Coronavirus disease 2019 (COVID-19): Global epidemiology related to cross-country differences in case fatality ratio. A systematic review and meta-analysis

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This systematic review and meta-analysis evaluated determinants of the COVID-19 case fatality ratio (CFR) across countries. A structured search was performed in PubMed, Medline, Google Scholar, MedRxiv, and SSRN for English-language studies published in 2020, using the terms “case fatality ratio OR CFR” AND “COVID-19 OR SARS-CoV-2.” Searches were conducted on April 25, 2021, and updated between May 20 and July 5, 2021. Studies were eligible if they reported population-level CFR estimates with country-specific epidemiological correlations; non-research formats were excluded. Of 269 records screened, 20 full-text articles were reviewed, and 15 met the inclusion criteria. Seven studies contributed to the quantitative meta-analysis. The pooled CFR was 4.47% (95% CI: 1.83–7.11) with no significant heterogeneity. Higher CFRs were consistently associated with larger proportions of adults aged ≥65 years (12 studies), diabetes prevalence (8 studies), female smoking rates (6 studies), population density (7 studies), and higher GDP per capita (5 studies). Climatic influences such as temperature and humidity were reported in 4 studies. In contrast, lower CFRs were observed with broader BCG vaccination coverage (6 studies), greater healthcare capacity, including ICU beds and workforce (8 studies), widespread PCR testing (5 studies), and stringent government interventions such as lockdowns (7 studies). Among these, advanced age and healthcare system capacity emerged as the most consistent predictors across studies. The findings highlight that reducing COVID-19 mortality requires prioritizing expansion of healthcare capacity, ensuring access to diagnostic testing, and implementing protective measures for older populations, while accounting for socio-economic and environmental contexts that shape country-level variations in outcomes.