The largest burden of COVID-19 is carried by the elderly, and persons living in nursing homes are particularly vulnerable. However, 94% of the global population is younger than 70 years and 86% is younger than 60 years. The objective of this study was to accurately estimate the infection fatality rate (IFR) of COVID-19 among non-elderly people in the absence of vaccination or prior infection. In systematic searches in SeroTracker and PubMed (protocol: https://osf.io/xvupr), we identified 40 eligible national seroprevalence studies covering 38 countries with pre-vaccination seroprevalence data. For 29 countries (24 high-income, 5 others), publicly available age-stratified COVID-19 death data and age-stratified seroprevalence information were available and were included in the primary analysis.
The IFRs had a median of 0.034% (interquartile range (IQR) 0.013–0.056%) for the 0–59 years old population, and 0.095% (IQR 0.036–0.119%) for the 0–69 years old. The median IFR was 0.0003% at 0–19 years, 0.002% at 20–29 years, 0.011% at 30–39 years, 0.035% at 40–49 years, 0.123% at 50–59 years, and 0.506% at 60–69 years.
IFR increases approximately 4 times every 10 years. Including data from another 9 countries with imputed age distribution of COVID-19 deaths yielded median IFR of 0.025–0.032% for 0–59 years and 0.063–0.082% for 0–69 years. Meta-regression analyses also suggested global IFR of 0.03% and 0.07%, respectively in these age groups. The current analysis suggests a much lower pre-vaccination IFR in non-elderly populations than previously suggested. Large differences did exist between countries and may reflect differences in comorbidities and other factors. These estimates provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants.