Country differences in transmissibility, age distribution and case-fatality of SARS-CoV-2: a global ecological analysis

Objectives The first COVID-19 pandemic waves in many low-income countries appeared milder than initially forecasted. We conducted a country-level ecological study to describe patterns in key SARS-CoV-2 outcomes by country and region and explore associations with potential explanatory factors, including population age structure and prior exposure to endemic parasitic infections. Methods We collected publicly available data and compared them using standardisation techniques. We then explored the association between exposures and outcomes using random forest and linear regression. We adjusted for potential confounders and plausible effect modifications. Results While mean time-varying reproduction number was highest in the European and Americas regions, median age of death was lower in the Africa region, with a broadly similar case-fatality ratio. Population age was strongly associated with mean (β=0.01, 95% CI, 0.005, 0.011) and median age of cases (β=-0.40, 95% CI, -0.53, -0.26) and deaths (β= 0.40, 95% CI, 0.17, 0.62). Conclusions Population age seems an important country-level factor explaining both transmissibility and age distribution of observed cases and deaths. Endemic infections seem unlikely, from this analysis, to be key drivers of the variation in observed epidemic trends. Our study was limited by the availability of outcome data and its causally uncertain ecological design.