High-Flow Nasal Cannula Outcomes in COVID-19-Associated Acute Hypoxemic Respiratory Failure: Illness Severity, Awake Prone Positioning, and Risk of Intubation in a Single-Center ICU Cohort

Background and Objectives: High-flow nasal cannula (HFNC) is widely used in acute hypoxemic respiratory failure, yet predictors of successful noninvasive support and the role of awake prone positioning remain incompletely defined, and observational analyses are vulnerable to immortal-time bias. We evaluated factors associated with HFNC success and the association of awake prone positioning with HFNC outcomes in critically ill adults with COVID-19-associated acute hypoxemic respiratory failure, using analyses designed to reduce time-related and indication-related bias. Materials and Methods: In this retrospective, single-center intensive care unit (ICU) cohort study, adults with virologically confirmed COVID-19 who received HFNC, with awake prone positioning considered as part of the initial HFNC strategy, between April 2020 and December 2021 were followed from HFNC initiation until endotracheal intubation or ICU discharge. HFNC success was defined as avoidance of intubation during the index ICU stay. Multivariable logistic regression with multiple imputation of missing covariates, propensity score-based inverse probability of treatment weighting (IPTW), and landmark time-to-event analyses were used to assess the association between awake prone positioning and HFNC failure.