SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

Magen Ellen Francis; Una Goncin; Andrea Kroeker; Cynthia Swan; Robyn Ralph; Yao Lu; Athema Louise Etzioni; Darryl Falzarano; Volker Gerdts; Steven Machtaler; Jason Kindrachuk; Alyson Ann Kelvin

doi:10.1371/journal.ppat.1009705

SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

PLoS Pathog. 2021 Jul 15;17(7):e1009705. doi: 10.1371/journal.ppat.1009705. eCollection 2021 Jul.

Authors

Magen Ellen Francis^{1

2}, Una Goncin³, Andrea Kroeker¹, Cynthia Swan¹, Robyn Ralph^{1

4}, Yao Lu¹, Athema Louise Etzioni⁵, Darryl Falzarano^{1

4}, Volker Gerdts¹, Steven Machtaler³, Jason Kindrachuk^{1

6}, Alyson Ann Kelvin^{1

7

8

9}

Affiliations

¹ Vaccine and Infectious Disease Organization VIDO, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
² Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
³ Department of Medical Imaging, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
⁴ Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
⁵ Department of Pathobiology, Tuskegee University College of Veterinary Medicine, Tuskegee Institute, Tuskegee, Alabama, United States of America.
⁶ Laboratory of Emerging and Re-Emerging Viruses, Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
⁷ Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
⁸ Department of Pediatrics, Division of Infectious Disease, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
⁹ Canadian Centre for Vaccinology, IWK Health Centre, Halifax, Nova Scotia, Canada.

Abstract

COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of myocarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COVID-19 / immunology*
COVID-19 / pathology
Cricetinae
Disease Models, Animal
Down-Regulation / immunology*
Humans
Inflammation / immunology
Inflammation / pathology
Interferon Type I / immunology*
Kidney / immunology*
Kidney / pathology
Kidney / virology
Male
Mesocricetus
Myocardium / immunology*
Myocardium / pathology
Respiratory System / immunology*
Respiratory System / pathology
Respiratory System / virology
SARS-CoV-2 / immunology*

Substances

Interferon Type I

Grants and funding

This work was supported by the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative the Canadian Institutes of Health Research (CIHR) (https://cihr-irsc.gc.ca/e/193.html) (grant numbers OV5-170349 to AAK, DF, JK; VRI-172779 to AAK, OV2 – 170357 to AAK, 950-231498 to JK) and Atlantic Genome/Genome Canada (https://genomeatlantic.ca/) (no grant number to AAK), and the Nova Scotia Health Research Foundation (Nova Scotia COVID-19 Health Research Coalition) (https://researchns.ca/) (no grant number to AAK). This article is published with the permission of the Director of VIDO manuscript 936. VIDO receives operational funding from the Canada Foundation for Innovation (https://www.innovation.ca/) through the Major Science Initiatives Fund (no grant number) and by Government of Saskatchewan through Innovation Saskatchewan (https://innovationsask.ca/) (no grant number) and the Ministry of Agriculture (no grant number) (https://www.saskatchewan.ca/government/government-structure/ministries/agriculture). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.