Long-term cardiac symptoms following COVID-19: a systematic review and meta-analysis (preprint)

ABSTRACT

Background There is growing body of literature on the long-term cardiac symptoms following COVID-19. We conducted a systematic review and meta analysis to synthesize and evaluate related evidence to inform clinical management and future studies. Methods We searched two preprint and seven peer reviewed article databases from January 1, 2020 to January 8, 2022 for studies investigating cardiac symptoms that persisted for at least 4 weeks among individuals who survived COVID-19. A customized Newcastle Ottawa scale was used to evaluate the quality of included studies. Random effects meta analyses were performed to estimate the proportion of symptoms with 95% confidence intervals (CI), and stratified analyses were conducted to quantify the proportion of symptoms by study characteristics and quality. Results A total of 101 studies describing 49 unique long-term cardiac symptoms met the inclusion criteria. Based on quality assessment, only 15.8% of the studies (n=16) were of high quality, and most studies scored poorly on sampling representativeness. The two most examined symptoms were chest pain and arrhythmia. Meta-analysis showed that the proportion of chest pain was 10.1% (95% CI 6.4, 15.5) and arrhythmia was 9.8% (95% CI 5.4, 17.2). Stratified analyses showed that studies with low-quality score, small sample size, unsystematic sampling method, and cross-sectional design were most likely to report high proportions of symptoms. For example, the proportion of chest pain was 21.3% (95% CI 10.5, 38.5), 9.3% (95% CI 6.0, 14.0), and 4.0% (95% CI 1.3, 12.0) in studies with low, medium, and high-quality scores, respectively. Similar patterns were observed for other cardiac symptoms including hypertension, cardiac abnormalities, myocardial injury, thromboembolism, stroke, heart failure, coronary disease, and myocarditis. Discussion There is a wide spectrum of long-term cardiac symptoms following COVID-19. Findings of existing studies are strongly related to study quality, size and design, underscoring the need for high-quality epidemiologic studies to characterize these symptoms and understand their etiology.