Sex and age bias viral burden and interferon responses during SARS-CoV-2

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.

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Fig: Intranasal SARS-CoV-2 infection in sexually intact ferrets leads to significantly lower temperature in males compared to females. (A) Sexually intact 1-year-old female and 1-year-old male ferrets were intranasally inoculated with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) (106 TCID50) and weight was recorded for 14 days post inoculation and represented as percentage of original temperature and (B) raw temperature. (C) Weight was also measured for 14 days after inoculation and represented percentage of original weight. Results show the mean of at least 6 ferrets per group. Results show the mean of at least 6 ferrets per group. *A p-value less than 0.05 determined by ANOVA comparing females to males. Error bars indicate ± standard deviation (SD).

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.

Francis, M.E., Richardson, B., Goncin, U. et al. Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets. Sci Rep 11, 14536 (2021). https://doi.org/10.1038/s41598-021-93855-9

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