Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Dose, Infection, and Disease Outcomes for Coronavirus Disease 2019 (COVID-19): A Review

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dose, infection, and coronavirus disease 2019 (COVID-19) outcomes remains poorly understood. This review summarizes the existing literature regarding this issue, identifies gaps in current knowledge, and suggests opportunities for future research. In humans, host characteristics, including age, sex, comorbidities, smoking, and pregnancy, are associated with severe COVID-19. Similarly, in animals, host factors are strong determinants of disease severity, although most animal infection models manifest clinically with mild to moderate respiratory disease. The influence of variants of concern as it relates to infectious dose, consequence of overall pathogenicity, and disease outcome in dose-response remains unknown. Epidemiologic data suggest a dose-response relationship for infection contrasting with limited and inconsistent surrogate-based evidence between dose and disease severity. Recommendations include the design of future infection studies in animal models to investigate inoculating dose on outcomes and the use of better proxies for dose in human epidemiology studies. This article reviews evidence on the relationship between SARS-CoV-2 dose, infection, and COVID-19 outcomes; identifies gaps in understanding; and suggests future research opportunities. While data suggest a dose-infection relationship, limited, inconsistent surrogate-based evidence exists for a dose-severity relationship.

Automated summary

This review article summarizes the existing literature on the relationship between SARS-CoV-2 dose, infection, and COVID-19 outcomes. It identifies gaps in understanding and suggests opportunities for future research. Host characteristics play a significant role in disease severity, but the influence of infectious dose on disease outcome remains unknown.