Potential impact of individual exposure histories to endemic human coronaviruses on age-dependent severity of COVID-19

1. Based on mathematical modeling, cross-reactivity between SARS-CoV-2 and other endemic human coronaviruses may explain variations in disease severity across age groups.

Evidence Rating Level: 3 (Average)

SARS-CoV-2 is the seventh known coronavirus to infect humans. Its resultant coronavirus disease 2019 (COVID-19) has resulted in over 400,000 deaths in the United States. With significant variations in symptom severity, based on a wide range of risk factors such as age and medical history, it is important to understand how cross-reactivity between SARS-CoV-2 and other endemic human coronaviruses (eHCoVs) impacts symptom severity. This study aimed to investigate the role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission. An individual-based model was utilized, calibrated based on known eHCoV dynamics, to track individual eHCoV exposure histories. Emergent dynamics of SARS-CoV-2 and risk of hospitalization upon infection were also modeled. Epidemiological parameters characterizing SARS-CoV-2 and eHCoVs were informed, when feasible, by extant literature. Susceptibility to reinfection was set to match empirical estimates of age at first eHCoV infection, thus yielding a realistic force of infection for eHCoVs. Assumptions were compatible with studies on kinetics of antibody responses after both eHCoVs and SARS-CoV-2 infections. It was found that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection. However, lifelong re-exposure to the same eHCoV diminishes cross-protection over time, increasing the risk of severe disease. This proposed mechanism was found to explain observable age patterns of COVID-19 hospitalizations in EU/EEA countries and the UK. Also under this model, variations in healthcare capacity and testing efforts are compatible with country-specific differences in hospital rates. Overall, the proposed modeling offers “proof of possibility” for certain epidemiological and biological mechanisms that may be driving COVID-19 variations across age groups. Future studies will need to focus on cross-reactivity to eHCoVs in the context of SARS-CoV-2.

Click to read the study in BMC Medicine

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