Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Department of Microbiology, National Veterinary Institute Uppsala, Sweden.
J Infect Dis. 2023 Feb 14;227(4):543-553. doi: 10.1093/infdis/jiac452.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40%-100% of the population, which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-19 symptoms. This effect could contribute to the disparity of disease severity seen in ethnic minorities and those with lower socioeconomic status, due to their higher CMV seroprevalence. Our results warrant further clinical investigation as to whether HCMV infection influences the pathogenesis of SARS-CoV-2.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是导致 2019 年冠状病毒病（COVID-19）的病原体，自 2019 年末爆发以来，已造成广泛的发病率和死亡率。在这里，我们证明人类巨细胞病毒（HCMV）的先前感染会大大增加 SARS-CoV-2 的体外感染。HCMV 是一种常见的疱疹病毒，在 40%-100%的人群中携带，在肺部炎症条件下（例如由 SARS-CoV-2 感染引起的炎症条件下）会重新激活。我们在血管内皮细胞和上皮细胞类型中都表明，HCMV 感染会上调 SARS-CoV-2 的细胞进入受体 ACE2。这些观察结果表明，健康的 HCMV 携带者肺部的 HCMV 再激活事件可能会加重 SARS-CoV-2 感染和随后的 COVID-19 症状。由于少数族裔和社会经济地位较低的人群的 CMV 血清阳性率较高，因此这种影响可能导致疾病严重程度的差异。我们的研究结果表明，需要进一步进行临床研究，以确定 HCMV 感染是否会影响 SARS-CoV-2 的发病机制。
