Cardiac Biomarkers and COVID-19

This article on biomarkers and COVID-19 was co-written by Oluwabunmi Ogungbe, MPH, RN and Yvonne Commodore-Mensah, PhD, MHS, RN.

What Nurses Should Know About Cardiac and Inflammatory Biomarkers and COVID-19

Increases in cardiac-specific biomarkers, electrocardiographic changes, or new imaging features of impaired cardiac function indicate acute myocardial damage during a viral illness,1 such as COVID-19. A biomarker is “a characteristic that is objectively measured and quantified as an indicator of normal biological processes, pathogenic processes or pharmacological response to a therapeutic intervention”.2 Cardiac biomarkers are proteins, which when measured may indicate some pathological process in the cardiovascular system. Therefore, they help classify and predict the progression of cardiovascular diseases, including in the context of COVID-19.

The extent of cardiovascular involvement in COVID-19 is determined by the infectious dose, magnitude of host immune response, and the presence of underlying comorbidities such as hypertension, diabetes, obesity, chronic lung disease, and cardiovascular disease, etc.3 Direct and indirect cardiac injury may occur in the context of COVID-19 through inflammation, endothelial activation, and microvascular thrombosis.3 Thus, there is a strong association between cardiac and inflammatory biomarkers and worse COVID-19 outcomes; these include elevation of the following biomarkers, which predict poor clinical outcomes:

  • cardiac troponins (cTn)
  • N-terminal pro-b-type natriuretic peptide (NT-proBNP)
  • D-dimer
  • C-Reactive Protein (CRP)
  • Creatinine Kinase MB isoenzyme (CK-MB)
  • Myoglobin, Galectin-3 (Gal-3)
  • Tumor Necrosis Factor – a (TNF-a)
  • Interleukin 6 (IL-6)4
Cardiac and Inflammatory Biomarkers associated with COVID-19

Cardiac Troponins

Troponins are proteins found in cardiac and skeletal muscle fibers that regulate muscular contraction, including troponin C, troponin T, and troponin I. Troponins are usually present in very small to undetectable quantities in the blood; detectable levels of troponins indicate myocardial damage.2 Thus, cardiac troponins are established biomarkers of cardiomyocyte damage and myocyte death. Troponin release has been reported in patients hospitalized with COVID-19.5 Among 416 patients with COVID-19 in China, elevated high-sensitivity cardiac troponin I (hs-cTnI) concentrations were reported in 1 of 5 patients, and the observed rate of mortality was 10-fold higher in patients with myocardial injury compared to those without myocardial injury.6  A recent meta-analysis reported abnormal hs-cTnI values (>99th percentile) in 8% to 51% of hospitalized patients with COVID-19, which were associated with more severe complications.7 

Brain Natriuretic Peptide (BNP)

N-terminal pro-b-type natriuretic peptide (NT-proBNP) is a precursor protein that is released due to myocardial wall stress from volume overload and is a well-established biomarker for diagnosis of heart failure (HF) and acute coronary syndrome (ACS). In the context of COVID-19, a recent meta-analysis of over 10,000 patients reported elevated levels of NT-proBNP in 46.5% of patients.8 Higher NT-proBNP levels (using best cut-off value of 88.64 pg/mL) was significantly associated with a higher risk of death, bleeding, arrhythmias, and HF decompensations among hospitalized with COVID-19 in location.9

C-Reactive Protein

C-Reactive Protein (CRP) is a biomarker indicative of systemic inflammation.6 CRP is a non-specific acute-phase protein produced by liver cells and elevated in acute infection or inflammation. CRP has been found elevated in 36% of patients with COVID-19.10 Although CRP is generally considered a non-specific inflammatory biomarker, the predictive value of CRP and Interleukin 6 (IL-6) has been reported in COVID-19 due to their efficiency in predicting respiratory deterioration COVID-19 prognosis. High concentrations of CRP are associated with COVID-19 severity and in-hospital deaths.6

Interleukin 6 (IL-6) and Tumor Necrosis Factor – a (TNF-a)

Interleukin 6 is a pro-inflammatory cytokine produced in response to infections and tissue injury.11 IL-6 activation stimulates the production of acute-phase inflammatory reactants like C-Reactive Protein. IL-6 elevation was reported in two-thirds of patients hospitalized with COVID-19.8 Compared to those who survive, elevated IL-6 is almost 3-fold higher in non-survivors and remains elevated through the clinical course of the disease as the illness worsens.8 IL-6 elevation seen in cardiac involvement of COVID-19 may explain the postulated cardiac microvascular abnormalities suspected in COVID-19. In severe COIVD-19 cases, ‘cytokine storm’ results from overactivation of the immune system, leading to the release of high levels of cytokines, particularly IL-6 and TNF- , causing local and systemic inflammatory response.11 Among COVID-19 patients, the frequency of elevated TNF-  has been reported to be 58.3%.8 As such, it has been suggested that anti-TNF therapy may be a potential treatment for COVID-19.12

Creatinine Kinase MB isoenzyme (CK-MB) and Myoglobin

Creatinine Kinase is a marker of myocardial damage and a sensitive biomarker of myocardial injury.  CK-MB usually peaks within 12-36 hours of the myocardial damage, and the severity of myocardial injury results in higher measurable levels of the CK-MB.13 A recent meta-analysis reported that elevated CK was associated with a three-fold increased risk of poor COVID-19 outcomes such as severe COVID-19 and death.13 Myoglobin, a heme protein found in cardiac (and skeletal) muscle cells, is an early marker of myocardial damage. Myoglobin was reported significantly higher in persons who died from COVID-19 and a significant predictor of mortality in COVID-19. The predictive value of myoglobin was reported superior to troponin.14 Independent of troponin and CK-MB, elevated myoglobin levels have been reported as a risk factor for in-hospital death.14


D-Dimer is indicative of coagulopathy, and one of the biomarkers used to detect thrombosis has been reported to be elevated in 41.5% of COVID-19 patients.8 D-dimer is a degradation product of fibrin (a protein involved in the formation of blood clots), which is a normal part of fibrinolysis. However, abnormally high d-dimer levels could indicate possible coagulopathies such as venous thromboembolism and deep vein thrombosis.  A 3-4 fold increase in D-dimer levels on admission is associated with poor prognosis, including cytokine storm, multi-organ failure, and mortality.8

Galectin-3 (Gal-3)

Gal-3 is a biomarker of inflammation and fibrosis and high prognostic value in HF progression, including in the prediction of increased morbidity and death. Gal-3 amplifies the cytokine storm syndrome associated with severe COVID-19, and patients with severe forms of COVID-19 are more likely to have elevated Gal-3 than those with mild disease.15 Gal-3 have been associated with higher complications and mortality among patients with COVID-19.15


  1. Hendren Nicholas S, Drazner Mark H, Biykem B, Cooper Leslie T. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation. 2020;141(23):1903-1914. doi:10.1161/CIRCULATIONAHA.120.047349; 2710.1161/CIRCULATIONAHA.120.047349
  2. Jacob R, Khan M. Cardiac Biomarkers: What Is and What Can Be. Indian J Cardiovasc Dis Women WINCARS. Dec 2018;3(4):240-244. doi:10.1055/s-0039-1679104
  3. Giustino G, Pinney SP, Lala A, et al. Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia: JACC Focus Seminar. Journal of the American College of Cardiology. 2020;76(17):2011-2023. doi:10.1016/j.jacc.2020.08.059
  4. Khan S, Rasool ST, Ahmed SI. Role of Cardiac Biomarkers in COVID-19: What Recent Investigations Tell Us? Curr Probl Cardiol. 2021:100842-100842. doi:10.1016/j.cpcardiol.2021.100842
  5. Kotecha T, Knight DS, Razvi Y, et al. Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance. Eur Heart J. Feb 18 2021;doi:10.1093/eurheartj/ehab075
  6. Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiology. 2020;5(7):802-810. doi:10.1001/jamacardio.2020.0950
  7. Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Progress in cardiovascular diseases. 2020;63(3):390-391. doi:10.1016/j.pcad.2020.03.001
  8. Momtazmanesh S, Shobeiri P, Hanaei S, Mahmoud-Elsayed H, Dalvi B, Malakan Rad E. Cardiovascular disease in COVID-19: a systematic review and meta-analysis of 10,898 patients and proposal of a triage risk stratification tool. The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology. 2020;72(1):41. doi:10.1186/s43044-020-00075-z
  9. Gao L, Jiang D, Wen X-S, et al. Prognostic value of NT-proBNP in patients with severe COVID-19. Respiratory research. 2020;21(1):83. doi:10.1186/s12931-020-01352-w
  10. Shi F, Wu T, Zhu X, et al. Association of viral load with serum biomarkers among COVID-19 cases. Virology. 2020;546:122-126. doi:10.1016/j.virol.2020.04.011
  11. Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). 2021 Jul 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 32150360.
  12. Robinson PC, Richards D, Tanner HL, Feldmann M. Accumulating evidence suggests anti-TNF therapy needs to be given trial priority in COVID-19 treatment. Lancet Rheumatol. 2020;2(11):e653-e655. doi:10.1016/S2665-9913(20)30309-X
  13. Akbar MR, Pranata R, Wibowo A, Lim MA, Sihite TA, Martha JW. The prognostic value of elevated creatine kinase to predict poor outcome in patients with COVID-19 – A systematic review and meta-analysis. Diabetes Metab Syndr. Mar-Apr 2021;15(2):529-534. doi:10.1016/j.dsx.2021.02.012
  14. Zhu F, Li W, Lin Q, Xu M, Du J, Li H. Myoglobin and troponin as prognostic factors in patients with COVID-19 pneumonia. Med Clin (Barc). Feb 27 2021;doi:10.1016/j.medcli.2021.01.013
  15. Caniglia JL, Asuthkar S, Tsung AJ, Guda MR, Velpula KK. Immunopathology of galectin-3: an increasingly promising target in COVID-19 [version 2; peer review: 2 approved]. F1000Research. 2020;9(1078)doi:10.12688/f1000research.25979.2

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