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  3. Biological Rhythms In Coronavirus Pneumonia Pathogenesis.

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Biological Rhythms in Coronavirus Pneumonia Pathogenesis.

Huram Mok1, Carrie Gierasch1, Elaine Ostendorf1

  • 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.

Journal of Biological Rhythms
|June 17, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

The timing of coronavirus infection significantly impacts disease severity, particularly in males. Alveolar macrophages play a key role in this time-dependent immune response, influencing outcomes in mouse hepatitis virus-1 pneumonia.

Keywords:
COVID-19MERSMHV-1SARSalveolar macrophagecircadiancoronavirusdiurnal

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Published on: November 10, 2023

Area of Science:

  • Immunology
  • Chronobiology
  • Virology

Background:

  • Night shift work is associated with increased severity of coronavirus pneumonia.
  • Host resilience to pathogens may depend on the timing of exposure.
  • Circadian rhythms influence various physiological processes, including immune responses.

Purpose of the Study:

  • To investigate the influence of the time of day on the severity of coronavirus pneumonia in a mouse model.
  • To identify the specific immune cells and mechanisms involved in time-dependent disease outcomes.

Main Methods:

  • Used mouse hepatitis virus-1 (MHV-1) as a natural infection model in mice.
  • Infected mice at different times of day to assess disease severity, viral load, and lung inflammation.
  • Examined the role of the clock gene Bmal1 and alveolar macrophages (AMs) in time-dependent disease severity.
  • Depleted AMs using clodronate or liposomes to evaluate their contribution.

    • Main Results:

    • The timing of MHV-1 infection significantly influenced pneumonia severity, with midday infections (mid-rest phase) showing the highest mortality, viral load, and inflammation.
    • Time-of-day effects were more pronounced in male mice and were dependent on the clock gene Bmal1.
    • Midday infection led to increased MHV-1 binding and replication in alveolar macrophages.
    • Depletion or manipulation of AMs before infection abolished the time-of-day differences in survival and viral load.

    Conclusions:

    • An immunologic rhythm underlies coronavirus pneumonia outcomes.
    • Oscillations in the interaction between alveolar macrophages and the virus at the time of initial exposure shape subsequent disease severity.
    • Targeting circadian-regulated immune cell functions could offer new therapeutic strategies for viral respiratory infections.