H1N1 exposure during the convalescent stage of SARS-CoV-2 infection results in enhanced lung pathologic damage in hACE2 transgenic mice

Emerg Microbes Infect. 2021 Dec;10(1):1156-1168. doi: 10.1080/22221751.2021.1938241.

Abstract

ABSTRACTThe risk of secondary infection with SARS-CoV-2 and influenza A virus is becoming a practical problem that must be addressed as the flu season merges with the COVID-19 pandemic. As SARS-CoV-2 and influenza A virus have been found in patients, understanding the in vivo characteristics of the secondary infection between these two viruses is a high priority. Here, hACE2 transgenic mice were challenged with the H1N1 virus at a nonlethal dose during the convalescent stage on 7 and 14 days post SARS-CoV-2 infection, and importantly, subsequent H1N1 infection showed enhanced viral shedding and virus tissue distribution. Histopathological observation revealed an extensive pathological change in the lungs related to H1N1 infection in mice recovered from SARS-CoV-2 infection, with severe inflammation infiltration and bronchiole disruption. Moreover, upon H1N1 exposure on 7 and 14 dpi of SARS-CoV-2 infection, the lymphocyte population activated at a lower level with T cell suppressed in both PBMC and lung. These findings will be valuable for evaluating antiviral therapeutics and vaccines as well as guiding public health work.

Keywords: H1N1; SARS-CoV-2; alternate infection; convalescent stage; hACE2 transgenic mice.

MeSH terms

  • Acute Lung Injury / pathology*
  • Acute Lung Injury / virology
  • Angiotensin-Converting Enzyme 2 / genetics*
  • Animals
  • COVID-19 / pathology*
  • COVID-19 / therapy
  • Coinfection / pathology
  • Coinfection / virology
  • Cytokines / blood
  • Disease Models, Animal
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / isolation & purification
  • Lung / pathology
  • Lymphocyte Count
  • Lymphocytes / immunology
  • Mice
  • Mice, Transgenic
  • Orthomyxoviridae Infections / pathology*
  • Orthomyxoviridae Infections / therapy
  • SARS-CoV-2 / isolation & purification
  • Viral Load
  • Virus Replication / physiology
  • Virus Shedding / physiology

Substances

  • Cytokines
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grants and funding

This work was supported by National Natural Science Foundation of China [Grant Number 32070923] and CAMS Initiative for Innovative Medicine [Grant Numbers 2016-I2M-1-014; 2020-I2M-2-014].