Age-stratified infection fatality rate of COVID-19 in the non-elderly population

Abstract

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.

Keywords: Bias; COVID-19; Epidemics; Infection fatality rate; Seroprevalence.

Fig. 1

Infection fatality rate (IFR) and 95% confidence interval per country. Panel (A) for <60 years old people. Panel (B) for <70 years old people. Note: For multiple estimates from the same country (France and USA), we calculated the sample size-weighted IFR per country. The 95% confidence intervals are estimated primarily as direct extractions from the seroprevalence studies. For studies that did not report 95% confidence intervals, we complemented with a calculation using the number of sampled and seropositive individuals. For those that provided adjusted estimates for age brackets (e.g., 0–9, 10–19, 20–29, etc.), we combined estimates for each study using a fixed effects inverse variance meta-analysis (of arcsine transformed proportions) to obtain 95% confidence intervals. Asymmetry around point estimates may be observed for these cases, since point estimates were calculated by multiplying age bracket seroprevalence by the corresponding population count (which is preferable, since it takes into account population distribution). Please note that uncertainty in seroprevalence estimates is larger than conveyed by typical 95% confidence intervals.

Fig. 1

Infection fatality rate (IFR) and 95% confidence interval per country. Panel (A) for <60 years old people. Panel (B) for <70 years old people. Note: For multiple estimates from the same country (France and USA), we calculated the sample size-weighted IFR per country. The 95% confidence intervals are estimated primarily as direct extractions from the seroprevalence studies. For studies that did not report 95% confidence intervals, we complemented with a calculation using the number of sampled and seropositive individuals. For those that provided adjusted estimates for age brackets (e.g., 0–9, 10–19, 20–29, etc.), we combined estimates for each study using a fixed effects inverse variance meta-analysis (of arcsine transformed proportions) to obtain 95% confidence intervals. Asymmetry around point estimates may be observed for these cases, since point estimates were calculated by multiplying age bracket seroprevalence by the corresponding population count (which is preferable, since it takes into account population distribution). Please note that uncertainty in seroprevalence estimates is larger than conveyed by typical 95% confidence intervals.

Fig. 2

Box plot of infection fatality rate (IFR) estimates across countries per each specified age bin. Note: The 25th percentile for 0–19 and 20–29 age bins is not shown (0.0000%).

Fig. 3

Meta-regressions of IFR as a function of the proportion of the population <50 years old among (A) among those 0–59 years old and (B) among those 0–69 years old.

Fig. 3

Meta-regressions of IFR as a function of the proportion of the population <50 years old among (A) among those 0–59 years old and (B) among those 0–69 years old.