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Peer reviewed: True, Comparing age and sex differences in SARS-CoV-2 hospitalization and mortality with MERS-CoV, seasonal coronaviruses, influenza and other health outcomes opens the way to generating hypotheses as to underlying mechanisms driving disease risk. Using 60-year-olds as a reference age group, we find that relative rates of hospitalization and mortality associated with the emergent coronaviruses are lower during childhood and start to increase earlier (around puberty) as compared with influenza and seasonal coronaviruses. The changing distribution of disease risk by age for emerging pathogens appears to broadly track the gradual deterioration of the immune system (immunosenescence), which starts around puberty. By contrast, differences in severe disease risk by age from endemic pathogens are more decoupled from the immune ageing process. Intriguingly, age-specific sex differences in hospitalizations are largely similar across endemic and emerging infections. We discuss potential mechanisms that may be associated with these patterns.

Case distributions for COVID-19, MERS and Influenza. (A) COVID-19 hospitalizations in France by age comparing females (red) and males (blue). (B) COVID-19 hospitalizations requiring ICU in France by age comparing females (red) and males (blue). (C) COVID-19 deaths in France by age comparing females (red) and males (blue). (D) Total MERS hospitalizations by age comparing females (red) and males (blue). (E) Total MERS hospitalizations requiring ICU by age comparing females (red) and males (blue). (F) Total MERS deaths by age comparing females (red) and males (blue). (G) Total influenza hospital emergency visits in France (2004-2020) by age comparing females (red) and males (blue). (H) Total hospital visits for influenza requiring ICU in France (2012-2017) by age. (I) Total hospital influenza deaths in US (2019) by age and sex.