Excitement around hydroxychloroquine for treating COVID-19 causes challenges for rheumatology.
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ABSTRACT:
SUBMITTER: Owens B
PROVIDER: S-EPMC7193144 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Early during the current coronavirus disease 19 (COVID-19) pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only has the effectiveness of HCQ remained questionable, but mainly based on preclinical and a few small clinical studies, HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. OBJECTIVE:The purpose of this study was to investigate the arrhythmic effects of HCQ, as the heightened risk is especially relevant to COVID-19 patients, who are at higher risk for cardiac complications and arrhythmias at baseline. METHODS:An optical mapping technique utilizing voltage-sensitive fluorescent dyes was used to determine the arrhythmic effects of HCQ in ex vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL). RESULTS:HCQ markedly increased action potential dispersion, resulted in development of repolarization alternans, and initiated polymorphic ventricular tachycardia. CONCLUSION:The study results further highlight the proarrhythmic effects of HCQ.
| S-EPMC7256542 | biostudies-literature
Project description:BackgroundEffective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19.MethodsWe conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14.ResultsA total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between the HCQ (n = 67) and placebo (n = 61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression end point, but this did not achieve statistical significance (P = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay.ConclusionsIn hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.
| S-EPMC7543602 | biostudies-literature
Project description:COVID-19 (coronavirus disease 2019) pandemic caused by SARS-CoV-2, is a global public health issue threatening millions of lives worldwide. Although the infection is mild in most of the affected individuals, it may cause severe clinical manifestations such as acute respiratory distress syndrome or cytokine storm leading to death. Children are affected less, and most experience a milder disease. As rheumatologists, we deal with the uncontrolled response of the immune system, and most of the drugs we use are either immune modulators or immunosuppressants. Thus, the rheumatologists participate in the multidisciplinary management of COVID-19 patients. On the other hand, our patients with rheumatic diseases constitute a vulnerable group in this pandemic. In this review, a systematic literature search was conducted utilizing MEDLINE/PubMed and Scopus databases, and 231 COVID-19 patients with rheumatic diseases have been identified. Only one of these patients was a child. Among these, 9 (3.9%) died due to COVID-19. In light of the current data, the aspects of COVID-19 resembling rheumatic diseases, the possible reasons for why children are affected less severely, the hypothetic role of available vaccines in preventing COVID-19, the unique position of patients with rheumatic diseases in this pandemic, and the use of anti-rheumatic drugs in COVID-19 treatment are discussed.
| S-EPMC7270517 | biostudies-literature
Project description: Not available
| S-EPMC6835042 | biostudies-literature
Project description:The COVID-19 pandemic has disrupted healthcare services and rheumatology staff were redeployed to the frontline. The purpose of this survey was to evaluate the impact of the COVID-19 pandemic on the provision of rheumatology services as viewed by rheumatologists in the UK. Survey monkey questionnaire weblink was sent to 804 clinicians including consultant rheumatologists, speciality trainees, nurse specialists, and allied health professionals in 4 regions of the UK to evaluate personal effects of COVID-19 and redeployment, impact on current out-patient clinic activity, immunosuppressive drug use, and future rheumatology care. Response rate was 21%. One-fifth of the responders reported that their rheumatology departments were functioning less than 50% capacity during the pandemic. Two-third of responders felt anxious about the ill-effects of COVID-19 on their health and well-being, and one-third of them were redeployed. During the peak of the pandemic, 75% of clinicians stopped intravenous biologics. Although access to video consultation was available for up to three-fourths of the clinicians, the majority (90%) used this modality in less than 1 in 4 consultations. This survey highlights rheumatologists' perception in the delivery of future care and anxiety they faced. As demonstrated by this survey, the National Institute for Health and Care Excellence (NICE) guidance did not influence clinician decision making in some aspects of patient care. Underutilization of tele-rheumatology in this survey should be considered whilst planning the restoration of rheumatology services in the post-COVID era. Key points • COVID-19 has generated significant concerns among rheumatology community about their mental well-being. • In over 50% of cases, rheumatologists stopped IV biologic drugs as per patients' wishes during the first wave of the pandemic. • Tele-rheumatology has been used more widely during the pandemic, but the extent of its use in the post-COVID era is less clear. Evolving evidence will determine its future wider use.
| S-EPMC7832421 | biostudies-literature
Project description:The impact of the COVID-19 pandemic worldwide has led to a desperate search for effective drugs and vaccines. There are still no approved agents for disease prophylaxis. We thus decided to use a drug repositioning strategy to perform a state-of-the-art review of a promising but controversial drug, hydroxychloroquine (HCQ), in an effort to provide an objective, scientific and methodologically correct overview of its potential prophylactic role. The advantage of using known drugs is that their toxicity profile is well known and there are fewer commercial interests (e.g., expired patents), thus allowing the scientific community to be freer of constraints. The main disadvantage is that the economic resources are almost always insufficient to promote large multinational clinical trials. In the present study, we reviewed the literature and available data on the prophylactic use of HCQ. We also took an in-depth look at all the published clinical data on the drug and examined ongoing clinical trials (CTs) from the most important CT repositories to identify a supporting rationale for HCQ prophylactic use. Our search revealed a substantial amount of preclinical data but a lack of clinical data, highlighting the need to further assess the translational impact of in vitro data in a clinical setting. We identified 77 CTs using a multiplicity of HCQ schedules, which clearly indicates that we are still far from reaching a standard of care. The majority of the CTs (92%) are randomized and 53% are being conducted in a phase 3 or 2/3 setting. The comparator is placebo or control in 55 (77%) of the randomized studies. Forty-eight (62%) CTs expect to enroll up to 1,000 subjects and 50 (71%) plan to recruit healthcare workers (HCW). With regard to drug schedules, 45 (58.5%) CTs have planned a loading dose, while 18 (23.4%) have not; the loading dose is 800 mg in 19 trials (42.2%), 400 mg in 19 (42.2%), 600 mg in 4 (8.9%) and 1,200 mg in 1 (2.2%). Forty trials include at least one daily schedule, while 19 have at least one weekly schedule. Forty-one (53.2%) will have a treatment duration of more than 30 days. Awaiting further developments that can only derive from the results of these prospective randomized CTs, the take-home message of our review is that a correct methodological approach is the key to understanding whether prophylactic HCQ can really represent an effective strategy in preventing COVID-19.
| S-EPMC7744418 | biostudies-literature
Project description:ObjectiveTo synthesize findings from systematic reviews and meta-analyses on the efficacy and safety of chloroquine (CQ) and hydroxychloroquine (HCQ) with or without Azithromycin for treating COVID-19, and to update the evidence using a meta-analysis.MethodsA comprehensive search was carried out in electronic databases for systematic reviews, meta-analyses and experimental studies which investigated the efficacy and safety of CQ, HCQ with or without Azithromycin to treat COVID-19. Findings from the reviews were synthesised using tables and forest plots and the quality effect model was used for the updated meta-analysis. The main outcomes were mortality, the need for intensive care services, disease exacerbation, viral clearance and occurrence of adverse events.ResultsThirteen reviews with 40 primary studies were included. Two meta-analyses reported a high risk of mortality, with ORs of 2.2 and 3.0, and the two others found no association between HCQ and mortality. Findings from two meta-analyses showed that HCQ with Azithromycin increased the risk of mortality, with similar ORs of 2.5. The updated meta-analysis of experimental studies showed that the drugs were not effective in reducing mortality (RR 1.1, 95%CI 1.0-1.3, I2 = 0.0%), need for intensive care services (OR 1.1, 95%CI 0.9-1.4, I2 = 0.0%), virological cure (OR 1.5, 95%CI 0.5-4.4, I2 = 39.6%) or disease exacerbation (OR 1.2, 95%CI 0.3-5.9, I2 = 31.9%) but increased the odds of adverse events (OR 12,3, 95%CI 2.5-59.9, I2 = 76.6%).ConclusionThere is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation.RegistrationPROSPERO: CRD42020191353.
| S-EPMC8273040 | biostudies-literature
Project description:The COVID-19 pandemic is an unprecedented challenge and will require novel therapeutic strategies. Affected patients are likely to be at risk of arrhythmia due to underlying comorbidities, polypharmacy and the disease process. Importantly, a number of the medications likely to receive significant use can themselves, particularly in combination, be pro-arrhythmic. Drug-induced prolongation of the QT interval is primarily caused by inhibition of the hERG potassium channel either directly and/or by impaired channel trafficking. Concurrent use of multiple hERG-blocking drugs may have a synergistic rather than additive effect which, in addition to any pre-existing polypharmacy, critical illness or electrolyte imbalance, may significantly increase the risk of arrhythmia and Torsades de Pointes. Knowledge of these risks will allow informed decisions regarding appropriate therapeutics and monitoring to keep our patients safe.
| S-EPMC7214683 | biostudies-literature
Project description:The unprecedented pandemic of coronavirus disease 2019 (COVID-19) demands effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The infection of SARS-CoV-2 critically depends on diverse viral or host proteases, which mediate viral entry, viral protein maturation, as well as the pathogenesis of the viral infection. Endogenous and exogenous agents targeting for proteases have been proved to be effective toward a variety of viral infections ranging from HIV to influenza virus, suggesting protease inhibitors as a promising antiviral treatment for COVID-19. In this Review, we discuss how host and viral proteases participated in the pathogenesis of COVID-19 as well as the prospects and ongoing clinical trials of protease inhibitors as treatments.
| S-EPMC7640965 | biostudies-literature
Project description:OBJECTIVES:To identify the changes in rheumatology service delivery across the five regions of Africa from the impact of the COVID-19 pandemic. METHODS:The COVID-19 African Rheumatology Study Group created an online survey consisting of 40 questions relating to the current practices and experiences of rheumatologists across Africa. The CHERRIES checklist for reporting results of internet e-surveys was adhered to. RESULTS:A total of 554 completed responses were received from 20 countries, which include six in Northern Africa, six in West Africa, four in Southern Africa, three in East Africa and one in Central Africa. Consultant grade rheumatologists constituted 436 (78.7%) of respondents with a mean of 14.5?±?10.3?years of experience. A total of 77 (13.9%) rheumatologists avoided starting a new biologic. Face-to-face clinics with the use of some personal protective equipment continued to be held in only 293 (52.9%) rheumatologists' practices. Teleconsultation modalities found usage as follows: telephone in 335 (60.5%), WhatsApp in 241 (43.5%), emails in 90 (16.3%) and video calls in 53 (9.6%). Physical examinations were mostly reduced in 295 (53.3%) or done with personal protective equipment in 128 (23.1%) practices. Only 316 (57.0%) reported that the national rheumatology society in their country had produced any recommendation around COVID-19 while only 73 (13.2%) confirmed the availability of a national rheumatology COVID-19 registry in their country. CONCLUSION:COVID-19 has shifted daily rheumatology practices across Africa to more virtual consultations and regional disparities are more apparent in the availability of local protocols and registries.
| S-EPMC7665741 | biostudies-literature