Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19: A Phase 2 Randomized Clinical Trial.

Importance: Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. Objective: To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. Design, Setting, and Participants: This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. Interventions: In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule. Main Outcomes and Measures: Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase-polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. Results: Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to 72.73%) of participants receiving placebo had oropharyngeal SARS-CoV-2 clearance at day 3 (P = .37). Among 63 participants with symptoms, niclosamide did not significantly shorten symptom duration, which was 12.01 (95% CI, 8.82 to 15.2) days in the niclosamide group vs 14.61 (95% CI, 11.25 to 17.96) days in the placebo group (mean difference, -2.6 [95% CI, -7.23 to 2.03] days). Niclosamide was well-tolerated; the most commonly reported adverse events in the placebo and niclosamide groups were headaches (11 patients [32.4%] vs 7 patients [21.2%]; P = .31) and cough (8 patients [23.5%] vs 7 patients [21.2%]; P = .82). Conclusions and Relevance: In this randomized clinical trial, there was no significant difference in oropharyngeal clearance of SARS-CoV-2 at day 3 between placebo and niclosamide groups. Confirmation in larger studies is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04399356.

Impact of the first wave of the COVID-19 pandemic on systemic lupus erythematosus patients: Results from a multi-center prospective cohort.

OBJECTIVE: The aim of this study was to evaluate the initial impact of the COVID-19 pandemic on individuals with systemic lupus erythematosus (SLE). METHODS: Patients with SLE participating in a multi-center longitudinal cohort study in New York and Boston were invited to complete a supplemental web-based questionnaire in the summer of 2020. Participants completed standardized patient-reported outcome (PRO) measures and a combination of Likert scale and open-ended questions exploring the impact of the COVID-19 pandemic on their health and access to health care. Changes in PROs were evaluated with paired t-tests and frequencies of worsened symptoms were calculated. A thematic qualitative analysis was conducted on free text responses. RESULTS: Of 97 patients invited, 63 (65%) completed a supplemental questionnaire. Nearly 50% of respondents exhibited increases in anxiety (47.5%) and depression (48.3%) and over 40% scored worse in measures of pain interference, fatigue, and cognitive abilities. Respondents with pre-existing diagnoses of anxiety did not differ from other participants in PRO scores, but were more than three times as likely to report worsened health status. Patients denied difficulties accessing medications (85%) or medical care (84%) and over 50% participated in telehealth visits. Anxiety and increased health risks due to immunosuppression were recurring themes in free text responses. CONCLUSIONS: SLE patients experienced a significant physical and emotional toll in the initial months of the COVID-19 pandemic. Comprehensive patient-centered care, including monitoring and addressing anxiety and health-related quality of life, is critical to improving health outcomes in this population during the ongoing health crisis.