Hydroxychloroquine (HCQ), which was initially used as an antimalarial drug, is now being used to treat other illnesses, especially rheumatic autoimmune disorders  such as systemic lupus erythematosus, primary Sjögren's syndrome, and rheumatoid arthritis, because it is safe, effective, and cost efficient. This drug has shown high efficacy and has become the first-line treatment for many of these diseases. Although HCQ has many therapeutic effects, it has unfortunately shown some complications, especially with its long-term use. One of these side effects is arrhythmia through prolongation of the QT interval. This narrative literature review focuses on the effects of HCQ on the QT interval in patients with rheumatologic diseases who have been prescribed this drug. In particular, we will focus on the increased risk of arrhythmia when HCQ is administered with other drugs, such as azithromycin and many others, along with drug-drug interactions. In addition, we investigated the safety of this drug in pregnant women.

Aims: To evaluate the efficacy and safety of hydroxychloroquine/chloroquine, with or without azithromycin, in treating hospitalized COVID-19 patients. Materials & methods: Data from randomized and observational studies were included in a random-effects meta-analysis. Primary outcomes included time to negative conversion of SARS-CoV-2 tests, length of stay, mortality, incidence of mechanical ventilation, time to normalization of body temperature, incidence of adverse events and incidence of QT prolongations. Results: Fifty-one studies (n = 61,221) were included. Hydroxychloroquine/chloroquine showed no efficacy in all primary efficacy outcomes, but was associated with increased odds of QT prolongations. Conclusion: Due to a lack of efficacy and increased odds of cardiac adverse events, hydroxychloroquine/chloroquine should not be used for treating hospitalized COVID-19 patients.

Hydroxychloroquine/chloroquine (HCQ/CQ) treatment for COVID-19 was associated with QT interval prolongation and arrhythmia risks. This study aimed to investigate QTc interval and ventricular repolarization dispersion changes, as markers of arrhythmia risks, after HCQ/CQ administration with/without azithromycin (AZT) during COVID-19 pandemic.

A prospective observational study was performed in two academic hospitals in Indonesia. Adult patients who received HCQ/CQ alone and HCQ/CQ + AZT concomitant treatments for COVID-19 infection were enrolled. Baseline and post HCQ/CQ treatment electrocardiograms were obtained. Baseline and post HCQ/CQ treatment QT interval by Bazett (B-QTc) and Fridericia (F-QTc) formulas and ventricular repolarization dispersion indices by Tpeak-Tend (Tp-e) interval and Tpeak-Tend/QT (Tp-e/QT) ratio were calculated and analyzed.

The study enrolled 55 (HCQ/CQ alone) and 77 subjects (HCQ/CQ + AZT concomitant). F-QTc interval significantly lengthened in subjects with HCQ/CQ + AZT (mean difference 11.89 ms [P = .028]). The incidences of severe B-QTc and F-QTc lengthening were 13.1% and 12.3%, B-QTc and F-QTc prolongation were 25.4% and 12.3%, and severe B-QTc and F-QTc prolongation were 6.2% and 3.2%. Tp-e interval lengthened significantly from baseline to posttreatment in HCQ/CQ alone and HCQ/CQ + AZT (mean difference 10.83 ms [P = .006] and 18.73 ms [P < .001], respectively). Tp-e/QT ratio increased significantly from baseline to posttreatment in HCQ/CQ + AZT concomitant (mean difference 0.035 [P < .001]). No fatal arrhytmia occurred.

During COVID-19 pandemic, HCQ/CQ + AZT concomitant treatment caused significant F-QTc lengthening, significantly increased Tp-e interval and increased Tp-e/QT ratio. HCQ/CQ alone only caused significant increase of Tp-e interval. Incidences of severe QTc lengthening and prolongation were low in both HCQ/CQ alone and HCQ/CQ + AZT concomitant.

Background: The review seeks to shed light on the administered and recommended COVID-19 treatment medications through an evaluation of their efficacy. Methods: Data were collected from key databases, including Scopus, Medline, Google Scholar, and CINAHL. Other platforms included WHO and FDA publications. The review's literature search was guided by the WHO solidarity clinical trials for COVID-19 scope and trial-assessment parameters. Results: The findings indicate that the use of antiretroviral drugs as an early treatment for COVID-19 patients has been useful. It has reduced hospital time, hastened the clinical cure period, delayed and reduced the need for mechanical and invasive ventilation, and reduced mortality rates. The use of vitamins, minerals, and supplements has been linked to increased immunity and thus offering the body a fighting chance. Nevertheless, antibiotics do not correlate with improving patients' wellbeing and are highly discouraged from the developed clinical trials. Conclusions: The review demonstrates the need for additional clinical trials with a randomized, extensive sample base and over a more extended period to examine the potential side effects of the medications administered. Critically, the findings underscore the need for vaccination as the only viable medication to limit the SARS-CoV-2 virus spread.

Substantial efforts have been recently committed to develop coronavirus disease-2019 (COVID-19) medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. Although these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluated the proarrhythmia risk and inotropic effects of these drugs in the cardiomyocyte contractility-based model of the human heart. We found Hydroxychloroquine to have a low proarrhythmia risk, whereas Chloroquine and Azithromycin were associated with high risk. Hydroxychloroquine proarrhythmia risk changed to high with low level of K+, whereas high level of Mg2+ protected against proarrhythmic effect of high Hydroxychloroquine concentrations. Moreover, therapeutic concentration of Hydroxychloroquine caused no enhancement of elevated temperature-induced proarrhythmia. Polytherapy of Hydroxychloroquine plus Azithromycin and sequential application of these drugs were also found to influence proarrhythmia risk categorization. Hydroxychloroquine proarrhythmia risk changed to high when combined with Azithromycin at therapeutic concentration. However, Hydroxychloroquine at therapeutic concentration impacted the cardiac safety profile of Azithromycin and its proarrhythmia risk only at concentrations above therapeutic level. We also report that Hydroxychloroquine and Chloroquine, but not Azithromycin, decreased contractility while exhibiting multi-ion channel block features, and Hydroxychloroquine's contractility effect was abolished by Azithromycin. Thus, this study has the potential to inform clinical studies evaluating repurposed therapies, including those in the COVID-19 context. Additionally, it demonstrates the translational value of the human cardiomyocyte contractility-based model as a key early discovery path to inform decisions on novel therapies for COVID-19, malaria, and inflammatory diseases.