Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine (HERO-HCQ).

OBJECTIVES: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCWs). METHODS: In a 1: 1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCWs at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo. The HCQ dosing included a loading dose of HCQ 600 mg twice on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by day 30, defined as new-onset fever, cough, or dyspnea and either a positive SARS-CoV-2 polymerase chain reaction test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). RESULTS: Study enrollment closed before full accrual due to recruitment challenges. The primary end point occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6-0.9%, P = 0.20) was identified nor any significant safety issues. CONCLUSION: Oral HCQ taken as prescribed appeared safe among HCWs. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection. TRIAL REGISTRATION: NCT04334148.

Racial/Ethnic Disparities in Healthcare Worker Experiences During the COVID-19 Pandemic: An Analysis of the HERO Registry.

Background: The extent to which healthcare worker (HCWs) experiences during the COVID-19 pandemic vary by race or ethnicity after adjustment for confounding factors is not currently known. Methods: We performed an observational prospective cohort study of 24,769 healthcare workers from 50 U.S. states and the District of Columbia, enrolled between April 10, 2020 and June 30, 2021, and evaluated participant experiences during the COVID-19 pandemic, including testing, diagnosis with COVID-19, emotional experiences, burnout, and interest in vaccines and vaccine clinical trials. Findings: After adjustment for professional role, medical history, and community characteristics, Black and Asian participants were less likely to receive SARS-CoV-2 viral testing (adjusted odds ratio (aOR) 0·82 [0·70, 0·96], p=0·012 and aOR 0·77 [0·67, 0·89], p<0·001 respectively) than White participants. Hispanic participants were more likely to have evidence of COVID-19 infection (aOR 1·23 (1·00, 1·50, p=0·048). Black and Asian participants were less likely to report interest in a COVID-19 vaccine (aOR 0·11 [0·05, 0·25], p<0·001 and aOR 0·48 [0·27, 0·85] p=0·012). Black participants were less likely to report interest in participating in a COVID-19 vaccine trial (aOR = 0·39 [0·28, 0·54], p<0·001). Black participants were also less likely to report 3 or more daily emotional impacts of COVID-19 (aOR = 0·66 [0·53, 0·82], p=<0·001). Black participants were additionally less likely to report burnout (aOR = 0·66 ([0·49, 0·95], p=0·025). Interpretation: In a large, national study of healthcare workers, after adjustment for individual and community characteristics, race/ethnicity disparities in COVID-19 outcomes persist. Future work is urgently needed to understand precise mechanisms behind these disparities and to develop and implement targeted interventions to improve health equity for healthcare workers. Funding: This work was funded by the Patient-Centered Outcomes Research Institute (PCORI), Contract # COVID-19-2020-001.

Design of the Healthcare Worker Exposure Response and Outcomes (HERO) research platform.

BACKGROUND: The SARS CoV-2 virus has caused one of the deadliest pandemics in recent history, resulting in over 170 million deaths and global economic disruption. There remains an urgent need for clinical trials to test therapies for treatment and prevention. DESIGN: An online research platform was created to support a registry community of healthcare workers (HCWs) to understand their experiences and conduct clinical studies to address their concerns. The first study, HERO-HCQ, was a double-blind, multicenter, randomized, pragmatic trial to evaluate the superiority of hydroxychloroquine (HCQ) vs placebo for pre-exposure prophylaxis (PrEP) of COVID-19 clinical infection in HCWs. Secondary objectives were to assess the efficacy of HCQ in preventing viral shedding of COVID-19 among HCWs and to assess the safety and tolerability of HCQ. METHODS: HCWs joined the Registry and were pre-screened for trial interest and eligibility. Trial participants were randomized 1:1 to receive HCQ or placebo. On-site baseline assessment included a COVID-19 nasopharyngeal PCR and blood serology test. Weekly follow-up was done via an online portal and included screening for symptoms of COVID-19, self-reported testing, adverse events, and quality of life assessments. The on-site visit was repeated at Day 30. DISCUSSION: The HERO research platform offers an approach to rapidly engage, screen, invite and enroll into clinical studies using a novel participant-facing online portal interface and remote data collection, enabling limited onsite procedures for conduct of a pragmatic clinical trial. This platform may be an example for future clinical trials of common conditions to enable more rapid evidence generation.