• Emerging preclinical evidence does not support broad use of hydroxychloroquine in COVID-19 patients

      Funnell, S. G.P.; Dowling, W. E.; Muñoz-Fontela, C.; Gsell, P. S.; Ingber, D. E.; Hamilton, G. A.; Delang, L.; Rocha-Pereira, J.; Kaptein, S.; Dallmeier, K. H.; et al. (Springer Nature, 2020-12-01)
    • Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial

      Barnabas, R.V.; Brown, E.R.; Bershteyn, A.; Stankiewicz, Karita, H.C.; Johnston, C.; Thorpe, L.E.; Kottkamp, A.; Neuzil, K.M.; Laufer, M.K.; Deming, M.; et al. (American College of Physicians, 2020-12-08)
      Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. Objective: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. Design: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961) Setting: National U.S. multicenter study. Participants: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. Intervention: Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. Measurements: Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. Results: Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026). Limitation: The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. Conclusion: This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection.
    • Insights from nanomedicine into chloroquine efficacy against COVID-19

      Hu, T.Y.; Frieman, M.; Wolfram, J. (32203437, 2020)
      Recent multicentre clinical trials and cell culture studies suggest that the 70-year-old malaria drug, chloroquine, may potentially display therapeutic efficacy against COVID-19 (corona virus disease 2019), a rapidly spreading viral infection that can cause pneumonia-induced death in approximately 2.5% of infected individuals. Based on the preliminary clinical trial findings, chloroquine has been included in federal guidelines for treatment of COVID-19 in the People’s Republic of China. However, caution should be exercised when making premature interpretations, as clinical trials are still ongoing and interim trial data have not yet been made available. Given the current lack of an approved and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, it is important to evaluate potential prophylactic and/or therapeutic effects of drugs that are clinically approved for other indications. Chloroquine and its derivative, hydroxychloroquine, have a long history as safe and inexpensive drugs for use as prophylactic measures in malaria-endemic regions and as daily treatments for autoimmune diseases with the most common side effect being eye damage after long-term use. Although previous studies have revealed that chloroquine has therapeutic activity against viruses5, including human coronavirus OC43 in animal models and SARS-CoV in cell culture studies, anti-viral mechanisms of chloroquine remain speculative. Chloroquine has been used in the field of nanomedicine for the investigation of nanoparticle uptake in cells, and, therefore, insights from synthetic nanoparticle interactions with cells in the presence of chloroquine may reveal mechanisms that are active at early stages prior to viral replication. Specifically, nanomedicine studies may provide clues on chloroquine-induced alterations of SARS-CoV-2 cellular uptake.