• IoannidisJohn P AJPA0000-0003-3118-6859Departments of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA, Francesco Zonta, and Michael Levitt.
• Departments of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA.
• Eur. J. Clin. Invest. 2023 Aug 1; 53 (8): e14008e14008.

AbstractSeveral teams have been publishing global estimates of excess deaths during the COVID-19 pandemic. Here, we examine potential flaws and underappreciated sources of uncertainty in global excess death calculations. Adjusting for changing population age structure is essential. Otherwise, excess deaths are markedly overestimated in countries with increasingly aging populations. Adjusting for changes in other high-risk indicators, such as residence in long-term facilities, may also make a difference. Death registration is highly incomplete in most countries; completeness corrections should allow for substantial uncertainty and consider that completeness may have changed during pandemic years. Excess death estimates have high sensitivity to modelling choice. Therefore different options should be considered and the full range of results should be shown for different choices of pre-pandemic reference periods and imposed models. Any post-modelling corrections in specific countries should be guided by pre-specified rules. Modelling of all-cause mortality (ACM) in countries that have ACM data and extrapolating these models to other countries is precarious; models may lack transportability. Existing global excess death estimates underestimate the overall uncertainty that is multiplicative across diverse sources of uncertainty. Informative excess death estimates require risk stratification, including age groups and ethnic/racial strata. Data to-date suggest a death deficit among children during the pandemic and marked socioeconomic differences in deaths, widening inequalities. Finally, causal explanations require great caution in disentangling SARS-CoV-2 deaths, indirect pandemic effects and effects from measures taken. We conclude that excess deaths have many uncertainties, but globally deaths from SARS-CoV-2 may be the minority of calculated excess deaths.© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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