Efficacy of Inhaled Ciclesonide for Outpatient Treatment of Adolescents and Adults With Symptomatic COVID-19: A Randomized Clinical Trial.

Importance: Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear. Objective: To determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19-related symptoms among nonhospitalized participants with symptomatic COVID-19 infection. Design, Setting, and Participants: This phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020. Interventions: Participants were randomly assigned to receive ciclesonide MDI, 160 µg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 µg) or placebo for 30 days. Main Outcomes and Measures: The primary end point was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19. Results: A total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19-related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study. Conclusions and Relevance: The results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19-related symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04377711.

Evidence-based crisis standards of care for out-of-hospital cardiac arrests in a pandemic.

BACKGROUND & PURPOSE: Pandemics such as COVID-19 can lead to severe shortages in healthcare resources, requiring the development of evidence-based Crisis Standard of Care (CSC) protocols. A protocol that limits the resuscitation of out-of-hospital cardiac arrests (OHCA) to events that are more likely to result in a positive outcome can lower hospital burdens and reduce emergency medical services resources and infection risk, although it would come at the cost of lives lost that could otherwise be saved. Our primary objective was to evaluate candidate OHCA CSC protocols involving known predictors of survival and identify the protocol that results in the smallest resource burden, as measured by the number of hospitalizations required per favorable OHCA outcome achieved. Our secondary objective was to describe the effects of the CSC protocols in terms of health outcomes and other measures of resource burden. METHODS: We conducted a retrospective cohort study of adult patients in the Cardiac Arrest Registry to Enhance Survival (CARES) database. Non-traumatic OHCA events from 2018 were included (n = 79,533). Candidate CSC protocols involving combinations of known predictors of good survival for OHCA were applied to the existing dataset to measure the resulting numbers of resuscitation attempts, transportations to hospital, hospital admissions, and favorable neurological outcomes. These outcomes were also assessed under Standard Care, defined as no CSC protocol applied to the data. RESULTS: The CSC protocol with the smallest number of hospitalizations per survivor with a favorable neurological outcome was that an OHCA resuscitation should only be attempted if the arrest was witnessed by emergency medical services or the first monitored rhythm was shockable (number of hospitalizations: 2.26 [95% CI: 2.21-2.31] vs. 3.46 [95% CI: 3.39-3.53] under Standard Care). This rule resulted in significant reductions in resource utilization (46.1% of hospitalizations and 29.2% of resuscitation attempts compared to Standard Care) while still preserving 70.5% of the favorable neurological outcomes under Standard Care. For every favorable neurological outcome lost under this CSC protocol, 6.3 hospital beds were made free that could be used to treat other patients. CONCLUSION: In a pandemic scenario, pre-hospital CSC protocols that might not otherwise be considered have the potential to greatly improve overall survival, and this study provides an evidence-based approach towards selecting such a protocol. As this study was performed using data generated before the COVID-19 pandemic, future studies incorporating pandemic-era data will further help develop evidence-based CSC protocols.

Symptom Criteria for COVID-19 Testing of Heath Care Workers.

BACKGROUND: Symptom criteria for COVID-19 testing of heath care workers (HCWs) limitations on testing availability have been challenging during the COVID-19 pandemic. An evidence-based symptom criteria for identifying HCWs for testing, based on the probability of positive COVID-19 test results, would allow for a more appropriate use of testing resources. METHODS: This was an observational study of outpatient COVID-19 testing of HCWs. Prior to testing, HCWs were asked about the presence of 10 symptoms. Their responses were then compared to their subsequent pharyngeal swab COVID-19 polymerase chain reaction test results. These data were used to derive and evaluate a symptom-based testing criteria. RESULTS: A total of 961 HCWs were included in the analysis, of whom 225 (23%) had positive test results. Loss of taste or smell was the symptom with the largest positive likelihood ratio (3.33). Dry cough, regardless of the presence or absence of other symptoms, was the most sensitive (74%) and the least specific (32%) symptom. The existing testing criteria consisting of any combination of one or more of three symptoms (fever, shortness of breath, dry cough) was 93% sensitive and 9% specific (area unce the curve [AUC] = 0.63, 95% confidence interval [CI] = 0.59 to 0.67). The derived testing criteria consisting of any combination of one or more of two symptoms (fever, loss of taste or smell) was 89% sensitive and 48% specific (AUC = 0.75, 95% CI = 0.71 to 0.78). The hybrid testing criteria consisting of any combination of one or more of four symptoms (fever, shortness of breath, dry cough, loss of taste or smell) was 98% sensitive and 8% specific (AUC = 0.77, 95% CI = 0.73 to 0.80). CONCLUSION: An evidence-based approach to COVID-19 testing that at least includes fever and loss of taste or smell should be utilized when determining which HCWs should be tested.