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.

Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ) (preprint)

ABSTRACT Objective To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW). Design Multicenter, 1:1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial. Setting 34 clinical centers in the United States. Participants 1360 HCW at risk for COVID-19 infection enrolled between April and November 2020. Interventions A loading dose of HCQ 600 mg twice on Day 1 followed by 400 mg daily for 29 days or matching placebo taken orally. Main Outcome Measure 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 PCR test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). Results Enrollment for the study was closed before full accrual due to difficulties recruiting additional participants. The primary composite endpoint occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No statistically significant difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6% to 0.9%, p=0.20). We identified no significant safety issues. Conclusion Oral HCQ taken as prescribed appeared to be safe in a group of HCW. No significant clinical benefits were observed. The study was underpowered to rule out a small but potentially important reduction in COVID-19 infections. Trial Registration NCT04334148

Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Infusions in High-Risk Outpatients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to stress the health care system. Neutralizing monoclonal antibodies (mAbs) were effective in reducing COVID-19-related hospitalizations and emergency department (ED) visits in their respective clinical trials. However, these results have yet to be reproduced in a practical setting following implementation of current US Food and Drug Administration (FDA) guidance. METHODS: This retrospective cohort study included outpatients with confirmed COVID-19 infection, who had mild/moderate symptoms for 10 days or less, and who were deemed high-risk for severe COVID-19 under FDA's Emergency Use Authorization for mAbs. Patients who received either bamlanivimab or casirivimab/imdevimab from 18 November 2020 through 5 January 2021 were included (n = 200). This was compared against a control cohort of randomly selected high-risk COVID-19 outpatients who declined or were not referred for mAb treatment during the same period (n = 200). The primary outcome was a composite of 29-day COVID-19-related hospitalizations and/or ED visits. Prespecified secondary outcomes included the individual components of the primary endpoint, 29-day all-cause mortality, and serious adverse drug events. RESULTS: Patients treated with mAbs were significantly less likely to be hospitalized or visit the ED compared with patients not treated with mAb (13.5% vs 40.5%; odds ratio, 0.23 [95% confidence interval, .14-.38]; P < .001). The mortality rate was 0% in the mAb group compared with 3.5% in the control group (P = .02). Only 2 patients receiving mAb experienced a serious adverse event requiring treatment. CONCLUSIONS: Among high-risk COVID-19 outpatients with mild/moderate symptoms, early administration of mAbs can potentially reduce the strain on the health care system during the current pandemic.

SARS-CoV-2 Infection (COVID-19) and Herpes Simplex Virus-1 Conjunctivitis: Concurrent Viral Infections or a Cause-Effect Result?

The pulmonary effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), are well documented; however, more evidence is needed to understand its effect on multiple organ systems. We present the case of a 69-year-old male with dyspnea for two weeks and bilateral conjunctivitis who tested positive for SARS-CoV-2. He was found to be hypoxic, requiring supplemental oxygen. On hospital day two, he complained of worsening left eye pain with the development of a left lower eyelid ulcer. He underwent a CT of facial bones, which showed findings consistent with pre-septal cellulitis and abscess. Samples from bilateral conjunctival secretions and left lower eyelid ulcer tested positive for herpes simplex virus-1 (HSV-1), and negative for SARS-CoV-2. He received supportive care, antibiotics, and famciclovir with almost complete resolution of his ocular complaints. This case illustrates an atypical COVID-19 presentation and raises concern as to how this virus modulates the immune system, allowing for concurrent viral infections.

Pancytopenia and Profound Neutropenia as a Sequela of Severe SARS-CoV-2 Infection (COVID-19) With Concern for Bone Marrow Involvement.

Pancytopenia and neutropenia due to coronavirus disease 2019 (COVID-19) are rare. Here we report a case of neutropenia as a sequela of COVID-19 with concern for bone marrow infiltration. The patient was successfully treated with granulocyte colony-stimulating factor.