Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model
Santosh Dhakal, Camilo A. Ruiz-Bedoya, Ruifeng Zhou, Patrick S. Creisher, Jason Villano, Kirsten Littlefield, Jennie Ruelas Castillo, Paula M. Marinho, Anne Jedlicka, Alvaro A. Ordoñez, Melissa Bahr, Natalia I. Majewska, Michael J. Betenbaugh, Kelly Flavahan, Alice R. L. Mueller, Monika M. Looney, Darla Quijada, Filipa Mota, Sarah E. Beck, Jacqueline Brockhurst, Alicia M. Braxton, Natalie Castell, Mitchel Graham Stover, Franco R. D’Alessio, Kelly A. Metcalf Pate, Petros C. Karakousis, Joseph L. Mankowski, Andrew Pekosz, Sanjay K. Jain, Sabra L. Klein
Abstract
Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human isolate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After inoculation, male hamsters experienced greater sickness, developed more severe lung pathology, and recovered more slowly than females. Sex differences in disease could not be reversed by estradiol treatment in males and were not explained by either virus replication kinetics or the concentrations of inflammatory cytokines in the lungs. During the recovery period, antiviral antibody responses in the respiratory tract and plasma, including to newly emerging SARS-CoV-2 variants, were greater in female than in male hamsters. Greater lung pathology during the acute phase combined with lower antiviral antibody responses during the recovery phase of infection in males than in females illustrate the utility of golden Syrian hamsters as a model to explore sex differences in the pathogenesis of SARS-CoV-2 and vaccine-induced immunity and protection.