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

Cross-reactivity to SARS-CoV-2 from previous exposure to endemic coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and severity of COVID-19 disease. Here, we use a stochastic individual-based model to show that heterogeneities in individual exposure histories to endemic coronaviruses are able to explain observed age patterns of hospitalisation due to COVID-19 in EU/EEA countries and the UK, provided there is (i) a decrease in cross-protection to SARS-CoV-2 with the number of eHCoV exposures and (ii) an increase in potential disease severity with number of eHCoV exposures or as a result of immune senescence. We also show that variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates. Our findings call for further research on the role of cross-reactivity to endemic coronaviruses and highlight potential challenges arising from heterogeneous health care capacity and testing.