Role of antibodies, inflammatory markers, and echocardiographic findings in postacute cardiopulmonary symptoms after SARS-CoV-2 infection

Abstract

Shortness of breath, chest pain, and palpitations occur as postacute sequelae of COVID-19, but whether symptoms are associated with echocardiographic abnormalities, cardiac biomarkers, or markers of systemic inflammation remains unknown. In a cross-sectional analysis, we assessed symptoms, performed echocardiograms, and measured biomarkers among adults more than 8 weeks after confirmed SARS-CoV-2 infection. We modeled associations between symptoms and baseline characteristics, echocardiographic findings, and biomarkers using logistic regression. We enrolled 102 participants at a median of 7.2 months following COVID-19 onset; 47 individuals reported dyspnea, chest pain, or palpitations. Median age was 52 years, and 41% of participants were women. Female sex, hospitalization, IgG antibody against SARS-CoV-2 receptor binding domain, and C-reactive protein were associated with symptoms. Regarding echocardiographic findings, 4 of 47 participants (9%) with symptoms had pericardial effusions compared with 0 of 55 participants without symptoms; those with effusions had a median of 4 symptoms compared with a median of 1 symptom in those without effusions. There was no strong evidence for a relationship between symptoms and echocardiographic functional parameters or other biomarkers. Among adults more than 8 weeks after SARS-CoV-2 infection, SARS-CoV-2 RBD antibodies, markers of inflammation, and, possibly, pericardial effusions are associated with cardiopulmonary symptoms. Investigation into inflammation as a mechanism underlying postacute sequelae of COVID-19 is warranted.

Keywords: COVID-19; Cardiology; Cardiovascular disease; Cellular immune response.

Figure 1. Cardiopulmonary symptoms represented in study sample.

Bar plot of the number of participants who reported potentially cardiopulmonary symptoms in the 2 weeks prior to echocardiogram at a median of 7.2 months (IQR, 4.1–9.1 months) after COVID-19 onset (n = 102). The primary composite outcome is the presence of dyspnea, chest pain, or palpitations. These are not prevalence estimates within the population of those recovering from COVID-19, but are presented to provide context for the associations between echocardiographic findings, biomarkers, and symptoms reported here.

Figure 2. Left ventricular ejection fraction, left ventricular mass index, and diastolic function by cardiopulmonary symptoms.

(A) Box plot of left ventricular (LV) ejection fraction (LVEF) by symptoms, (B) box plot of LV mass index by symptoms, and (C) diastolic function by symptoms (n = 101, 99, and 101, respectively). Odds of symptoms were 1.16 times higher per 5% decrease in LVEF, which was not statistically significant (95% CI, 0.83–1.62; P = 0.40). The odds of symptoms were not significantly higher with increased LV mass (1.01 per 5 g/m²; 95% CI, 0.89–1.16; P = 0.81). With regards to diastolic function, 7% of those without symptoms and 11% with symptoms had mild diastolic dysfunction; the odds of symptoms were 1.77 times higher among those with diastolic dysfunction compared with those with normal diastolic function, which was not statistically significant but could not exclude a meaningful effect (95% CI, 0.35–8.88; P = 0.78), especially because there were no participants with more than mild diastolic dysfunction. In A and B, boxes represent the 25th and 75th percentile, the lines inside the boxes represent medians, whiskers represent the upper and lower adjacent values (3/2 times the IQR from the end of the box) as defined by Tukey, and dots represent outliers outside the whiskers.

Figure 3. Biomarkers by presence of cardiopulmonary symptoms.

Box-and-whisker plots of biomarkers plotted on log scale by presence of cardiopulmonary symptoms (no symptoms in blue on the left for each plot, symptoms in pink on the right), including hs-troponin I (n = 95), NT-pro-BNP (n = 87), hsCRP (n = 95), IL-6 (n = 73), IL-10 (n = 73), IFN-γ (n = 69), TNF-α (n = 73), and SARS-CoV-2 receptor binding domain IgG antibodies (n = 73), with P values listed for unadjusted t tests of log-transformed markers. The adjusted odds of having dyspnea, chest pain, or palpitations were 1.32 times higher per doubling of hsCRP (95% CI, 1.01–1.73; P = 0.02) and 1.42 times higher per doubling of antibody levels (95% CI, 1.06–1.90; P = 0.02). Other biomarkers were not strongly associated with symptoms. Boxes represent the 25th and 75th percentile, lines inside the boxes represent medians, whiskers represent the upper and lower adjacent values (3/2 times the IQR from the end of the box) as defined by Tukey, and dots represent outliers outside the whiskers.

Figure 4. Relationship between antibodies and hsCRP.

Natural log-transformed antibody levels and hsCRP are correlated (adjusted β = 0.27; 95% CI, 0.08–0.45; P = 0.005). Both antibody levels and hsCRP are higher in those with symptoms (red triangles) than those without symptoms (blue circles). The association between antibody levels and hsCRP did not vary by symptom status (P for interaction = 0.51 and minimal change in β coefficient). Those with pericardial effusions (green squares) had higher antibody levels and higher hsCRP.