Low Environmental Temperature Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Golden Syrian Hamsters

Background: The effect of low environmental temperature on viral shedding and disease severity of Coronavirus Disease 2019 (COVID-19) is uncertain. Methods: We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21°C), low (12-15°C), and high (30-33°C) temperature after challenge by 105 plaque-forming units of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: The nasal turbinate, trachea, and lung viral load and live virus titer were significantly higher (~0.5-log10 gene copies/β-Actin, P<.05) in the low-Temperature group at 7 days postinfection (dpi). The low-Temperature group also demonstrated significantly higher level of tumor necrosis factor-α, interferon-γ(IFN-γ), interleukin-1β, and C-C motif chemokine ligand 3, and lower level of the antiviral IFN-α in lung tissues at 4 dpi than the other 2 groups. Their lungs were grossly and diffusely hemorrhagic, with more severe and diffuse alveolar and peribronchiolar inflammatory infiltration, bronchial epithelial cell death, and significantly higher mean total lung histology scores. By 7 dpi, the low-Temperature group still showed persistent and severe alveolar inflammation and hemorrhage, and little alveolar cell proliferative changes of recovery. The viral loads in the oral swabs of the low-Temperature group were significantly higher than those of the other two groups from 10 to 17 dpi by about 0.5-1.0 log10 gene copies/β-Actin. The mean neutralizing antibody titer of the low-Temperature group was significantly (P<.05) lower than that of the room temperature group at 7 dpi and 30 dpi. Conclusions: This study provided in vivo evidence that low environmental temperature exacerbated the degree of virus shedding, disease severity, and tissue proinflammatory cytokines/chemokines expression, and suppressed the neutralizing antibody response of SARS-CoV-2-infected hamsters. Keeping warm in winter may reduce the severity of COVID-19.