A systematic review of whether COVID-19 randomized controlled trials reported on demographic and clinical characteristics.

PURPOSE: We aim to assess the reporting of key patient-level demographic and clinical characteristics among COVID-19 related randomized controlled trials (RCTs). METHODS: We queried English-language articles from PubMed, Web of Science, clinicaltrials.gov, and the CDC library of gray literature databases using keywords of "coronavirus," "covid," "clinical trial" and "randomized controlled trial" from January 2020 to June 2021. From the search, we conducted an initial review to rule-out duplicate entries, identify those that met inclusion criteria (i.e., had results), and exclude those that did not meet the definition of an RCT. Lastly, we abstracted the demographic and clinical characteristics reported on within each RCT. RESULTS: From the initial 43 627 manuscripts, our final eligible manuscripts consisted of 149 RCTs described in 137 articles. Most of the RCTs (113/149) studied potential treatments, while fewer studied vaccines (29), prophylaxis strategies (5), and interventions to prevent transmission among those infected (2). Study populations ranged from 10 to 38 206 participants (median = 100, IQR: 60-300). All 149 RCTs reported on age, 147 on sex, 50 on race, and 110 on the prevalence of at least one comorbidity. No RCTs reported on income, urban versus rural residence, or other indicators of socioeconomic status (SES). CONCLUSIONS: Limited reporting on race and other markers of SES make it difficult to draw conclusions about specific external target populations without making strong assumptions that treatment effects are homogenous. These findings highlight the need for more robust reporting on the clinical and demographic profiles of patients enrolled in COVID-19 related RCTs.

Rationale and design of the Prone Position and Respiratory Outcomes in Non-intubated COVID-19 PatiEnts: The "PRONE" Study.

While benefits of prone position in mechanically-ventilated patients have been well-described, a randomized-control trial to determine the effects of prone positioning in awake, spontaneously-breathing patients with an acute pneumonia has not been previously conducted. Prone Position and Respiratory Outcomes in Non-Intubated COVID-19 PatiEnts: the "PRONE" Study (PRONE) was conducted in non-intubated hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia as defined by respiratory rate ≥ 20/min or an oxyhemoglobin saturation (SpO2) ≤ 93% without supplemental oxygen [1]. The PRONE trial was designed to investigate the effects of prone positioning on need for escalation in respiratory support, as defined by need for transition to a higher acuity level of care, increased fraction of inspired oxygen (FiO2), or the initiation of invasive mechanical ventilation. Secondary objectives were to assess the duration of effect of prone positioning on respiratory parameters such as respiratory rate and SpO2, as well as other outcomes such as time to discharge or transition in level of care.

Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome.

BACKGROUND: Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples. METHODS: We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48-96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs. RESULTS: The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood. CONCLUSION: Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+ cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.