Does death from Covid-19 arise from a multi-step process?

The Covid-19 death rate increases exponentially with age, and the main risk factors are having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. These characteristics are consistent with the multi-step model of disease. We applied this model to Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of log(CFR) against log(age) was approximately linear with a slope of about 5. We also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log–log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multi-step model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s10654-020-00711-7).