Mahamat-Saleh · BMJ open 2021 · systematic review and meta-analysis of observational studies · n=186 studies (1,304,587 patients)

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

Cited 199 times in the scientific literature.

Level 3 - non-randomized controlled study

Systematic review and meta-analysis of observational studies

PubMed 34697120 · doi:10.1136/bmjopen-2021-052777 · record verified 2026-08-29

What was done

Authors conducted a systematic review and meta-analysis of observational studies indexed in PubMed, Cochrane Library, and Embase through November 14, 2020. They evaluated associations between diabetes, hypertension, body mass index (BMI), or smoking status and mortality in COVID-19 patients. Summary relative risks (SRRs) and 95% confidence intervals were estimated using random-effects models, and evidence certainty was evaluated using the GRADE framework.

What was found

Across 186 studies comprising 1,304,587 patients and 210,447 deaths: - Diabetes was associated with higher mortality: SRR 1.54 (95% CI 1.44 to 1.64; I² = 92%; n = 145; low certainty). - Hypertension was associated with higher mortality: SRR 1.42 (95% CI 1.30 to 1.54; I² = 90%; n = 127; low certainty). - Obesity (BMI ≥30 vs <30 kg/m²) increased mortality risk: SRR 1.45 (95% CI 1.31 to 1.61; I² = 91%; n = 54; high certainty), with an SRR of 1.12 (95% CI 1.07 to 1.17; I² = 68%; n = 25) per 5 kg/m² increase. Dose-response modeling showed a J-shaped curve with a nadir at BMI 22–24 and a 1.5–2-fold increase at BMI 40–45. - Smoking status showed increased risk compared to never-smokers: ever smokers SRR 1.28 (95% CI 1.17 to 1.40; I² = 74%; n = 28; low certainty), current smokers SRR 1.29 (95% CI 1.03 to 1.62; I² = 84%; n = 19), and former smokers SRR 1.25 (95% CI 1.11 to 1.42; I² = 75%; n = 14). - Absolute risk of COVID-19 death increased by 14% (diabetes), 11% (hypertension), 12% (obesity), and 7% (smoking), with population attributable fractions estimated at 8%, 7%, 11%, and 2%, respectively.

Why it matters

This large meta-analysis synthesizes early-pandemic global data, indicating that diabetes, hypertension, obesity, and smoking collectively accounted for nearly 30% of COVID-19 deaths.

Limits

All included studies were observational, leaving risk of residual confounding. Statistical heterogeneity across primary analyses was high (I² values between 68% and 92%), resulting in low GRADE certainty ratings for diabetes, hypertension, and smoking. The search concluded in November 2020, reflecting outcomes prior to widespread vaccination and the emergence of later SARS-CoV-2 variants.

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