OBJECTIVETo evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19.DESIGN, SETTING, AND PARTICIPANTS Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (Ն40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021.INTERVENTION Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). MAIN OUTCOMES AND MEASURESThe primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. RESULTS Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, −6.37% [95% CI, −15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, −1.15% [95% CI, −9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. CONCLUSIONS AND RELEVANCEIn patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit.

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.

Few studies have discussed the role of peritoneal dialysis (PD) in managing acute kidney injury (AKI) in critically ill patients. The present study compares the outcome of AKI in intensive care unit (ICU) patients randomized to treatment with tidal PD (TPD) or continuous venovenous hemodiafiltration (CVVHDF). One hundred and twenty-five ICU patients with AKI were randomly allotted to CVVHDF, (Group A, N = 62) or TPD, (group B, N = 63). Cause and severity of renal injury were assessed at the time of initiating dialysis. The primary outcome was hospital mortality at 28 days, and secondary outcomes were time to recovery of renal function, duration of stay in the ICU, metabolic and fluid control, and improvement of sensorial and hemodynamic parameters. No statistically significant differences were observed between groups in regard to patients' characteristics. The survival at 28 days was significantly better in the patients treated with TPD when compared to CVVHDF (69.8% vs. 46.8%, P < 0.01). Infectious complications were significantly less (P < 0.01) in the TPD group (9.5%) when compared to the CVVHDF group (17.7%). Recovery of kidney function (60.3% vs. 35.5%), median time to resolution of AKI and the median duration of ICU stay of 9 days (7-11) vs. 19 days (13-20) were all in favor of TPD (P < 0.01). This study suggests that there are better outcomes with TPD compared to CRRT in the treatment of critically ill patients with AKI.

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