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BackgroundAerosol-generating procedures increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers (HCWs). An effective pre-exposure prophylaxis would mitigate this risk. ObjectiveTo determine the efficacy of pre-exposure prophylactic hydroxychloroquine for the prevention of SARS-CoV-2 infection and symptomatic coronavirus 19 disease (COVID-19) among HCWs at high occupational risk of SARS-CoV-2 exposure. Methods130 HCWs in the New York University Langone Health System (NYULHS) who performed aerosol-generating procedures on patients with COVID-19 or provided bedside care for inpatients with COVID-19 or persons with suspected COVID-19 in an emergency department, for at least three shifts in a 7-day period, during the first 2020 COVID-19 wave in New York City were enrolled. Participants elected to take oral hydroxychloroquine, 600 mg on day 1 followed by 200 mg daily, or not take hydroxychloroquine for up to 90 days. Participants self-collected dried blood spots and completed digital questionnaires regarding COVID-19 symptoms, adverse events, and other COVID-19 medication use. ResultsSix participants (7.5%) seroconverted during the trial: four who took hydroxychloroquine (6.8%) and two who declined hydroxychloroquine (9.5%). All participants not taking hydroxychloroquine reported COVID-19 symptoms at seroconversion compared to one of four participants (25%) who took hydroxychloroquine. Adverse events occurred in eight participants (9.6%) on hydroxychloroquine and were mostly mild. ConclusionsThis study (ClinicalTrials.gov NCT04354870) did not demonstrate a statistically significant difference in SARS-CoV-2 seroconversion associated with hydroxychloroquine pre-exposure prophylaxis among HCWs at high risk of occupational SARS-CoV-2 exposure, although was underpowered and a high rate of hydroxychloroquine discontinuation was observed.
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SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection. One Sentence SummaryLY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.
