Journal of anesthesia, analgesia and critical care · 2026
High-flow nasal therapy vs conventional oxygen therapy in mild COVID-19 hypoxaemia: a Bayesian reanalysis of the COVID-HIGH Trial.
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Crimi Claudia, Sardo Salvatore, Noto Alberto, Madotto Fabiana, Ippolito Mariachiara, Nolasco Santi, Campisi Raffaele, Fiorentino Giuseppe, Pantazopoulos Ioannis, Chalkias Athanasios, Mattei Alessio, Scala Raffaele, Clini Enrico, Ergan Begum, Lujan Manel, Winck João Carlos, Giarratano Antonino, Carlucci Annalisa, Gregoretti Cesare, Groff Paolo, Cortegiani Andrea, COVID-HIGH Investigators
Аннотация
BACKGROUND: Clinical effectiveness of high-flow nasal therapy (HFNT) over conventional oxygen therapy (COT) in patients with mild COVID-19-related acute hypoxaemic respiratory failure (AHRF) remains uncertain. The COVID-HIGH trial did not demonstrate statistically significant benefits of HFNT over COT. However, the trial was slightly underpowered, and the event rate lower-than-expected. Bayesian methods provide deeper insight by incorporating prior knowledge and quantifying uncertainty intuitively. This analysis aimed to quantify the probability of benefit or harm associated with HFNT, adopting a Bayesian approach.
METHODS: We performed a Bayesian reanalysis of the COVID-HIGH trial (NCT, which randomised 364 patients with PaO₂/FiO₂ between 200-300 mmHg to receive HFNT or COT. The primary outcome was escalation of respiratory support (continuous positive airway pressure, noninvasive ventilation or invasive mechanical ventilation) within 28 days. A key secondary outcome was clinical recovery at day 14. Bayesian logistic models with noninformative and informative priors were used to estimate the posterior probability of treatment effects.
RESULTS: Escalation of respiratory support occurred in 23.6% (HFNT) versus 30.2% (COT) (risk difference - 6.6%, 95% CI - 15.1 to 2.1; p = 0.14). Across a wide range of priors, the posterior probability mass on the beneficial side remained high, generally > 70%, while the proportion on the harm side remained consistently low at ≤ 6% for all models, underscoring a favourable benefit-risk profile. The acute respiratory failure meta-analysis model (OR 0.76, 95% CrI 0.60-0.97), the COVID-19 randomised evidence model (OR 0.76, 95% CrI 0.60-0.97), the COVID-19 observational evidence model (OR 0.60, 95% CrI 0.45-0.80), and the COVID-19 Bayesian meta-analysis mixed evidence model (OR 0.66, 95% CrI 0.52-0.86) showed posterior probability mass on the beneficial side of 70%-94%. Clinical recovery at day 14 occurred in 61.5% (HFNT) versus 53.3% (COT), with 61-73% of posterior probability mass on the clinical benefit side.
CONCLUSIONS: This Bayesian re-analysis of the COVID-HIGH trial suggests that HFNT likely reduces escalation of respiratory support and improves clinical recovery in patients with COVID-19 pneumonia and mild hypoxaemia, although the magnitude of benefit remains uncertain and sensitive to prior assumptions.
TRIAL REGISTRATION: The trial was prospectively registered in ClinicalTrials.gov on December 7, 2020 (NCT04655638).
METHODS: We performed a Bayesian reanalysis of the COVID-HIGH trial (NCT, which randomised 364 patients with PaO₂/FiO₂ between 200-300 mmHg to receive HFNT or COT. The primary outcome was escalation of respiratory support (continuous positive airway pressure, noninvasive ventilation or invasive mechanical ventilation) within 28 days. A key secondary outcome was clinical recovery at day 14. Bayesian logistic models with noninformative and informative priors were used to estimate the posterior probability of treatment effects.
RESULTS: Escalation of respiratory support occurred in 23.6% (HFNT) versus 30.2% (COT) (risk difference - 6.6%, 95% CI - 15.1 to 2.1; p = 0.14). Across a wide range of priors, the posterior probability mass on the beneficial side remained high, generally > 70%, while the proportion on the harm side remained consistently low at ≤ 6% for all models, underscoring a favourable benefit-risk profile. The acute respiratory failure meta-analysis model (OR 0.76, 95% CrI 0.60-0.97), the COVID-19 randomised evidence model (OR 0.76, 95% CrI 0.60-0.97), the COVID-19 observational evidence model (OR 0.60, 95% CrI 0.45-0.80), and the COVID-19 Bayesian meta-analysis mixed evidence model (OR 0.66, 95% CrI 0.52-0.86) showed posterior probability mass on the beneficial side of 70%-94%. Clinical recovery at day 14 occurred in 61.5% (HFNT) versus 53.3% (COT), with 61-73% of posterior probability mass on the clinical benefit side.
CONCLUSIONS: This Bayesian re-analysis of the COVID-HIGH trial suggests that HFNT likely reduces escalation of respiratory support and improves clinical recovery in patients with COVID-19 pneumonia and mild hypoxaemia, although the magnitude of benefit remains uncertain and sensitive to prior assumptions.
TRIAL REGISTRATION: The trial was prospectively registered in ClinicalTrials.gov on December 7, 2020 (NCT04655638).