Cardiac biomarker analyses of population-based postCOVID cohorts in Germany – subtle troponin changes

J. Thiele (Kiel)¹, A. Hamza (Rendsburg)², N. E. El Mokhtari (Rendsburg)³, J. Frank (Kiel)⁴, J. Heyckendorf (Kiel)⁵, S. Störk (Würzburg)⁶, C. Morbach (Würzburg)⁷, P. U. Heuschmann (Würzburg)⁸, A. Dempfle (Kiel)⁹, S. Schreiber (Kiel)¹⁰, D. Frank (Kiel)^4
1University Hospital Schleswig-Holstein Department of Internal Medicine III Kiel, Deutschland; ²Schön Klinik Innere Medizin, Kardiologie Rendsburg, Deutschland; ³Schön Klinik Rendsburg Klinik für Innere Medizin I -Kardiologie, Pneumologie, Nephrologie Rendsburg, Deutschland; ⁴Universitätsklinikum Schleswig-Holstein Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin Kiel, Deutschland; ⁵University Medical Center Schleswig-Holstein Department of Internal Medicine I, Kiel, Deutschland; ⁶Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz/DZHI Würzburg, Deutschland; ⁷Universitätsklinikum Würzburg Medizinische Klinik I, Kardiologie Würzburg, Deutschland; ⁸Universitätsklinikum Würzburg Institut für klinische Epidemiologie und Biometrie Würzburg, Deutschland; ⁹Universitätsklinikum Schleswig-Holstein, Campus Kiel /Christian–Albrechts–Universität zu Kiel Institut für Medizinische Informatik und Statistik Kiel, Deutschland; ¹⁰University Medical Center Schleswig-Holstein Department of Internal Medicine I Kiel, Deutschland

Background:
Elevated cardiac biomarkers, troponin and natriuretic peptides, are well documented during acute COVID-19 patients, where they are associated with disease severity and acute outcome. However, less is known about whether low-grade myocardial involvement persists once the acute disease has clinically resolved, particularly after mild infection in the general population. These analyses are often difficulat to interpret, as studies with appropriate non-infected controls recruited before the pandemic are largely missing. We compared the distribution of cardiac biomarkers between a population-based post-COVID cohort and a pre-pandemic population sample (the STAAB cohort). 

Methods:
We prospectively enrolled participants approximately 6-9 months after a PCR-confirmed SARS-CoV-2 infection at Kiel, Berlin and Würzburg university hospitals (COVIDOM cohort). The population-based STAAB cohort (Würzburg) which was recruited before 2019 served as controls. Standard laboratory biomarker analysis was performed, including high-sensitivity troponin T (hsTnT) and NT-proBNP. Proportions of participants with high normal or slightly elevated hsTnT (dichotomized at 10 ng/l and at 14 ng/l, or NT-proBNP values (dichotomised at 125 ng/l or at age- and sex-specific upper reference values) were compared between the COVIDOM and STAAB cohorts by logistic regression. All analyses were adjusted for age, sex, BMI, height, eGFR, hypertension, type 2 diabetes, previous heart failure, coronary heart disease and centre. 

Results:
We analysed 1829 COVIDOM participants (age range 27 to 83, mean age 49.14 (SD 14.02), 1002 (54.78%) female) and 4965 STAAB participants (age range 29 to 81, mean age 54.88 (SD 11.81), 2604 (52.45%). About 6.2% of participants in both cohorts had an NT-proBNP value above age- and sex-specific upper reference values (p=0.98 in adjusted logistic regression).  The proportion of participants with high normal or slightly elevated values of hsTnT was higher in the COVIDOM cohort than in the STAAB cohort (>10 ng/l: 9.4% vs. 7.4% and 10 ng/l and >14 ng/l: 4.2% vs. 3.1%), translating to OR=1.73 and OR=1.91 (p= 0.0002 and p= 0.002 in adjusted logistic regression).

Conclusion:
Months after mostly mild SARS-CoV-2 infection, NT-proBNP values were indistinguishable from pre-pandemic controls, whereas high-normal and mildly elevated hsTnT values were moderately more frequent in the post-COVID cohort. This pattern suggests a potential subtle, low-grade myocardial involvement without overt cardiac dysfunction. Although absolute differences are small and their long-term relevance remain unclear, longitudinal follow-up is warranted to determine whether they translate into measurable clinical risk.

Keywords: high-sensitivity troponin T; hsTnT; NT-proBNP; cardiac biomarkers; heart failure, COVID-19.