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

Cell Res. 2021 Apr;31(4):395-403. doi: 10.1038/s41422-021-00473-1. Epub 2021 Feb 18.

Abstract

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.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / deficiency
  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Cathepsin L / genetics
  • Cathepsin L / metabolism
  • Cell Line
  • Coinfection / pathology*
  • Coinfection / virology
  • Humans
  • Influenza A virus / isolation & purification
  • Influenza A virus / physiology*
  • Lung / pathology
  • Mice
  • Mice, Transgenic
  • Orthomyxoviridae Infections / pathology*
  • Orthomyxoviridae Infections / virology
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / physiology*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Severity of Illness Index
  • Viral Load
  • Virus Internalization

Substances

  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, mouse
  • Cathepsin L