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1.
Cardiol Rev ; 29(6): 289-291, 2021.
Article in English | MEDLINE | ID: covidwho-20244180

ABSTRACT

The ongoing coronavirus infection-2019 (COVID-19) global pandemic has had devastating impacts on the global population since 2019. Cardiac complications are a well-documented sequala of COVID-19, with exposed patients experiencing complications such as myocardial infarction, myocarditis, and arrythmias. This article aims to review prominent literature regarding COVID-19 and its link with arrhythmias, as well as to discuss some of the possible mechanisms by which arrhythmogenesis may occur in patients with COVID-19.


Subject(s)
Arrhythmias, Cardiac/epidemiology , COVID-19/epidemiology , Anti-Bacterial Agents/adverse effects , Antirheumatic Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/physiopathology , Azithromycin/adverse effects , COVID-19/physiopathology , Humans , Hydroxychloroquine/adverse effects , Intensive Care Units , SARS-CoV-2 , Severity of Illness Index , COVID-19 Drug Treatment
3.
Medicina (Kaunas) ; 59(5)2023 Apr 29.
Article in English | MEDLINE | ID: covidwho-20239767

ABSTRACT

Background and Objectives: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular, the potential of prolong cardiac repolarization when using this combination has been discussed. Materials and Methods: We report a pragmatic and simple safety approach which we implemented among the first patients treated for COVID-19 in our center in early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) > 500 ms, hypokalemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 h of the initial prescription. Results: Among the 424 consecutive adult patients (mean age 46.3 ± 16.1 years; 216 women), 21.5% patients were followed in conventional wards and 78.5% in a day-care unit. A total of 11 patients (2.6%) had contraindications to the HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after 2 days of treatment (p = 0.003). QTc prolongation was particularly observed in female outpatients <65 years old without cardiovascular disease. Ten patients (2.4%) developed QTc prolongation > 60 ms, and none had QTc > 500 ms. Conclusions: This report does not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, it shows that a simple initial assessment of patient medical history, electrocardiogram (ECG), and kalemia identifies contraindicated patients and enables the safe treatment of COVID-19 patients with HCQ-AZ. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are applied.


Subject(s)
COVID-19 , Long QT Syndrome , Adult , Humans , Female , Middle Aged , Aged , Hydroxychloroquine/adverse effects , Azithromycin/adverse effects , SARS-CoV-2 , Long QT Syndrome/chemically induced , COVID-19 Drug Treatment , Electrocardiography/methods
4.
Pharmacol Res Perspect ; 11(3): e01072, 2023 06.
Article in English | MEDLINE | ID: covidwho-20239666

ABSTRACT

The current COVID-19 pandemic was an exceptional health situation, including for drug use. As there was no known effective drug for COVID-19 at the beginning of the pandemic, different drug candidates were proposed. In this article, we present the challenges for an academic Safety Department to manage the global safety of a European trial during the pandemic. The National Institute for Health and Medical Research (Inserm) conducted a European multicenter, open-label, randomized, controlled trial involving three repurposed and one-in development drugs (lopinavir/ritonavir, IFN-ß1a, hydroxychloroquine, and remdesivir) in adults hospitalized with COVID-19. From 25 March 2020 to 29 May 2020, the Inserm Safety Department had to manage 585 Serious Adverse Events (SAEs) initial notification and 396 follow-up reports. The Inserm Safety Department's staff was mobilized to manage these SAEs and to report Expedited safety reports to the competent authorities within the legal timeframes. More than 500 queries were sent to the investigators due to a lack of or incoherent information on SAE forms. At the same time, the investigators were overwhelmed by the management of patients suffering from COVID-19 infection. These particular conditions of missing data and lack of accurate description of adverse events made evaluation of the SAEs very difficult, particularly the assessment of the causal role of each investigational medicinal product. In parallel, working difficulties were accentuated by the national lockdown, frequent IT tool dysfunctions, delayed implementation of monitoring and the absence of automatic alerts for SAE form modification. Although COVID-19 is a confounding factor per se, the delay in and quality of SAE form completion and the real-time medical analysis by the Inserm Safety Department were major issues in the quick identification of potential safety signals. To conduct a high-quality clinical trial and ensure patient safety, all stakeholders must take their roles and responsibilities.


Subject(s)
COVID-19 , Adult , Humans , Pandemics , Pharmacovigilance , Communicable Disease Control , Hydroxychloroquine/adverse effects , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
5.
J Dermatolog Treat ; 33(2): 1104-1106, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-20237534

ABSTRACT

The utility of hydroxychloroquine for the prophylaxis and treatment of alarmingly rising COVID-19 infection has been widely explored in several studies. However, its cutaneous adverse effects among health care workers and COVID patients taking prophylactic doses has not been reported. We report cases of palmoplantar among health care workers who were on prophylactic doses of hydroxychloroquine and their management with cetirizine and methylprednisolone.


Subject(s)
COVID-19 Drug Treatment , Hydroxychloroquine , Health Personnel , Hospitals , Humans , Hydroxychloroquine/adverse effects , Referral and Consultation , SARS-CoV-2
6.
Sci Total Environ ; 892: 164309, 2023 Sep 20.
Article in English | MEDLINE | ID: covidwho-2324753

ABSTRACT

Water contamination by pharmaceuticals is a global concern due to their potential negative effects on aquatic ecosystems and human health. This study examined the presence of three repositioned drugs used for COVID-19 treatment: azithromycin (AZI), ivermectin (IVE) and hydroxychloroquine (HCQ) in water samples collected from three urban rivers in Curitiba, Brazil, during August and September 2020. We conducted a risk assessment and evaluated the individual (0, 2, 4, 20, 100 and 200 µg.L-1) and combined (mix of the drugs at 2 µg.L-1) effects of the antimicrobials on the cyanobacterium Synechococcus elongatus and microalga Chlorella vulgaris. The liquid chromatography coupled to mass spectrometry results showed that AZI and IVE were present in all collected samples, while HCQ occurred in 78 % of them. In all the studied sites, the concentrations found of AZI (up to 2.85 µg.L-1) and HCQ (up to 2.97 µg.L-1) represent environmental risks for the studied species, while IVE (up to 3.2 µg.L-1) was a risk only for Chlorella vulgaris. The hazard quotients (HQ) indices demonstrated that the microalga was less sensitive to the drugs than the cyanobacteria. HCQ and IVE had the highest values of HQ for the cyanobacteria and microalga, respectively, being the most toxic drugs for each species. Interactive effects of drugs were observed on growth, photosynthesis and antioxidant activity. The treatment with AZI + IVE resulted in cyanobacteria death, while exposure to the mixture of all three drugs led to decreased growth and photosynthesis in the cells. On the other hand, no effect on growth was observed for C. vulgaris, although photosynthesis has been negatively affected by all treatments. The use of AZI, IVE and HCQ for COVID-19 treatment may have generated surface water contamination, which could increased their potential ecotoxicological effects. This raises the need to further investigation into their effects on aquatic ecosystems.


Subject(s)
COVID-19 , Chlorella vulgaris , Microalgae , Water Pollutants, Chemical , Humans , Ecosystem , COVID-19 Drug Treatment , Hydroxychloroquine/analysis , Hydroxychloroquine/pharmacology , Azithromycin/toxicity , Pharmaceutical Preparations , Water , Water Pollutants, Chemical/analysis
7.
Curr Opin Crit Care ; 27(5): 544-550, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-2318644

ABSTRACT

PURPOSE OF REVIEW: If developed using rigorous methods and produced in a timely manner, clinical practice guidelines have the potential to improve patient outcomes. Although the COVID-19 pandemic has highlighted the challenges involved in generating reliable clinical guidance, it has also provided an opportunity to address these challenges. RECENT FINDINGS: New research addressing drugs for COVID-19 is being produced at unprecedented rates. Incorporating this new knowledge into patient care can be daunting for the average clinician. In collaboration with the BMJ and MAGIC, the WHO has developed a living guideline initiative with the goal of providing rapid and trustworthy clinical guidance in response to practice-changing evidence. As new evidence becomes available, it is incorporated into a living network meta-analysis that informs these guidelines, which are iteratively updated. Until this point, the group has generated guidelines addressing the use of corticosteroids, remdesivir, hydroxychloroquine, lopinavir/ritonavir, and ivermectin for COVID-19. SUMMARY: We provide an example of how rapid and rigorous guidelines can be accomplished, even in the setting of a pandemic, capitalizing on expertise, large and dedicated teams, and focused scope. We highlight the benefits of multifaceted knowledge dissemination through multiple formats to ensure global dissemination and in order to maximize impact.


Subject(s)
COVID-19 , Pandemics , Humans , Hydroxychloroquine , Lopinavir , SARS-CoV-2
8.
Curr Opin Rheumatol ; 32(5): 449-457, 2020 09.
Article in English | MEDLINE | ID: covidwho-2319043

ABSTRACT

PURPOSE OF REVIEW: The current review highlights recent insights into direct antiviral effects by antimalarials against severe acute respiratory syndrome (SARS)-CoV-2 and other viruses and their potential indirect effects on the host by avoiding exaggerated immune responses (reduced cytokine release, Toll-like receptor response, antigen presentation related to lysosomal processing). RECENT FINDINGS: Currently, there is a large debate on the use of antimalarials for prophylaxis and treatment of SARS-CoV-2-induced disease based on preclinical in-vitro data, small case series and extrapolation from earlier studies of their effect on intracellular pathogens, including many viruses. Hydroxychloroquine (HCQ) or chloroquine have not demonstrated robust efficacy in prior randomized controlled studies against several other viruses. In-vitro data indicate a reduced viral replication of SARS-CoV-2. Especially immunomodulatory effects of antimalarials might also contribute to a clinical efficacy. For SARS-CoV-2 various large studies will provide answers as to whether antimalarials have a place in prophylaxis or treatment of the acute virus infection with SARS-CoV-2 but compelling data are missing so far. SUMMARY: In-vitro data provide a theoretical framework for an efficacy of antimalarials in SARS-CoV-2-induced disease but clinical proof is currently missing.


Subject(s)
Antimalarials/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/therapeutic use , COVID-19 , Chloroquine/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Pandemics , SARS-CoV-2 , COVID-19 Drug Treatment
9.
Eur J Clin Pharmacol ; 79(6): 723-751, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2305199

ABSTRACT

INTRODUCTION: Drug repositioning is a strategy to identify a new therapeutic indication for molecules that have been approved for other conditions, aiming to speed up the traditional drug development process and reduce its costs. The high prevalence and incidence of coronavirus disease 2019 (COVID-19) underline the importance of searching for a safe and effective treatment for the disease, and drug repositioning is the most rational strategy to achieve this goal in a short period of time. Another advantage of repositioning is the fact that these compounds already have established synthetic routes, which facilitates their production at the industrial level. However, the hope for treatment cannot allow the indiscriminate use of medicines without a scientific basis. RESULTS: The main small molecules in clinical trials being studied to be potentially repositioned to treat COVID-19 are chloroquine, hydroxychloroquine, ivermectin, favipiravir, colchicine, remdesivir, dexamethasone, nitazoxanide, azithromycin, camostat, methylprednisolone, and baricitinib. In the context of clinical tests, in general, they were carried out under the supervision of large consortiums with a methodology based on and recognized in the scientific community, factors that ensure the reliability of the data collected. From the synthetic perspective, compounds with less structural complexity have more simplified synthetic routes. Stereochemical complexity still represents the major challenge in the preparation of dexamethasone, ivermectin, and azithromycin, for instance. CONCLUSION: Remdesivir and baricitinib were approved for the treatment of hospitalized patients with severe COVID-19. Dexamethasone and methylprednisolone should be used with caution. Hydroxychloroquine, chloroquine, ivermectin, and azithromycin are ineffective for the treatment of the disease, and the other compounds presented uncertain results. Preclinical and clinical studies should not be analyzed alone, and their methodology's accuracy should also be considered. Regulatory agencies are responsible for analyzing the efficacy and safety of a treatment and must be respected as the competent authorities for this decision, avoiding the indiscriminate use of medicines.


Subject(s)
COVID-19 , Humans , Drug Repositioning/methods , SARS-CoV-2 , Hydroxychloroquine/therapeutic use , Pandemics , Azithromycin , Ivermectin/therapeutic use , Reproducibility of Results , Chloroquine/therapeutic use , Dexamethasone/therapeutic use , Methylprednisolone , Antiviral Agents/therapeutic use
10.
Clin Transl Sci ; 16(7): 1243-1257, 2023 07.
Article in English | MEDLINE | ID: covidwho-2304186

ABSTRACT

Hydroxychloroquine (HCQ) is Food and Drug Administration (FDA)-approved for malaria, systemic and chronic discoid lupus erythematosus, and rheumatoid arthritis. Because HCQ has a proposed multimodal mechanism of action and a well-established safety profile, it is often investigated as a repurposed therapeutic for a range of indications. There is a large degree of uncertainty in HCQ pharmacokinetic (PK) parameters which complicates dose selection when investigating its use in new disease states. Complications with HCQ dose selection emerged as multiple clinical trials investigated HCQ as a potential therapeutic in the early stages of the COVID-19 pandemic. In addition to uncertainty in baseline HCQ PK parameters, it was not clear if disease-related consequences of SARS-CoV-2 infection/COVID-19 would be expected to impact the PK of HCQ and its primary metabolite desethylhydroxychloroquine (DHCQ). To address the question whether SARS-CoV-2 infection/COVID-19 impacted HCQ and DHCQ PK, dried blood spot samples were collected from SARS-CoV-2(-)/(+) participants administered HCQ. When a previously published physiologically based pharmacokinetic (PBPK) model was used to fit the data, the variability in exposure of HCQ and DHCQ was not adequately captured and DHCQ concentrations were overestimated. Improvements to the previous PBPK model were made by incorporating the known range of blood to plasma concentration ratios (B/P) for each compound, adjusting HCQ and DHCQ distribution settings, and optimizing DHCQ clearance. The final PBPK model adequately captured the HCQ and DHCQ concentrations observed in SARS-CoV-2(-)/(+)participants, and incorporating COVID-19-associated changes in cytochrome P450 activity did not further improve model performance for the SARS-CoV-2(+) population.


Subject(s)
COVID-19 , Hydroxychloroquine , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacokinetics , SARS-CoV-2 , Pandemics , COVID-19 Drug Treatment
11.
BMC Pharmacol Toxicol ; 24(1): 26, 2023 04 21.
Article in English | MEDLINE | ID: covidwho-2303429

ABSTRACT

BACKGROUND: Medical therapies can cause cardiotoxicity. Chloroquine (QC) and hydroxychloroquine (HQC) are drugs used in the treatment of malaria and skin and rheumatic disorders. These drugs were considered to help treatment of coronavirus disease (COVID-19) in 2019. Despite the low cost and availability of QC and HQC, reports indicate that this class of drugs can cause cardiotoxicity. The mechanism of this event is not well known, but evidence shows that QC and HQC can cause cardiotoxicity by affecting mitochondria and lysosomes. METHODS: Therefore, our study was designed to investigate the effects of QC and HQC on heart mitochondria. In order to achieve this aim, mitochondrial function, reactive oxygen species (ROS) level, mitochondrial membrane disruption, and cytochrome c release in heart mitochondria were evaluated. Statistical significance was determined using the one-way and two-way analysis of variance (ANOVA) followed by post hoc Tukey to evaluate mitochondrial succinate dehydrogenase (SDH) activity and cytochrome c release, and Bonferroni test to evaluate the ROS level, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling. RESULTS: Based on ANOVA analysis (one-way), the results of mitochondrial SDH activity showed that the IC50 concentration for CQ is 20 µM and for HCQ is 50 µM. Based on two-way ANOVA analysis, the highest effect of CQ and HCQ on the generation of ROS, collapse in the MMP, and mitochondrial swelling were observed at 40 µM and 100 µM concentrations, respectively (p < 0.05). Also, the highest effect of these two drugs has been observed in 60 min (p < 0.05). The statistical results showed that compared to CQ, HCQ is able to cause the release of cytochrome c from mitochondria in all applied concentrations (p < 0.05). CONCLUSIONS: The results suggest that QC and HQC can cause cardiotoxicity which can lead to heart disorders through oxidative stress and disfunction of heart mitochondria.


Subject(s)
COVID-19 , Hydroxychloroquine , Humans , Hydroxychloroquine/toxicity , Chloroquine/toxicity , Reactive Oxygen Species/metabolism , Cardiotoxicity/etiology , Cardiotoxicity/drug therapy , Cytochromes c/metabolism , Cytochromes c/pharmacology , COVID-19 Drug Treatment , Mitochondria
12.
J Bras Nefrol ; 44(3): 321-328, 2022.
Article in English, Portuguese | MEDLINE | ID: covidwho-2292558

ABSTRACT

INTRODUCTION: COVID-19 is currently a global health issue and an important cause of mortality. Chronic kidney disease (CKD) is one of the risk factors for infection, morbidity and mortality by SARS-CoV-2. In our study, we aimed to evaluate the clinical presentation and outcomes of CKD patients with COVID-19, as well as identify predictors of mortality. METHODS: This was a retrospective study of CKD patients admitted in a tertiary-care Portuguese hospital between March and August of 2020. Variables were submitted to univariate and multivariate analysis to determine factors predictive of in-hospital mortality. RESULTS: 130 CKD patients were analyzed (median age 73.9 years, male 60.0%). Hypertension (81.5%), cardiovascular disease (36.2%), and diabetes (54.6%) were frequent conditions. Cough, dyspnea, fever and respiratory failure were also common. Almost 60% had anemia, 50% hypoalbuminemia, 13.8% hyperlactacidemia and 17% acidemia. Mean serum ferritin was 1531 µg/L, mean CRP 8.3 mg/dL and mean LDH 336.9 U/L. Most patients were treated with lopinavir/ritonavir, hydroxychloroquine or corticosteroids and only 2 with remdesivir. Eighty percent had acute kidney injury and 16.2% required intensive care unit admission. The 34 patients who died were older and more likely to have heart failure. They had higher neutrophils/lymphocytes ratio, ferritin, lactate, and LDH levels. Multivariate analysis identified an association between older age [OR 1.1 (CI 1.01-1.24), p=0.027], higher ferritin [OR 1.0 (CI 1.00-1.00), p=0.009] and higher LDH levels [OR 1.0 (CI 1.00-1.01), p=0.014] and mortality. CONCLUSION: In our cohort of CKD patients with COVID-19, older age, higher ferritin, and higher LDH levels were independent risk factors for mortality.


Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Aged , COVID-19/complications , Ferritins , Hospital Mortality , Humans , Hydroxychloroquine , Lactates , Lopinavir/therapeutic use , Male , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Retrospective Studies , Risk Factors , Ritonavir/therapeutic use , SARS-CoV-2
13.
Arq Bras Cardiol ; 120(4): e20220380, 2023.
Article in English, Portuguese | MEDLINE | ID: covidwho-2299182

ABSTRACT

BACKGROUND: Previous systematic reviews have identified no benefit of hydroxychloroquine and chloroquine in non-hospitalized COVID-19 patients. After publication of these reviews, the results of COPE, the largest randomized trial conducted to date, became available. OBJECTIVES: To conduct a systematic review and meta-analyses of randomized clinical trials (RCTs) to synthesize the evidence on the efficacy and safety of hydroxychloroquine and chloroquine for non-hospitalized COVID-19 patients compared to placebo or standard of care. METHODS: Searches were conducted in PubMed, Embase, The Cochrane Library, and ClinicalTrials.gov complemented by manual search. Pairwise meta-analyses, risk of bias, and evidence certainty assessments were conducted, including optimal information size analysis (OIS). A level of significance of 0.05 was adopted in the meta-analysis. PROSPERO: CRD42021265427. RESULTS: Eight RCTs with 3,219 participants were included. COVID-19 hospitalization and any adverse events rates were not significantly different between hydroxychloroquine (5.6% and 35.1%) and control (7.4% and 20.4%) (risk ratio, RR, 0.77, 95% confidence interval, CI, 0.57-1.04, I2: 0%; RR 1.78, 95%-CI 0.90; 3.52, I2: 93%, respectively). The OIS (7,880) was not reached for COVID-19 hospitalization, independently of the simulation for anticipated event rate and RR reduction estimate. CONCLUSION: Evidence of very low certainty showed lack of benefit with hydroxychloroquine in preventing COVID-19 hospitalizations. Despite being the systematic review with the largest number of participants included, the OIS, considering pre-vaccination response to infection, has not yet been reached.


FUNDAMENTO: Revisões sistemáticas anteriores não identificaram benefício do uso da hidroxicloroquina ou da cloroquina em pacientes com COVID-19 não hospitalizados. Após a publicação dessas revisões, os resultados do COPE, o maior ensaio clínico randomizado até hoje, tornaram-se disponíveis. OBJETIVOS: Conduzir uma revisão sistemática e metanálise de ensaios clínicos randomizados (ECRs) para sintetizar as evidências sobre a eficácia e a segurança da hidroxicloroquina e da cloroquina em pacientes com COVID-19 não hospitalizados em comparação a controle ou tratamento padrão. MÉTODOS: As buscas foram conduzidas nos bancos de dados PubMed, Embase, The Cochrane Library e ClinicalTrials.gov, e complementadas por busca manual. Foram realizadas metanálises diretas e avaliações de risco de viés e certeza da evidência, incluindo análise do tamanho ótimo da informação (OIS, optimal information size). Um nível de significância de 0,05 foi adotado na metanálise. PROSPERO: CRD42021265427. RESULTADOS: Oito ECRs com 3219 participantes foram incluídos. As taxas de internação por COVID-19 e de eventos adversos não foram significativamente diferentes entre hidroxicloroquina (5,6% e 5,1%) e controle (7,4% e 20,4%) [risco relativo (RR) 0,77, intervalo de confiança 95% (IC95%), 0,57-1,04, I2: 0%; RR 1,78, IC95% 0,90; 3,52, I2: 93%, respectivamente)]. O OIS (7880) não foi alcançado para hospitalização por COVID-19, independentemente da simulação para a taxa de evento e redução do RR estimados. CONCLUSÃO: A evidência de muito baixa qualidade indicou falta de benefício com hidroxicloroquina em prevenir internações por COVID-19. Apesar de ser a revisão sistemática com o maior número de participantes incluídos, o OIS, considerando a resposta à infecção anterior à vacinação, não foi atingido.


Subject(s)
COVID-19 , Humans , Hydroxychloroquine/therapeutic use , COVID-19 Drug Treatment , Randomized Controlled Trials as Topic , Chloroquine/adverse effects
14.
Trials ; 24(1): 261, 2023 Apr 06.
Article in English | MEDLINE | ID: covidwho-2298532

ABSTRACT

BACKGROUND: Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus. METHODS: Double-blind, placebo-controlled multicentre trial recruiting 76 patients across 20 sites. Participants will be randomised 1:1 to hydroxychloroquine or placebo in addition to standard of care immunosuppressive therapies over the course of 52 weeks. A phase II selection design will be used to determine hdroxychloroquine's efficacy, using prednisolone dosage and Birmingham Vasculitis Activity Score as a measure of disease activity. Secondary outcomes will explore other elements of AAV progression, including disease flares and time to remission. DISCUSSION: This trial aims to explore Hydroxychloroquine as a treatment for patients with AAV. If effective, the need for immunosuppressive treatments such as prednisolone could be reduced. Hydroxychloroquine is safer, cheaper and has fewer adverse effects than conventional immunosuppressive treatments. This could improve patient outcomes while saving money for the NHS. TRIAL REGISTRATION: ISRCTN: ISRCTN79334891. Registered 07 June 2021. EudraCT: 2018-001268-40. Registered 13 September 2019. CLINICALTRIALS: gov: NCT04316494. Registered 20 March 2020.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , COVID-19 , Humans , SARS-CoV-2 , Hydroxychloroquine/adverse effects , Antibodies, Antineutrophil Cytoplasmic , Quality of Life , Double-Blind Method , Prednisolone , Immunosuppressive Agents/adverse effects , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Treatment Outcome , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
15.
Swiss Med Wkly ; 150: w20246, 2020 04 06.
Article in English | MEDLINE | ID: covidwho-2285064

ABSTRACT

Respiratory failure in COVID-19 is a common feature in fatal cases and has been considered as a failure of the immune system to control the virus. Here we report the case of COVID-19 affecting an immunocompromised women and her presumably immunocompetent spouse. A married couple (age 60 years) was simultaneously admitted to the emergency department on 10 March 2020 because of dyspnoea and fever, consistent with COVID-19. The wife (patient 1) was partially immunocompromised as a consequence of a recently started chemotherapy with fulvestrant and abemaciclid for recurring breast cancer, her husband (patient 2) had been healthy except for a history of controlled arterial hypertension. Both patients were treated with darunavir/cobicistat and hydroxychloroquine. The clinical course of the immunocompromised partner was benign, without need of intensive care. She was able to leave the hospital on day 6 after admission. In contrast, her husband needed intensive care and his recovery was slow, although eventually successful too. These findings suggest that the course of COVID-19 is not necessarily ominous in the presence of a compromised immune response and tend to reinforce the emerging therapeutic concepts of a controlled mitigation of the immune cascade following SARS CoV-2 infection.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Breast Neoplasms/complications , Cobicistat/therapeutic use , Coronavirus Infections/drug therapy , Darunavir/therapeutic use , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Betacoronavirus , COVID-19 , Coronavirus Infections/virology , Critical Care , Dyspnea/etiology , Emergency Service, Hospital , Female , Fever/etiology , Humans , Immunocompetence , Immunocompromised Host , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Spouses , Treatment Outcome , COVID-19 Drug Treatment
16.
Swiss Med Wkly ; 150: w20446, 2020 12 14.
Article in English | MEDLINE | ID: covidwho-2273782

ABSTRACT

AIMS OF THE STUDY: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , COVID-19/epidemiology , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/mortality , Child , Child, Preschool , Comorbidity , Drug Combinations , Drug Therapy, Combination , Health Expenditures , Hospital Mortality/trends , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Infant , Length of Stay/statistics & numerical data , Lopinavir/administration & dosage , Lopinavir/adverse effects , Middle Aged , Pandemics , Retrospective Studies , Ritonavir/administration & dosage , Ritonavir/adverse effects , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Socioeconomic Factors , Therapies, Investigational/methods , Young Adult
17.
Am J Transplant ; 20(7): 1849-1858, 2020 07.
Article in English | MEDLINE | ID: covidwho-2270901

ABSTRACT

The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after solid organ transplant (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%], and heart [22.2%]) recipients diagnosed with COVID-19 by March 23, 2020 at a tertiary-care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon-ß (16.7%). As of April 4, the case-fatality rate was 27.8% (5/18). After a median follow-up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C-reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS-CoV-2 infection has a severe course in SOT recipients.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Organ Transplantation , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Transplant Recipients , Aged , Antiviral Agents/administration & dosage , Betacoronavirus , COVID-19 , Drug Combinations , Female , Fever , Humans , Hydroxychloroquine/administration & dosage , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Interferon-beta/administration & dosage , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Radiography, Thoracic , Retrospective Studies , Ritonavir/administration & dosage , SARS-CoV-2 , Spain/epidemiology
19.
Indian J Tuberc ; 67(4S): S147-S154, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-2250937

ABSTRACT

COVID 19 infection is unarguably the worst pandemic of this century. Till date there is no promising drug and vaccine available to treat this deadly viral infection. In the early phase chloroquine phosphate and hydroxychloroquine sulphate have been used to fight this illness on the basis of handful observational and small randomized and small-randomized studies. The paucity of clinical evidences of an unequivocal beneficial effect of chloroquine and hydroxychloroquine on COVID-19 has resulted in the passionate use of the drug for moderate to severe cases only and stimulated the need for large clinical trials for this and other molecules. In this review, we describe in brief the mechanism of action, the clinical studies, factors for cardiac toxicity, guidelines and future directions for hydroxychloroquine use in management of COVID-19 infection.


Subject(s)
COVID-19 Drug Treatment , Enzyme Inhibitors/pharmacology , Hydroxychloroquine/pharmacology , SARS-CoV-2 , Enzyme Inhibitors/therapeutic use , Humans , Hydroxychloroquine/therapeutic use
20.
PLoS One ; 18(3): e0283165, 2023.
Article in English | MEDLINE | ID: covidwho-2276168

ABSTRACT

OBJECTIVES: To evaluate the impact of local therapeutic recommendation updates made by the COVID multidisciplinary consultation meeting (RCP) at the Hôpital Européen Marseille (HEM) through the description of the drug prescriptions for COVID-19 during the first two waves of the epidemic. METHODS: This retrospective observational study analysed data from the hospital's pharmaceutical file. We included all patients hospitalized for COVID-19 between February 1, 2020 and January 21, 2021 and extracted specific anti-COVID-19 therapies (ST) from computerized patient record, as well as patients' demographic characteristics, comorbidities and outcome. The evolution of ST prescriptions during the study period was described and put into perspective with the updates of local recommendations made during the first (V1, from 2/24/2020 to 7/27/2020), and second (V2, from 7/28/2020 to 1/21/2021) epidemic waves. RESULTS: A total of 607 COVID-19 hospitalized patients, 197 during V1 and 410 during V2. Their mean age was 65 years-old, and they presented frequent comorbidities. In total, 93% of hospitalized patients received ST: anticoagulants (90%), glucocorticoids (39%) mainly during V2 (49% vs 17%, P<0.001), and azithromycin (30%) mainly during V1 (71% vs 10%, P<0.001). Lopinavir/ritonavir and hydroxychloroquine were prescribed to 17 and 7 inpatients, respectively, and only during V1. Remdesivir was never administered. A total of 22 inpatients were enrolled into clinical trials. CONCLUSIONS: The effective dissemination of evidence-based and concerted recommendations seems to have allowed an optimized management of COVID-19 drug therapies in the context of this emerging infection with rapidly evolving therapeutic questions.


Subject(s)
COVID-19 , Humans , Aged , COVID-19/epidemiology , SARS-CoV-2 , COVID-19 Drug Treatment , Tertiary Care Centers , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Hydroxychloroquine/therapeutic use , Antiviral Agents/therapeutic use
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