Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 golden Syrian hamster model

• DOI: 10.1101/2021.04.02.438292
• Publication Date: 2021-04-04T22:35:10Z
• Authors: Santosh Dhakal; Camilo A. Ruiz-Be...; Ruifeng Zhou; Patrick S. Creisher; Jason S. Villano; Kirsten Littlefield; Jennie Ruelas Cas...; Paula Marinho; Anne Jedlicka; Alvaro A. Ordonez; Natalia Majewski; Michael J. Betenb...; Kelly Flavahan; Alice L. Mueller; Monika M. Looney; Darla Quijada; Filipa Mota; Sarah E. Beck; Jacqueline Brockh...; Alicia Braxton; Natalie Castell; Franco R. D’Alessio; Kelly A. Metcalf ...; Petros C. Karakousis; Joseph L. Mankowski; Andrew Pekosz; Sanjay K. Jain; Sabra L. Klein
• Keywords: Mesocricetus; Coronavirus; Pathogenesis; Viral Shedding

Abstract In the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2), more outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences pathogenesis SARS-CoV-2. Adult male female golden Syrian hamsters (8-10 weeks age) were inoculated intranasally 10 5 TCID 50 SARS-CoV-2/USA-WA1/2020 euthanized at several time points during (i.e., virus actively replicating) recovery after infectious has been cleared) phases infection. There was no mortality, but infected experienced greater morbidity, losing a percentage body mass, developing extensive pneumonia as noted on chest computed tomography, recovering slowly than females. Treatment estradiol did not alter pulmonary damage. Virus titers tissues, nasal turbinates, trachea, lungs, cytokine concentrations, IFNβ TNFα, comparable between sexes. However, phase infection, females mounted two-fold IgM, IgG, IgA responses against receptor-binding domain spike protein (S-RBD) both plasma tissues. Female also had significantly IgG antibodies whole inactivated SARS-CoV-2 mutant S-RBDs, well neutralizing plasma. The development animal model study COVID-19 will allow for mechanistic understanding associated seen human population. Importance Men experience from women. Golden used explore clinical isolate After inoculation, sickness, developed lung pathology, recovered Sex could be reversed treatment explained either replication kinetics or concentrations inflammatory cytokines lungs. During period, antiviral antibody tract plasma, newly emerging variants, hamsters. Greater pathology combined reduced infection illustrate utility vaccine-induced immunity protection. One Sentence Summary Following worse have lower