Abstract
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection. Gene expression analysis of the nasal turbinates indicated that 1-year-old female ferrets had significant increases in interferon response genes post infection which were delayed in males. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.
Highlights
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages
As COVID-19 severity has been associated with the male sex and age, we investigated these biological variables and their contribution to disease in ferrets infected with SARS-CoV-2
We employed ferrets to gain a better understanding of human SARS-CoV-2 infection and the increased risk of severe COVID-19 in 2-year-olds
Summary
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Animal models are indispensable for responses to newly emerging infectious diseases given their importance for preclinical evaluations of vaccines and therapeutics and corresponding insights into disease p athophysiology[18] Development of these models requires identification of species that are susceptible to infection as well as recapitulation of human clinical disease. Ferrets display similar symptoms and clinical features to humans during respiratory infections, including fever, nasal discharge, coughing, and weight loss[19,22,23,24,25] They have been used to investigate age-related host responses, disease severity, and pathogenic immune mechanisms during respiratory virus infection[23,24]. As COVID-19 severity has been associated with the male sex and age, we investigated these biological variables and their contribution to disease in ferrets infected with SARS-CoV-2. Our findings highlight that sociological and societal factors, and biological factors including sex hormones, sex chromosomes, and aging, contribute to COVID-19 sex-biases
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