Modeling SARS-CoV-2: Comparative Pathology in Rhesus Macaque and Golden Syrian Hamster Models

Shambhunath Choudhary, Isis Kanevsky, Soner Yildiz, Rani S. Sellers, Kena A. Swanson, Tania Franks, Raveen Rathnasinghe, Raquel Munoz-Moreno, Sonia Jangra, Olga Gonzalez, Philip Meade, Timothy Coskran, Jessie Qian, Thomas A. Lanz, Jillian G. Johnson, Cassandra A. Tierney, Justin D. Smith, Kristin Tompkins, Arthur Illenberger, Paula CortsTara Ciolino, Philip R. Dormitzer, Edward J. Dick, Vinay Shivanna, Shannan Hall-Ursone, Journey Cole, Deepak Kaushal, Jane A. Fontenot, Carles Martinez-Romero, Meagan McMahon, Florian Krammer, Michael Schotsaert, Adolfo García-Sastre

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Coronavirus disease 2019 (COVID-19) in humans has a wide range of presentations, ranging from asymptomatic or mild symptoms to severe illness. Suitable animal models mimicking varying degrees of clinical disease manifestations could expedite development of therapeutics and vaccines for COVID-19. Here we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulted in subclinical disease in rhesus macaques with mild pneumonia and clinical disease in Syrian hamsters with severe pneumonia. SARS-CoV-2 infection was confirmed by formalin-fixed, paraffin-embedded (FFPE) polymerase chain reaction (PCR), immunohistochemistry, or in situ hybridization. Replicating virus in the lungs was identified using in situ hybridization or virus plaque forming assays. Viral encephalitis, reported in some COVID-19 patients, was identified in one macaque and was confirmed with immunohistochemistry. There was no evidence of encephalitis in hamsters. Severity and distribution of lung inflammation were substantially more in hamsters compared with macaques and exhibited vascular changes and virus-induced cytopathic changes as seen in COVID-19 patients. Neither the hamster nor macaque models demonstrated evidence for multisystemic inflammatory syndrome (MIS). Data presented here demonstrate that macaques may be appropriate for mechanistic studies of mild asymptomatic COVID-19 pneumonia and COVID-19-associated encephalitis, whereas Syrian hamsters may be more suited to study severe COVID-19 pneumonia.

Original languageEnglish
Pages (from-to)280-293
Number of pages14
JournalToxicologic Pathology
Volume50
Issue number3
DOIs
StatePublished - Apr 2022

Keywords

  • SARS-CoV-2
  • animal models
  • hamster
  • pneumonia
  • rhesus macaque

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