The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis

Kunihiro Matsushita; Ning Ding; Minghao Kou; Xiao Hu; Mengkun Chen; Yumin Gao; Yasuyuki Honda; David Dowdy; Yejin Mok; Junichi Ishigami; Lawrence J Appel

Our study has some limitations. First, reflecting the fact that the outbreak started from China, most studies were from China. However, given similar case-fatality rates and clinical manifestations across different countries, it seems likely that these results are largely generalizable. Nonetheless, we need to acknowledge regional variations of some risk factors (e.g., ~25-fold difference in the prevalence of smoking in men vs. women in China 36 ) and thus future investigations in different regions would be valuable. Second, we did not include non-English publications. Third, most studies reported odds ratios, which are known to overestimate risk ratio when the prevalence of exposures is relatively high. Fourth, we cannot deny the possibility that some patients were included in multiple studies especially in the China CDC report 14 and other Chinese studies. Nonetheless, the pooled estimates were largely similar in analyses that excluded the China CDC data (data not shown). Finally, the literature of COVID-19 is growing rapidly, and thus there is a lag time from our literature search and publication. On the other hand, our systematic review has several strengths: in-depth review of CVD and its risk factors, a clinically relevant definitions of severe COVID-19 that minimize subjective reporting, meta-regression to explore potential confounding, and relatively short elapsed time of ~2 weeks between the literature search and manuscript submission.