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

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).

Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

“…Pulmonary and extrapulmonary clinical and histopathological changes associated with SARS-CoV-2 infection in humans have been described by several groups ( Chen and Li, 2020 ; Francis et al, 2021 ; Lamers et al, 2020 ; Mao et al, 2020 ; Moore and June, 2020 ; Neurath, 2020 ; Nishiga et al, 2020 ; Verity et al, 2020 ; Wang et al, 2020 , p. 19). Moreover, hamsters as a preclinical SARS-CoV-2 infection model were recently shown to mimic viral entry and replication in a manner naturally similar to humans, and therefore hamsters are regarded as a suitable and natural model for SARS-CoV-2-challenged studies ( Chan et al, 2020 ; Imai et al, 2020 ; Lee et al, 2020 ; Sia et al, 2020 ).…”

“…Symptomatic COVID-19 is typically characterized by symptoms ranging from mild to acute respiratory distress associated with cytokine release syndrome ( Chen and Li, 2020 ; Verity et al, 2020 ). Moreover, extrapulmonary signs, ranging from cardiovascular complication (CVC), coagulopathies, multiple-organ damage, and neurological disorders, were found to be recognized as post-COVID sequelae described in patients with mild to severe COVID-19 ( Chen and Li, 2020 ; Cortinovis et al, 2021 ; Francis et al, 2021 ; Huang et al, 2021 ; Lamers et al, 2020 ; Mao et al, 2020 ; Neurath, 2020 ; Nishiga et al, 2020 ; Wu et al, 2020b ; Xiao et al, 2020 ; Xydakis et al, 2020 ). The severity of COVID-19 is governed by several factors such as titer of virus, route of viral entry, gender, age, and comorbid conditions ( Chen and Li, 2020 ; Sungnak et al, 2020 ; Wang et al, 2020 ).…”

Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters

“…On the other hand, several limitations of the hamster model exist. SARS-CoV-2 infection in humans affects multiple organ systems including the heart, kidneys, liver, spleen and large intestine [ 81 , 82 ] whereas in hamsters live virus mainly replicates in respiratory tracts with little evidence of infectious virus in other organs, despite the detection of viral RNA in non-respiratory tissues [ 55 , 83 ]. Furthermore, a lack of hamster-specific biological reagents makes it difficult to characterize immune responses and the mechanisms of pathogenesis in hamsters.…”

Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19

“…2c. The classification of 'severe' is a comparative term for these mice, as we generally did not observe pathology equivalent to that of the more severe Syrian hamster model of SARS-CoV-2 infection [27][28][29] . Surprisingly, in comparison to F1 progeny of sensitive founder strains (K18-hACE2 and A/JxK18-hACE2), F1 progeny of resistant PWK, female NZO and 129S/J mice, as well as those of NOD and WSB tended to have higher pathology scores in lungs (Fig.…”