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Peer-reviewedCC BYMicrobiome

Immunosuppression is associated with loss of airway microbiome resilience in severe COVID-19.

  • Matthew Chung1
  • Clea R Barnett2,3
  • Lars Hunger4
  • Imran Sulaiman2,3
  • Benjamin G Wu2,3,5
  • Yonghua Li2,3
  • Jun-Chieh J Tsay2,3,5
  • Shari B Brosnahan2,3
  • Cecilia J Chung3
  • Luis Angel2,3
  • Gregg J Silverman6
  • James T Morton4
2 more authors
  • Leopoldo N Segal2,3,5,7
  • Elodie Ghedin8
8 affiliations
  1. 1Systems Genomics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  2. 2Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
  3. 3Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
  4. 4Gutz Technologies, Corvina, CA, USA.
  5. 5Division of Pulmonary and Critical Care Medicine, VA New York Harbor Healthcare System, New York, NY, USA.
  6. 6Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
  7. 7Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
  8. 8Systems Genomics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. [email protected].
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Abstract

Background

The role of the lower airway microbiome in COVID-19-associated mortality remains poorly understood despite evidence implicating secondary pathogens and non-airway commensals. The influence of prior immunosuppression on the lower airway microbiome and its contribution to mortality in mechanically ventilated patients has been largely unexplored. Given that host-microbiome interactions are dynamic, we assessed longitudinal patterns in the respiratory microbiome associated with mortality and immunosuppression status.Results

We conducted longitudinal forecasting, differential abundance, and comparative network analyses of metatranscriptomic data from 604 upper and lower airway samples collected from 243 mechanically ventilated COVID-19 patients to profile key microbial factors associated with immunosuppression and clinical outcome. SARS-CoV-2 was enriched over time in immunosuppressed patients and in both immunosuppressed and immunocompetent patients who died, highlighting the need for aggressive viral infection control early in the disease course. Using longitudinal forecasting and differential abundance analyses, we observed a progressive increase in opportunistic pathogens, such as Staphylococcus aureus and Escherichia coli, among the taxa most predictive of mortality. Concurrently, immunosuppressed individuals exhibited a significant decrease in typical airway commensals alongside a restructuring and marked destabilization of the microbial community compared with their immunocompetent counterparts.Conclusions

These findings indicate that loss of airway microbiome stability in immunosuppressed patients constitutes an independent factor contributing to increased susceptibility to opportunistic pathogens and poor clinical outcomes. Video Abstract.

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Cite

BibTeXRIS
BibTeX
@article{chung2026immunosuppression,
  title = {{Immunosuppression is associated with loss of airway microbiome resilience in severe COVID-19.}},
  author = {Matthew Chung and Clea R Barnett and Lars Hunger and Imran Sulaiman and Benjamin G Wu and Yonghua Li and Jun-Chieh J Tsay and Shari B Brosnahan and Cecilia J Chung and Luis Angel and Gregg J Silverman and James T Morton and Leopoldo N Segal and Elodie Ghedin},
  journal = {Microbiome},
  year = {2026},
  month = jul,
  doi = {10.1186/s40168-026-02462-1},
  url = {https://europepmc.org/article/MED/42897671},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Immunosuppression is associated with loss of airway microbiome resilience in severe COVID-19.
AU  - Matthew Chung
AU  - Clea R Barnett
AU  - Lars Hunger
AU  - Imran Sulaiman
AU  - Benjamin G Wu
AU  - Yonghua Li
AU  - Jun-Chieh J Tsay
AU  - Shari B Brosnahan
AU  - Cecilia J Chung
AU  - Luis Angel
AU  - Gregg J Silverman
AU  - James T Morton
AU  - Leopoldo N Segal
AU  - Elodie Ghedin
PY  - 2026
DA  - 2026/07/01
JO  - Microbiome
DO  - 10.1186/s40168-026-02462-1
UR  - https://europepmc.org/article/MED/42897671
AB  - Background  The role of the lower airway microbiome in COVID-19-associated mortality remains poorly understood despite evidence implicating secondary pathogens and non-airway commensals. The influence of prior immunosuppression on the lower airway microbiome and its contribution to mortality in mechanically ventilated patients has been largely unexplored. Given that host-microbiome interactions are dynamic, we assessed longitudinal patterns in the respiratory microbiome associated with mortality and immunosuppression status.Results  We conducted longitudinal forecasting, differential abundance, and comparative network analyses of metatranscriptomic data from 604 upper and lower airway samples collected from 243 mechanically ventilated COVID-19 patients to profile key microbial factors associated with immunosuppression and clinical outcome. SARS-CoV-2 was enriched over time in immunosuppressed patients and in both immunosuppressed and immunocompetent patients who died, highlighting the need for aggressive viral infection control early in the disease course. Using longitudinal forecasting and differential abundance analyses, we observed a progressive increase in opportunistic pathogens, such as Staphylococcus aureus and Escherichia coli, among the taxa most predictive of mortality. Concurrently, immunosuppressed individuals exhibited a significant decrease in typical airway commensals alongside a restructuring and marked destabilization of the microbial community compared with their immunocompetent counterparts.Conclusions  These findings indicate that loss of airway microbiome stability in immunosuppressed patients constitutes an independent factor contributing to increased susceptibility to opportunistic pathogens and poor clinical outcomes. Video Abstract.
SN  - 2049-2618
ER  -