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1.
PLoS One ; 16(3): e0248128, 2021.
Article in English | MEDLINE | ID: covidwho-1575679

ABSTRACT

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Data Management/methods , Drug Therapy, Combination/methods , Female , Hospitalization , Humans , Male , SARS-CoV-2/drug effects
2.
An Pediatr (Barc) ; 96(3): 213-220, 2022 Mar.
Article in Spanish | MEDLINE | ID: covidwho-1286263

ABSTRACT

Introduction: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. Patients and methods: Pediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h in treatment and after 72 h. Results: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March-July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs. 416.5 ms (29.4) (p = 0.716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms (IQR 48.7) (p = 0.062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. Conclusions: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc >500 ms.

3.
PLoS One ; 16(6): e0252302, 2021.
Article in English | MEDLINE | ID: covidwho-1278172

ABSTRACT

A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC50) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Hydroxychloroquine/pharmacology , SARS-CoV-2/drug effects , Animals , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/virology , Cell Survival/drug effects , Cells, Cultured , Chlorocebus aethiops , Drug Combinations , Hospitalization , Host-Pathogen Interactions/drug effects , Humans , Hydroxychloroquine/therapeutic use , Indonesia , Inhibitory Concentration 50 , Inpatients , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Time Factors , Vero Cells , Viral Load/drug effects
4.
Eur Respir J ; 59(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1264121

ABSTRACT

BACKGROUND: Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having in vitro antiviral properties. This may improve outcomes in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: Placebo-controlled double-blind randomised multicentre trial. Patients aged ≥18 years, admitted to hospital for ≤48 h (not intensive care) with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR test were recruited. The intervention was 500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice-daily hydroxychloroquine for all 15 days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14 days (DAOH14). RESULTS: After randomisation of 117 patients, at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria. Consequently, the trial was terminated on 1 February 2021. 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median (interquartile range) 9.0 (3-11) DAOH14 versus 9.0 (7-10) DAOH14 in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for one patient in the intervention group versus two patients receiving placebo (p=0.52), and readmittance or death within 30 days occurred for nine patients in the intervention group versus six patients receiving placebo (p=0.57). CONCLUSIONS: The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19.


Subject(s)
COVID-19 , Hydroxychloroquine , Adolescent , Adult , Azithromycin , COVID-19/drug therapy , Double-Blind Method , Humans , SARS-CoV-2 , Treatment Outcome
5.
Expert Rev Anti Infect Ther ; 20(1): 17-21, 2022 01.
Article in English | MEDLINE | ID: covidwho-1258702

ABSTRACT

INTRODUCTION: Mediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach. AREAS COVERED: We analyze selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the results that suggested a potential survival benefit of low-dose aspirin and colchicine when used for COVID-19. EXPERT OPINION: Nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that are unfortunately currently at best of second choice after paracetamol, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their anti-inflammatory and immunomodulatory properties. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Drug Repositioning , Interleukin-6/antagonists & inhibitors , Nitro Compounds/therapeutic use , Thiazoles/therapeutic use , COVID-19/complications , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Humans , Interferons/immunology , Interleukin-6/immunology , Observational Studies as Topic , SARS-CoV-2/pathogenicity
6.
Pharmacol Rep ; 73(6): 1513-1519, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1258294

ABSTRACT

In December 2019, a new variant coronavirus, SARS-CoV-2, emerged in China, which was initially described as a pneumonia of an unknown agent. The new coronavirus spreads mainly by person-to-person transmission through close contact. The pathophysiology of COVID-19 is related to a complex immune system response that varies between people and, in severe cases of the disease, is characterized by excessive responses called "cytokine storms," which are associated with complications that can lead to a state of hypercoagulation and death. Glucocorticoids and azithromycin are drugs that may be effective in the treatment. This review aims to highlight the clinical findings that demonstrate the effectiveness of glucocorticoid and azithromycin therapy in the treatment of COVID-19. To date, many drugs have been studied for use in combination therapy, and the rapid expansion of knowledge about the virology of SARS-CoV-2 generates a more accurate direction in therapy.


Subject(s)
Azithromycin/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , COVID-19/physiopathology , Drug Combinations , Humans , SARS-CoV-2
7.
SN Compr Clin Med ; : 1-5, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-1252328

ABSTRACT

The discovery of different antimicrobial agents has revolutionized the treatment against a variety of infections for many decades, but the emergence of antimicrobial resistance require rigorous measures, even amid the coronavirus disease 2019 (COVID-19) pandemic. This retrospective study aimed to examine the consumption of antibiotics in patients with COVID-19 admitted into the five hospitals in the province of Punjab, Pakistan. We collected data on the consumption of antibiotics, classified using the World Health Organization (WHO) AWaRe (Access, Watch, and Reserve), within two months-August and September, 2020, and the corresponding months in 2019. Consumption of antibiotics was presented as daily define dose (DDD) per 100 occupied bed-days. Eight different classes of antibiotics were prescribed to patients with COVID-19 without culture tests being performed, with the prescribing of antibiotics of the Watch category was especially prevalent. The consumption of antibiotics was higher during the COVID-19 pandemic compared to the pre-pandemic period: the consumption of azithromycin increased from 11.5 DDDs per 100 occupied bed-days in 2019 to 17.0 DDDs per 100 occupied bed-days in 2020, while the consumption of ceftriaxone increased from 20.2 DDDs per 100 occupied bed-days in 2019 to 25.1 DDDs per 100 occupied bed-days in 2020. The current study revealed non-evidence-based utilization of antibiotics among patients with COVID-19 admitted into the hospitals in Pakistan. Evidently, the current COVID-19 pandemic is a public health threat of notable dimensions which has compromised the ongoing antimicrobial stewardship program, potentially leading to the emergence of antimicrobial resistance among pathogens.

8.
Rev Med Virol ; 32(1): e2258, 2022 01.
Article in English | MEDLINE | ID: covidwho-1252046

ABSTRACT

Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta-analysis investigated the safety and efficacy of AZM in treating Covid-19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random-effects model was used to pool estimates using the Paule-Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as 'low' for five of the seven mortality results and as 'some concerns' and 'high' in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid-19 patients (OR = 0.96, 95% CI 0.88-1.05, p = 0.317 based on the random-effect meta-analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49-1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI -2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Anti-Bacterial Agents/adverse effects , Azithromycin/adverse effects , COVID-19/diagnosis , Humans , Middle Aged , Randomized Controlled Trials as Topic , SARS-CoV-2
10.
Tuberc Respir Dis (Seoul) ; 84(4): 299-316, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1236832

ABSTRACT

BACKGROUND: The lack of effective medications for coronavirus disease 2019 (COVID-19) has led to a trend of drug repurposing such as the case of azithromycin which shows immunomodulatory and anti-viral effect. Several clinical trials have shown conflicting results. It is currently unclear whether the available evidence is in favor or against the use of azithromycin in COVID-19 patients. Thus, the aim of this study was to investigate the efficacy and safety of azithromycin in COVID-19 patients. METHODS: Four independent reviewers selected relevant studies from PubMed, ScienceDirect, EBSCO, and ProQuest published prior to March 2021. The protocol used in this study has been registered in PROSPERO (CRD42020224967). RESULTS: We included 17 studies and found that the mortality rate (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.76-1.19), need of respiratory support (OR, 1.30; 95% CI, 0.98-1.73), hospitalization rate (standardized mean difference, 0.12; 95% CI, -0.02 to 0.27), and intensive care unit transfer (OR, 1.21; 95% CI, 0.79-1.86) of azithromycin-treated group did not differ significantly (p>0.05) from those of the control group. Azithromycin treatment did not significantly increase the risk of getting secondary infection (OR, 1.23; 95% CI, 0.83-1.82), hypoglycemia (OR, 0.73; 95% CI, 0.38-1.40), gastrointestinal problems (OR, 1.03; 95% CI, 0.73-1.45) or electrocardiogram abnormalities (OR, 1.16; 95% CI, 0.94-1.42). The overall quality of evidence ranged from low to very low. CONCLUSION: Azithromycin did not result in a superior clinical improvement in COVID-19 patients, although it was well-tolerated and safe to use.

11.
R Soc Open Sci ; 8(4): 210235, 2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1231061

ABSTRACT

Hydroxychloroquine (HCQ), the hydroxyl derivative of chloroquine (CQ), is widely used in the treatment of rheumatological conditions (systemic lupus erythematosus, rheumatoid arthritis) and is being studied for the treatment and prevention of COVID-19. Here, we investigate through mathematical modelling the safety profile of HCQ, CQ and other QT-prolonging anti-infective agents to determine their risk categories for Torsade de Pointes (TdP) arrhythmia. We performed safety modelling with uncertainty quantification using a risk classifier based on the qNet torsade metric score, a measure of the net charge carried by major currents during the action potential under inhibition of multiple ion channels by a compound. Modelling results for HCQ at a maximum free therapeutic plasma concentration (free C max) of approximately 1.2 µM (malaria dosing) indicated it is most likely to be in the high-intermediate-risk category for TdP, whereas CQ at a free C max of approximately 0.7 µM was predicted to most likely lie in the intermediate-risk category. Combining HCQ with the antibacterial moxifloxacin or the anti-malarial halofantrine (HAL) increased the degree of human ventricular action potential duration prolongation at some or all concentrations investigated, and was predicted to increase risk compared to HCQ alone. The combination of HCQ/HAL was predicted to be the riskiest for the free C max values investigated, whereas azithromycin administered individually was predicted to pose the lowest risk. Our simulation approach highlights that the torsadogenic potentials of HCQ, CQ and other QT-prolonging anti-infectives used in COVID-19 prevention and treatment increase with concentration and in combination with other QT-prolonging drugs.

12.
Eur J Pharmacol ; 905: 174191, 2021 Aug 15.
Article in English | MEDLINE | ID: covidwho-1230459

ABSTRACT

Azithromycin, a member of the macrolide family of antibiotics, is commonly used to treat respiratory bacterial infections. Nevertheless, multiple pharmacological effects of the drug have been revealed in several investigations. Conceivably, the immunomodulatory properties of azithromycin are among its critical features, leading to its application in treating inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Additionally, azithromycin may directly inhibit viral load as well as its replication, or it could demonstrate indirect inhibitory impacts that might be associated with the expression of antiviral genes. Currently, coronavirus disease 2019 (COVID-19) is an extra urgent issue affecting the entire world, and it is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress syndrome (ARDS), which is associated with hyper inflammation due to cytokine release, is among the leading causes of death in COVID-19 patients with critical conditions. The present paper aims to review the immunomodulatory and antiviral properties of azithromycin as well as its potential clinical applications in the management of COVID-19 patients.


Subject(s)
Azithromycin/pharmacology , COVID-19 , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/immunology , Humans , Immunologic Factors/pharmacology , SARS-CoV-2
13.
Cureus ; 13(4): e14574, 2021 Apr 20.
Article in English | MEDLINE | ID: covidwho-1229459

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), causing coronavirus disease-19 (COVID-19), has been responsible for approximately 75 million cases and 1.6 million deaths globally as of December 22, 2020. Currently, no treatment modalities or management options have been recommended by the National Institutes of Health (NIH) prior to patient hospitalization and supplemental oxygen requirement. This poses a unique challenge for outpatient primary care physicians, who are often tasked with initial care of patients early on in their disease course. During the pandemic, our family practice provided medical care to approximately 2,000 families located in the surrounding Brooklyn community. With only telemedicine at our disposal, our clinic was tasked with treating patients presenting remotely who may or may not have had COVID-19 - a large clinical diagnosis was made given the absence of in-person testing. Often co-administered, Azithromycin was considered a supportive agent that may or may not have increased the benefit of hydroxychloroquine. However, Azithromycin may perform well on its own for various reasons as it has been shown to have antiviral activity against other RNA viruses, anti-inflammatory properties, and antiviral effects within bronchial epithelial cells. Azithromycin has also shown efficacy as an add-on treatment for reducing asthma exacerbations - pertinent to the pro-inflammatory pulmonary conditions in COVID-19 progression - and may even prevent or treat bacterial co-infection in patients with SARS-COV-2. In order to investigate the association between Azithromycin and the COVID-19 disease process, our clinical study retrospectively identified patients who were prescribed Azithromycin (500 mg on day one + 250 mg on days two to five) during the peak months of the COVID-19 pandemic in New York City from March 2020 through May 2020. All patients prescribed Azithromycin with suspicion of COVID-19 infection were interviewed via telephone regarding their constellation of symptoms, compliance with the prescribed antibiotic for the intended course, symptom duration prior to and following antibiotic course initiation, as well as any further complications of their illness, if present. Ultimately, the majority of the patients who were interviewed over the phone concluded that a full course of Azithromycin helped improve their symptoms during their infection with COVID-19. Outcomes and complications in patients treated with Azithromycin were noteworthy in that there were no reports of pulmonary complications or deterioration of pulmonary function after treatment (e.g., no shortness of breath, wheezing, dyspnea, etc.), although some patients did experience residual coughing and nasal discharge post-treatment. We believe further study of this treatment in the setting of experimental, randomized controlled trials may reveal the benefits of Azithromycin in terms of reducing infection severity, length, and limiting the incidence of complications in patients with COVID-19.

14.
J Cardiovasc Dev Dis ; 8(5)2021 May 13.
Article in English | MEDLINE | ID: covidwho-1227033

ABSTRACT

BACKGROUND: Hydroxychloroquine or chloroquine with or without the concomitant use of azithromycin have been widely used to treat patients with SARS-CoV-2 infection, based on early in vitro studies, despite their potential to prolong the QTc interval of patients. OBJECTIVE: This is a systematic review and metanalysis designed to assess the effect of hydroxychloroquine with or without the addition of azithromycin on the QTc of hospitalized patients with COVID-19. MATERIALS AND METHODS: PubMed, Scopus, Cochrane and MedRxiv databases were reviewed. A random effect model meta-analysis was used, and I-square was used to assess the heterogeneity. The prespecified endpoints were ΔQTc, QTc prolongation > 500 ms and ΔQTc > 60 ms. RESULTS: A total of 18 studies and 7179 patients met the inclusion criteria and were included in this systematic review and meta-analysis. The use of hydroxychloroquine with or without the addition of azithromycin was associated with increased QTc when used as part of the management of patients with SARS-CoV-2 infection. The combination therapy with hydroxychloroquine plus azithromycin was also associated with statistically significant increases in QTc. Moreover, the use of hydroxychloroquine alone, azithromycin alone, or the combination of the two was associated with increased numbers of patients that developed QTc prolongation > 500 ms. CONCLUSION: This systematic review and metanalysis revealed that the use of hydroxychloroquine alone or in conjunction with azithromycin was linked to an increase in the QTc interval of hospitalized patients with SARS-CoV-2 infection that received these agents.

15.
J Electrocardiol ; 67: 1-6, 2021.
Article in English | MEDLINE | ID: covidwho-1222930

ABSTRACT

BACKGROUND: Minimizing direct patient contact among healthcare personnel is crucial for mitigating infectious risk during the coronavirus disease 2019 (COVID-19) pandemic. The use of remote cardiac telemetry as an alternative to 12­lead electrocardiography (ECG) for continuous QTc monitoring may facilitate this strategy, but its application has not yet been validated or implemented. METHODS: In the validation component of this two-part prospective cohort study, a total of 65 hospitalized patients with simultaneous ECG and telemetry were identified. QTc obtained via remote telemetry as measured by 3 independent, blinded operators were compared with ECG as assessed by 2 board-certified electrophysiologists as the gold-standard. Pearson correlation coefficients were calculated to measure the strength of linear correlation between the two methods. In a separate cohort comprised of 68 COVID-19 patients treated with combined hydroxychloroquine and azithromycin, telemetry-based QTc values were compared at serial time points after medication administration using Friedman rank-sum test of repeated measures. RESULTS: Telemetry-based QTc measurements highly correlated with QTc values derived from ECG, with correlation coefficients of 0.74, 0.79, 0.85 (individual operators), and 0.84 (mean of all operators). Among the COVID-19 cohort, treatment led to a median QTc increase of 15 milliseconds between baseline and following the 9th dose (p = 0.002), with 8 (12%) patients exhibiting an increase in QTc ≥ 60 milliseconds and 4 (6%) developing QTc ≥ 500 milliseconds. CONCLUSIONS: Cardiac telemetry is a validated clinical tool for QTc monitoring that may serve an expanding role during the COVID-19 pandemic strengthened by its remote and continuous monitoring capability and ubiquitous presence throughout hospitals.


Subject(s)
COVID-19 , Long QT Syndrome , Delivery of Health Care , Electrocardiography , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Pandemics , Prospective Studies , SARS-CoV-2 , Telemetry
16.
Ann Noninvasive Electrocardiol ; 26(4): e12846, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1218078

ABSTRACT

BACKGROUND: Since there was no proven treatment of coronavirus disease 2019 (COVID-19), hydroxychloroquine-azithromycin (HCQ-AZM) combination is being used in different countries as a treatment option. Many controversies exist related to the safety and effectiveness of this combination, and questions about how HCQ-AZM combination affects the ventricular repolarization are still unknown. OBJECTIVE: The aim of the study was to show whether the hydroxychloroquine-azithromycin (HCQ-AZM) combination prolonged Tpeak-to-end (TpTe) duration and TpTe/QT interval ratio or not. METHODS: One hundred and twenty-six consequent COVID-19(+) patients meeting the study criteria were enrolled in this study. Baseline ECGs were obtained immediately after hospitalization and before commencing the HCQ-AZM combination. On-treatment ECG was obtained 24-48 hr after the loading dose of HCQ/AZM. ECG parameters including PR interval, QRS duration, QT interval, QTc interval, TpTe duration, and TpTe/QT interval ratio were assessed. Demographic and laboratory findings were collected from an electronic recording system. RESULTS: ECGs of 126 COVID-19(+) patients who received HCQ-AZM combination were assessed. Mean baseline QTc (by Fridericia formula), TpTe, and TpTe/QT ratio were 420.0 ± 26.5 ms, 82.43 ± 9.77 ms, and 0.22 ± 0.02, respectively. On-treatment QTc, TpTe and TpTe/QT ratio were 425.7 ± 27.18 ms, 85.17 ± 11.17 ms, and 0.22 ± 0.03, respectively. No statistically significant acute impacts of HCQ-AZM combination on TpTe duration and TpTe/QT interval ratio were observed compared with baseline values. No ventricular tachycardia/fibrillation and the significant conduction delays were seen during in-hospital follow-up. CONCLUSION: HCQ-AZM combination increased TpTe duration. However, no significant impact on TpTe/QT interval ratio was observed.


Subject(s)
Azithromycin/pharmacology , COVID-19/drug therapy , Electrocardiography/drug effects , Heart Ventricles/drug effects , Hydroxychloroquine/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Administration Schedule , Drug Therapy, Combination , Enzyme Inhibitors/pharmacology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
17.
Front Med (Lausanne) ; 8: 642313, 2021.
Article in English | MEDLINE | ID: covidwho-1211822

ABSTRACT

Macrolides (e.g., erythromycin, fidaxomicin, clarithromycin, and azithromycin) are a class of bacteriostatic antibiotics commonly employed in medicine against various gram-positive and atypical bacterial species mostly related to respiratory tract infections, besides they possess anti-inflammatory and immunomodulatory effects. Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). It was first detected in Wuhan, Hubei, China, in December 2019 and resulted in a continuing pandemic. Macrolides have been extensively researched as broad adjunctive therapy for COVID-19 due to its immunostimulant abilities. Among such class of drugs, azithromycin is described as azalide and is well-known for its ability to decrease the production of pro-inflammatory cytokines, including matrix metalloproteinases, tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8. In fact, a report recently published highlighted the effectiveness of combining azithromycin and hydroxychloroquine for COVID-19 treatment. Indeed, it has been underlined that azithromycin quickly prevents SARS-CoV-2 infection by raising the levels of both interferons and interferon-stimulated proteins at the same time which reduces the virus replication and release. In this sense, the current review aims to evaluate the applications of macrolides for the treatment of COVID-19.

18.
J Nepal Health Res Counc ; 19(1): 1-9, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1209433

ABSTRACT

BACKGROUND: The global spread of COVID-19 and the lack of definite treatment have caused an alarming crisis in the world. We aimed to evaluate the outcome and potential harmful cardiac effects of hydroxychloroquine and azithromycin compared to hydroxychloroquine alone for COVID-19 treatment. METHODS: PubMed, Medline, Google Scholar, Cochrane Library, clinicaltrials.gov, and World Health Organization clinical trial registry were searched using appropriate keywords and identified six studies using PRISMA guidelines. The quantitative synthesis was performed using fixed or random effects for the pooling of studies based on heterogeneities. RESULTS: The risk of mortality (RR=1.16; CI: 0.92-1.46) and adverse cardiac events (OR=1.06; CI: 0.82-1.37) demonstrated a small increment though of no significance. There were no increased odds of mechanical ventilation (OR=0.84; CI: 0.33-2.15) and significant QTc prolongation (OR=0.84, CI: 0.59-1.21). Neither the critical QTc threshold (OR=1.92, CI: 0.81-4.56) nor absolute ?QTc ?60ms (OR=1.95, CI:0.55-6.96) increased to the level of statistical significance among hydroxychloroquine and azithromycin arm compared to hydroxychloroquine alone, but the slightly increased odds need to be considered in clinical practice. CONCLUSIONS: The combination of hydroxychloroquine and azithromycin leads to small increased odds of mortality and cardiac events compared to hydroxychloroquine alone. The use of hydroxychloroquine and azithromycin led to increased odds of QT prolongation, although not statistically significant.


Subject(s)
Azithromycin/therapeutic use , COVID-19/drug therapy , Cardiovascular Diseases/chemically induced , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Azithromycin/adverse effects , COVID-19/mortality , Cardiovascular Diseases/mortality , Drug Therapy, Combination , Humans , Hydroxychloroquine/adverse effects , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS-CoV-2
19.
Acta Neurol Scand ; 144(3): 334-340, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1207377

ABSTRACT

OBJECTIVE: To describe presenting symptoms, clinical outcomes, and therapeutic management of concurrent Coronavirus disease 2019 (COVID-19) infections in patients with a pre-existing myasthenia gravis (MG). METHODS: We conducted a retrospective study in patients with preexisting MG presenting with concurrent COVID-19 between September 21st and November 4th, 2020 when attending the emergency department or routine neurology consultation at the National Institute Mongi Ben Hamida of Neurology of Tunis, Tunisia. RESULTS: Five patients were identified. The Myasthenia Gravis Foundation of America scores (MGFA) prior to COVID-19 infection were class I in one patient, class II (IIa, IIb) in two patients, and class IIIb in one patient. Four patients had mild to moderate courses of COVID-19 infection. One patient presented a critical infection with acute respiratory disease syndrome (ARDS) requiring mechanical ventilation. Two of them also demonstrated signs of MG exacerbation requiring the use of intravenous immunoglobulin in one case. We maintained immunosuppressant therapy to MG in all our patients. All our patients received Azithromycin (AZM) as a part of specific drug treatment of COVID-19 infection. Outcome was favorable in 4 patients and rapidly fatal evolution was observed in the patient with ADRS. DISCUSSIONS AND CONCLUSION: The results from our study suggest that prior MG activity could partially influence the subsequent clinical outcomes. It emerged also that ongoing long-term immunosuppressive immunotherapy to MG should be maintained during the COVID-19 pandemic and that AZM can be used safely in MG patients and concurrent COVID-19 infection.


Subject(s)
COVID-19/complications , Myasthenia Gravis/complications , Adult , COVID-19/immunology , COVID-19/therapy , Female , Humans , Male , Middle Aged , Myasthenia Gravis/immunology , Myasthenia Gravis/therapy , Retrospective Studies , SARS-CoV-2 , Tunisia
20.
Int J Biol Sci ; 17(6): 1507-1520, 2021.
Article in English | MEDLINE | ID: covidwho-1206439

ABSTRACT

The severe cases of Coronavirus Disease 2019 (COVID-19) frequently exhibit excessive inflammatory responses, acute respiratory distress syndrome (ARDS), coagulopathy, and organ damage. The most striking immunopathology of advanced COVID-19 is cytokine release syndrome or "cytokine storm" that is attributable to the deficiencies in immune regulatory mechanisms. CD4+FoxP3+ regulatory T cells (Tregs) are central regulators of immune responses and play an indispensable role in the maintenance of immune homeostasis. Tregs are likely involved in the attenuation of antiviral defense at the early stage of infection and ameliorating inflammation-induced organ injury at the late stage of COVID-19. In this article, we review and summarize the current understanding of the change of Tregs in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and discuss the potential role of Tregs in the immunopathology of COVID-19. The emerging concept of Treg-targeted therapies, including both adoptive Treg transfer and low dose of IL-2 treatment, is introduced. Furthermore, the potential Treg-boosting effect of therapeutic agents used in the treatment of COVID-19, including dexamethasone, vitamin D, tocilizumab and sarilumab, chloroquine, hydroxychloroquine, azithromycin, adalimumab and tetrandrine, is discussed. The problems in the current study of Treg cells in COVID-19 and future perspectives are also addressed.


Subject(s)
CD4 Antigens/immunology , COVID-19/immunology , COVID-19/therapy , Forkhead Transcription Factors/immunology , T-Lymphocytes, Regulatory/immunology , COVID-19/virology , Cytokine Release Syndrome , Humans , SARS-CoV-2/isolation & purification
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