Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS

Abstract

The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a “cytokine storm,” we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

Immediate myeloid depot for SARS-CoV-2 in the human lung

“…Endotracheal aspirate (ETA) samples were prospectively collected from seven adults requiring mechanical ventilation for the acute respiratory distress syndrome (ARDS) from COVID-19 as part of the COVID Multiphenotyping for Effective Therapies (COMET) study, as previously described 23 . Human participants were enrolled at two tertiary care hospitals in San Francisco, CA (UCSF Medical Center, Zuckerberg San Francisco General Hospital) under research protocol 20-30497 approved by the University of California San Francisco Institutional Review Board.…”

Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients

“…These cytokines are associated to an increased risk of cardiovascular hyperpermeability, multiorgan failure, and eventually death when the high cytokine concentrations are unabated over time (15)(16)(17)(18)(19)(20)(21). It is also imperative to study the lungs and the upper airways in the context of SARS, which are of paramount importance for analyzing the resultant of the local molecular pattern in the respiratory milieu, essential for understanding the dynamics of immune activation/inflammation versus regulation during COVID-19 (10,13,18,22,23). Therefore, in the present study, several soluble mediators of serum and tracheal aspirate samples from a cohort of critically ill COVID-19 patients was evaluated in a longitudinal fashion.…”

Metagenomic prediction of antimicrobial resistance in critically ill patients with lower respiratory tract infections

“…Patients were enrolled via a previously described observational cohort study [ 6 , 38 ] which was approved by the UCSF Institutional Review Board (IRB), which granted a waiver of initial consent for respiratory sampling. Informed consent was subsequently obtained from patients or their surrogates for continued study participation, following the previously detailed IRB protocol #17–24056 [ 38 ]. This research conformed to the principles of the Helsinki Declaration.…”