenuates
lung injury via (i) stimulating alveolar epithelial type II
(ATII) cell proliferation and migration; (ii) reducing
epithelial cell apoptosis; and (iii) inhibiting the [73]
transforming growth factor (TGF-β) induced epithelial–
mesenchymal transition (EMT).
The study suggested that vitamin D has therapeutic
potential for the resolution of ARDS.
It was found that vitamin D treatment alleviated the
[74]
LPS-induced lung injury.

6. The Link between Vitamin D levels, Geographical Context, Ethnicity, and Age
The coronavirus pandemic that spread in European countries and the United States
in the initial stage (first wave) is claimed to have spread at a faster rate than in Asian and
African countries during the same period [3]. This is unusual compared to the low popu-
lation and population density in Europe and the US compared to south Asian countries.
However, studies have shown that in a typical year, around 40% of people in Europe and
those in the high latitudes of the US are vitamin D deficient [75,76]. This observation is
consistent with the insufficient levels of ambient UV radiation required to synthesize a
sufficient amount of vitamin D in high latitudes, coupled with cool summers and
covered bodies for warmth [75,76].

6.1. Vitamin D and Geographical Context during the First Wave

It is interesting to note that the most initially affected COVID-19 regions such as
the Wuhan area in China, Iran, Turkey, Italy, UK, France, Spain, and the USA are along
the same latitudinal corridor with approximately similar climatic conditions (specifically
low temperature and low humidity) and may be correlated with low serum vitamin D
levels in the populations. The COVID-19 hospitalisation and mortality rates have also
shown a similar latitudinal correlation with countries above 23.5 ◦ N latitude, specifically
more fatalities per million during the first wave, except in Nordic countries. The average
hospitalisation in the northern latitudes was 22%, and the mortality rate was 5.2% with
respect to the confirmed cases, whereas the corresponding figures in the equatorial regions
are much less (hospitalisation being 9.5% and mortality rate 3.1%) during the first wave [71].
The mortality rate, notwithstanding its definition as a percentage of confirmed cases or
as the rate per million of population, is less in the equatorial region than the northern
latitudes. The mortality rate with respect to the confirmed cases and deaths per million
population in
 the equatorial or tropical regions until the end of August 2020 are 2.3% and 77, respectively,
whereas the same figures in the northern latitudes (above 23.5 ◦ Lat) are 3.3% and 159,
respectively. The mortality rate is also less in regions south of 23.5 ◦ S latitude (2.1%), but
the deaths per million population are high (139) (Table 3). However, it is surmised that
the gap between the northern latitude and equatorial regions will reduce shortly as the
number of cases are increasing in the equatorial regions due to pressures related to
higher population and population density.

Table 3. Total confirmed cases, total mortality, mortality rate with respect to the confirmed cases, confirmed cases per
million, and deaths per million of the population (of COVID-19) as of 10 September 2020. Note the low mortality rate and
the number of deaths per million in the equatorial region compared to northern latitudes (above 23.5◦ N).

Confirmed
Percentage of Deaths
Total Confirmed Cases
Location Total Mortality Mortality to Per Total Population
Case Per
Confirmed Million
s Million
Population
Cases Population
North of 23.5◦ N Lat 13,201,342 483,004 3.3 5378 159 3,655,796,736
◦ ◦ 12,320,973 364,084 2.3 3295 77 3,918,475,190
23.5 N to 23.5 S
South of 23.5◦ S Lat 1,589,874 37,423 2.1 5811 139 197,607,413

The above figures are consistent with the high prevalence of solar radiation and
vitamin D in the equatorial regions and its low prevalence in the northern latitudes.
There are several observational studies already published, which emphasize the link
between the vitamin D status of people in the northern latitudes (the worst-hit areas of
COVID-19) and the occurrence of COVID-19 [7,27,67,77]. The serum vitamin D (25
(OH)D) status of 700 older Italian women (60 to 80 years old) was measured in the early
part of the last decade, and it showed that 76% of these women fell into the deficient
group [78]. It is suspected that if they were vitamin D deficient 17 years ago, it is likely
that the situation might be continuing. This is based on the observation that more people
may be sitting inside with electronic communication and entertainment devices, thus
reducing their incidental solar exposure. Even though the equatorial regions have higher
vitamin D compared to high latitude regions, some children in the former regions have been
shown to have lower vitamin D levels, which has shown a correlation with asthma in
these children [79].
Among the European countries, vitamin D status seems to be better in Nordic countries
compared to Mediterranean countries. It is claimed that this better status is mainly because
of the use of supplements, fortified foods, and more fatty fish and fish products in the
diet [80]. This trend is generally coincident with COVID-19 fatalities, noting, however, that
Sweden is an outlier.

6.2. Vitamin D and Ethnicity

Darker skin pigmentation and vitamin D synthesis demonstrate an inverse relation-
ship [81]. This is consistent with the levels of fatalities in the US and UK, where black
and brown-skinned people with high melanin levels in the skin have reduced amounts
of vitamin D [24,80]. However, after analysing the data of 10,000 US children between
the age of 1 to 21 years, researchers from National Health And Nutrition Examination
Survey (NHANES) revealed that 9% (around 7.6 million) were vitamin D deficient (<10
ng/mL), and 61% (50.8 million) were vitamin D insufficient (between 10 and 20 ng/mL)
[82]. This estimate does not appear to be consistent with the deficiency and insufficiency
mentioned by earlier experts [52]. Nevertheless, if we consider these populations
according to the vitamin D status mentioned by Holick [52], several additional millions
fall in the deficient and insufficient category, removing the inconsistency. Other studies
supported the claim that black and Hispanic ethnic groups have lower vitamin D serum
levels compared to pale-skinned people in the US [83,84]. Of concern was that more
black-skinned frontline health workers have died during this COVID-19 pandemic in the
UK, and this may be because they may be very deficient in vitamin D. Vitamin D variation
among various ethnic
groups in Australia has also shown similar results, with deficiency seen in 80% of dark-
skinned and veiled Australian women [53,85]. Of particular interest is that several
studies have highlighted the influence of vitamin D in reducing ARTI and ARDS, as
mentioned above, and this may have significant application in COVID-19 patients in
reducing the severity and mortality.

6.3. Vitamin D and Old Age

It has commonly been reported that nearly half of the deaths occurring globally
from the effects of COVID-19 are from aged care homes. Apart from a range of bodily
infirmities, which naturally accompany old age, elderly people commonly have vitamin
D deficiency, specifically due to aging systems, limited exposure to solar radiation,
culture, and their living environment. This will include less renal and cutaneous
synthesis and leads to a decrease in the level of 7-dehydrocholesterol in the skin [80,86–
88]. After 65 years, there is a four-fold decrease in vitamin D production compared to a
younger adult [39,54,89]. People of older age usually require more UVB exposure to
synthesise sufficient vitamin D compared with the younger generation. It is found that
in old age, osteoporosis is commonly associated with vitamin D deficiency due to the
limited calcium absorption and hypersecretion of parathyroid hormone [90]. The
presence of vitamin D receptors are also found in human muscles tissues, considered a
nuclear receptor that binds with 1,25 hydroxyvitamin D [91]. Therefore, muscle
weakness is an obvious symptom of vitamin D deficiency that may lead to falls and bone
fractures, which can be rectified by vitamin D supplementation [91]. Vitamin D also has
shown an association with cognitive performance in older adults with deficiency showing
low mood, depression, and impaired cognitive performance [92]. A recent study from
Ireland has been demonstrated that one in eight older adults are vitamin D deficient,
which increases to one in five in winter, and further increases to one in two when
examining the effect on the aging community (over 85 years) [93]. Reduction in vitamin
D with age is also supported by Bilezekian et al. [41], who claimed that the vast majority
of hospitalised elderly Italian patients presented with hypovitaminosis, with more than
half exhibiting severe deficiency.

7. Vitamin D and COVID-19

The efficacy of vitamin D in resisting rhinovirus and secondary bacterial infection
(upper respiratory tract infection) was also studied, and a positive response was found [94].
While there is little clear evidence linking sufficient vitamin D levels in the body with
other diseases, it is still worth considering whether adequate vitamin D levels will mitigate
similar respiratory virus symptoms, including COVID-19. There are some promising
results from various parts of the world, including a number of observational studies, the
details of which are mentioned in Table 4.
The influence of vitamin D as a predictor of poor prognosis for confirmed COVID-
19 patients with acute respiratory failure was conducted by Carpagnano et al. [21] with a
small cohort (n = 42) using a retrospective single-centre observational study. They analysed
the vitamin D serum levels of 42 ARDS patients treated in a Respiratory Intermediate
Care Unit (RICU) of the polyclinic in Bari (11 March to 30 April 2020) in Italy and found
81% of the patients had hypovitaminosis. Statistical analysis revealed that severe vitamin
D deficient patients had a mortality probability of 50% after 10 days of hospitalisation,
whereas it was reduced to 5% if the patient had a vitamin D level of >10 ng/mL [21].
Lau et al. [22] conducted a similar study using a cohort of 20 patients and found that
84.6% of patients admitted in the ICU were vitamin D deficient, whereas it was only
57.1% in the floor patients.
D’Avolio et al. [95] analysed the 25(OH)D level of 107 people tested for COVID-19
in a hospital in Switzerland and found that the median level of vitamin D was 22.2
ng/mL. This was similar to a control cohort in the same period in 2019, which showed a
level of
24.6 ng/mL. However, with 27 people who tested positive with SARS-CoV-2, the
median vitamin D (25(OH)D) level was significantly less, being only 11.1 ng/mL. With
those who
proved SARS-CoV-2 negative, the median vitamin D level was 24.6 ng/mL, and there
was a significant difference between these levels (p < 0.004). A recently published study
from Italy also showed that older people with Parkinson’s symptoms who took vitamin
D supplements had only milder COVID-19 symptoms [96].
Tan et al. [97] conducted a small cohort observational study to evaluate the effect
of vitamin D and vitamin B12, with magnesium (Mg) combination, on the severity of
COVID-19 on older patients (>50 years). The study was conducted in a tertiary
university hospital environment on 43 confirmed COVID-19 patients between 15 January
and 15 April 2020. Out of the 43 patients, 17 received a combination of vitamin D,
vitamin B12, and magnesium before the onset of the primary outcome, whilst the
remaining 26 did not. In the multivariate analysis (after separately adjusting for age or
hypertension), it has been observed that the interventional group retained a protective
significance compared to the non-interventional group (17.6% vs. 61.5%, p = 0.006). In
an effort to investigate the link between vitamin D concentration and COVID-19, Meltzer
et al. [98] from the USA retrieved the one-year-old vitamin D status of 489 COVID-19
positive patients and conducted a comparative analysis. The results revealed that the risk
of contracting COVID- 19 by vitamin D deficient people is 1.7 times greater than those
having sufficient vitamin D levels. Another observational study conducted in Germany
with 185 COVID-19 positive patients also highlights a link between vitamin D deficiency
and COVID-19 severity and mortality [99] Among the 185 patients, 41 (22%) were found
to be vitamin D deficient, and they had a higher risk of ARDS, requiring mechanical
ventilation, and an increased risk of death. A similar retrospective observational study,
conducted in Israel with 7807 participants, included 782 COVID-19 patients. This study
revealed a significant correlation between low serum vitamin D levels and the likelihood
of COVID-19 [100]. In addition to this work, Baktash et al. [101] conducted a prospective
cohort study in the UK among the older community (>65 years old). Their study also
found that the COVID-19 positive group had a lower median serum 25(OH)D level (10.8
ng/mL) compared to the COVID-19 negative group (20.8 ng/mL).
It is also interesting to note the ability of vitamin D treatment to inhibit the SARS-
CoV-2, which was shown in a study conducted in Singapore. Mok et al. [102] from the
National University of Singapore have conducted excellent research to identify potential
chemoprophylaxis against SARS-CoV-2 by performing virus-induced cytopathic effects
(CPE). Somewhat surprisingly, calcitriol was found to be effective against the virus
(SARS- CoV-2) with a 0.69 log10 reduction, which occurred upon post-treatment on Vero
E6 cells and human nasal epithelial cells (hNECs) [102].
The treatment efficacy of vitamin D against COVID-19 has been brought to light
by a university hospital in Spain [28]. In the Reina Sofia University Hospital, a group
of researchers conducted a randomised open-label, double-masked clinical pilot trial on
76 patients. Although this was a small trial, the results were remarkable. The researchers
divided the 75 COVID-19 positive patients (by RT-PCR test and radiographic pattern of
viral pneumonia) into two groups (25 patients in group A and 50 patients in group B)
randomly, and both groups received the standard care using the best available therapy.
Apart from this standard care, group B patients were treated with calcifediol (25(OH)D)
at a rate of 0.532 mg on day 1, followed by 0.266 mg on days 3 and 7, and then weekly
until discharge or ICU admission. The objective was to assess the efficacy of vitamin D
on ICU admission and mortality. The results showed that with group B (treated with
calcifediol), only one patient (2%) required admission to the ICU. By comparison, those
from group A (no treatment with calcifediol) had 13 patients (50%) who required
admission to the ICU, followed by two deaths (Fischer test p < 0.001) [28]. Another
significant highlight is that group B had 14 (28%) patients above 60 years of age, whereas
in group A, it was 5 (19%) only. Even though this was a pilot study, it presages the
efficacy of treating COVID-19 patients with 25(OH)D (calcifediol). Apart from this
observation, a small cohort study (four patients) in the USA also found that those who
received supplementation had lower oxygen requirements, an inflammatory marker
reduction, and shorter hospital stay [103].
 In support of this, Annweiler et al. [104] conducted a prospective cohort study in France
and found that in the non-vitamin D arm, there was the occurrence of 55.5% mortality,
whereas, in the intervention group, the mortality was only 17.5%. They concluded that
bolus vitamin D supplementation during or just before COVID-19 was associated with less
severity and a better survival rate in the elderly population [104].
Table 4. Some significant test results showing the link between vitamin D and COVID-19 (severity, mortality, and treatment).
Study Details/Objective(S)
Measured serum vitamin D levels of 42 COVID-19
patients with ARDS in a hospital in Italy.
The study analysed the serum vitamin D levels of
COVID-19 patients in a single hospital (small
cohort).
Probed the efficacy of vitamin D (calcifediol) in
treating COVID-19 patients—specifically the link
between ICU admission and mortality.
A retrospective analysis in Switzerland investigated
the association between vitamin D and COVID-19.
Influence of vitamin D/ B12 and Mg combination
was investigated in older (above 50 years) COVID-
19 patients.
Investigated the link between vitamin D and
COVID-19 severity, including mortality.
Researchers compared the COVID-19 test results
of 14,000 people with their previous vitamin D
levels.
This study assessed the significance of vitamin D
in older COVID-19 patients.
In the absence of vaccines and proper
treatment, probed the potentiality of
chemoprophylaxis.
Results/Conclusions Reference(s)
It was found that the potential mortality of
hypovitaminosis patients was 50% after 10 days of
[21]
hospitalisation, whereas it was 5% for only those with
vitamin D levels above 10 ng/mL
The serum 25(OH)D levels of 20 confirmed COVID-19
patients found that 65% required ICU admissions. Among
the ICU patients, 84.6% were vitamin D deficient than
floor patients (57.1% only). Apart from this, 100% of the
ICU patients less than 75 years of age were vitamin D [22]
deficient. Even though it was a small observational study,
it highlighted a link between vitamin D deficiency and
COVID-19 risk.
Seventy-five COVID-19 positive patients were randomly
selected and divided into two groups: both received
standard care, and one group received vitamin D
(calcifediol) oral supplement as additional care.
From the vitamin D treated group, only 2% went to ICU,
[28]
whereas it was 50% from the untreated group.
Treatment with vitamin D (calcifediol) significantly
reduced the ICU admission and mortality.
In this study, significantly lower serum 25(OH)D level
obtained in COVID-19 positive (27 patients) (11.1 ng/mL)
cohort compared to the negative patients (80 people)
(22.2 ng/mL), which was comparable to that of the [95]
control group (n = 1377).
The result has shown that the combination therapy
[97]
reduced the need for oxygen therapy and/or ICU support.
The study revealed a link between severe vitamin D
[99]
deficiency and COVID-19 severity and mortality.
The mean vitamin D level was significantly lower in the
cohort found positive for COVID-19, compared to those
[100]
who tested negative. Low plasma 25(OH)D
concentration was found to be an independent risk factor
for COVID-19.
The study found that the COVID-19 positive group had a
[101]
lower median serum 25(OH)D level (10.8 ng/mL)
compared to the negative group (20.8 ng/mL).
An in vitro study has shown that calcitriol (vitamin D)
among various potential libraries was found to be
effective against SARS-CoV-2 with 0.69 log10 inhibition in
human nasal epithelial cells (in vitro). [102]
If the result is replicated in clinical trials, host-directed
therapy receives consideration, and calcitriol can be
used as ring prophylaxis of the contacts of COVID-19
patients.
 Table 4.
Cont.

Study Details/Objective(S) Results/Conclusions Reference(s)

Researchers have given vitamin D oral
supplementation to four COVID-19 confirmed
patients—cholecalciferol 1000 or
ergocalciferol 50,000 IU/day/5 days.
Determined the efficacy of bolus vitamin D3
supplementation during or just before COVID-19 in
elderly adults.
The vitamin D serum levels of two cohorts of
COVID-19 patients (active and expired)
were statistically analysed.
Patients who received high dose supplementation
achieved normal vitamin D levels, which was seen in
their clinical recovery level (lower oxygen requirements, [103]
reduction in inflammatory marker status, and shorter
length of stay).
They observed that 82.5% of the intervention group
survived COVID-19, whereas only 44.4% survived in the [104]
comparator group.
Univariate analysis results showed that vitamin D
deficiency is associated with the odds of death.
While controlling the age, sex, and comorbidity, vitamin D
deficiency has shown a strong association with [105]
COVID-19 mortality.

8. The Role of Vitamin D in Infection Control

Most of the patients with respiratory diseases, including COVID-19, were found to
be associated with vitamin D deficiency, implying that vitamin D supplementation or
solar radiation exposure might improve their potential for healing [106]. Studies pointed
out that vitamin D influences both the innate and adaptive arms of immunity,
particularly in making proper cell signalling pathways due to the presence of vitamin D
receptors (VDR) in the immune cells [107,108]. In summary, vitamin D may:
• Reduce microbial (including viral) respiratory tract infections [74,107,109,110];
• Boost immunity through the induction of antimicrobial peptides such as catheli-
cidins (hCAP-18/LL-37) and defensins, which can lower the viral replications in the
body [44,46,110,111];
• Reduce cytokine and chemokine storms, and reduce the production of pro-inflammatory
cytokines, tumour necrosis factor-´α, and interferon-γ—which usually produce inflam-
mation in lung alveoli causing ARDS [46,74,109–112];
• Increase the expression of anti-inflammatory cytokines [110];
• Promote the production of regulatory T cells, which inhibit the inflammatory process
• [113]; Act as a negative regulator of RAS in the form of 1,25 dihydroxyvitamin D/VDR
• [114,115]; Maintain pulmonary epithelial barrier integrity and stimulate
epithelial repair [43,116]; and
• Protect against ALI through calcitriol/VDR signalling [17].
Angiotensin-Converting Enzyme-2 (ACE-2) receptors are highly expressed on type
II pneumocytes; therefore, they are primary targets for SARS-CoV-2. Bombardini and
Picano [117] are of the opinion that impaired functions of these cells decrease their sur-
factant levels and thus increase their surface tension, making it more favourable for the
SARS-CoV-2 to infect the cells. However, it was reported that 1,25 dihydroxyvitamin D can
stimulate surfactant levels in alveolar type II cells during in vitro studies [118,119],
which potentially makes the situation detrimental for the SARS-CoV-2 to infect the ACE-
2.
In line with the current COVID-19 seriousness and the need for treatment method-
ology, various previous clinical studies have shown that treatment with high doses of
vitamin D (250,000–500,000 IU) is safe for both critically ill and mechanically ventilated
patients [70,120]. This treatment has helped to increase the haemoglobin level and
oxygen- carrying capacity of blood in patients and reduce their length of stay in the
hospital environment [70,120]. In another study by Sabetta et al. [64], it was found that
acute viral respiratory tract infection was two-fold less prevalent in patients if their
vitamin D serum levels were above 36 ng/mL (hazard ratio 0.51, 95% CI, 0.25–0.84, p <
0.0001) and the per- centage of sick days was five times less in comparison with other
patients whose vitamin D serum levels were less than 38 ng/mL [64]. In an in vitro
study, vitamin D also showed antiviral activity against rhinovirus in human epithelial cells
[121]. It thus seems likely that
maintaining sufficient levels of vitamin D in the serum is a significant issue in vulnerable
people in the community, such as older adults, those that are immunocompromised, and
patients with chronic conditions. In these situations, such people’s bodies are already
pre-set for an elevated level of inflammatory response if exposed to SARS-CoV-2
infection, as mentioned by Laird et al. [7].

9. Acquiring Sufficient Levels of Vitamin D

Exposure to sunlight has traditionally been considered a therapy for several ill-
nesses [122], but as indicated earlier, there is a progressive fall in UVB radiation and
subsequent vitamin D production with a progressive increase in distance from the equa-
tor [24,123]. Exacerbating the issue is that there has been recent advice to limit sun exposure
because of the correlation between high UV exposure levels and the increased risk of
skin cancer (cell carcinoma and melanoma) [124]. In ideal conditions, around 50% to 90%
of the required vitamin D in the body develops on the skin from UVB radiation, with the
remainder having to be supplied through diet [24,82]. However, notwithstanding the
specific barriers introduced by modern living conditions, there are suitable methods to
acquire enough vitamin D levels, including:
1. Exposing the body sensibly to natural solar radiation;
2. Consuming a vitamin D-rich diet consisting of: egg yolk, cod liver oil, vitamin D
fortified dairy products/juice/or other foods, wild mushroom, oily fish such as tuna,
mackerel, herring, sardine, and wild salmon;
3. Regularly taking vitamin D supplements in tablet form (recommended under medical
supervision to those who have any health risk).
Although exposing the body to solar radiation is the best and the cheapest option to
develop sufficient vitamin D, revealing enough skin to ambient sunlight and the calculation
of optimal exposure is a complicated procedure, as there are several parameters
involved, including climate, weather, location (latitude and elevation from the mean sea
level), atmospheric pollution, and area of the body exposed [24,123,125,126]. Serrano et
al. [126] analysed the solar ultraviolet erythemal (UVER) irradiance (W/m 2) at Valencia
in Spain from 2003 to 2010 to estimate the solar UV radiation and the exposure time
necessary for the production of the recommended daily dosage of vitamin D (1000 IU)
and found that it varies from 7 minutes in summer to around 2 hours in winter. For
exposure between 10 a.m. and 3 p.m., where there are high UVB radiation levels, the
optimum time and duration of solar exposure should be advised by the local
meteorological and/or health authorities. The second method of obtaining vitamin D is
from consuming vitamin D-rich food, but it may prove challenging to receive sufficient
vitamin D from food alone [58]. The third route is the regular intake of supplements,
which is useful for people who have low sun exposure and dietary restrictions. According
to the US National Academy of Medicine, an adult requires around 600–800 IU of vitamin
D per diem, with no variation being noted between men and women. In 2016, the
scientific panel on Dietetic Products, Nutrition and Allergies (NDA) of the European
Food Safety Authority (EFSA), defined adequate intakes (AIs) of vitamin D for all
population groups as shown in Table 5. This general recommendation was made
without taking any infection control or pandemic issues into consideration. These
previous studies showed that vitamin D supplementation should be beneficial to those
with deficiency, and further, that daily or weekly supplementation is more beneficial
compared to the bolus dose [11]. However, a randomized controlled double-masked
pilot study conducted in Spain has shown that the bolus dose is also effective in treating
COVID-19 [28]. Though large-scale controlled study results have not yet been
published, it appears better to recommend a high dose of vitamin D to the COVID-
19 patients and people under quarantine as adjuvant therapy in support of other
recommendations [127]. In such cases, calcifediol’s direct supplementation is highly
recommended as it can quickly raise the serum vitamin D level [28]. Though the
recommended dosage of vitamin D supplementation is normally safe, prolonged use of
very excessive supplementation may create hypervitaminosis D leading to
hypercalcemia,
 with subsequent renal and cardiovascular damage [128]. By taking this excess effect
into account, the Food and Nutrition Board of the Institute of Medicine of the National
Academies in the US has recommended 4000 IU per day as the upper recommended
level for adults [129]. They further suggested that the circulating vitamin D (25(OH)D)
level above 50–60 ng/mL (125–150 nmol/L) should not be allowed as it can create
cardiovascular and renal complications [129]. Even though several vitamin D oral
supplementation recommendations have been proposed, specifically in recent times due
to the COVID-19 pandemic, it appears that it will be more effective and healthier if the
recommending agencies consider the following factors: (i) initial vitamin D level; (ii)
living environment (latitude, types of work); (iii) skin pigmentation; and (iv) obesity.
Table 5. The adequate intake (AI) of vitamin-D for all populations as recommended by the European
Food Safety Authority (EFSA) [130] and the American National Academy of Medicine (ANAM) [129].

Age EFSA (mcg/day) (IU/day) ANAM (mcg/day)/(IU/day)

1–11 months 10 400 -
1–18 years 15 600 -
>18 years 15 600 20/800
Note: mcg—microgram; IU—international unit. For persons with existing health problems, especially cardiac
and renal issues, a local doctor should be consulted before taking any supplement.
Based on several observational studies [21,22,97,99,102,105] and through a random-
ized pilot study conducted in Spain [28], it was found that people with COVID-19
require a sufficient level of vitamin D to prevent severity. The effects of vitamin D will be
more significant in people with low vitamin D levels. Therefore, we suggest that a high
dose of oral calcifediol supplementation be offered to COVID-19 patients immediately
after the confirmation of their status and also to people under quarantine conditions (Figure
4). Sup- plementation is also suggested for vulnerable people in the community as either
calcifediol or cholecalciferol, and other people can be vitamin D sufficient through
adequate solar exposure. The later mode is clearly the cheapest option with the caveat of
considering the potential for melanoma in pale-skinned people.

Figure 4. Suggested vitamin D pathways for COVID-19 patients, the vulnerable group, and the general public.
 3.3.1.2 10. Conclusions
Vitamin D is unarguably a significant factor in general bodily health, but of
particular interest in the context of COVID-19, it is correlated to a positive impact in reducing
infection and symptoms. Hypovitaminosis of vitamin D results in many conditions such
as rickets, osteoporosis, osteomalacia, certain cancers, hypertension, cardiovascular
disease, and can be considered a significant factor in the development of cytokine
storms that lead to ARDS among COVID-19 patients. At this time (December 2020), no
large, high-quality randomised placebo-controlled multicentral study has been
published that establishes vitamin D level measurements or high dose vitamin D
performance on COVID-19 patients. However, the results of existing observational, small
cohort, and pilot studies are promising. Therefore, it is suggested that measurements of
vitamin D levels in all COVID-19 confirmed patients in various stages of the diseases
would lead to a significant database that would assist in understanding the relationship
between vitamin D levels and significant COVID- 19 symptoms, which will allow the
creation of an evidential model. Work to date also suggests that increasing vitamin D
levels in all COVID-19 patients will alleviate the severity of symptoms and mortality.
Vitamin D serum level deficiency is commonly seen in older adults, those with obesity,
those having pre-existing chronic conditions, and people living in high latitudes, specifically
with darker skin pigmentation. This is considered to be the vulnerable group in respect
to COVID-19, which is based on the correlation of low vitamin D levels and COVID-19
seriousness and mortality. Whilst there are various other medical explanations, the data
lead to the suggestion that solar exposure and raised vitamin D serum levels can
alleviate the severity of COVID-19 symptoms. Information from all the previous studies
suggests that a sufficient level of vitamin D serum level in the body can move a person
from pro- inflammatory levels to anti-inflammatory levels, which can save the lives of
the majority of COVID-19 patients. Therefore, an adequate level of exposure to solar
radiation or supplementation of vitamin D should be considered as prophylactic against
COVID-19, which may be very beneficial to low- and middle-income countries.
Notwithstanding this evidence, additional evidence from well-designed placebo-controlled
studies is required to more clearly understand the therapeutic potential of vitamin D
regarding COVID-19 and many other similar diseases. However, waiting for the results of a
comprehensive study for several months (without suggesting vitamin D) cannot be
tolerated as tens of thousands of people are succumbing to the virus each day.

Author Contributions: J.A.: conceptualisation, methodology, original draft; K.D.: discussion and
editing; S.F.: discussion and editing. All authors have read and agreed to the published version of
the manuscript.
Funding: There has been no funding received for this study.

Informed Consent Statement: Not applicable.

Data Availability Statement: Not applicable.

Acknowledgments: The authors are thankful to the Federation University Australia for providing
the facilities to prepare this article.
Conflicts of Interest: The authors declared that there is no conflict of interest.

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ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
https://doi.org/10.1080/13813455.2020.1791188

REVIEW ARTICLE

Nutrients in prevention, treatment, and management of viral infections;

special focus on Coronavirus
Fatemeh BourBoura, Samaneh Mirzaei Dahkab, Maryam Gholamalizadehc, Mohammad Esmail
Akbarid,
Mahdi Shadnoushe, Mohammad Haghighif, Hamidreza Taghvaye-Masoumig, Narjes Ashoorih and Saied
Doaeii
a
Department of Clinical Nutrition and Dietetic, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food
Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran;bStudent Research Committee,
Guilan university of Medical Sciences, Rasht, Iran; cStudent Research Committee, Cancer Research Center, Shahid Beheshti
University of Medical Sciences, Tehran, Iran; dCancer Research Center, Shahid Beheshti University of Medical Sciences,
Tehran, Iran; eDepartment of Clinical Nutrition, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food
Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran; fAnesthesiology Research Center,
Guilan University of Medical Sciences (GUMS), Rasht, Iran; gDepartment of Clinical Pharmacy, Faculty of Pharmacy, Gilan
University of Medical Sciences, Rasht, Iran; hDepartment of Community Nutrition, School of Nutrition and Food Sciences, Shahid
Beheshti University of Medical Sciences, Tehran, Iran; iResearch Center of Health and Environment, Guilan University of
Medical Sciences, Rasht, Iran

ABSTRACT ARTICLE HISTORY

Background: The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus Received 12 May 2020
with mild to severe respiratory symptoms. This paper aimed to investigate the effect of Revised 18 June 2020
nutrients on the immune system and their possible roles in the prevention, treatment, and Accepted 29 June 2020
management of COVID-19 in adults. Methods: This Systematic review was designed based on Published online 7 July
the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that 2020
focussed on nutrition, immune system, viral infection, and coronaviruses were collected by
KEYWORDS
searching databases for both published papers and accepted manuscripts from 1990 to
Infections;
2020. Irrelevant papers and articles without English abstract were excluded from the review Coronavirus; nutrition
process. therapy
Results: Some nutrients are actively involved in the proper functioning and strengthening of the
human immune system against viral infections including dietary protein, omega-3 fatty acids,
vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and
selenium. Few studies were done on the effect of dietary components on prevention of
COVID-19, but supplementation with these nutrients may be effective in improving the health
status of patients with viral infections.
Conclusion: Following a balanced diet and supplementation with proper nutrients may play a
vital role in prevention, treatment, and management of COVID-19. However, further clinical
trials are needed to confirm these findings and presenting the strong recommendations
Introduction

The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory
symp- toms in both men and women with different ages (Cheng and Shan 2020). Coronaviruses are a large
family of viruses that are common in humans and many different species of animals including camels, cattle,
cats, and bats (Brian and Baric 2005). The symptoms usually start between 2 and 14 days after a person
gets infected and mainly includes fever, cough, and shortness of breath (Lake 2020). The molecular
mechanisms involved in COVID-19 are not yet clear, but probably include inter- and intramolecular interac-
tions that facilitate viral replication (de Wilde et al. 2018). Currently, there are no approved vaccines or
pharmaceutical therapies available for treatment of COVID-19. Social distanc- ing, self-quarantine, and
maintain a healthy immune system are among the best ways to prevent the spread of the infec- tion (Derwand
and Scholz 2020, Jayawardena et al. 2020)
The human immune system is a complex and efficient defense system consisting of an integrated set of
cells, chem- ical mediators, and a series of defensive “modular” factors to modulate immune response and
protect the body from external insults (Scully et al. 2017). One of the most import- ant factors that influence the
human immune system is nutri- tion (Lopez Plaza and Bermejo Lopez 2017). Individuals with nutrient
deficiencies have weakened immune system and they are more susceptible to viral infections such as COVID-
19, and also for exacerbations of the condition after the dis- ease (Lopez Plaza and Bermejo Lopez 2017).
Supplementation with some nutrients may support the body’s natural defense system by enhancing the
immunity, epithelial barriers, cellular immunity, and antibody produc- tion (Wintergerst et al. 2007). A
balanced diet, especially in terms of adequate immune boosting components such as protein, vitamins, and
minerals enhances the resistance against infections (Cotter et al. 2019). Therefore, providing a good nutritional
status and correction of the deficiency of
immune-related nutrients may be essential for 4 Study question
prevention and treatment of viral infections (Pae et al.
2012). This review aimed to investigate the latest The formula question was based on the PICO style as
findings on identifying the effective nutrients on the follows: What is the effect of nutrients and dietary
immune system against viral infec- tions and to supplements on boosting the immune system on
present the potentially effective nutrients in the preventing and treating COVID-19 compared to other
prevention, treatment, and management of COVID- people who do not get enough nutrients? P: People with
19. or without infection; I: Eating a healthy diet or
supplement; C: People who don’t get a healthy diet or
supplement; O: Not getting coronavirus or treating
Methods people with coronavirus. The study protocol was
approved by ethics committee of Guilan University of
3 Study framework Medical Sciences, Rasht, Iran (code
IR.GUMS.REC.1399.003).
In this systematic review, all articles that focussed on
nutri- tion, the immune system, viral infection, and 5 Search strategy
coronaviruses were collected by searching databases
including PubMed, Scopus, Google Scholar, ISI, The current research was performed using the terms
Embase (Elsevier), and Researchgate for both the of med- ical subject headings (MeSH) and
accepted manuscripts in peer- reviewed journals and combinations of the key- words according to the
the published papers in the indexed journals from following search strategy: "corona or coronavirus or
1990 to 2020. COVID or COVID-19 or viral or virus or Middle East
Respiratory Syndrome or MERS" AND "nutrient or
vita- min or mineral or macronutrient or
micronutrient or protein or fat or carbohydrate or
retinol or calcitriol or tocopherol or phyllo Quinone
or thiamine or pyridoxine or ascorbic acid or
cobalamin or folic acid or pantothenic acid or biotin
or cal- cium or phosphorus or magnesium or sulphur
or iron or iod- ine or copper or zinc or selenium".
6 Inclusion and exclusion criteria
All articles collected in the electronic search process
as well as the references used in these articles were
reviewed (n ¼ 670). Duplicated articles were removed
(n ¼ 430), and then titles and
abstracts of all imported studies were screened by two
research- ers according to the specific selection
criteria. Inclusion criteria were: randomised clinical
Identification
trials (RCTs), case-control, in-vivo stud- ies, and meta-
analyses on RCTs which focussed on the role of
nutrients on immune system and viral infections.
Irrelevant papers and articles without English abstract
were excluded from the review process. Finally, 51
articles including 14 meta-analy- ses were included in
review process (17–68) (Figure 1).
7 Data extraction
Full texts of the studies were independently
reviewed by two researchers. Data were extracted
from included studies

Records identified through database searching

(PubMed, Scopus, Embase, and Cochrane (n =670)

Records after duplicates removed

(n =240)

Records screened Records excluded

(n =240) (n = 84)
Eligibility

Full-text articles assessed Records excluded

for eligibility (n = 105)
(n = 156)
Included

Studies included in
qualitative synthesis
(n =51)

Figure 1. The flow diagram according to the PRISMA guidelines.

Screening

for evidence synthesis including author/date, type of
study, sample size, intervention, control, primary
outcome, results, and p values. Then, the accuracy
and quality of the included data were checked by a
third investigator.
Results
Some nutrients were reported to be actively involved
in the proper functioning and strengthening of the
immune system, including dietary protein, omega-3
fatty acids, vitamin A, vitamin D, vitamin E, vitamin
B1, vitamin B6, vitamin B12, vita- min C, iron, zinc, and
selenium. Supplementation with some of these
dietary components was also reported to be effect- ive
in improving the health status of patients with viral
infec- tions. Strong evidences including meta-
analyses on RCTs are presented in Table 1. The roles
of these immune-boosting nutrients are discussed
below.
3 Dietary protein
Dietary protein is considered a vital component in the
sup- port and strength the immune system and in the
prevention and treatment of viral infections (Kurpad
2006). Amino acids have some critical roles in
immune responses including (1) the proliferation
and activation of T lymphocytes, B lympho- cytes,
natural killer cells, and macrophages; (2) regulation of
intracellular redox status and gene expression; and (3)
the production of antibodies, cytokines and other
cytotoxic sub- stances (Li et al. 2007). Protein
recommendation is estimated
0.8 gr/kg/day in healthy adults, and 1 gr/kg/day in
patients with risk of viral infection in order to
strengthen the immune system against infections
(Kurpad 2006, Wilson et al. 2019).
Moreover, some amino acids have key roles in the
func- tion of the immune system against viruses. For
example, arginine improves the immune system by
enhancing T-cells activity. Åkerstrom et al. identified
that Nitric oxide (NO), which is produced by
arginine, may inhibit the SARS-CoV replication cycle
(Akerstrom et al. 2005). NO was also reported to has
an important role in regulating airway func- tion and
in treating airway inflammation and lung diseases
(The 2020, Zhu et al. 2020). Supportive results were
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY 3
reported in healthy subjects who had significantly
increased lympho- cyte counts after an oral dose of
30 grams of arginine for 3 days (Visek 1986). However,
there are some evidences that additional arginine is not
safe in severe septic conditions, especially in patients
with shock. This effect of arginine could be due to NO
over production, which might have detrimen- tal
effects on cardiovascular stability. No direct study
has been conducted in the case of Covid-19, but it
seems that a dose of 2% of energy (about 10 gr in a
standard 2000 kcal diet) is optimal, safe, and effective
when given before a severe infection (Shils and Shike
2006, Alexander and Supp 2014, Mahan and Raymond
2017).
4 Omega-3 fatty acids
Omega-3 (x-3) fatty acids can boost the immune
system through different mechanisms such as
improving B cell activity, decreasing cytokines,
decrease inflammatory eicosa- noids, and increasing
phagocytosis (Chen et al. 2010, Zhao and Wang 2018,
Guti´errez et al. 2019, Kunisawa et al. 2019). Moreover,
Kelch like ECH associated protein 1 (KEAP1) is a
docosahexaenoic acid (DHA)-dependent protein and
provides a cell protection mechanism against
oxidative insults when endogenous stress defense
mechanisms are imbalanced (Mildenberger et al. 2017).
The result of a study on healthy subjects indicated that
an eicosapentaenoic acid (EPA) intake of 2.7 g/day
significantly decreased PGE2 production (Miles and
Calder 2012).
The role of omega-3 in improving the health status
of patients with infection and respiratory
complications has been frequently reported. A meta-
analysis identified that omega-3 fatty acids have some
effects in improving the situ- ation of the patients
with sepsis (Chen et al. 2018). Several studies found
that omega-3 fatty acids can improve the ratio of
CD4–CD8 in patients with severe sepsis which is an
indica- tor for improving patient’s immune function
and may reduce the mortality rate of these patients
(Gao et al. 2016, Chang et al. 2017, Chen et al. 2018).
Three studies investigating a formula containing
EPA, DHA, and gamma-Linolenic acid (GLA) in
critically ill patients with severe sepsis, acute
respiratory distress syndrome (ARDS), and Acute
Lung Injury (ALI) reported that this for- mula could
decrease duration of mechanical ventilation and
improve oxygenation (Gadek et al. 1999, Pontes-
Arruda et al. 2006, Singer et al. 2006). Another meta-
analysis on omega-3 found that x-3 fatty acids in
enteral nutrition formulas may be associated with
improved rate of the partial pressure of oxygen to
fraction of inspired oxygen (PaO2-to-FiO2 ratio),
improved ICU length of stay (LOS), and decreased
duration of mechanical ventilation in critically ill
patients with ARDS. The infection rate, Gas
exchange, and liver function were also improved
(Langlois et al. 2019). No studies are available on the
effect of omega-3 on COVID-19. However, the x-3
PUFA-derived lipid mediator could markedly
attenuate influ- enza virus replication via the RNA
export machinery (Messina et al. 2020).

5 Vitamin A

Vitamin A (also called “anti-infection” vitamin) acts

as an anti-inflammatory factor involved in
improving immune sys- tem function and mucosal
integrity which protects the body against infections
(Stephensen 2001).
Semba et al. reported that vitamin A could
decrease the mortality and morbidity rates in
infectious diseases such as measles, diarrheal
disease, measles-related pneumonia, human
immunodeficiency virus (HIV) infection, and malaria
(Semba 1999). Children with acute measles infection
who received high-dose vitamin A supplementation
(60 mg RE on admission and the following day)
had higher IgG responses to measles virus and
higher circulating lymphocyte counts (Coutsoudis et
al. 1992). Vitamin A was suggested as an option to
the treatment of coronavirus and prevention of
the lung infection (Zhang and Liu 2020). Several
mechanisms are reported for the anti-infection
effects of vitamin A.
Table 1. characteristics of meta-analyses on the effect of nutrients on viral infections. 4
Study Design Sample size Intervention Control Primary outcome Results p value
Heys et al. (1999) A meta- Eleven prospective, randomised L-arginine þ n-3 standard diet The effect of nutritional support Nutritional support NS F.
analysis of controlled trials evaluating on infectious complications. supplemented with key
B
RCTs
RNAþ
EFAs O
1009 patients supplementation nutrients to patients with U
critical illnesses could reduce
R
infection and reduced the
hospital stay. B
Chen et al. (2018) A meta-analysis Twenty five studies involving Omega 3 fatty acid Standard diet The effect of omega-3 fatty acids Omega-3 fatty acid .02 O
of RCTs 2417 participants. supplementation. on reducing the mortality of supplementation reduced the
sepsis and sepsis-induced mortality rate of sepsis and
acute respiratory distress sepsis-induced ARDS.
syndrome (ARDS) in adults
Zhao and A meta-analysis Sixteen RCTs involving 1008 Omega 3 fatty acid Standard diet The immune efficacy of x-3 Early intervention with Omega-3 .001
Wang (2018) of RCTs patients (506 in the omega-3 supplementation. polyunsaturated fatty acid- fatty acid emulsion improved
group, 502 in the supplemented parenteral the postoperative indicators of
control group) nutrition in patients with immune function, reduced
gastrointestinal inflammatory reactions, and
malignancy. improved the
postoperative status.
Chen et al. (2010) A meta-analysis 13 RCTs involving 892 patients fish oil-enriched Standard diet Fish oil-supplemented parenteral <.001
The safety and efficacy of a fish
of RCTs parenteral nutrition oil-enriched parenteral nutrition was safe,
nutrition regimen in patients improved clinical outcomes,
undergoing major as well as leukotriene
abdominal surgery synthesis.
Langlois et al. (2019) A meta- Twelve RCTs (n ¼ 1280 patients) Administration of Standard diet The clinical benefits of x-3 .003
analysis of x-3 PUFA PUFA administration on gas In critically ill patients with
RCTs ARDS, x-3 PUFAs in
enteral
exchange and clinical immune modulatory diets was
outcomes in Acute respiratory associated with an
distress syndrome improvement in early and late
(ARDS) patients. PaO2-to-FiO2 ratio, and
improved ICU length of stay
and mechanical
ventilation duration.
Martineau A meta-analysis 25 RCTs (a total of 11,321 Administation vitamin —— The overall effect of vitamin D Vitamin D supplementation was p < .001
et al. (2017) of RCTs participants) D supplemention. supplementation on the risk safe, and it protected
of acute respiratory against ARIs.
infections (ARIs).
Hu et al. A meta-analysis A total of 7 studies involving 814 Vitamin D level in Standard diet To determine whether vitamin D vitamin D level was lower in p < .001
(2019)
of RCTs chronic hepatitis B patients patients with levels were correlated with chronic hepatitis B (CHB)
and 696 healthy controls hepatitis B. hepatitis B virus loads patients than that of healthy
controls and was inversely
correlated with hepatitis B
virus) HBV viral loads
Saboori et al. (2015) A meta-analysis 12 articles involving 246 Vitamin E Standard diet To assess the effect of vitamin E Vitamin E supplementation .001
of randomised participants in the supplementation. supplementation on reduced CRP level
controlled intervention groups and 249 CRP levels.
trials participants in control groups
Jafarnejad A meta analysis 12 studies were included with Administation vitamin C Standard diet The effects of vitamin C vitamin C supplementation .02
et al. (2018) of RCTs 446 participants in supplementation supplementation on serum reduced the circulating
supplementation groups and CRP levels CRP level
447 in control groups
Wang et al. A meta-analysis 12 RCTs Intravenous Placebo The effects of ascorbic acid high Intravenous ascorbic acid .015
(2019)
of RCTs administation dose (3–10 g) on the mortality reduced the duration of
vitamin C of critically ill adults vasopressor support,
supplementation to mechanical ventilation,
critically ill and overall mortality rates
patients
(continued)
 ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
5

Vitamin A contributes to the phagocytic and

p value

.009
oxidative activ- ities of macrophages. Vitamin A
helps regulate the number and function of NK cells.
Vitamin A also helps to regulate the production of IL-
Results

2 and the pro-inflammatory TNF-a, which activates

the microbial action of macrophages. Vitamin A is
also involved in development and differentiation of
Th1 and Th2 cells (Gombart et al. 2020).

6 Vitamin D

Vitamin D has antimicrobial and anti-oxidative effects

ill patients.was associated with a reduction in 28-day mortality

and helps to the immune system against lung

infection and air- way inflammation (Hansdottir and
Monick 2011). Recent studies reported that vitamin D
Primary outcome

may prevent respiratory infections, especially viral

infections (Laplana et al. 2018, Teymoori-Rad et al.
2019). A meta-analysis on vitamin D found that
vitamin D supplementation has protective effects
against acute respiratory infections (ARIs) (Martineau
et al. 2017). Another meta-analysis indicated that
vitamin D level was lower in chronic hepatitis B
(CHB) patients than that of healthy controls and its
level was inversely correlated with hepatitis B virus
(HBV) loads (Hu et al. 2019). Vitamin D enhances
Control
supplementation

placebo

innate cellular immunity partly through the induc-

tion of antimicrobial peptides, including human
placebo

cathelicidin, LL-37, and defensins. These host-

in critically

derived peptides kill the invading pathogens by

perturbing their cell membranes and can neutralise
Selenium

the biological activities of endotoxins.

Effect of selenium supplementation on outcome

Vitamin D reduces the expression of pro-

inflammatory cyto- kines such as tumour necrosis
factor and interferon-gamma (INF), and increases the
Intervention

expression of anti-inflammatory cyto- kines.

Furthermore, 1,25(OH)2D3 promotes the induction of
the T regulatory cells, thereby inhibiting
for patient with sepsis

inflammatory proc- esses (Agier et al. 2015). Vitamin

D also promotes differenti- ation of monocytes to
macrophages, increases their killing capacity;
patients supplementation

modulates the production of inflammatory cytokines;

Sample size

and supports antigen presentation. Furthermore,

vitamin D metabolites regulate production of specific
supplementation

antimicrobial pro- teins that directly kill pathogens,

and thus are likely to help reduce infection in the
921 selenium

sepsis

lungs (Calder et al. 2020).

A few studies were done on the association of
seleniumwith
intravenous

vitamin D and coronaviruses. The combined

9 RCTs including

of 1922 patients

—
inistration
 supplementation of vita- min D with melatonin could
offer a synergistic alternative for the prevention and
treatment of pulmonary infection by COVID 19.
Nonnecke et al. reported that lower levels of vitamin
D in calves caused the increased risk of infection
with bovine coronavirus (Nonnecke et al. 2014). A
recent study reported that the goal should be to raise
25(OH) D serum concentrations above 40–60 ng/mL
(100–150 nmol/L) for the treatment of people who
become infected with COVID-19. It is recommended
that people at risk of influenza and/or COVID-19
consider taking 10,000 IU/d of vitamin D3 for a few
weeks to rapidly raise 25(OH) D concentrations, fol-
lowed by 5000 IU/d [43].

7 Vitamin E
3

Vitamin E boosts the immune system and fights

disease- causing pathogens such as bacteria and
viruses through its
6 F. BOURBOUR ET AL.

Figure 2. Immune system supporting nutrients.

strong anti-oxidative activity and maintaining the integrity of T-cell membranes (Lewis et al. 2019, Calder et al.
2020). No direct study has been conducted in the case of association of vitamin E and Covid-19. However,
recent studies indicated that vitamin E reduced the duration of infection with the influenza virus (Galabov et al.
2015). Meydani et al. reported that vitamin E–treated group (received 200 IU daily) had fewer days with
common cold per person-year (Meydani et al. 2004).
Suggested mechanisms involved in the effects of vitamin E are: 1) the reduction of PGE2 production by
the inhibition of COX2 activity mediated through decreasing NO produc- tion, 2) the improvement of effective
immune synapse for- mation in naive T cells and the initiation of T cell activation signals, and 3) the
modulation of Th1/Th2 balance. Higher NK cells activity and lower IL-12 production and migration were
induced by vitamin E, but the underlying mechanisms need to be further elucidated (Lee and Han 2018).

8 Vitamin B1 (thiamine)

Vitamin B1 has some anti-inflammatory effects through influ- ences on pro-apoptotic proteins, mitochondrial
membrane integrity, cytochrome C release, P38 mitogen-activated pro- tein kinase (p38-MAPK) activity, and
the oxidative stress- induced NF-kappaB pathway. Deficiency of vitamin B 1 may cause inflammation, T cell
infiltration, overexpression of pro- inflammatory cytokines such as IL-1, TNF, and IL-6, and increasing the level
of arachidonic acid-derived eicosanoids (Spinas et al. 2015). Donnino et al. reported that administra- tion 200
mg thiamine in 50 ml of dextrose 5%, twice daily for 7 days, decreased the mortality rate in adult patients with
septic shock and elevated lactate (Donnino et al. 2016).
9 Vitamin B6 (pyridoxine)

Pyridoxine has a key role in the production of T cells and interleukins (Qian et al. 2017). Vitamin B6 has a role
in lymphocyte maturation (Gombart et al. 2020) and vitamin B6 deficiency has been associated with a dramatic
depletion of thoracic duct lymphocytes and a reduction in lymphocyte proliferation (Qian et al. 2017). Future
studies are required to evaluate the possible effects of pyridoxine on coronavirus and COVID-19(Gombart et
al. 2020).

10 Vitamin B12 (cobalamin)

Cobalamin plays a vital role in the immune system through helping in the production of white blood cells.
Vitamin B12 may act as an immunomodulatory factor and enhance the number of cytotoxic T cells against
viral infections (Tamura et al. 1999, Gombart et al. 2020). Vitamin B12 may also be used as a therapeutic agent
in sepsis and systemic inflamma- tory response syndrome (SIRS). Vitamin B12 may help to maintain the
normal function of macrophages. It also has some anti-inflammatory effects such as regulating Nuclear factor-
jB (NF-ŒB), a key activator of the pro-inflammatory pathways. It also has a proven role in bacteriostasis and
phagocytosis (Romain et al. 2016).

11 Vitamin C (ascorbic acid)

Ascorbic acid improves the chemotaxis of phagocytes and helps to kill bacteria and viruses by modulation of
the accu- mulation of phagocytic cells such as neutrophils (Carr and Maggini 2017). Vitamin C affects several
aspects of immunity, including supporting epithelial barrier function, growth and function of both innate and
adaptive immune cells, white blood cell migration to sites of infection, phagocytosis and microbial killing,
and antibody production (Calder et al.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY 7
2020). Hemil€a reported that vitamin C might affect the immune system through improving the
function of phago- cytes, the transformation of T lymphocytes, and the produc- tion of interferon (Hemila and
Douglas 1999). There is also some evidence that vitamin C may improve the health status of patients with
pneumonia (Hemila and Douglas 1999).
Vitamin C may protect against infection caused by cor- onavirus (Zhang and Liu 2020). Atherton et al.
reported that vitamin C improved immune functions of chick embryo tra- cheal organ cultures against
coronavirus infection (Atherton et al. 1978). When sepsis happens, the immune cells such as the cytokine is
activated, and neutrophils accumulate in the lungs, destroying alveolar capillaries. Vitamin C may help to
prevent the excess activation and accumulation of neutro- phils, and decrease alveolar epithelial water
channel damage. A controlled, randomised trial found that 200 mg/day of vita- min C improved respiratory
symptoms and lowered the mor- tality rate in severely ill elderly patients [34]. However, a meta-analysis
reported that vitamin C administration is asso- ciated with no significant effect on survival, length of ICU or
hospital stay (Putzu et al. 2019). Further studies are needed to investigate the association of vitamin C with
COVID-19.

12 Iron

Iron is a vital mineral for both health and infection. Iron is essential for differentiation and growth of
epithelial tissue and some iron-containing proteins, such as the haem scaven- ger HPX, are a central
component of the immune system (Nunez et al. 2018). Moreover, iron is required for the pro- duction of
reactive oxygen species (ROS) by neutrophils to kill pathogens (Gombart et al. 2020). De Silva et al. reported
that 60 mg/daily elemental Fe reduced respiratory infection in children (de Silva et al. 2003).

13 Zinc

Zinc is essential for the development, differentiation, and activation of T lymphocytes (Gombart et al. 2020).
Zinc defi- ciency weakens the immune system by reducing macro- phages and monocytes and increasing
oxidative stress (Maywald et al. 2017, Sanna et al. 2018). The various func- tions of macrophages include
phagocytosis and the secretion of immune-mediating factors can be impaired by zinc imbal- ance. Despite
extensive research, the molecular mechanisms by which zinc regulates the function of macrophages remain
poorly understood (Gao et al. 2018). Increased intracellular Zn2þ concentrations are known to efficiently impair
the repli- cation of several RNA viruses. Velthuis et al. reported that coronavirus replication can be inhibited by
increased Zn2þ levels. The concentration of 2 mM Zn2þ inhibited the replica-
tion of SARS-coronavirus (SARS-CoV) in cell culture (te Velthuis et al. 2010).

14 Selenium

Adequate intake of selenium improves immunity and reduces inflammation, mainly through boosting the
synthesis of glutamine peroxidase, which protects neutrophils from oxidative stress (Avery and Hoffmann
2018, Gombart et al. 2020). Selenium deficiency and suppressed selenoprotein expression have been associated
with higher levels of inflam- matory cytokines in various tissues including the gastrointes- tinal tract, the
uterus, mammary gland, and other tissues. Dietary selenium deficiency that causes oxidative stress in the
host can alter the viral genome, so that a normally benign or mildly pathogenic virus can become highly
viru- lent in the deficient host under oxidative stress (Zhang and Liu 2020). Lei et al. reported that selenium
supplementation might improve the immune function and the response to viral infections such as lethal
influenza infection (Yu et al. 2011).
On the other hand, a mouse model of allergic asthma showed that selenium deficiency reduced airway
inflamma- tion while adequate selenium intake induced higher levels of inflammation. In addition, increasing
the selenium intake through diet raised expression levels of stress-related seleno- proteins as well as genes
 involved in inflammation and inter- feron c (IFNc) responses (Avery and Hoffmann 2018).

Discussion

This review indicated that some nutrients including dietary protein, omega-3 fatty acids, vitamin A, vitamin
D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium have important effects on
the immune system (Figure 2). These nutrients increase the body’s ability to cop- ing with viral infections.
High doses of vitamins and minerals do not yet have a proven protective effect in prevention of infectious
diseases in healthy people. However, supplementa- tion according to the Recommended Dietary Allowance
(RDA) is recommended for most of healthy people who do not have sufficient intake of nutrient rich sources.
On the other hand, some studies demonstrated that supplementa- tion with these nutrients can significantly
improve the health-related outcomes in patients with COVID-19.
There are very few studies that have examined the exact effect of nutrients on the coronaviruses. Erol et al.
indicated that intravenous high-dose vitamin C could be an effective choice of treatment in the early stages of
COVID-19 (Erol 2020). Vitamin C reinforces the maintenance of the alveolar epithelial barrier and
transcriptionally upregulates the protein
channels (aquaporin-5, ENaC, and Naþ/K þ ATPase) regulat-
ing the alveolar fluid clearance. High dose intravenous vita- min C (HDIVC) has been implicated in reducing
plasma cell- free DNA which is the facilitator of systemic inflammation in sepsis-induced multi-organ failure.
Interestingly, syndecan-1 in the plasma which is associated with increased mortality in severe sepsis and
ARDS patients can be reduced significantly by HDIVC (Kakodkar et al. 2020). Gant et al. in a review study
reported that vitamin D supplementation can reduce the risk of influenza and COVID-19 infections [38].
The exact molecular mechanism of the effect of the nutrients on corona virus infection are not clear.
Kesrtom et al. found that NO inhibited the synthesis of viral protein and RNA (Akerstrom et al. 2005).
Moreover, COVID-19 is 8 F. BOURBOUR ET AL.

significantly associated with extreme rise in pro- Conclusion

inflammatory cytokines such as IL6 and and C-
reactive protein (CRP) (Chen et al. 2020). Vitamin D
may help in treatment of COVID 19 infection through
decrease viral replication rates and reduce the
concentrations of inflammatory cytokines [38]. Te
Velthuis et al. found that the combination of zinc and
pyri- thione can efficiently impair the replication of
SARS-corona- virus (SARS-CoV) (Yu et al. 2011). It is
Suggested that chloroquine (CQ) is effective in the
control of COVID 19 infection and this drug has an
immune-modulating activity (Wang et al. 2020).
Chloroquine is a zinc ionophore increas-
ing Zn2þ flux into the cell. Intracellular Zn 2þ
concentration may mediate the CQ and its
metabolite hydroxychloroquine
(HCQ) antiviral effects against SARS-coV-2 (Xue et al.
2014). Future longitudinal studies are needed to
investigate the association of dietary components
with COVID-19 and to identify the underlying
mechanisms.
This study comprehensively investigated the role of
macro- and micro nutrients in supporting the
immune system and in the prevention and treatment
of infections. Moreover, findings of recent papers on
the association of nutrients and coronaviruses were
presented. Some nutrients have key roles in the
function of the immune system against viral infections.
Following an immune-boosting diet is important in
order to the prevention of viral infections such as
COVID-19. Supplementation with proper dietary
components may also improve the health-related
outcome of patients with COVID-
19. However, there are some limitations including lack
of clinical trial studies on the effects of the nutrients on
COVID- 19 and insufficient data on the effects of
supplementation in healthy subjects for the prevention
of COVID-19. Further studies are needed to confirm
these findings and presenting the strong
recommendations for patients with viral
infections.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This study was funded by Student Research Committee, Guilan
University of medical Sciences [No: 255–2012], Rasht, Iran. We
acknow- ledge the staff of the mentioned centers for their kind
cooperation.
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