TY - JOUR

T1 - Severity of respiratory tract infections depends on the infectious dose. Perspectives for the next pandemic

AU - Mølbak, Kåre

AU - Sørensen, Thorkild I.A.

AU - Bhatt, Samir

AU - Lyngse, Frederik Plesner

AU - Simonsen, Lone

AU - Aaby, Peter

N1 - Funding Information: The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. FL was supported in part by grants from Independent Research Fund Denmark (grant no. 3165-00103B); Novo Nordisk Foundation (grant no. NNF20OC0059309). SB acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/X020258/1), funded by the UK Medical Research Council (MRC). This UK funded award is carried out in the frame of the Global Health EDCTP3 Joint Undertaking. SB was funded by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Modelling and Health Economics, a partnership between UK Health Security Agency, Imperial College London and LSHTM (grant code NIHR200908). SB acknowledges support from the Novo Nordisk Foundation via The Novo Nordisk Young Investigator Award (NNF20OC0059309). SB acknowledges the Danish National Research Foundation (DNRF160) through the chair grant. SB acknowledges support from The Eric and Wendy Schmidt Fund for Strategic Innovation via the Schmidt Polymath Award (G-22-63345). LS acknowledges support from the Danish National Research Foundation DNRF170.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - dose response

KW - mathematical model

KW - pandemic planning

KW - respiratory infections

KW - SARS-CoV-2

U2 - 10.3389/fpubh.2024.1391719

DO - 10.3389/fpubh.2024.1391719

M3 - Journal article

C2 - 38746005

AN - SCOPUS:85192946835

VL - 12

JO - Frontiers in Public Health

JF - Frontiers in Public Health

SN - 2296-2565

M1 - 1391719

ER -