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Updated: Nov 21, 2025
Author Spotlight: Advancements in Multiplex Detection of Respiratory Viruses
Published on: November 10, 2023
Does death from Covid-19 arise from a multi-step process?
Neil Pearce1, Giovenale Moirano2, Milena Maule2
1London School of Hygiene and Tropical Medicine, London, UK. Neil.Pearce@lshtm.ac.uk.
Insights
The COVID-19 (coronavirus disease 2019) case fatality rate rises exponentially with age, particularly in individuals with underlying health conditions. This pattern aligns with a multi-step disease model, distinct from influenza.
Area of Science:
- Epidemiology
- Public Health
- Infectious Diseases
Background:
- COVID-19 (coronavirus disease 2019) exhibits a significantly higher fatality rate in older individuals.
- Underlying health conditions like hypertension, diabetes, and cardiovascular disease are major risk factors for severe COVID-19 outcomes.
- These observations suggest a complex disease progression influenced by age and comorbidities.
Purpose of the Study:
- To investigate the age-specific case fatality rates (CFRs) of COVID-19.
- To evaluate the applicability of the multi-step model of disease to COVID-19 mortality patterns.
- To compare the age-related CFR patterns of COVID-19 with other respiratory diseases like SARS and influenza.
Main Methods:
- Analysis of COVID-19 case fatality rates (CFRs) across different age groups in China, South Korea, Italy, Spain, and Japan.
- Application of the multi-step disease model to log-log plots of CFR against age.
- Comparative analysis of age-specific mortality patterns for COVID-19, SARS, and influenza.
Main Results:
- A consistent, approximately linear relationship was observed between log(CFR) and log(age) across all studied countries, with a slope around 5.
- The age-related fatality pattern for COVID-19 closely resembled that of SARS, but differed significantly from seasonal and pandemic influenza.
- These findings support the hypothesis that COVID-19 and SARS mortality follow a distinct, multi-step progression influenced by age and comorbidities.
Conclusions:
- COVID-19 and SARS mortality exhibit a distinct age-dependent pattern consistent with a multi-step disease model.
- Comorbidities and advanced age likely contribute to immune-related susceptibility, defining this pattern in COVID-19.
- The multi-step model provides a framework for understanding age-related risk in severe respiratory infections.
Abstract:
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.
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