Microbial dynamics and pulmonary immune responses in COVID-19 secondary bacterial pneumonia
Authors: Spottiswoode Natasha , Tsitsiklis Alexandra , Chu Victoria T. , Phan Hoang Van , DeVoe Catherine , Love Christina , Ghale Rajani , Bloomstein Joshua , Zha Beth Shoshana , Maguire Cole P. , Glascock Abigail , Sarma Aartik , Mourani Peter M. , Kalantar Katrina L. , Detweiler Angela , Neff Norma , Haller Sidney C. ,   COMET Consortium, Caldera Saharai , Doernberg Sarah B. , Mick Eran , Van Phan Hoang , Serpa Paula Hayakawa , Lee Deanna , Phelps Maira , Calfee Carolyn S. , Chak Suzanna , Christenson Stephanie , Eckalbar Walter L. , Erle David J. , Jauregui Alejandra , Jones Chayse , Leroux Carolyn , Matthay Michael , Neyton Lucile P. A. , Nguyen Viet , Sigman Austin , Willmore Andrew , Woodruff Prescott G. , Adkisson Michael , Asthana Saurabh , Collins Zachary , Fragiadakis Gabriela K. , Maliskova Lenka , Patel Ravi , Rao Arjun , Samad Bushra , Schroeder Andrew , Shaw Cole , Kangelaris Kirsten N. , Kushnoor Divya , Lea Tasha , Hu Kenneth , Shen Alan , Tsui Jessica , Bueno Raymund , Lee David , Sun Yang , Tumurbaatar Erden , Ward Alyssa , van der Wijst Monique , Ye Jimmie , Ansel K. Mark , Chan Vincent , Hiam Kamir , McCarthy Elizabeth , Muñoz-Sandoval Priscila , Ogorodnikov Anton , Spitzer Matthew , Zhu Wandi S. , Gordon Gracie , Hartoularos George , Rashid Sadeed , Rodriguez Nicklaus , Tang Kevin , Altamirano Luz Torres , Whatley Alexander , Song Yun S. , Leligdowicz Aleksandra , Wilson Michael , Chew Nayvin , Combes Alexis , Courau Tristan , Jones Norman , Milush Jeff , Kumar Nitasha , Huang Billy , Mahboob Salman , Parada Randy , Reeder Gabriella , DeRisi Joseph L. , Erle David J. , Hendrickson Carolyn M. , Kangelaris Kirsten N. , Krummel Matthew F. , Matthay Michael A. , Woodruff Prescott G. , Calfee Carolyn S. , Langelier Charles R. 
Published: October 2024

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.