Abstract & Authors:展开
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.
Elodie Ghedin,Leopoldo N Segal
Imran Sulaiman,Matthew Chung,Luis Angel,Jun-Chieh J Tsay,Benjamin G Wu,Stephen T Yeung,Kelsey Krolikowski,Yonghua Li,Ralf Duerr,Rosemary Schluger,Sara A Thannickal,Akiko Koide,Samaan Rafeq,Clea 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 Brosnahan,Vikramjit Mukherjee,David Kaufman,Jan Bakker,Anthony Lubinsky,Deepak Pradhan,Daniel H Sterman,Michael Weiden,Adriana Heguy,Laura Evans,Timothy M Uyeki,Jose 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