Microbial dynamics and pulmonary immune responses in COVID-19 secondary bacterial pneumonia

Natasha Spottiswoode, Alexandra Tsitsiklis, Victoria T. Chu, Hoang Van Phan, Catherine DeVoe, Christina Love, Rajani Ghale, Joshua Bloomstein, Beth Shoshana Zha, Cole P. Maguire, Abigail Glascock, Aartik Sarma, Peter M. Mourani, Katrina L. Kalantar, Angela Detweiler, Norma Neff, Sidney C. Haller, Joseph L. DeRisi, David J. Erle, Carolyn M. Hendrickson, Kirsten N. Kangelaris, Matthew F. Krummel, Michael A. Matthay, Prescott G. Woodruff, Carolyn S. Calfee and Charles R. Langelier ()
Additional contact information
Natasha Spottiswoode: University of California
Alexandra Tsitsiklis: University of California
Victoria T. Chu: University of California
Hoang Van Phan: University of California
Catherine DeVoe: University of California
Christina Love: University of California
Rajani Ghale: University of California
Joshua Bloomstein: University of Washington
Beth Shoshana Zha: University of California
Cole P. Maguire: University of Texas
Abigail Glascock: Chan Zuckerberg Biohub San Francisco
Aartik Sarma: University of California
Peter M. Mourani: Arkansas Children’s
Katrina L. Kalantar: Chan Zuckerberg Initiative
Angela Detweiler: Chan Zuckerberg Biohub San Francisco
Norma Neff: Chan Zuckerberg Biohub San Francisco
Sidney C. Haller: University of California
Joseph L. DeRisi: Chan Zuckerberg Biohub San Francisco
David J. Erle: University of California
Carolyn M. Hendrickson: University of California
Kirsten N. Kangelaris: University of California
Matthew F. Krummel: University of California
Michael A. Matthay: University of California
Prescott G. Woodruff: University of California
Carolyn S. Calfee: University of California
Charles R. Langelier: University of California

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assess longitudinal airway microbiome dynamics and the pulmonary transcriptome of patients who developed 2°BP versus controls who did not. We find that 2°BP is significantly associated with both mortality and corticosteroid treatment. The pulmonary microbiome in 2°BP is characterized by increased bacterial RNA mass and dominance of culture-confirmed pathogens, detectable days prior to 2°BP clinical diagnosis, and frequently also present in nasal swabs. Assessment of the pulmonary transcriptome reveals suppressed TNFα signaling in patients with 2°BP, and sensitivity analyses suggest this finding is mediated by corticosteroid treatment. Further, we find that increased bacterial RNA mass correlates with reduced expression of innate and adaptive immunity genes in both 2°BP patients and controls. Taken together, our findings provide fresh insights into the microbial dynamics and host immune features of COVID-19-associated 2°BP, and suggest that suppressed immune signaling, potentially mediated by corticosteroid treatment, permits expansion of opportunistic bacterial pathogens.

Date: 2024
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DOI: 10.1038/s41467-024-53566-x

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