Coinfection with influenza A virus enhances SARS-CoV-2 infectivity

• Published in: Cell research Vol. 31; no. 4; pp. 395 - 403
• Main Authors: Bai, Lei, Zhao, Yongliang, Dong, Jiazhen, Liang, Simeng, Guo, Ming, Liu, Xinjin, Wang, Xin, Huang, Zhixiang, Sun, Xiaoyi, Zhang, Zhen, Dong, Lianghui, Liu, Qianyun, Zheng, Yucheng, Niu, Danping, Xiang, Min, Song, Kun, Ye, Jiajie, Zheng, Wenchao, Tang, Zhidong, Tang, Mingliang, Zhou, Yu, Shen, Chao, Dai, Ming, Zhou, Li, Chen, Yu, Yan, Huan, Lan, Ke, Xu, Ke
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.04.2021; Nature Publishing Group
• Subjects: 14/19; 38/90; 631/337/572/2102; 631/80/304; 96/109; ACE2; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - deficiency; Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Biomedical and Life Sciences; Cathepsin L - genetics; Cathepsin L - metabolism; Cell Biology; Cell Line; Coinfection - pathology; Coinfection - virology; Coronaviruses; COVID-19; COVID-19 - pathology; COVID-19 - virology; Humans; Infectivity; Influenza; Influenza A; Influenza A virus - isolation & purification; Influenza A virus - physiology; Life Sciences; Lung - pathology; Mice; Mice, Transgenic; Northern Hemisphere; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; Pandemics; Public health; SARS-CoV-2 - isolation & purification; SARS-CoV-2 - physiology; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Viral diseases; Viral Load; Virus Internalization; Viruses
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/s41422-021-00473-1

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.