State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, Hainan, China.
Clin Infect Dis. 2022 Aug 24;75(1):e1101-e1111. doi: 10.1093/cid/ciab817.
The effect of low environmental temperature on viral shedding and disease severity of Coronavirus Disease 2019 (COVID-19) is uncertain.
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).
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.
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.
环境低温对 2019 年冠状病毒病(COVID-19)病毒脱落和疾病严重程度的影响尚不确定。
我们研究了在严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)105 噬菌斑形成单位攻击后,在室温(21°C)、低温(12-15°C)和高温(30-33°C)下饲养的仓鼠的病毒学、临床、病理学和免疫学变化。
在感染后 7 天(dpi),低温组的鼻甲骨、气管和肺部病毒载量和活病毒滴度显著升高(~0.5-log10 基因拷贝/β-肌动蛋白,P<.05)。与其他两组相比,低温组在感染后 4 dpi 时肺部组织中的肿瘤坏死因子-α、干扰素-γ(IFN-γ)、白细胞介素-1β和 C-C 基序趋化因子配体 3 的水平显著升高,抗病毒 IFN-α的水平显著降低。它们的肺组织大体上广泛出血,肺泡和细支气管周围炎症浸润更严重、更广泛,支气管上皮细胞死亡,总肺组织学评分显著升高。到 7 dpi 时,低温组仍表现出持续而严重的肺泡炎症和出血,肺泡细胞增殖恢复变化很小。在感染后 10 至 17 dpi 期间,低温组口腔拭子中的病毒载量比其他两组高约 0.5-1.0 log10 基因拷贝/β-肌动蛋白。与室温组相比,低温组在 7 dpi 和 30 dpi 时的平均中和抗体滴度显著降低(P<.05)。
本研究提供了体内证据,表明低温环境加重了 SARS-CoV-2 感染仓鼠的病毒脱落程度、疾病严重程度和组织促炎细胞因子/趋化因子表达,并抑制了中和抗体反应。冬季保暖可能会降低 COVID-19 的严重程度。