摘要：SummaryThe golden hamster model of SARS-CoV-2 infection recapitulates key characteristics of COVID-19. In this work we examined the influence of the route of exposure, sex, and age on SARS-CoV-2 pathogenesis in hamsters. We report that delivery of SARS-CoV-2 by a low- versus high-volume intranasal or intragastric route results in comparable viral titers in the lung and viral shedding. However, low-volume intranasal exposure results in milder weight loss, whereas intragastric exposure leads to a diminished capacity to regain body weight. Male hamsters, and particularly older male hamsters, display an impaired capacity to recover from illness and delayed viral clearance. These factors were found to influence the nature of the host inflammatory cytokine response but had a minimal effect on the quality and durability of the humoral immune response and susceptibility to re-infection. These data further elucidate key factors that impact pre-clinical challenge studies carried out in the hamster model of COVID-19.Graphical abstractDisplay OmittedHighlights•Low-volume intranasal delivery of SARS-CoV-2 leads to milder weight loss in hamsters•Intragastric exposure of hamsters to SARS-CoV-2 results in delayed weight recovery•Male and older male hamsters exhibit delayed SARS-CoV-2 clearance from the lungs•Route, sex, and age only mildly influence susceptibility of hamsters to re-infectionCellular physiology; Microbiology; Virology
