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Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome

2021; Nature Portfolio; Volume: 6; Issue: 10 Linguagem: Inglês

10.1038/s41564-021-00961-5

2058-5276

Imran Sulaiman, Matthew Chung, Luis F. Angel, Jun-Chieh J. Tsay, Benjamin G. Wu, Stephen T. Yeung, K. Krolikowski, Yonghua Li, Ralf Duerr, Rosemary Schluger, Sara A. Thannickal, Akiko Koide, Samaan Rafeq, C.R. Barnett, Radu Postelnicu, Chang Wang, Stephanie Banakis, Lizzette Pérez-Pérez, Guomiao Shen, George Jour, Peter Meyn, Joseph Carpenito, Xiuxiu Liu, Kun Ji, Destiny Collazo, Anthony Labarbiera, Nancy Amoroso, Shari B. Brosnahan, Vikramjit Mukherjee, David A. Kaufman, Jan Bakker, Anthony Lubinsky, Deepak Pradhan, Daniel H. Sterman, Michael D. Weiden, Adriana Heguy, Laura Evans, Timothy M. Uyeki, José C. Clemente, Emmie de Wit, Ann Marie Schmidt, Bo Shopsin, Ludovic Desvignes, Chan Wang, Huilin Li, Bin Zhang, Christian V. Forst, Shohei Koide, Kenneth A. Stapleford, Kamal M. Khanna, Elodie Ghedin, Leopoldo N. Segal,

COVID-19 Clinical Research Studies

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2. Analysis of lower respiratory tract microbiome of mechanically ventilated COVID-19 patients rules out a role for secondary respiratory infections as drivers of increased mortality.