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1.
Mayo Clin Proc ; 95(6): 1213-1221, 2020 06.
Article in English | MEDLINE | ID: covidwho-1450185

ABSTRACT

As the coronavirus disease 19 (COVID-19) global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the "off-label" repurposing of drugs such as hydroxychloroquine and lopinavir/ritonavir, which have the potential for unwanted QT-interval prolongation and a risk of drug-induced sudden cardiac death. With the possibility that a considerable proportion of the world's population soon could receive COVID-19 pharmacotherapies with torsadogenic potential for therapy or postexposure prophylaxis, this document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment.


Subject(s)
Death, Sudden, Cardiac , Hydroxychloroquine , Long QT Syndrome , Lopinavir , Risk Adjustment/methods , Ritonavir , Torsades de Pointes , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Betacoronavirus/drug effects , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Drug Combinations , Drug Monitoring/methods , Drug Repositioning/ethics , Drug Repositioning/methods , Electrocardiography/methods , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/mortality , Long QT Syndrome/therapy , Lopinavir/administration & dosage , Lopinavir/adverse effects , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Ritonavir/administration & dosage , Ritonavir/adverse effects , SARS-CoV-2 , Torsades de Pointes/chemically induced , Torsades de Pointes/mortality , Torsades de Pointes/therapy
2.
Am J Respir Cell Mol Biol ; 64(6): 677-686, 2021 06.
Article in English | MEDLINE | ID: covidwho-1259048

ABSTRACT

There is an urgent need for new drugs for patients with acute respiratory distress syndrome (ARDS), including those with coronavirus disease (COVID-19). ARDS in influenza-infected mice is associated with reduced concentrations of liponucleotides (essential precursors for de novo phospholipid synthesis) in alveolar type II (ATII) epithelial cells. Because surfactant phospholipid synthesis is a primary function of ATII cells, we hypothesized that disrupting this process could contribute significantly to the pathogenesis of influenza-induced ARDS. The goal of this study was to determine whether parenteral liponucleotide supplementation can attenuate ARDS. C57BL/6 mice inoculated intranasally with 10,000 plaque-forming units/mouse of H1N1 influenza A/WSN/33 virus were treated with CDP (cytidine 5'-diphospho)-choline (100 µg/mouse i.p.) ± CDP -diacylglycerol 16:0/16:0 (10 µg/mouse i.p.) once daily from 1 to 5 days after inoculation (to model postexposure influenza prophylaxis) or as a single dose on Day 5 (to model treatment of patients with ongoing influenza-induced ARDS). Daily postexposure prophylaxis with CDP-choline attenuated influenza-induced hypoxemia, pulmonary edema, alterations in lung mechanics, impairment of alveolar fluid clearance, and pulmonary inflammation without altering viral replication. These effects were not recapitulated by the daily administration of CTP (cytidine triphosphate) and/or choline. Daily coadministration of CDP-diacylglycerol significantly enhanced the beneficial effects of CDP-choline and also modified the ATII cell lipidome, reversing the infection-induced decrease in phosphatidylcholine and increasing concentrations of most other lipid classes in ATII cells. Single-dose treatment with both liponucleotides at 5 days after inoculation also attenuated hypoxemia, altered lung mechanics, and inflammation. Overall, our data show that liponucleotides act rapidly to reduce disease severity in mice with severe influenza-induced ARDS.


Subject(s)
Alveolar Epithelial Cells/metabolism , Cytidine Diphosphate Choline/pharmacology , Cytidine Diphosphate Diglycerides/pharmacology , Influenza A Virus, H1N1 Subtype/metabolism , Orthomyxoviridae Infections/drug therapy , Respiratory Distress Syndrome/prevention & control , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , Animals , COVID-19/drug therapy , COVID-19/pathology , Mice , Orthomyxoviridae Infections/complications , Orthomyxoviridae Infections/metabolism , Orthomyxoviridae Infections/pathology , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/pathology , SARS-CoV-2/metabolism
3.
Cell Discov ; 7(1): 37, 2021 May 24.
Article in English | MEDLINE | ID: covidwho-1241945

ABSTRACT

Treatment options for COVID-19 remain limited, especially during the early or asymptomatic phase. Here, we report a novel SARS-CoV-2 viral replication mechanism mediated by interactions between ACE2 and the epigenetic eraser enzyme LSD1, and its interplay with the nuclear shuttling importin pathway. Recent studies have shown a critical role for the importin pathway in SARS-CoV-2 infection, and many RNA viruses hijack this axis to re-direct host cell transcription. LSD1 colocalized with ACE2 at the cell surface to maintain demethylated SARS-CoV-2 spike receptor-binding domain lysine 31 to promote virus-ACE2 interactions. Two newly developed peptide inhibitors competitively inhibited virus-ACE2 interactions, and demethylase access to significantly inhibit viral replication. Similar to some other predominantly plasma membrane proteins, ACE2 had a novel nuclear function: its cytoplasmic domain harbors a nuclear shuttling domain, which when demethylated by LSD1 promoted importin-α-dependent nuclear ACE2 entry following infection to regulate active transcription. A novel, cell permeable ACE2 peptide inhibitor prevented ACE2 nuclear entry, significantly inhibiting viral replication in SARS-CoV-2-infected cell lines, outperforming other LSD1 inhibitors. These data raise the prospect of post-exposure prophylaxis for SARS-CoV-2, either through repurposed LSD1 inhibitors or new, nuclear-specific ACE2 inhibitors.

4.
Vaccine ; 40(17): 2506-2513, 2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1201872

ABSTRACT

Several vaccines for SARS-CoV-2 are expected to be available in Australia in 2021. Initial supply is limited and will require a judicious vaccination strategy until supply is unrestricted. If vaccines have efficacy as post-exposure prophylaxis (PEP) in contacts, this provides more policy options. We used a deterministic mathematical model of epidemic response with limited supply (age-targeted or ring vaccination) and mass vaccination for the State of New South Wales (NSW) in Australia. For targeted vaccination, the effectiveness of vaccinating health workers, young people and older adults was compared. For mass vaccination, we tested varying vaccine efficacy (VE) and distribution capacities. With a limited vaccine stockpile enough for 1 million people in NSW, if there is efficacy as PEP, the most efficient way to control COVID-19 will be ring vaccination, however at least 90% of contacts per case needs to be traced and vaccinated. Health worker vaccination is required for health system resilience. Age based strategies with restricted doses make minimal impact on the epidemic, but vaccinating older people prevents more deaths. Herd immunity can only be achieved with mass vaccination. With 90% VE against all infection, herd immunity can be achieved by vaccinating 66% of the population. A vaccine with less than 70% VE cannot achieve herd immunity and will result in ongoing risk of outbreaks. For mass vaccination, distributing at least 60,000 doses per day is required to achieve control. Slower rates of vaccination will result in the population living with COVID-19 longer, and higher cases and deaths.


Subject(s)
COVID-19 , Vaccines , Adolescent , Aged , Australia/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Herd , New South Wales/epidemiology , SARS-CoV-2 , Vaccination
5.
Ann Intern Med ; 174(3): 344-352, 2021 03.
Article in English | MEDLINE | ID: covidwho-1190610

ABSTRACT

BACKGROUND: 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. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Hydroxychloroquine/therapeutic use , Post-Exposure Prophylaxis , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Double-Blind Method , Female , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , SARS-CoV-2 , Time Factors , Treatment Outcome , United States , Young Adult
6.
Trials ; 22(1): 224, 2021 Mar 22.
Article in English | MEDLINE | ID: covidwho-1147039

ABSTRACT

BACKGROUND: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. METHODS: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment. DISCUSSION: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection. TRIAL REGISTRATION: This trial was registered at www.ClinicalTrials.gov ( NCT04321174 ) on March 25, 2020.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/prevention & control , Lopinavir/therapeutic use , Post-Exposure Prophylaxis/methods , Ritonavir/therapeutic use , Drug Combinations , Hospitalization , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
7.
J Indian Assoc Pediatr Surg ; 26(2): 76-88, 2021.
Article in English | MEDLINE | ID: covidwho-1134320

ABSTRACT

COVID-19 which emerged in Wuhan, China has rapidly spread all over the globe and the World Health Organisation has declared it a pandemic. COVID-19 disease severity shows variation depending on demographic characteristics like age, history of chronic illnesses such as cardio-vascular/renal/respiratory disease; pregnancy; immune-suppression; angiotensin converting enzyme inhibitor medication use; NSAID use etc but the pattern of disease spread is uniform - human to human through contact, droplets and fomites. Up to 3.5% of health care workers treating COVID-19 contact an infection themselves with 14.8% of these infections severe and 0.3% fatal. The situation has spread panic even among health care professionals and the cry for safe patient care practices are resonated world-wide. Surgeons, anesthesiologists and intensivists who very frequently perform endotracheal intubation, tracheostomy, non-invasive ventilation and manual ventilation before intubation are at a higher odds ratio of 6.6, 4.2, 3.1 and 2.8 respectively of contacting an infection themselves. Elective surgery is almost always deferred in fever/infection scenarios. A surgeon and an anesthesiologist can anytime encounter a situation where in a COVID-19 patient requires an emergency surgery. COVID-19 cases requiring surgery predispose anesthesiologists and surgeons to cross-infection threats. This paper discusses, the COVID-19 precautionary outlines which has to be followed in the operating room; personal protective strategies available at present; methods to raise psychological preparedness of medical professionals during a pandemic; conduct of anesthesia in COVID-19 cases/suspect cases; methods of decontamination after conducting a surgery for COVID-19 case in the operating room; and post-exposure prophylaxis for medical professionals.

8.
Front Pharmacol ; 11: 593099, 2020.
Article in English | MEDLINE | ID: covidwho-1005534

ABSTRACT

Hydroxychloroquine has gained much attention as one of the candidate drugs that can be repurposed as a prophylactic agent against SARS-CoV-2, the agent responsible for the COVID-19 pandemic. Due to high transmissibility and presence of asymptomatic carriers and presymptomatic transmission, there is need for a chemoprophylactic agent to protect the high-risk population. In this review, we dissect the currently available evidence on hydroxychloroquine prophylaxis from a clinical and pharmacological point of view. In vitro studies on Vero cells show that hydroxychloroquine effectively inhibits SARS-CoV-2 by affecting viral entry and viral transport via endolysosomes. However, this efficacy has failed to replicate in in vivo animal models as well as in most clinical observational studies and clinical trials assessing pre-exposure prophylaxis and postexposure prophylaxis in healthcare workers. An analysis of the pharmacology of HCQ in COVID-19 reveals certain possible reasons for this failure-a pharmacokinetic failure due to failure to achieve adequate drug concentration at the target site and attenuation of its inhibitory effect due to the presence of TMPRSS2 in airway epithelial cells. Currently, many clinical trials on HCQ prophylaxis in HCW are ongoing; these factors should be taken into account. Using higher doses of HCQ for prophylaxis is likely to be associated with increased safety concerns; thus, it may be worthwhile to focus on other possible interventions.

9.
Curr Opin HIV AIDS ; 16(1): 25-35, 2021 01.
Article in English | MEDLINE | ID: covidwho-940835

ABSTRACT

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has caught the world unprepared, with no prevention or treatment strategies in place. In addition to the efforts to develop an effective vaccine, alternative approaches are essential to control this pandemic, which will most likely require multiple readily available solutions. Among them, monoclonal anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been isolated by multiple laboratories in record time facilitated by techniques that were first pioneered for HIV-1 antibody discovery. Here, we summarize how lessons learned from anti-HIV-1 antibody discovery have provided fundamental knowledge for the rapid development of anti-SARS-CoV-2 antibodies. RECENT FINDINGS: Research laboratories that successfully identified potent broadly neutralizing antibodies against HIV-1 have harnessed their antibody discovery techniques to isolate novel potent anti-SARS-CoV-2 antibodies, which have efficacy in animal models. These antibodies represent promising clinical candidates for treatment or prevention of COVID-19. SUMMARY: Passive transfer of antibodies is a promising approach when the elicitation of protective immune responses is difficult, as in the case of HIV-1 infection. Antibodies can also play a significant role in post-exposure prophylaxis, in high-risk populations that may not mount robust immune responses after vaccination, and in therapy. We provide a review of the recent approaches used for anti-SARS-CoV-2 antibody discovery and upcoming challenges in the field.


Subject(s)
Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/virology , HIV Infections/immunology , HIV-1/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Viral/administration & dosage , Biomedical Research/trends , Broadly Neutralizing Antibodies/administration & dosage , COVID-19/drug therapy , COVID-19/immunology , HIV Infections/virology , HIV-1/genetics , Humans , SARS-CoV-2/genetics
10.
Ann Intern Med ; 173(8): JC41, 2020 10 20.
Article in English | MEDLINE | ID: covidwho-881504

ABSTRACT

SOURCE CITATION: Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med. 2020;383:517-25. 32492293.


Subject(s)
Coronavirus Infections , Hydroxychloroquine , Medical Futility , Pandemics , Pneumonia, Viral , Adult , Betacoronavirus , COVID-19 , Coronavirus Infections/drug therapy , Humans , Hydroxychloroquine/adverse effects , SARS-CoV-2
11.
Open Forum Infect Dis ; 7(11): ofaa500, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-873054

ABSTRACT

BACKGROUND: Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials. METHODS: We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. RESULTS: We enrolled 2795 participants. The median age of research participants (interquartile range) was 40 (34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and 748 (29%) reported at least 1 medication side effect. Side effects were reported in 40% with once-daily, 36% with twice-weekly, 31% with once-weekly hydroxychloroquine, compared with 19% with placebo. The most common side effects were upset stomach or nausea (25% with once-daily, 19% with twice-weekly, and 18% with once-weekly hydroxychloroquine, vs 11% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for once-daily, 17% twice-weekly, and 13% once-weekly hydroxychloroquine, vs 7% for placebo). Two individuals were hospitalized for atrial arrhythmias, 1 on placebo and 1 on twice-weekly hydroxychloroquine. No sudden deaths occurred. CONCLUSIONS: Data from 3 outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials, in cohorts of healthy outpatients, can safely investigate whether hydroxychloroquine is efficacious for COVID-19. CLINICALTRIALSGOV IDENTIFIER: NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for pre-exposure prophylaxis trial.

12.
MMWR Morb Mortal Wkly Rep ; 69(35): 1210-1215, 2020 Sep 04.
Article in English | MEDLINE | ID: covidwho-745358

ABSTRACT

Hydroxychloroquine and chloroquine, primarily used to treat autoimmune diseases and to prevent and treat malaria, received national attention in early March 2020, as potential treatment and prophylaxis for coronavirus disease 2019 (COVID-19) (1). On March 20, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate in the Strategic National Stockpile to be used by licensed health care providers to treat patients hospitalized with COVID-19 when the providers determine the potential benefit outweighs the potential risk to the patient.* Following reports of cardiac and other adverse events in patients receiving hydroxychloroquine for COVID-19 (2), on April 24, 2020, FDA issued a caution against its use† and on June 15, rescinded its EUA for hydroxychloroquine from the Strategic National Stockpile.§ Following the FDA's issuance of caution and EUA rescindment, on May 12 and June 16, the federal COVID-19 Treatment Guidelines Panel issued recommendations against the use of hydroxychloroquine or chloroquine to treat COVID-19; the panel also noted that at that time no medication could be recommended for COVID-19 pre- or postexposure prophylaxis outside the setting of a clinical trial (3). However, public discussion concerning the effectiveness of these drugs on outcomes of COVID-19 (4,5), and clinical trials of hydroxychloroquine for prophylaxis of COVID-19 continue.¶ In response to recent reports of notable increases in prescriptions for hydroxychloroquine or chloroquine (6), CDC analyzed outpatient retail pharmacy transaction data to identify potential differences in prescriptions dispensed by provider type during January-June 2020 compared with the same period in 2019. Before 2020, primary care providers and specialists who routinely prescribed hydroxychloroquine, such as rheumatologists and dermatologists, accounted for approximately 97% of new prescriptions. New prescriptions by specialists who did not typically prescribe these medications (defined as specialties accounting for ≤2% of new prescriptions before 2020) increased from 1,143 prescriptions in February 2020 to 75,569 in March 2020, an 80-fold increase from March 2019. Although dispensing trends are returning to prepandemic levels, continued adherence to current clinical guidelines for the indicated use of these medications will ensure their availability and benefit to patients for whom their use is indicated (3,4), because current data on treatment and pre- or postexposure prophylaxis for COVID-19 indicate that the potential benefits of these drugs do not appear to outweigh their risks.


Subject(s)
Chloroquine/therapeutic use , Hydroxychloroquine/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Specialization/statistics & numerical data , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Female , Humans , Male , Treatment Outcome , United States
14.
Emerg Infect Dis ; 26(10): 2513-2515, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-623269

ABSTRACT

Because of in vitro studies, hydroxychloroquine has been evaluated as a preexposure or postexposure prophylaxis for coronavirus disease (COVID-19) and as a possible COVID-19 curative treatment. We report a case of COVID-19 in a patient with sarcoidosis who was receiving long-term hydroxychloroquine treatment and contracted COVID-19 despite adequate plasma concentrations.


Subject(s)
Antimalarials/therapeutic use , Coronavirus Infections/complications , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/complications , Sarcoidosis, Pulmonary/complications , Sarcoidosis, Pulmonary/drug therapy , Adult , Antimalarials/blood , COVID-19 , Coronavirus Infections/diagnosis , France , Humans , Hydroxychloroquine/blood , Male , Pandemics , Pneumonia, Viral/diagnosis , Time Factors , Tomography, X-Ray Computed
15.
N Engl J Med ; 383(6): 517-525, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-505858

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. RESULTS: We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was -2.4 percentage points (95% confidence interval, -7.0 to 2.2; P = 0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. CONCLUSIONS: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.).


Subject(s)
Coronavirus Infections/prevention & control , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Post-Exposure Prophylaxis , Adult , Betacoronavirus , COVID-19 , Canada , Double-Blind Method , Female , Humans , Hydroxychloroquine/adverse effects , Inhalation Exposure , Male , Middle Aged , Occupational Exposure , SARS-CoV-2 , Treatment Failure , United States
16.
Int J Antimicrob Agents ; 55(6): 105988, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-142757

ABSTRACT

In the context of the ongoing global outbreak of coronavirus disease 2019 (COVID-19), management of exposure events is a concern. Long-term care hospitals (LTCHs) are particularly vulnerable to cluster outbreaks because facilities for patient isolation and healthcare personnel to care for these patients in isolation are difficult to arrange in a large outbreak situation. Although several drugs have been proposed as treatment options, there are no data on the effectiveness and safety of post-exposure prophylaxis (PEP) for COVID-19. After a large COVID-19 exposure event in an LTCH in Korea, PEP using hydroxychloroquine (HCQ) was administered to 211 individuals, including 189 patients and 22 careworkers, whose baseline polymerase chain reaction (PCR) tests for COVID-19 were negative. PEP was completed in 184 (97.4%) patients and 21 (95.5%) careworkers without serious adverse events. At the end of 14 days of quarantine, all follow-up PCR tests were negative. Based on our experience, further clinical studies are recommended for COVID-19 PEP.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/prevention & control , Hydroxychloroquine/therapeutic use , Immunomodulation/drug effects , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Post-Exposure Prophylaxis/methods , COVID-19 , Cross Infection/prevention & control , Cross Infection/virology , Disease Outbreaks , Hospitals , Humans , Long-Term Care , Republic of Korea , SARS-CoV-2
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