Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: A systematic review and meta-analysis of observational studies

Objectives We conducted a systematic literature review and meta-analysis of observational studies to investigate the association between diabetes, hypertension, body mass index (BMI) or smoking with the risk of death in patients with COVID-19 and to estimate the proportion of deaths attributable to these conditions. Methods Relevant observational studies were identified by searches in the PubMed, Cochrane library and Embase databases through 14 November 2020. Random-effects models were used to estimate summary relative risks (SRRs) and 95% CIs. Certainty of evidence was assessed using the Cochrane methods and the Grading of Recommendations, Assessment, Development and Evaluations framework. Results A total of 186 studies representing 210 447 deaths among 1 304 587 patients with COVID-19 were included in this analysis. The SRR for death in patients with COVID-19 was 1.54 (95% CI 1.44 to 1.64, I 2 =92%, n=145, low certainty) for diabetes and 1.42 (95% CI 1.30 to 1.54, I 2 =90%, n=127, low certainty) for hypertension compared with patients without each of these comorbidities. Regarding obesity, the SSR was 1.45 (95% CI 1.31 to 1.61, I 2 =91%, n=54, high certainty) for patients with BMI ≥30 kg/m 2 compared with those with BMI <30 kg/m 2 and 1.12 (95% CI 1.07 to 1.17, I 2 =68%, n=25) per 5 kg/m 2 increase in BMI. There was evidence of a J-shaped non-linear dose-response relationship between BMI and mortality from COVID-19, with the nadir of the curve at a BMI of around 22-24, and a 1.5-2-fold increase in COVID-19 mortality with extreme obesity (BMI of 40-45). The SRR was 1.28 (95% CI 1.17 to 1.40, I 2 =74%, n=28, low certainty) for ever, 1.29 (95% CI 1.03 to 1.62, I 2 =84%, n=19) for current and 1.25 (95% CI 1.11 to 1.42, I 2 =75%, n=14) for former smokers compared with never smokers. The absolute risk of COVID-19 death was increased by 14%, 11%, 12% and 7% for diabetes, hypertension, obesity and smoking, respectively. The proportion of deaths attributable to diabetes, hypertension, obesity and smoking was 8%, 7%, 11% and 2%, respectively. Conclusion Our findings suggest that diabetes, hypertension, obesity and smoking were associated with higher COVID-19 mortality, contributing to nearly 30% of COVID-19 deaths. Trial registration number CRD42020218115.