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Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence

There are no seroprevalence terms in the subcorpus

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    Mitigating Arrhythmia HP Risk in Hydroxychloroquine and Azithromycin Treated COVID-19 Patients using Arrhythmia HP Risk Management Plan

    Authors: Kazimieras Maneikis M.D.; Ugne Ringeleviciute M.D.; Justinas Bacevicius M.D.; Egle Dieninyte-Misiune M.D.; Emilija Burokaite M.D.; Gintare Kazbaraite M.D.; Marta Monika Janusaite M.D.; Austeja Dapkeviciute M.D.; Andrius Zucenka M.D.; Valdas Peceliunas M.D. Ph.D.; Lina Kryzauskaite M.D.; Vytautas Kasiulevicius M.D. Ph.D.; Donata Ringaitiene M.D. Ph.D.; Birute Zablockiene M.D. Ph.D.; Tadas Zvirblis; Germanas Marinskis M.D. Ph.D.; Ligita Jancoriene M.D. Ph.D.; Laimonas Griskevicius M.D. Ph.D.

    doi:10.21203/rs.3.rs-50501/v1 Date: 2020-07-29 Source: ResearchSquare

    Background: Hydroxychloroquine and Azithromycin use is associated with QT interval prolongation and arrhythmias HP. Despite ongoing multiple clinical trials for treatment of COVID19 infection MESHD, no definite cardiac safety protocols were proposed. The aim of our study was to assess cardiac safety in COVID-19 patients treated with the combination of Hydroxychloroquine and Azithromycin using close monitoring and arrhythmia HP risk management plan.Methods and results: We retrospectively examined arrhythmia HP safety of treatment with Hydroxychloroquine and Azithromycin in the setting of pre-defined cardiac arrhythmia MESHD arrhythmia HP risk management plan. 81 patients were included from March 23rd to May 10th 2020. The median age TRANS was 59 years, 58.0% were female TRANS. The majority of the study population (82.7%) had comorbidities, 98.8% had radiological signs of pneumonia MESHD pneumonia HP. 7 patients (8.6%) had QTc prolongation of ≥500 ms. The treatment was discontinued in 4 patients (4.9%). 14 patients (17.3%) experienced QTc≥480 ms and 16 patients (19.8%) had an increase of QTc≥60 ms. None of the patients developed ventricular tachycardia MESHD ventricular tachycardia HP. The risk factors significantly associated with QTc≥500 ms were hypokalemia MESHD hypokalemia HP (p = 0.032) and use of diuretics during the treatment (p = 0.020). Three patients had a lethal outcome; none of them associated with ventricular arrhythmias HP.Conclusion: We recorded a low incidence of QTc prolongation ≥500 ms and no ventricular tachycardia MESHD ventricular tachycardia HP events in COVID-19 patients treated with Hydroxychloroquine and Azithromycin using cardiac arrhythmia MESHD arrhythmia HP risk management plan.

    Chloroquine, but not hydroxychlorquine, prolongs the QT interval HP in a primary care population

    Authors: Jonas L Isaksen; Anders Gaarsdal Holst; Adrian Pietersen; Jonas Bille Nielsen; Claus Graff; Jorgen K Kanters

    doi:10.1101/2020.06.19.20135475 Date: 2020-06-20 Source: medRxiv

    Background: Chloroquine (CQ) and Hydroxychloroquine (HCQ) have recently been suggested as treatment for the current Corona Virus Disease MESHD 2019 (COVID-19) pandemic. However, despite their long-term use and only few case reports on adverse effects, CQ and HCQ are listed as a known risk of the lethal ventricular arrhythmia HP Torsade de Pointes MESHD Torsade de Pointes HP and their cardiac safety profile is being questioned. Thus, we aimed to investigate the electrocardiographic and mortality effects of CQ and HCQ in a primary care population. Methods: We used Danish health care registers and electrocardiograms (ECGs) from primary care to define three studies. 1) A paired study of subjects with ECGs before and during use of CQ/HCQ, 2) a matched ECG study of subjects taking CQ/HCQ compared to controls, and 3) a mortality study on people taking HCQ matched to control. In both matched studies, we adjusted for connective tissue diseases MESHD, use of QT-prolonging drugs, and cardiac disease MESHD. We used the QTc interval as the marker for electrocardiographic safety. In the mortality study, cases were followed from first claimed prescription until 300 days after estimated completion of the last prescription. 95% confidence intervals follow estimates in parenthesis. Results: Use of CQ was associated with a 5.5 (0.7;10) ms increase in QTc in the paired study (n=10). In the matched study (n=28, controls=280), QTc was insignificantly increased in subjects taking CQ by 4.7 (-3.4;13) ms. With a {Delta}QTc of 1.0 (-5.6;7.5), use of HCQ was not associated with an increased QTc in the paired study (n=32). In the matched study (n=172, controls=1,720), QTc also was not different between groups (p=0.5). In the mortality study (n=3,368), use of HCQ was associated with a hazard ratio of 0.67 (0.43;1.05). Conclusions: In subjects free of COVID-19, we found a small increase in QTc associated with use of chloroquine, but not hydroxychloroquine. We found no increased mortality associated with use of hydroxychloroquine.

    The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis

    Authors: Imad Tleyjeh; Zakariya Kashour; Oweida AlDosary; Muhammad Riaz; Haytham Tlayjeh; Musa A Garbati; Rana Tleyjeh; Mouaz H Al-Mallah; Rizwan M Sohail; Dana Gerberi; Aref A Bin Abdulhak; John R Giudicessi; Michael John Ackerman; Tarek Kashour

    doi:10.1101/2020.06.16.20132878 Date: 2020-06-18 Source: medRxiv

    Abstract Importance The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects. Objective To systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19. Data Sources A systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists. Study Selection Studies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias MESHD arrhythmias HP. Data Extraction and Synthesis Study characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes MESHD torsades de pointes HP (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori. Main Outcomes and Measures Pooled Incidence of: (1) change in QTc value from baseline [≥] 60 ms, (2) QTc [≥] 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular HP ventricular tachycardia MESHD tachycardia HP (VT) or cardiac arrest HP, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias HP. Results A total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia HP or VT or cardiac arrest HP was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias HP was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of [≥] 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc [≥] 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of [≥] 60 ms or QTc [≥] 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age TRANS, coronary artery disease MESHD, hypertension MESHD hypertension HP, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions and Relevance Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest HP. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.

    Risk factors and electrocardiogram characteristics for mortality of critical inpatients with COVID-19

    Authors: Lingzhi Li; Shudi Zhang; Bing He; Xiaobei Chen; Shihong Wang; Zhao Qingyan

    doi:10.21203/rs.3.rs-33824/v1 Date: 2020-06-05 Source: ResearchSquare

    Background The novel severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has subsequently spread worldwide. The number of death MESHD has increased rapidly. However, the possible risk factors that lead to death MESHD in critical inpatients with coronavirus disease MESHD 2019 (COVID-19) are not yet fully known. This study was to explore the risk factors for mortality of critical inpatients with COVID-19.Methods In this single-centered, retrospective study, we enrolled 113 critical patients with COVID-19 in Renmin Hospital of Wuhan University between Feb 1, 2020 and Mar 15, 2020. Data were collected using a standard method including clinical records and laboratory findings. Outcomes of survivors and death MESHD were compared.Results A total of 113 critical patients (from 29 to 95 years) with COVID-19 were recruited, 50 (44.25%) died and 63 recovered (55.75%). The proportion of patients with ventricular arrhythmia HP was higher in the death MESHD group than the recovery group (24.0% vs 4.4%; p = 0.021), and was higher among myocardial damage cases than non-myocardial damage cases (26.1% vs 4.3%; p = 0.013). Multivariate analysis confirmed four independent predictors related to mortality of COVID-19: age > 70 yrs (HR 1.84, 95% CI 1.03–3.28), initial neutrophil count more than 6.5 × 109/L (HR 3.43, 95% CI 1.84–6.40), C-reactive protein greater more than 100 mg/L (HR 1.93, 95% CI 1.04–3.59), and lactate dehydrogenase more than 300 U/L (HR 2.90, 95% CI 1.26–6.67). Immunoglobulin treatment (HR 0.39, 95% CI 0.21–0.73) can reduce the risk of death MESHD. There was no significant difference in the QT interval between patients with and without hydroxychloroquine treatment.Conclusions Old age TRANS (> 70 years), neutrophilia HP, C-reactive protein greater more than 100 mg/L and lactate dehydrogenase more than 300 U/L are high-risk factors for mortality of critical patients with COVID-19. The incidence of ventricular arrhythmia HP was higher in deceased patients than survivors.

    Investigational treatments for COVID-19 may increase ventricular arrhythmia HP risk through drug interactions

    Authors: Meera Varshneya; Itziar Irurzun-Arana; Chiara Campana; Rafael Dariolli; Amy Gutierrez; Taylor K Pullinger; Eric A Sobie

    doi:10.1101/2020.05.21.20109397 Date: 2020-05-26 Source: medRxiv

    Many drugs that have been proposed for treatment of COVID-19 are reported to cause cardiac adverse events, including ventricular arrhythmias HP. In order to properly weigh risks against potential benefits, particularly when decisions must be made quickly, mathematical modeling of both drug disposition and drug action can be useful for predicting patient response and making informed decisions. Here we explored the potential effects on cardiac electrophysiology of 4 drugs proposed to treat COVID-19: lopinavir, ritonavir, chloroquine, and azithromycin, as well as combination therapy involving these drugs. Our study combined simulations of pharmacokinetics (PK) with quantitative systems pharmacology (QSP) modeling of ventricular myocytes to predict potential cardiac adverse events caused by these treatments. Simulation results predicted that drug combinations can lead to greater cellular action potential prolongation, analogous to QT prolongation, compared with drugs given in isolation. The combination effect can result from both pharmacokinetic and pharmacodynamic drug interactions. Importantly, simulations of different patient groups predicted that females TRANS with pre-existing heart disease MESHD are especially susceptible to drug-induced arrhythmias HP, compared males TRANS with disease MESHD or healthy individuals of either sex. Overall, the results illustrate how PK and QSP modeling may be combined to more precisely predict cardiac risks of COVID-19 therapies.

    Hydroxychloroquine alone or in combination with azithromycin to prevent major clinical events in hospitalised patients with coronavirus infection MESHD (COVID-19): rationale and design of a randomised, controlled clinical trial

    Authors: Alexandre B Cavalcanti; Fernando G Zampieri; Luciani CP Azevedo; Regis G Rosa; Alvaro Avezum; Viviane C Veiga; Renato D Lopes; Leticia Kawano-Dourado; Lucas P Damiani; Adriano J Pereira; Ary Serpa Neto; Remo Furtado; Bruno Tomazini; Fernando A Bozza; Israel S Maia; Maicon Falavigna; Thiago C Lisboa; Henrique Fonseca; Flavia R Machado; Otavio Berwanger; COALITION COVID-19 Brazil I Investigators

    doi:10.1101/2020.05.19.20106997 Date: 2020-05-26 Source: medRxiv

    Introduction: Hydroxychloroquine and its combination with azithromycin have been suggested to improve viral clearance in patients with COVID-19, but its effect on clinical outcomes remains uncertain. Methods and analysis: We describe the rationale and design of an open-label pragmatic multicentre randomised (concealed) clinical trial of 7 days of hydroxychloroquine (400 mg BID) plus azithromycin (500 mg once daily), hydroxychloroquine 400 mg BID, or standard of care for moderately severe hospitalised patients with suspected or confirmed COVID-19 (in-patients with up to 4L/minute oxygen supply through nasal catheter). Patients are randomised in around 50 recruiting sites and we plan to enrol 630 patients with COVID-19. The primary endpoint is a 7-level ordinal scale measured at 15-days: 1)not hospitalised, without limitations on activities; 2)not hospitalised, with limitations on activities; 3)hospitalised, not using supplementary oxygen; 4)hospitalised, using supplementary oxygen; 5)hospitalised, using high-flow nasal cannula or non-invasive ventilation; 6)hospitalised, on mechanical ventilation; 7) death MESHD. Secondary endpoints are the ordinal scale at 7 days, need for mechanical ventilation and rescue therapies during 15 days, need of high-flow nasal cannula or non-invasive ventilation during 15 days, length of hospital stay, in-hospital mortality, thromboembolic events, occurrence of acute kidney injury MESHD acute kidney injury HP, and number of days free of respiratory support at 15 days. Secondary safety outcomes include prolongation of QT interval on electrocardiogram, ventricular arrhythmias HP, and liver toxicity. The main analysis will consider all patients with confirmed COVID-19 in the groups they were randomly assigned. Ethics and dissemination: This study has been approved by Brazil's National Ethic Committee (CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete, as well as presented and reported to local health agencies. ClinicalTrials.gov identifier: NCT04322123

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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