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

Autor: Yonghua Li, David Kaufman, Peter Meyn, Nancy Amoroso, Huilin Li, Clea Barnett, Stephen T. Yeung, Bo Shopsin, Laura Evans, Luis Angel, Imran Sulaiman, Jan Bakker, Ann Marie Schmidt, Deepak Pradhan, Christian V. Forst, Ralf Duerr, Timothy M. Uyeki, Kenneth A. Stapleford, Sara A Thannickal, J. Carpenito, Vikramjit Mukherjee, Jose C. Clemente, Anthony Lubinsky, Michael D. Weiden, Guomiao Shen, Shari B. Brosnahan, Kun Ji, Lizzette Pérez-Pérez, R. Schluger, Daniel H. Sterman, Adriana Hegu, Stephanie Banakis, Xiuxiu Liu, Chang Wang, Bin Zhang, Chan Wang, Leopoldo N. Segal, Benjamin G. Wu, Destiny Collazo, Jun-Chieh J. Tsay, Radu Postelnicu, Matthew Chung, George Jour, Kamal M. Khanna, Elodie Ghedin, Emmie de Wit, Kelsey Krolikowski, Ludovic Desvignes, Samaan Rafeq, Anthony Labarbiera, Akiko Koide, Shohei Koide
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Research Square
article-version (status) pre
article-version (number) 1
medRxiv
Nat Microbiol
Popis: 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.
Databáze: OpenAIRE