Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome

Abstract

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Tissue Specific Age Dependence of the Cell Receptors Involved in the SARS-CoV-2 Infection

“…Data from PBMCs and cell lines were excluded. For validation purposes, we have further secured data from a second cohort of 142 patients from the NYU Langone Health Manhattan campus that required invasive mechanical ventilation 16 .…”

Dynamics of the Upper Respiratory Tract Microbiota and Its Association with Mortality in COVID-19

“…First, although pharyngeal microbiota can potentially serve as a proxy for the lower respiratory tract (LRT) microbiota( 42), an investigation of the lung microbiota would be more valuable to reveal the host-microbiome interactions in COVID-19. Unfortunately, it is hard to collect serial LRT samples due to practicalities and safety concerns (43). Second, many confounding factors related to the severity of the disease could potentially influence the URT microbiota, including the use of antibiotics, diet, and intubation, although multivariate regression analysis had been applied, we cannot fully control for the confounding effect due to the limited sample size and unavailability of some data.…”

The Upper Airway Microbiome and Lung Injury in COVID-19

“…Even as this was from the pre-antibiotic era, the findings have been foundational knowledge for bacterial-viral co-pathogenesis. In contrast to general agreement on the importance of bacterial superinfection in influenza infection, the role of bacterial co-pathogenesis in COVID-19 is less clear (2)(3)(4)(5) and interactions may operate through indirect pathways.…”