Creation and impact of containment units with high-risk zones during the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) required swift preparation to protect healthcare personnel (HCP) and patients, especially considering shortages of personal protective equipment (PPE). Due to the lack of a pre-existing biocontainment unit, we needed to develop a novel approach to placing patients in isolation cohorts while working with the pre-existing physical space. OBJECTIVES: To prevent disease transmission to non-COVID-19 patients and HCP caring for COVID-19 patients, to optimize PPE usage, and to provide a comfortable and safe working environment. METHODS: An interdisciplinary workgroup developed a combination of approaches to convert existing spaces into COVID-19 containment units with high-risk zones (HRZs). We developed standard workflow and visual management in conjunction with updated staff training and workflows. The infection prevention team created PPE standard practices for ease of use, conservation, and staff safety. RESULTS: The interventions resulted in 1 possible case of patient-to-HCP transmission and zero cases of patient-to-patient transmission. PPE usage decreased with the HRZ model while maintaining a safe environment of care. Staff on the COVID-19 units were extremely satisfied with PPE availability (76.7%) and efforts to protect them from COVID-19 (72.7%). Moreover, 54.8% of HCP working in the COVID-19 unit agreed that PPE monitors played an essential role in staff safety. CONCLUSIONS: The HRZ model of containment unit is an effective method to prevent the spread of COVID-19 with several benefits. It is easily implemented and scaled to accommodate census changes. Our experience suggests that other institutions do not need to modify existing physical structures to create similarly protective spaces.

Rapid analysis of local data to inform off-label tocilizumab use early in the COVID-19 pandemic.

The interleukin-6 receptor antagonist tocilizumab became widely used early in the coronavirus disease 2019 (COVID-19) pandemic based on small observational studies that suggested clinical benefit in COVID-19 patients with a hyperinflammatory state. To inform our local treatment algorithms in the absence of randomized clinical trial results, we performed a rapid analysis of the first 11 hospitalized COVID-19 patients treated with tocilizumab at our academic medical center. We report their early clinical outcomes and describe the process by which we assembled a team of diverse trainees and stakeholders to extract, analyze, and disseminate data during a time of clinical uncertainty.

Randomized, Placebo-controlled Trial of Inhaled Treprostinil for Patients at Risk for Acute Respiratory Distress Syndrome.

Rationale: Inhaled treprostinil may improve oxygenation and have additional antiinflammatory effects in early acute hypoxemic respiratory failure, potentially preventing or reducing the severity of acute respiratory distress syndrome (ARDS).Objectives: To determine whether administration of inhaled treprostinil to patients at risk for ARDS is feasible, safe, and efficacious.Methods: We performed a double-blind, placebo-controlled, single-center randomized pilot trial at a quaternary care academic medical center. Patients with acute hypoxemia due to pneumonia or signs of low-pressure pulmonary edema with a unilateral or bilateral infiltrate on chest imaging and a 4 L/min supplemental oxygen requirement not requiring positive pressure ventilation were evaluated. Randomized patients received study drug or placebo (2:1 ratio). Treatment was initiated at 6 breaths every 4 hours and titrated up to 12 breaths. Subjects were maintained on treatment for 7 days and then tapered off over a period of 4 days. Study drug was stopped if positive pressure ventilation was required (invasive or noninvasive).Results: Fourteen patients were enrolled over a period of 31 months. Baseline characteristics were not significantly different between treatment groups with respect to age, sex, race, Acute Physiologic Assessment and Chronic Health Evaluation score, lung injury prediction score, or baseline mean oxygen saturation as measured by pulse oximetry (SpO2):fraction of inspired oxygen (FiO2) ratio. Trends in daily baseline and 30-minute postdose SpO2:FiO2 ratio for all treatment points were not significantly different between placebo and treprostinil. Four patients required positive pressure ventilation in the treprostinil group versus one in the placebo group.Conclusions: Inhaled treprostinil administration is feasible in patients at risk for ARDS but was not associated with improvement in the SpO2:FiO2 ratio relative to placebo. Drug-associated adverse events were not severe nor unexpected based on the known adverse effect profile of inhaled treprostinil. The clinical benefit of this intervention is unclear at this time in the absence of larger studies.Clinical trial registered with Clinicaltrials.gov (NCT02370095).

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.