Abnormalities in cardiac and inflammatory biomarkers in ambulatory subjects after COVID-19 infection

Abstract

Background: Coronavirus-2019 (COVID-19) is known to affect the heart and is associated with a pro-inflammatory state. Most studies to date have focused on clinically sick subjects. Here, we report cardiac and proinflammatory biomarkers levels in ambulatory young adults with asymptomatic or mild COVID-19 infection compared to those without infection 4-8 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) testing.

Methods: 131 asymptomatic or mildly symptomatic subjects were enrolled following testing for SARS-COV-2. Fifty subjects tested negative, and 81 subjects tested positive. Serum samples were collected for measurement of C-reactive protein, ferritin, interleukin-6, NT-pro-B-type natriuretic peptide, and cardiac troponin 28-55 days after SARS-COV-2 RT-PCR testing.

Results: Biomarker levels trended higher in SARS-COV-2-positive vs negative subjects, but differences in biomarker levels or proportion of subjects with elevated biomarkers were not statistically significant with respect to SARS-COV-2 status. Among individuals with ≥ 1 comorbidity, odds of elevated CRP were greater compared to individuals without any comorbidities (odds ratio [OR] = 2.90); this effect size was increased 1.4-fold among SARS-COV-2-positive subjects (OR = 4.03). Similarly, NT-pro-BNP was associated with CVD, with the strongest association in COVID-positive individuals (OR = 16.9).

Conclusions: In a relatively young, healthy adult population, mild COVID-19 infection was associated with mild elevations in cardiac and proinflammatory biomarkers within 4-8 weeks of mild or asymptomatic COVID-19 infection in individuals with preexisting comorbidities, but not among individuals without comorbidities. For the general population of young adults, we did not find evidence of elevation of cardiac or proinflammatory biomarkers 4-8 weeks after COVID-19 infection.Clinical Perspective: This is a characterization of cardiac and proinflammatory biomarkers in ambulatory subjects following asymptomatic or mild COVID-19 infection. Young, ambulatory individuals did not have cardiac and proinflammatory biomarker elevation 4-8 weeks after mild COVID-19 infection. However, COVID-19 infection was associated with biomarker elevations in select individuals with comorbidities.Clinical study number: H-47423.

Keywords: BNP, B-type natriuretic peptide; Biomarkers; COVID-19; COVID-19, corona virus 2019; CRP, C-reactive protein; CVD, cardiovascular disease; Co-morbidities; Heart failure; IL-6, interleukin 6; OR, odds ratio; RT-PCR, real-time reverse-transcription polymerase chain reaction; SARS-COV-2; SARS-COV2, severe acute respiratory syndrome coronavirus 2.

Fig. 1

Biomarker levels by COVID-19 status. Serum levels of CRP (A), ferritin (B), IL-6 (C), NT-pro-BNP (D), and cardiac troponin (E) in COVID-negative (blue) and COVID-positive (red) individuals. Error bars denote mean +/- SEM. Blue line denotes upper limit of normal (see methods). BNP, B-type natriuretic peptide; CRP, C-reactive protein; IL-6, interleukin 6; SEM, standard error of the mean. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Odds ratios of elevated biomarkers among individuals with comorbidities. Odds of elevated CRP, ferritin, IL-6, NT-pro-BNP, and troponin among individuals with >=1 comorbidity. ORs are derived from logistic regression adjusted for age and plotted along with 95 % confidence intervals. BNP, B-type natriuretic peptide; CRP, C-reactive protein; OR, odds ratio.

Fig. 3

Odds ratios of CVD and metabolic disease in individuals with elevated CRP or NT-pro-BNP levels. Odds of metabolic disease in individuals with elevated CRP (A) and CVD in individuals with elevated NT-pro-BNP (B) Both analyses were conducted in the overall sample and strata defined by COVID-19 status. ORs are derived from logistic regression adjusted for age and plotted along with 95% confidence intervals. BNP, B-type natriuretic peptide; CVD, cardiovascular disease; CRP, C-reactive protein; OR, odds ratio.