IMPORTANCE High-flow nasal oxygen therapy is increasingly used for acute hypoxemic respiratory failure (AHRF). OBJECTIVE To determine whether high-flow oxygen therapy decreases mortality among immunocompromised patients with AHRF compared with standard oxygen therapy. DESIGN, SETTING, AND PARTICIPANTS The HIGH randomized clinical trial enrolled 776 adult immunocompromised patients with AHRF (PaO 2 <60 mm Hg or SpO 2 <90% on room air, or tachypnea >30/min or labored breathing or respiratory distress, and need for oxygen Ն6 L/min) at 32 intensive care units (ICUs) in France between May 19, 2016, and December 31, 2017. INTERVENTIONS Patients were randomized 1:1 to continuous high-flow oxygen therapy (n = 388) or to standard oxygen therapy (n = 388). MAIN OUTCOMES AND MEASURES The primary outcome was day-28 mortality. Secondary outcomes included intubation and mechanical ventilation by day 28, PaO 2 :FIO 2 ratio over the 3 days after intubation, respiratory rate, ICU and hospital lengths of stay, ICU-acquired infections, and patient comfort and dyspnea. RESULTS Of 778 randomized patients (median age, 64 [IQR, 54-71] years; 259 [33.3%] women), 776 (99.7%) completed the trial. At randomization, median respiratory rate was 33/min (IQR, 28-39) vs 32 (IQR, 27-38) and PaO 2 :FIO 2 was 136 (IQR, 96-187) vs 128 (IQR, 92-164) in the intervention and control groups, respectively. Median SOFA score was 6 (IQR, 4-8) in both groups. Mortality on day 28 was not significantly different between groups (35.6% vs 36.1%; difference, −0.5% [95% CI, −7.3% to +6.3%]; hazard ratio, 0.98 [95% CI, 0.77 to 1.24]; P = .94). Intubation rate was not significantly different between groups (38.7% vs 43.8%; difference, −5.1% [95% CI, −12.3% to +2.0%]). Compared with controls, patients randomized to high-flow oxygen therapy had a higher PaO 2 :FIO 2 (150 vs 119; difference, 19.5 [95% CI, 4.4 to 34.6]) and lower respiratory rate after 6 hours (25/min vs 26/min; difference, −1.8/min [95% CI, −3.2 to −0.2]). No significant difference was observed in ICU length of stay (8 vs 6 days; difference, 0.6 [95% CI, −1.0 to +2.2]), ICU-acquired infections (10.0% vs 10.6%; difference, −0.6% [95% CI, −4.6 to +4.1]), hospital length of stay (24 vs 27 days; difference, −2 days [95% CI, −7.3 to +3.3]), or patient comfort and dyspnea scores. CONCLUSIONS AND RELEVANCE Among critically ill immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly decrease day-28 mortality compared with standard oxygen therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02739451.

In neutropenic patients with severe sepsis or septic shock, survival improved over time. Aminoglycoside use and early catheter removal in patients with undocumented sepsis may improve survival. Acute noninfectious conditions are associated with increased mortality, underlining the need for thorough and repeated clinical assessments.

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.

Hospital mortality decreased significantly over the last 15 years in myeloma patients admitted to the ICU. Risk factors for death were organ failure and poor chronic health status. Early ICU admission was associated with lower mortality, suggesting opportunities for further improving survival.