Time-Dependent Increase in Susceptibility and Severity of Secondary Bacterial Infection during SARS-CoV-2 Infection

  1. Amanda P. Smith
  2. Evan P. Williams
  3. Taylor R. Plunkett
  4. Muneeswaran Selvaraj
  5. Lindey C. Lane
  6. Lillian Zalduondo
  7. Yi Xue
  8. Peter Vogel
  9. Rudragouda Channappanavar
  10. Colleen B. Jonsson
  11. Amber M. Smith

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Abstract

Secondary bacterial infections can exacerbate SARS-CoV-2 infection, but their prevalence and impact remain poorly understood. Here, we established that a mild to moderate SARS-CoV-2 infection increased the risk of pneumococcal coinfection in a time-dependent, but sexindependent, manner in the transgenic K18-hACE mouse model of COVID-19. Bacterial coinfection was not established at 3 d post-virus, but increased lethality was observed when the bacteria was initiated at 5 or 7 d post-virus infection (pvi). Bacterial outgrowth was accompanied by neutrophilia in the groups coinfected at 7 d pvi and reductions in B cells, T cells, IL-6, IL-15, IL-18, and LIF were present in groups coinfected at 5 d pvi. However, viral burden, lung pathology, cytokines, chemokines, and immune cell activation were largely unchanged after bacterial coinfection. Examining surviving animals more than a week after infection resolution suggested that immune cell activation remained high and was exacerbated in the lungs of coinfected animals compared with SARS-CoV-2 infection alone. These data suggest that SARS-CoV-2 increases susceptibility and pathogenicity to bacterial coinfection, and further studies are needed to understand and combat disease associated with bacterial pneumonia in COVID-19 patients.

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    SciScore for 10.1101/2022.02.28.482305: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIACUC: All experimental procedures were performed under protocol 20-0132 approved by the Animal Care and Use Committee at University of Tennessee Health Science Center (UTHSC) under relevant institutional and American Veterinary Medical Association (AVMA) guidelines and were performed in a biosafety level 3 facility that is accredited by the American Association for Laboratory Animal Science (AALAS).
    Sex as a biological variableMice: Adult (10-13 week old) male and female K18-hACE2 transgenic mice (B6.Cg-Tg(K18-ACE2)2Prlmn/J) were obtained from Jackson Laboratories (Bar Harbor, ME).
    Randomizationnot detected.
    BlindingStained sections were counterstained with hematoxylin, dehydrated, and …
  2. Version published to 10.1101/2022.02.28.482305v1 on bioRxiv