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

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.

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.

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.

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.