Reconciling estimates of global spread and infection fatality rates of COVID-19: An overview of systematic evaluations

Eur J Clin Invest. 2021 May;51(5):e13554. doi: 10.1111/eci.13554. Epub 2021 Apr 9.


Background: Estimates of community spread and infection fatality rate (IFR) of COVID-19 have varied across studies. Efforts to synthesize the evidence reach seemingly discrepant conclusions.

Methods: Systematic evaluations of seroprevalence studies that had no restrictions based on country and which estimated either total number of people infected and/or aggregate IFRs were identified. Information was extracted and compared on eligibility criteria, searches, amount of evidence included, corrections/adjustments of seroprevalence and death counts, quantitative syntheses and handling of heterogeneity, main estimates and global representativeness.

Results: Six systematic evaluations were eligible. Each combined data from 10 to 338 studies (9-50 countries), because of different eligibility criteria. Two evaluations had some overt flaws in data, violations of stated eligibility criteria and biased eligibility criteria (eg excluding studies with few deaths) that consistently inflated IFR estimates. Perusal of quantitative synthesis methods also exhibited several challenges and biases. Global representativeness was low with 78%-100% of the evidence coming from Europe or the Americas; the two most problematic evaluations considered only one study from other continents. Allowing for these caveats, four evaluations largely agreed in their main final estimates for global spread of the pandemic and the other two evaluations would also agree after correcting overt flaws and biases.

Conclusions: All systematic evaluations of seroprevalence data converge that SARS-CoV-2 infection is widely spread globally. Acknowledging residual uncertainties, the available evidence suggests average global IFR of ~0.15% and ~1.5-2.0 billion infections by February 2021 with substantial differences in IFR and in infection spread across continents, countries and locations.

Keywords: COVID-19; bias; global health; infection fatality rate; meta-analysis; seroprevalence.

Publication types

  • Review

MeSH terms

  • COVID-19 / epidemiology*
  • COVID-19 / mortality
  • COVID-19 / transmission
  • COVID-19 Serological Testing
  • Disease Transmission, Infectious / statistics & numerical data*
  • Humans
  • Internationality
  • Mortality
  • SARS-CoV-2
  • Seroepidemiologic Studies
  • Systematic Reviews as Topic