HUBUNGAN KADAR TROPONIN I DENGAN MORTALITAS

PADA PASIEN DEWASA TERKONFIRMASI COVID-19

PENELITIAN

Oleh:
Lastri Supriatin, dr
NPM. 130921190006

Pembimbing :
Nida Suraya, dr., SpPK(K)
Dr. Delita Prihatni, dr., SpPK(K), M.Kes

Dipresentasikan di:
KONFERENSI KERJA X
PERTEMUAN ILMIAH TAHUNAN XX VIRTUAL
PDS PatkLIn
Banjarmasin, 24 November 2021

PROGRAM PENDIDIKAN DOKTER SPESIALIS I PATOLOGI KLINIK

FAKULTAS KEDOKTERAN UNPAD/RSUP Dr. HASAN SADIKIN
BANDUNG
2021
HUBUNGAN KADAR TROPONIN I DENGAN MORTALITAS
PADA PASIEN DEWASA TERKONFIRMASI COVID-19

Lastri Supriatin1, Nida Suraya2, Delita Prihatni3

1
PPDS Patologi Klinik, Fakultas Kedokteran Universitas Padjadjaran;
2,3
Departemen Patologi Klinik, Fakultas Kedokteran Universitas Padjadjaran,
Rumah Sakit Umum Pusat Dr. Hasan Sadikin Bandung
lastri.supriatin@gmail.com, 081221797960

ABSTRAK

Pendahuluan: Jantung adalah organ kedua setelah paru-paru yang banyak

terpengaruh oleh SARS-CoV-2, menyebabkan cedera jantung yang ditandai
dengan peningkatan kadar troponin. Kadar troponin I secara signifikan lebih
tinggi pada pasien COVID-19 yang berat, yang mendapat perawatan intensif, dan
yang meninggal. Peneliti bertujuan menganalisis hubungan kadar troponin I
dengan mortalitas pada pasien dewasa terkonfirmasi COVID-19.
Metode: Penelitian retrospective cohort dilakukan pada pasien COVID-19 rawat
inap di RSUP Dr. Hasan Sadikin Bandung dari Desember 2020 hingga Maret
2021 sesuai kriteria inklusi dan eksklusi. Data kadar troponin I dan karakteristik
pasien diambil dari sistem informasi laboratorium dan rekam medis. Hubungan
kadar troponin I dengan mortalitas dianalisis secara bivariate dengan uji chi-
square menggunakan program SPSS Versi 25.
Hasil penelitian: Total subjek adalah 90 pasien dengan usia 20-60 tahun
sebanyak 48 (53,3%), pasien laki-laki sebanyak 57 (63,3%), dan pasien dengan
komorbid sebanyak 64 (71,1%). Kadar troponin I berhubungan secara signifikan
dengan mortalitas (p 0,0001) dan nilai Odds Ratio (OR) sebesar 6,40 yang berarti
pasien dengan kadar troponin I meningkat memiliki kemungkinan untuk
meninggal 6,4 kali lebih besar daripada pasien dengan kadar troponin I normal.
Pembahasan: Cedera miokardium berkaitan dengan kematian pada COVID-19,
namun apakah cedera jantung merupakan penyebab langsung atau hanya penanda
kematian belum diketahui dengan jelas.
Simpulan dan saran: Pasien COVID-19 dengan kenaikan kadar troponin I pada
masa perawatan memiliki risiko kematian lebih tinggi daripada pasien dengan
kadar troponin I yang normal. Diperlukan analisis multivariat untuk mengevaluasi
apakah troponin I merupakan faktor penyebab kematian yang kuat pada pasien
COVID-19 dewasa.

Kata kunci: Troponin I, COVID-19

i
 CORRELATION OF TROPONIN I LEVELS AND MORTALITY
IN ADULTS CONFIRMED COVID-19

Lastri Supriatin1, Nida Suraya2, Delita Prihatni3

1
Resident of Clinical Pathology, Medical Faculty of Padjadjaran University;
2,3
Clinical Pathology Departement Medical Faculty of Padjadjaran University,
Dr.Hasan Sadikin General Hospital Bandung
lastri.supriatin@gmail.com, 081221797960

ABSTRACT

Preliminary: Heart is the second organ after lungs to be heavily affected by

SARS-CoV-2 causing cardiac injury characterized by elevated troponin levels.
Troponin I were significantly higher in severe COVID-19 patients, those
receiving intensive care and those who died. The researcher aims to analyze the
correlation between troponin I levels and mortality in adult patients with
confirmed COVID-19.
Method: This retrospective cohort study was conducted on COVID-19 patients
treated at RSUP Dr. Hasan Sadikin Bandung from December 2020 to March
2021 according to inclusion and exclusion criteria. Troponin I levels and patient
characteristic data were taken from laboratory information system and medical
records. The correlation between troponin I levels and mortality was analyzed
bivariately using the Chi-square test in SPSS 25.
Results: Total subjects was 90 patients aged 20-60 years as 48 (53,3%), male
patients as 57 (63,3%), and patients with comorbid as 64 (71,1%). Troponin I
was significantly associated with mortality (p 0,0001). Odds ratio (OR) was 6,40
which means increased troponin I levels patients are 6,4 times more likely to die
than normal troponin I levels patients.
Discussion: Myocardial injury associated with death in COVID-19, but whether
cardiac injury is the direct cause or only a marker of death is not clear.
Conclusions: COVID-19 patients with elevated troponin I levels during
hospitalization have a higher risk of death than patients with normal troponin I
levels. Multivariate analysis is needed to evaluate whether troponin I is a strong
cause of death in adult COVID-19 patients.

Keyword: Troponin I, COVID-19

ii
 Correlation Of Troponin I Levels And Mortality in Adults
Confirmed Covid-19

Lastri Supriatin1, Nida Suraya2, Delita Prihatni3

1
Resident of Clinical Pathology, Medical Faculty of Padjadjaran University;
2,3
Clinical Pathology Departement Medical Faculty of Padjadjaran University,
Dr.Hasan Sadikin General Hospital Bandung
lastri.supriatin@gmail.com, 081221797960

I. INTRODUCTION
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was
first identified in Wuhan, China, in December 2019 has caused a pandemic called
Coronavirus Disease 2019 (COVID-19).1 Transmission of this virus is through
close contact with infected people, through respiratory droplets that are released
onto environmental surfaces and then transferred to the human hand, with an
incubation period of 2 to 11 days after exposure. 2 The genetic sequence of the
virus encodes the formation of four proteins that make up the structure of the
virus, namely the spike glycoprotein (S), matrix (M), nucleocapsid (N), and
capsule (E). The S protein binds to Angiotensin-converting enzyme 2 (ACE2) as a
viral receptor to enter human host cells. Angiotensin-converting enzyme 2
(ACE2) is a type 1 transmembrane protein with 805 amino acids that attaches to
the outer surface of cells.1 In lung tissue, ACE2 is highly expressed by type II
alveolar epithelial cells and type I alveolar epithelial cells, which are the gateway
for SARS-CoV-2 infection. In addition to the lungs, ACE2 is also highly
expressed in the heart, the intestinal epithelium, vascular endothelium, and
kidneys.3 Zou et al said that the heart is the second organ after the lungs that is
heavily affected by SARS-CoV-2 infection because ACE2 receptors are widely
expressed in the lungs, heart, and blood vessels.4
Shi et al in their study reported that 12% of patients experienced acute heart
injury related to COVID-19 marked by elevated troponin I level and 68.5% of
them died. The group of patients with elevated troponin I level in the study
reported having an older age, comorbidities, and a higher risk of death. 5 Imazio et
al in their article stated that cardiac troponin levels were significantly higher in

1
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patients with severe COVID-19 infection, who were treated in intensive care
settings, and in patients who died.6 There was no significant difference in
symptoms of COVID-19 patients with or without myocardial injury. However,
there are differences in the results of laboratory tests, namely the examination of
troponin I between those with myocardial injury and those without myocardial
injury. Myocardial injury due to COVID-19 had higher troponin elevation values
on average on day 5 of treatment. 7 This study aimed to determine the relationship
between troponin I levels and mortality in adult patients with confirmed COVID-
19.

II. METHODS
This study was a retrospective cohort study by taking data retrospectively from
patient medical records and the Laboratory Information System (LIS). The study
was conducted at the Clinical Pathology Department, Dr. Hasan Sadikin Hospital
Bandung from April to August 2021. Patient data taken for this study were data
on confirmed COVID-19 patients by nasopharyngeal and oropharyngeal swab
examination using the Polymerase Chain Reaction (PCR) in the biomolecular
laboratory, and receiving treatment in the COVID-19 isolation ward at Dr. Hasan
Sadikin Hospital Bandung from December 2020 to March 2021. Researchers
obtained a total of 90 patient medical records that met the inclusion and exclusion
criteria of this study.
Kriteria inklusi untuk subjek penelitian ini adalah (1) pasien COVID-19
dewasa usia lebih dari 19 tahun, (2) pasien COVID-19 dengan derajat sakit
sedang yaitu pasien dengan tanda klinis pneumonia (demam, batuk, sesak, napas
cepat ≥ 30 kali/menit) namun tidak ada tanda pneumonia berat termasuk SpO2 ≥
93% dengan udara ruangan, (3) pasien COVID-19 dengan derajat sakit berat yaitu
pasien dengan tanda klinis pneumonia (demam, batuk, sesak) ditambah satu dari:
frekuensi napas > 30 x/menit, distres pernapasan berat, atau SpO2 < 93% pada
udara ruangan, (4) pasien COVID-19 yang kritis yaitu dengan acute respiratory
distress syndrome (ARDS), sepsis dan syok sepsis, (5) diperiksa kadar troponin I
selama masa perawatan. Kriteria ekslusi untuk subjek penelitian ini adalah (1)
 3

pasien yang terdiagnosis sindrom koroner akut pada saat masuk ke rumah sakit
namun terkonfirmasi positif COVID-19, (2) data rekam medis yang tidak lengkap.
All patient data were collected and recorded the results of the first troponin I
examination ever performed and the day on which the troponin I examination was
performed. If the troponin I value is more than 0.02 ng/mL (>0.02 ng/mL) it is
defined as an increase in troponin I, whereas if the troponin I value is less than or
equal to 0.02 ng/mL (≤0.02 ng/mL) it is called as normal troponin I. Statistical
analysis was performed using the SPSS Version 25 software. Descriptively,
categorical variables were presented in terms of frequency and percentage. The
analysis used to determine the relationship between troponin I level and mortality
was carried out in a bivariate manner using the chi-square test and the results were
significant if the p-value <0.05. The Odds Ratio (OR) value was determined as a
large parameter of the risk of troponin I level on mortality.

III. RESULTS
The characteristics of a total of 90 study subjects based on age, sex,
comorbidities, disease severity and troponin I examination days are described in
table 4.1 below.

Table 4.1 Subject Characteristics

Variable N=90 Percentage (%)
Age (years)
20-60 years 48 53,3%
>60 years 42 46,7%

Gender
Male 57 63,3%
Female 33 36,7%

Comorbidity
Without comorbidity 26 28,9%
With comorbidity 64 71,1%
Has 1 comorbidity 32 35,6%
Has > 1 comorbidities 32 35,6%
 4

Tabel 4.1 Subject Characteristics

Variable N=90 Percentage (%)
Comorbidity
Hypertension 45 50,0%
Heart Disease 17 18,9%
Diabetes Mellitus 26 28,9%
Chronic Kidney Disease 10 11,1%
Previous History of Stroke 3 3,3%
Malignancy 4 4,4%
Autoimmune Disease 1 1,1%

Disease Severity
Moderate 31 34,4%
Severe 49 54,4%
Critical 10 11,1%

Troponin I Exam
< day 5 of care 73 81,1%
> day 5 of care 17 18,9%

The group of patients aged 20-60 years was more than the group of patients
aged > 60 years. The group of patients aged 20-60 years was 48 people (53.3%),
while the group of patients aged > 60 years were 42 people (46.7%). Based on
gender, there were more male patients than female patients. There were 57 male
patients (63.3%) compared to 33 female patients (36.7%).
There were 64 patients (71.1%) who had co-morbidities while those without
co-morbidities were 26 people (28.9%). In the group of patients with
comorbidities, 32 people (35.6%) had one comorbidity and 32 people (35.6%) had
more than one comorbidity. Hypertension was the most common comorbidity
found in this study, among as many as 45 people (50.0%). Patients with diabetes
mellitus were the second highest, as many as 26 people (28.9%). Furthermore,
patients with heart disease were 17 people (18.9%), patients with chronic kidney
disease were 10 (11.1%), patients with a previous history of stroke were 3 (3.3%),
patients with malignancy were as many as 10 people (11.1%). 4 people (4.4%)
and one patient has autoimmune disease (1.1%). Based on the severity of COVID-
19 disease, 31 people or 34.4% were categorized as moderately ill, 49 people or
54.4% were categorized as severe illness and as many as 10 people or 11.1% were
in the critical category. Based on the day of troponin I examination, as many as 73
people (81.1%) had their first troponin I test done before the 5th day of treatment
 5

and 17 people (18.9%) had their troponin I test done more than the 5th day of
treatment.
The relationship between troponin I levels and mortality was analyzed using
the Chi-square statistical test to obtain a p-value, then the Odds Ratio (OR) value
was calculated as a major parameter of troponin I risk on mortality, as described
in table 4.2 below.

Tabel 4.2 Correlation of Troponin I and Mortality

Variable Death Recovery OR CI (95%) p-value
N=25 N=65
Troponin I Level 6.40 (2.13 – 19.23) 0,0001*
Increased 20(80,0%) 25(38,5%)
Normal 5(20,0%) 40(61,5%)

The significance value is based on the p-value <0.05, which means it is statistically significant.
* significance <0.05

Table 4.2 shows that in the group of patients who died, as many as 20 people
(80.0%) had elevated troponin I levels and as many as 5 people (20.0%) had
normal troponin I levels. In the group of recovered patients, 25 people (38.5%)
had elevated troponin I levels and 40 (61.5%) had normal troponin I levels.
The results of the analysis of the relationship between troponin I levels and
mortality obtained a p-value of 0.0001 (p<0.05), which means statistically
significant so it can be stated that there is a statistically significant relationship
between troponin I levels and mortality. The Odds Ratio (OR) value was obtained
at 6.40 with a 95% Confidence Interval (CI) of 2.130-19.227, which means that
patients with elevated troponin I levels have a 6.4 times greater chance of dying
than patients with normal troponin I levels.

IV. DISCUSSIONS
In this study, the percentage of patients aged 20-60 years (53.3%) was higher
than the group of patients aged >60 years (46.7%). The percentage of male
patients (63.3%) was higher than the percentage of female patients (46.7%). In a
study conducted by Al Abbasi et al obtained data on the mean age of patients 63
years with the percentage of male patients being more than female patients. 8
 6

Hypertension, diabetes mellitus and heart disease were the three most common
comorbidities found in this study. This is in accordance with the research of Al
Abbasi et al who found hypertension, heart failure, coronary heart disease, and
diabetes mellitus as the most common comorbidity.8
This study included chronic kidney disease as a comorbid factor because
chronic kidney disease is a risk factor for severe COVID-19 symptoms. 9 History
of stroke in COVID-19 patients was included in this study as comorbidity, taking
into account other factors that might contribute to the occurrence of cardiac injury
due to systemic inflammatory response and plaque destabilization.10
Malignancy and autoimmune comorbid factors were also included in this
study. Patients with malignancy are considered as a population susceptible to
SARS-CoV-2 virus infection and are at risk of experiencing more severe COVID-
19 symptoms due to a systemic immunosuppressive state caused directly by
cancer cell growth or indirectly due to the effects of anticancer treatment. 11
Patients with autoimmunity also include groups that are susceptible to infection
with the SARS-CoV-2 virus and are associated with a higher risk of complications
of respiratory syndrome. Most autoimmune patients with COVID-19 who require
treatment are female patients who are older and have other comorbid factors such
as hypertension, chronic kidney disease, and heart disease.12
Troponin I examinations were mostly performed at the beginning of hospital
admission, in this study 73 patients (81.1%) were examined for troponin I level
less than the 5th day of treatment. This is in accordance with the study by Al
Abbasi et al, wherein his study troponin examination was carried out at the time
of initial hospital admission.8 Troponin I levels in this study were significantly
associated with mortality in accordance with previous studies which obtained data
that increased troponin I levels were associated with mortality. 5,8 In COVID-19,
myocardial injury is defined as elevated troponin levels that occur due to non-
ischemic processes such as severe respiratory tract infection with hypoxia, sepsis,
systemic inflammation, pulmonary thrombosis, embolism, adrenergic
hyperstimulation of the heart during cytokine storms. , and myocarditis.
 7

Myocardial injury is strongly associated with death in COVID-19, but whether

cardiac injury is the direct cause or only a marker of death is not clear.6,13
Other examination modalities to evaluate myocardial injury such as
electrocardiography or echocardiography was not analyzed because most of the
medical record data collected did not have other cardiac results. In the study by
Manocha et al., it was obtained data that among patients who underwent
echocardiography examination there was no significant difference in left or right
ventricular dysfunction between groups of patients who had increased troponin
and those who did not experience an increase in troponin. 13 Elderly (>60 years),
male, and the presence of comorbidities are known to be major risk factors for
mortality in COVID-19. The presence of cardiac injury, myocarditis, and acute
respiratory distress syndrome (ARDS) are other strong symptoms and are
independent factors associated with death in COVID-19. 2 Although elevated
troponin I levels are not the only cause of death in hospitalized COVID-19
patients, In this study, other causes of death were not analyzed more deeply so
that it became a weakness of the study.

V. CONCLUSION
Troponin I levels are associated with mortality in adult COVID-19 patients
who receive treatment, whereas patients with elevated troponin I level during
hospitalization have a higher risk of death than patients with normal troponin I
levels. A multivariate analysis is needed to evaluate whether the troponin I
parameter is a strong cause of death in adult COVID-19 patients.
 8

VI. REFERENCES

1. Tahmineh M, et al. COVID-19 and multiorgan failure: A narrative review

on potential mechanisms. Journal of Moleculer Histology. Springer, 2020.

2. Madjid, M, et al. Potential Effects of Coronavirus on the Cardiovascular

System A Review. JAMA Cadiology. 2020. 5(7):831-840.

3. Clerkin KJ, et al. In depth: COVID-19 and Cardiovascular Disease.

American Heart Association Journal. Circulation 2020. 141: 1648-1655.

4. Zou X., et al. Single-cell RNA-seq data analysis on the receptor ACE2
expression reveals the potential risk of different human organs vulnerable to
2019-nCoV infection. Front. Med. 2020:1–8.

5. Shi S, et al. Association of cardiac injury with mortality in hospitalized

patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020. 5(7):802-
810.

6. Imazio M, et al. Covid-19 pandemic and troponin: indirect myocardial

injury, myocardial inflammation or myocarditis? Heart. 2020. 106: 1127-
1131

7. Pedoman Tatalaksana COVID-19. Edisi 3. Desember 2020. Hal 76-78.

8. Abbasi B, et al. Cardiac Troponin I and Covid-19: A prognostic Tool for In-
Hospital Mortality. Cardiol Res. 2020. 11(6). 398-404.

9. Rao A, et al. Associated of Kidney Disease With Outcomes in Covid-19:

Result from The American Heart Association Covid-19 Cardiovascular
Disease Registry. Journal of The American Heart Association. 2021.
10:e020910.

10. Bhatia R, Srivastava MPV. Covid-19 and Stroke: Incidental, Triggered, or

Causative. Annals of Indian Academy of Neurology. 2020. 23(3): 318-324.

11. Liu C, et al. Covid-19 in cancer patients: risk, clinical features, and
management. Cancer Biol Med. 2020. 17(3): 519-527.

12. Liu Y, et al. Covid-19 and autoimmune diseases. Current Opinions in

Rheumatology. 2021. 33(2):155-162.

13. Manocha KK, et al. Troponin and Other Biomarker Levels and Outcomes
Among Patients Hospitalized with Covid-19: Derivation and Validation of
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The HA2T2 Covid-19 Mortality Risk Score. Journal of American Heart

Association. 2021. 10:e018477.