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 COVID-19 is uncertain. METHODS: We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21 oC), low (12-15 oC), and high (30-33 oC) temperature after challenge by 10 5 plaque-forming units of SARS-CoV-2. RESULTS: The nasal turbinate, trachea, and lung viral load and live virus titre were significantly higher (~0.5-log10 gene copies/s-actin, p<0.05) in the low temperature group at 7 days post-infection (dpi). The low temperature group also demonstrated significantly higher level of TNF-α, IFN-I³, IL-1s, and CCL3, and lower level of the antiviral IFN-α in lung tissues at 4dpi than the other two groups. Their lungs were grossly and diffusely haemorrhagic, with more severe and diffuse alveolar and peribronchiolar inflammatory infiltration, bronchial epithelial cell death, and significantly higher mean total lung histology scores. By 7dpi, the low temperature group still showed persistent and severe alveolar inflammation and haemorrhage, and little alveolar cell proliferative changes of recovery. The viral loads in the oral swabs of the low temperature group were significantly higher from 10-17dpi by about 0.5-1.0-log10 gene copies/s-actin. The mean neutralizing antibody titre of the low temperature group was significantly (p<0.05) lower than that of the room temperature group at 7dpi and 30dpi. 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.