Abstract
Background:Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex.Methods:We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses.Results:Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60–65 versus <50 years. Three studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR = 1.73, [95% CI 1.50–2.01]), hypertension (8 studies; 2.87 [2.09–3.93]), diabetes (9 studies; 3.20 [2.26–4.53]), and CVD (10 studies; 4.97 [3.76–6.58]). RR for male sex was likely to be independent of age. For the other three factors, meta-regression analyses suggested confounding by age. Only four studies reported multivariable analysis, but most of them showed adjusted RR ~2 for hypertension, diabetes, and CVD. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19.Conclusions:Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be informative for predicting the risk of severe COVID-19.
Highlights
Cases of coronavirus disease 2019 (COVID-19) are rapidly increasing globally
The meta-regression analysis did not indicate that a higher proportion of male sex confounded the association of these clinical factors with severe COVID-19 (Web Figure 6). This is the first systematic review and meta-analysis focusing on the relationship of severe COVID-19 with cardiovascular disease (CVD) and its risk factors
We confirmed a robust association of age and male sex with severe COVID-19
Summary
Cases of coronavirus disease 2019 (COVID-19) are rapidly increasing globally. As of April 25, 2020, more than 2.8 million cases have been confirmed and ~200,000 deaths have been reported in ~190 countries [1]. Risk factors for the severity and prognosis of COVID-19 are poorly understood Such information is critical to identify high risk patients and to facilitate planning (e.g., forecasting the need for hospital beds and mechanical ventilators). Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. Factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR = 1.73, [95% CI 1.50–2.01]), hypertension (8 studies; 2.87 [2.09–3.93]), diabetes (9 studies; 3.20 [2.26–4.53]), and CVD (10 studies; 4.97 [3.76–6.58]). Conclusions: Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be informative for predicting the risk of severe COVID-19
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