Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract

Nat Rev Microbiol. 2021 Jul;19(7):425-441. doi: 10.1038/s41579-021-00542-7. Epub 2021 Apr 6.


Influenza viruses cause annual epidemics and occasional pandemics of respiratory tract infections that produce a wide spectrum of clinical disease severity in humans. The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and has since caused a pandemic. Both viral and host factors determine the extent and severity of virus-induced lung damage. The host's response to viral infection is necessary for viral clearance but may be deleterious and contribute to severe disease phenotypes. Similarly, tissue repair mechanisms are required for recovery from infection across the spectrum of disease severity; however, dysregulated repair responses may lead to chronic lung dysfunction. Understanding of the mechanisms of immunopathology and tissue repair following viral lower respiratory tract infection may broaden treatment options. In this Review, we discuss the pathogenesis, the contribution of the host response to severe clinical phenotypes and highlight early and late epithelial repair mechanisms following influenza virus infection, each of which has been well characterized. Although we are still learning about SARS-CoV-2 and its disease manifestations in humans, throughout the Review we discuss what is known about SARS-CoV-2 in the context of this broad knowledge of influenza virus, highlighting the similarities and differences between the respiratory viruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • COVID-19 / immunology
  • COVID-19 / virology*
  • Humans
  • Influenza, Human / immunology
  • Influenza, Human / virology*
  • Orthomyxoviridae / physiology*
  • Respiratory System / virology*
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / virology*
  • SARS-CoV-2 / physiology*