Male sex and age biases viral burden, viral shedding, and type 1 and 2 interferon responses during SARS-CoV-2 infection in ferrets

Magen E Francis; Brian Richardson; Mara McNeil; Melissa Rioux; Mary K Foley; Anni Ge; Roger D Pechous; Jason Kindrachuk; Cheryl M Cameron; Christopher Richardson; Jocelyne Lew; Mark J Cameron; Volker Gerdts; Darryl Falzarano; Alyson A Kelvin

doi:10.1101/2021.01.12.426381

Male sex and age biases viral burden, viral shedding, and type 1 and 2 interferon responses during SARS-CoV-2 infection in ferrets

bioRxiv [Preprint]. 2021 Jan 12:2021.01.12.426381. doi: 10.1101/2021.01.12.426381.

Authors

Magen E Francis^{1

2}, Brian Richardson³, Mara McNeil¹, Melissa Rioux¹, Mary K Foley¹, Anni Ge¹, Roger D Pechous⁴, Jason Kindrachuk^{2

5}, Cheryl M Cameron⁶, Christopher Richardson¹, Jocelyne Lew², Mark J Cameron³, Volker Gerdts^{2

7}, Darryl Falzarano^{2

7}, Alyson A Kelvin^{1

2

8

9}

Affiliations

¹ Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada.
² Vaccine and Infectious Disease Organization - International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, SK, Canada.
³ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA44106.
⁴ University of Arkansas for Medical Sciences, Department of Microbiology and Immunology, Little Rock, AK, USA.
⁵ Laboratory of Emerging and Re-Emerging Viruses, Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
⁶ Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
⁷ Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
⁸ Department of Pediatrics, Division of Infectious Disease, Faculty of Medicine, Dalhousie University, Halifax, NS B3K 6R8, Canada.
⁹ Canadian Centre for Vaccinology, IWK Health Centre, Halifax, NS B3K 6R8, Canada.

Abstract

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and the elderly. Here we investigated the impact of male sex and age by infecting adult male, aged male, and adult female ferrets with SARS-CoV-2. Aged male ferrets had a decrease in temperature which was accompanied by prolonged viral replication with increased pathology in the upper respiratory tract after infection. Transcriptome analysis of the nasal turbinates and lungs indicated that female ferrets had significant increases in interferon response genes (OASL, MX1, ISG15, etc.) on day 2 post infection which was delayed in aged males. In addition, genes associated with taste and smell such as RTP1, CHGA, and CHGA1 at later time points were upregulated in males but not in females. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.

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