During the COVID-19 pandemic, much has been said about the importance of host-specific and virus-specific factors as predictors of the risk of infection and severity of disease. For example, host factors such as increased age, male gender, ethnicity, and comorbidities such as metabolic and pulmonary disorders have been recognized as risk factors for severe disease, whereas host immunity stemming from prior infection or vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with reduced severity. Similarly, the viral evolution of SARS-CoV-2 over the past 4 years has been scrutinized to estimate changes in the relative transmissibility, virulence and vaccine-match of each emerging variant over time during the COVID-19 pandemic. However, despite this scrutiny, variation in transmissibility and severity of disease remain imperfectly understood.

An aspect that has been comparatively ignored is the importance of transmission factors such as the size of viral inoculation and the duration of exposure, i.e., the dose of exposure (see Figure 1). The dose of exposure is determined by human behavior, environmental conditions and mitigation strategies, such as indoor versus outdoor exposure, indoor crowding, indoor air ventilation and physical distancing. As observed for a range of pathogens, the risk of getting infected, and in some studies, also the disease severity and post infection sequelae depend on the dose encountered (1–10). In 2021, Van Damme et al. (11) postulated that the dose of SARS-CoV-2 at infection was an important missing factor in understanding several incompletely explained observations in the epidemiology of COVID-19. Nevertheless, epidemiological models (and common thinking) continue to parameterize exposure as a dichotomous phenomenon, where the susceptible host is being considered as either exposed (and at risk of infection and severe disease) or unexposed (and therefore not at risk). We hypothesize that a quantitative exposure approach, where dose of exposure is included as a factor that determine important factors such as risk of infection, incubation period, outcome of infection and transmissibility, may be helpful for our understanding of the epidemiology of COVID-19, also in the ongoing transition of the pandemic to endemicity. But more importantly, if this hypothesis can be generalized across other pathogens, a quantitative exposure approach to infection epidemiology may open new options for mitigation of a future severe pandemic, Disease X, and point a way forward to a control strategy with a gentler impact on society.