Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 µg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 µg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care.

BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. CLINICAL TRIALS REGISTRATION: NCT04292899 and EUPAS34303.

From Testing to Decision-Making: A Data-Driven Analytics COVID-19 Response.

In March 2020, NorthShore University Health System laboratories mobilized to develop and validate polymerase chain reaction based testing for detection of SARS-CoV-2. Using laboratory data, NorthShore University Health System created the Data Coronavirus Analytics Research Team to track activities affected by SARS-CoV-2 across the organization. Operational leaders used data insights and predictions from Data Coronavirus Analytics Research Team to redeploy critical care resources across the hospital system, and real-time data were used daily to make adjustments to staffing and supply decisions. Geographical data were used to triage patients to other hospitals in our system when COVID-19 detected pavilions were at capacity. Additionally, one of the consequences of COVID-19 was the inability for patients to receive elective care leading to extended periods of pain and uncertainty about a disease or treatment. After shutting down elective surgeries beginning in March of 2020, NorthShore University Health System set a recovery goal to achieve 80% of our historical volumes by October 1, 2020. Using the Data Coronavirus Analytics Research Team, our operational and clinical teams were able to achieve 89% of our historical volumes a month ahead of schedule, allowing rapid recovery of surgical volume and financial stability. The Data Coronavirus Analytics Research Team also was used to demonstrate that the accelerated recovery period had no negative impact with regard to iatrogenic COVID-19 infection and did not result in increased deep vein thrombosis, pulmonary embolisms, or cerebrovascular accident. These achievements demonstrate how a coordinated and transparent data-driven effort that was built upon a robust laboratory testing capability was essential to the operational response and recovery from the COVID-19 crisis.

Emergency department bounceback characteristics for patients diagnosed with COVID-19.

BACKGROUND: The global healthcare burden of COVID-19 continues to rise. There is currently limited information regarding the disease progression and the need for hospitalizations in patients who present to the Emergency Department (ED) with minimal or no symptoms. OBJECTIVES: This study identifies bounceback rates and timeframes for patients who return to the ED due to COVID-19 after initial discharge on the date of testing. METHODS: Using the NorthShore University Health System's (NSUHS) Enterprise Data Warehouse (EDW), we conducted a retrospective cohort analysis of patients who were tested positive for COVID-19 and were discharged home on the date of testing. A one-month follow-up period was included to ensure the capture of disease progression. RESULTS: Of 1883 positive cases with initially mild symptoms, 14.6% returned to the ED for complaints related to COVID-19. 56.9% of the mildly symptomatic bounceback patients were discharged on the return visit while 39.5% were admitted to the floor and 3.6% to the ICU. Of the 1120 positive cases with no initial symptoms, only four returned to the ED (0.26%) and only one patient was admitted. Median initial testing occurred on day 3 (2-5.6) of illness, and median ED bounceback occurred on day 9 (6.3-12.7). Our statistical model was unable to identify risk factors for ED bouncebacks. CONCLUSION: COVID-19 patients diagnosed with mild symptoms on initial presentation have a 14.6% rate of bounceback due to progression of illness.