Host-Microbe Metagenomics: a Lens To Refocus Our Perspective on Infectious and Inflammatory Diseases

Kalantar, Katrina; Langelier, Charles

doi:10.1128/msystems.00404-21

Cited by 1 publication

(1 citation statement)

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“…Hospital-acquired 2°BP has been especially problematic during the COVID-19 pandemic, leading to longer hospitalizations 3,6 , increased mortality 7,8 , and often involving antimicrobialresistant (AMR) pathogens 9,10 . A dynamic relationship between pathogens, the lung microbiome and the host immune response underpins the pathophysiology of pneumonia 11,12 , yet few studies have assessed the dynamics of these biological features in patients with 2°BP, leaving gaps in our understanding of this important sequela of viral illness.…”

Section: Introductionmentioning

confidence: 99%

Microbial Dynamics and Pulmonary Immune Responses in COVID-19 Secondary Bacterial Pneumonia

Langelier,

Spottiswoode,

Tsitsiklis

et al. 2024

Preprint

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Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet mechanistically remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assessed longitudinal airway microbiome dynamics and studied the pulmonary transcriptome of patients who developed 2°BP versus controls who did not. We found that 2°BP was significantly associated with both mortality and corticosteroid treatment. The pulmonary microbiome in 2°BP was characterized by increased bacterial RNA load, dominance of culture-confirmed pathogens, and lower alpha diversity. Bacterial pathogens were detectable days prior to 2°BP clinical diagnosis, and in most cases were also present in nasal swabs. Pathogen antimicrobial resistance genes were also detectable in both the lower airway and nasal samples, and in some cases were identified prior to 2°BP clinical diagnosis. Assessment of the pulmonary transcriptome revealed suppressed TNFa signaling via NF-kB in patients who developed 2°BP, and a sub-analysis suggested that this finding was mediated by corticosteroid treatment. Within the 2°BP group, we observed a striking inverse correlation between innate and adaptive immune gene expression and bacterial RNA load. Together, our findings provide fresh insights into the microbial dynamics and host immune features of COVID-19-associated 2°BP.

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