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

Francesco Pinotti*, Paul S. Wikramaratna, Uri Obolski, Robert S. Paton, Daniel S.C. Damineli, Luiz C.J. Alcantara, Marta Giovanetti, Sunetra Gupta, José Lourenço

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Cross-reactivity to SARS-CoV-2 from exposure to endemic human coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and COVID-19 severity. Here we explore the potential role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission. Methods: We use an individual-based model, calibrated to prior knowledge of eHCoV dynamics, to fully track individual histories of exposure to eHCoVs. We also model the emergent dynamics of SARS-CoV-2 and the risk of hospitalisation upon infection. Results: We hypothesise that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection, while life-long re-exposure to the same eHCoV diminishes cross-protection, and increases the potential for disease severity. We show numerically that our proposed mechanism can explain age patterns of COVID-19 hospitalisation in EU/EEA countries and the UK. We further show that some of the observed variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates under this model. Conclusions: This study provides a “proof of possibility” for certain biological and epidemiological mechanisms that could potentially drive COVID-19-related variation across age groups. Our findings call for further research on the role of cross-reactivity to eHCoVs and highlight data interpretation challenges arising from health care capacity and SARS-CoV-2 testing.

Original languageEnglish
Article number19
JournalBMC Medicine
Issue number1
StatePublished - Dec 2021


  • COVID-19
  • Cross-reactivity
  • Endemic coronaviruses
  • Immunopathology
  • Individual-based model
  • Infectious disease dynamics
  • Mathematical model
  • SARS-CoV-2


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