IMPORTANCE Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. OBJECTIVE To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants. INTERVENTIONS Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants. RESULTS Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, −9 to 17; vs placebo: 3 milliseconds; 95% CI, −5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04329923

Background Widespread vaccination is an essential component of the public health response to the COVID‐19 pandemic, yet vaccine hesitancy remains pervasive. This prospective survey investigation aimed to measure the prevalence of vaccine hesitancy in a patient cohort at two urban Emergency Departments (EDs) and characterize underlying factors contributing to hesitancy. Methods Adult ED patients with stable clinical status (Emergency Severity Index 3‐5) and without active COVID‐19 disease or altered mental status were considered for participation. Demographic elements were collected, as well as reported barriers/concerns related to vaccination and trusted sources of health information. Data were collected in‐person via a survey instrument proctored by trained research assistants. Results 1,555 patients were approached, and 1,068 patients completed surveys (completion rate 68.7%). Mean age was 44.1 y (SD 15.5, range 18‐93), 61% were female, and 70% were Black. 31.6% of ED patients reported vaccine hesitancy. Of note, 19.7% of the hesitant cohort were healthcare workers. In multivariable regression analysis, Black race (OR 4.24, 95%CI 2.62‐6.85) and younger age (age 18‐24 y, OR 4.57, 95%CI 2.66‐7.86; age 25‐35 y, OR 5.71, 95% CI 3.71‐8.81) were independently associated with hesitancy, to a greater degree than level of education (high school education or less, OR 2.27, 95%CI 1.23‐4.19). Hesitant patients were significantly less likely to trust governmental sources of vaccine information than non‐hesitant patients (39.6% vs 78.9%, p<0.001); less difference was noted in the domain of trust towards friends/family (51.1% vs. 61.0%, p=0.004). Hesitant patients also reported perceived vaccine safety concerns and perceived insufficient research. Conclusions Vaccine hesitancy is common among ED patients, and more common among Black and younger patients, independent of education level. Hesitant patients report perceived safety concerns and low trust in government information sources, but less so friends or family. This suggests strategies to combat hesitancy may need tailoring to specific populations.

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