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1.
Diagn. tratamento ; 27(2): 61-71, abr-jun. 2022. tab, tab
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1369116

RESUMO

Contextualização: A pandemia do novo coronavírus é uma das maiores preocupações da sociedade atualmente. O elevado número de mortes associadas ao vírus levou à busca urgente de estratégias terapêuticas eficazes na luta contra a doença. Objetivos: Avaliar a efetividade das intervenções terapêuticas para COVID-19, segundo as revisões sistemáticas da Colaboração Cochrane. Métodos: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca na Cochrane Library (2022), sendo utilizado o termo MeSH "COVID-19". Todos os estudos relacionados ao tratamento da COVID-19 foram incluídos. O desfecho primário de análise foi a melhora clínica. Resultados: Nove estudos foram incluídos, totalizando 75 ensaios clínicos randomizados (ECRs) (n = 72.859 participantes). Remdesivir, cloroquina/ hidroxicloroquina, ivermectina e colchicina não reduziram a mortalidade. Corticosteroide sistêmico reduziu discretamente a mortalidade de pacientes internados e diminuiu o número de dias de ventilação mecânica. Tocilizumabe reduziu discretamente a mortalidade até o 28o dia. Não há evidência de benefício de uso de vitamina D, azitromicina e anticorpos monoclonais. Discussão: Embora haja boa evidência para algumas intervenções, a maioria carece de estudos de melhor qualidade. No caso da cloroquina/hidroxicloroquina a evidência é fortemente desfavorável ao uso e suficiente para desencorajar novos estudos. Sugere-se a realização de novos ECRs de qualidade para intervenções cuja efetividade é ainda incerta, seguindo-se as recomendações do CONSORT (Consolidated Standards of Reporting Trials) Statement para melhor elucidação da questão. Conclusão: Não há suporte com bom nível de evidência atualmente para a maioria das intervenções para COVID-19, à luz das revisões sistemáticas da Cochrane.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35503307

RESUMO

The COVID-19 pandemic continues to pose a serious global challenge, with the world engulfed in fighting second, third and fourth waves of the disease, which is reaching scary proportions in terms of cases and mortality in countries like India. Despite the urgent need of proven management protocols, there is still confusion about the best practices for treating COVID-19 with different pharmaceutical interventions. Antimicrobials are empirically used in COVID-19 patients. During the initial phase of this pandemic, hydroxychloroquine, ivermectin, azithromycin and doxycycline were widely suggested for possible prophylaxis or treatment for COVID-19 in outpatient as well as hospitalized settings. Various national and international guidelines recommended its use. However, cumulative evidence from subsequent clinical trials has revealed no significant clinical benefits in any setting, with the risk of adverse effects being high particularly in combination with azithromycin. Yet, there is continued use of antimicrobials particularly in outpatient settings which should be avoided because there is no justifiable rationale for doing so. Antimicrobial resistance (AMR) was one of the top problems for global public health before the coronavirus 2019 (COVID-19) pandemic began. AMR, which is already a difficult problem, must now be handled in the context of a changing healthcare sector.

3.
Ther Adv Drug Saf ; 13: 20420986221094141, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493401

RESUMO

During the COVID-19 pandemic, the behavior of self-medication has increased. The dissemination of misleading information regarding the efficacy of certain drugs or substances for the prevention and treatment of COVID-19 has been the major contributing factor for this phenomenon. Alongside with the increase in self-medication behavior, the inherent risks to this act such as drug-drug interactions, adverse events, drug toxicity, and masking of symptoms have also increased. Self-medication in the context of COVID-19 has led to drug misuse leading in some cases to the development of fatal adverse drug reactions. It is important that during this ongoing pandemic drugs with potential clinical efficacy against COVID-19 are adequately analyzed regarding their efficacy, safety, and monitoring. The aim of this review is to describe the available evidence regarding the efficacy, safety, and monitoring of the drugs and substances that have been shown to be frequently used for self-medication in patients with COVID-19 (hydroxychloroquine, non-steroidal anti-inflammatory drugs, ivermectin, azithromycin, vitamins, aspirin, and chlorine dioxide) to adequately characterize their risks, safe use, monitoring strategies, and to reinforce the concept that these substances should not be used for self-medication and require a medical prescription. Plain Language Summary: Drug safety of frequently used drugs and substances for self-medication in COVID-19 Dissemination of information about potential COVID-19 treatments has led individuals to self-medicate and expose themselves to risks such as drug-drug interactions, side effects, antibiotic resistance, and misdiagnosis. There is a need to review the medical literature to evaluate the safety and efficacy of the drugs and substances commonly used by the population for the treatment and prevention of SARS CoV-2 infection. In this review, we included drugs that are frequently used for self-medication and commonly advertised such as ivermectin, hydroxychloroquine, chlorine dioxide, azithromycin, and non-steroidal anti-inflammatory drugs, among others. A brief introduction of the drug and its mechanism of action, followed by a summary of the efficacy in COVID-19 and safety, will be described for each drug in order to promote their responsible use.

4.
J Family Med Prim Care ; 11(3): 1140-1145, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35495846

RESUMO

Background: Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities. Objectives: Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19. Methods: Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3-7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results. Results: Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3-9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (P < 0.001). Odds ratio with HCQ intake was 0.34 (95% CI 0.13-0.83, P = 0.01) and the number needed to treat was 12. Conclusion: HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19.

5.
Ann Med Surg (Lond) ; : 103653, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35495962

RESUMO

Introduction: Mixed connective tissue disease (MCTD) is a rare autoimmune condition characterized by Scleroderma, Polymyositis, and Systemic Lupus Erythematous (SLE). Though a possible relationship between COVID-19 and autoimmune diseases has been recently reported, its pathophysiological mechanism behind flares in Lupus Nephritis (LN), a complication of SLE, remains unknown. Case presentation: A 22-year-old COVID-19 positive female presented with anemia, bilateral pitting edema, periorbital swelling, and posterior cervical lymphadenitis. Further inspection revealed lower abdominal striae, hepatosplenomegaly, and hyperpigmented skin nodules. Complete blood counts showed elevated inflammatory markers and excessively high protein creatinine ratio. Antinuclear antibody titers were elevated (anti-smith and U1 small nuclear ribonucleoprotein) and Rheumatoid Factor was positive. She was diagnosed with MCTD associated with a flare of LN. To control her lupus flare, a lower dose of steroids was initially administered, in addition to oral hydroxychloroquine and intravenous cyclophosphamide. Her condition steadily improved and was discharged on oral steroid maintenance medication. Discussion: We present a rare phenomenon of newly diagnosed LN, a complication of SLE, with MCTD in a PCR-confirmed COVID-19 patient. The diagnostic conundrum and treatment hurdles should be carefully addressed when patients present with lupus and COVID-19 pneumonia, with further exploration of the immuno-pathophysiology of COVID-19 infection in multi-systemic organ dysfunction in autoimmune disorders. Conclusion: In COVID-19 patients with LN and acute renal injury, it is critical to promptly and cautiously treat symptomatic flares associated with autoimmune disorders such as SLE and MCTD that may have gone unnoticed to prevent morbidity from an additional respiratory infection.

6.
J Mater Sci ; : 1-23, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35502407

RESUMO

A micro-molecule of dimension 125 nm has caused around 479 million human infections (80 M for the USA) and 6.1 million human deaths (977,000 for the USA) worldwide and slashed the global economy by US$ 8.5 Trillion over two years period. The only other events in recent history that caused comparative human life loss through direct usage (either by human or nature, respectively) of structure-property relations of 'nano-structures' (either human-made or nature, respectively) were nuclear bomb attacks during World War II and 1918 Flu Pandemic. This molecule is called SARS-CoV-2, which causes a disease known as COVID-19. The high liability cost of the pandemic had incentivized various private, government, and academic entities to work towards finding a cure for this and emerging diseases. As an outcome, multiple vaccine candidates are discovered to avoid the infection in the first place. But so far, there has been no success in finding fully effective therapeutic candidates. In this paper, we attempted to provide multiple therapy candidates based upon a sophisticated multi-scale in-silico framework, which increases the probability of the candidates surviving an in-vivo trial. We have selected a group of ligands from the ZINC database based upon previously partially successful candidates, i.e., Hydroxychloroquine, Lopinavir, Remdesivir, Ritonavir. We have used the following robust framework to screen the ligands; Step-I: high throughput molecular docking, Step-II: molecular dynamics analysis, Step-III: density functional theory analysis. In total, we have analyzed 242,000(ligands)*9(proteins) = 2.178 million unique protein binding site/ligand combinations. The proteins were selected based on recent experimental studies evaluating potential inhibitor binding sites. Step-I had filtered that number down to 10 ligands/protein based on molecular docking binding energy, further screening down to 2 ligands/protein based on drug-likeness analysis. Additionally, these two ligands per protein were analyzed in Step-II with a molecular dynamic modeling-based RMSD filter of less than 1Å. It finally suggested three ligands (ZINC001176619532, ZINC000517580540, ZINC000952855827) attacking different binding sites of the same protein(7BV2), which were further analyzed in Step-III to find the rationale behind comparatively higher ligand efficacy. Supplementary Information: The online version contains supplementary material available at 10.1007/s10853-022-07195-8.

7.
PLoS One ; 17(5): e0267645, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507600

RESUMO

OBJECTIVES: To assess efficacy and safety of the combined treatment of antibiotics (3rd-generation cephalosporin and azithromycin) and antiviral agents (lopinavir/ritonavir or hydroxychloroquine) on moderate COVID-19 patients in South Korea. METHODS: A retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 299 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were used to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with either CA/LoP (cephalosporin, azithromycin, and lopinavir/ritonavir) (n = 57), CA/HQ (cephalosporin, azithromycin, and hydroxychloroquine) (n = 25) or standard supportive care (n = 217). We analyzed the association between treatment group and standard supportive group in terms of three endpoints: time to symptom resolution, time to viral clearance, and hospital stay duration. Using propensity-score matching analysis, three rounds of propensity-matching analysis were performed to balance baseline characteristics among three cohorts. RESULTS: Kaplan-Meier curves fitted using propensity score-matched data revealed no significant differences on time to symptom resolution, time to viral clearance, hospital stay duration among the three treatment arms (CA/LoP vs Standard, log-rank p-value = 0.2, 0.58, and 0.74 respectively for the three endpoints) (CA/HQ vs Standard, log-rank p-value = 0.46, 0.99, and 0.75 respectively). Similarly, Cox regression analysis on matched cohorts of CA/LoP and standard supportive group showed that hazard ratios of time to symptom resolution (HR: 1.447 [95%-CI: 0.813-2.577]), time to viral clearance(HR: 0.861, [95%-CI: 0.485-1.527]), and hospital stay duration (HR: 0.902, [95%-CI: 0.510-1.595]) were not significant. For CA/HQ and standard supportive group, hazard ratios of the three endpoints all showed no statistical significance (HR: 1.331 [95%-CI:0.631-2.809], 1.005 [95%-CI:0.480-2.105], and 0.887, [95%-CI:0.422-1.862] respectively). No severe adverse event or death was observed in all groups. CONCLUSIONS: Combined treatment of 3rd cephalosporin, azithromycin and either low-dose lopinavir/ritonavir or hydroxychloroquine was not associated with better clinical outcomes in terms of time to symptom resolution, time to viral clearance, and hospital stay duration compared to standard supportive treatment alone. Microbiological evidence should be closely monitored when treating SARS-CoV-2 patients with antibiotics to prevent indiscreet administration of empirical antimicrobial treatments.


Assuntos
COVID-19 , SARS-CoV-2 , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Cefalosporinas/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Estudos Retrospectivos , Ritonavir/uso terapêutico , Resultado do Tratamento
8.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35557428

RESUMO

The novel coronavirus SARS-Cov-2 or COVID-19 became a global pandemic and currently few medically approved curative treatments exist. SARS-Cov-2 acts similarly to SARS-CoV-1 from where it may have evolved. The COVID-19 virus can survive ~3 hours in air and < 72 hours on distinct surfaces. COVID-19 mutates by introducing sequence errors in the host's RNA genome or by modifying proteins and enzymes. Vaccination, including booster shots, social distancing and isolation are the most generally practiced guidelines in the global management of COVID-19. Globally the most frequently utilized pharmacologic treatments include ivermectin, hydroxychloroquine, glucocorticoids, the anti-viral agent remdesivir, monoclonal antibodies, and convalescent plasma in combination with an antimicrobial agent such as azithromycin to minimize secondary microbial infection and nutritional supplementation (vitamins C, D3, and zinc) to enhance cellular immune responses and are included in the routine protocols of some emergency rooms. COVID-19 viral transmission occurs via respiratory microdroplets, by inhaling COVID-19 laden airborne particles and contact with contaminated surfaces on which these droplets have been deposited. SARS-CoV-2 targets ACE2 receptors in the upper and lower respiratory tracts in addition to the heart, brain, and gastrointestinal tract, and may cause thromboses in the liver, heart, and kidney. Significant risk factors for the severity of COVID-19 infection include advanced age and pre-existing comorbid conditions obesity, hypertension, cardiovascular disease, diabetes, and compromised immune status, which all correlate with greater mortality. Outcome-effecting factors include viral load, viral mutations, and pre-existing conditions. Since its origination, genomic studies of the virus have identified numerous variants which have become regionally prevalent in different countries. Infective factors, comorbidities and viral load strongly affect outcomes; patients infected with the greatest viral load showed a higher mortality. It is opined that the number of deaths attributed to COVID-19 may be inaccurate due to errors in diagnosing and reporting, since other similar illnesses may exhibit similar symptoms. Future research should focus on prevention practices, comorbidities, genetic prevalence, reliable systematic and consistency in country-by-country testing and reporting procedures, further scrutiny regarding the efficacy of current vaccines and protocols, and the pursuit for innovative therapies for Coronaviruses and variants including biophotonics and exploration of emerging bioenergetic, nutritional, pharmacological, immunotherapeutic and vaccination-preventive applications for eradication of COVID-19. Refs: 1. Cheng, RZ. (2020a). Med Drug Disc, 5, 100028; 2. Shankar, AH, & Prasad, AS. (1998). ACJN, 68(2), 447S-463S; 3. Petrilli, CM, Jones, SA, et al. (2020); medRxiv; 4.van Doremalen, N, Bushmaker, T et al. (2020). NEJM, 382(16), 1564-1567.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35504274

RESUMO

Herein, we report a computational investigation of the binding affinity of dexamethasone, betamethasone, chloroquine and hydroxychloroquine to SARS-CoV-2 main protease using Molecular and Quantum Mechanics as well as Molecular Docking methodologies. We aim to provide information on the anti-COVID-19 mechanism of the abovementioned potential drugs against SARS-CoV-2 coronavirus. Hence, the 6w63 structure of the SARS-CoV-2 main protease was selected as potential target site for the Docking analysis. The study includes an initial conformational analysis of dexamethasone, betamethasone, chloroquine and hydroxychloroquine. For the most stable conformers, a spectroscopic analysis has been carried out. In addition, global and local reactivity indexes have been calculated to predict the chemical reactivity of these molecules. The Molecular Docking results indicate that dexamethasone and betamethasone have a higher affinity than chloroquine and hydroxychloroquine for their theoretical 6w63 target. Additionally, dexamethasone and betamethasone show a hydrogen bond with the His41 residue of the 6w63 protein, while the interaction between chloroquine and hydroxychloroquine with this amino acid is weak. Thus, we confirm the importance of His41 amino acid as a target to inhibit the SARS-CoV-2 Mpro activity.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35499739

RESUMO

The COVID-19 pandemic not only has caused a global health crisis but also has significant environmental consequences. Although many studies are confirming the short-term improvements in air quality in several countries across the world, the long-term negative consequences outweigh all the claimed positive impacts. As a result, this review highlights the positive and the long-term negative environmental effects of the COVID-19 pandemic by evaluating the scientific literature. Remarkable reduction in the levels of CO (3 - 65%), NO2 (17 - 83%), NOx (24 - 47%), PM2.5 (22 - 78%), PM10 (23 - 80%), and VOCs (25 - 57%) was observed during the lockdown across the world. However, according to this review, the pandemic put enormous strain on the present waste collection and treatment system, resulting in ineffective waste management practices, damaging the environment. The extensive usage of face masks increased the release of microplastics/nanoplastics (183 to 1247 particles piece-1) and organic pollutants in land and water bodies. Furthermore, the significant usages of anti-bacterial hand sanitizers, disinfectants, and pharmaceuticals have increased the accumulation of various toxic emerging contaminants (e.g., triclocarban, triclosan, bisphenol-A, hydroxychloroquine) in the treated sludge/biosolids and discharged wastewater effluent, posing great threats to the ecosystems. This review also suggests strategies to create long-term environmental advantages. Thermochemical conversions of solid wastes including medical wastes and for treated wastewater sludge/biosolids offer several advantages through recovering the resources and energy and stabilizing/destructing the toxins/contaminants and microplastics in the precursors.

11.
Health Sci Rep ; 5(3): e541, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35509384

RESUMO

Objectives: This study examines the conduct of systematic reviews during the early stages of the COVID-19 pandemic, including compliance to protocol registration and duplication of reviews on similar topics. The methodological and reporting quality were also explored. Methods: A cross-sectional, bibliometric study was undertaken of all systematic review manuscripts on a COVID-19 intervention published between January 1st and June 30th, 2020. Protocol registration on a publicly accessible database was recorded. Duplication was determined by systematically recording the number of reviews published on each topic of analysis. Methodological quality and reporting quality were assessed using the AMSTAR-2 and PRISMA 2009 instruments, respectively. Results: Thirty-one eligible systematic reviews were identified during the inclusion period. The protocol of only four (12.9%) studies was registered on a publicly accessible database. Duplication was frequent, with 15 (48.4%) of the 31 included studies focusing on either hydroxychloroquine (and/or chloroquine) or corticosteroids. Only one study (3.2%) was of "high" methodological quality, four (12.9%) were "low" quality, and the remainder (n = 26, 83.9%) were of "critically low" quality. The median completeness of reporting was 20 out of 27 items (74.1%) with a range of 5-26 (interquartile range: 14-23). Conclusion: Systematic reviews during the early stages of the COVID-19 pandemic were uncommonly registered, frequently duplicated, and mostly of low methodological quality. In contrast, the reporting quality of manuscripts was generally good but varied substantially across published reports. There is a need for heightened stewardship of systematic review research, particularly during times of medical crisis where the generation of primary evidence may be rapid and unstable.

12.
Lancet ; 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35512728

RESUMO

BACKGROUND: The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-ß1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date. METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-ß1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948. FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings. INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both). FUNDING: WHO.

13.
Sisli Etfal Hastan Tip Bul ; 56(1): 62-69, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35515968

RESUMO

Objectives: The pandemic of coronavirus disease 2019 (COVID-19) is still effective all over the world. Compared to adults, data on pediatric patients are limited. In this study, we aimed to retrospectively examine the demographic, clinical, and laboratory characteristics of pediatric patients who were followed up with the diagnosis of COVID-19 in the first 3 months of the pandemic in our hospital. Methods: A total of 190 patients, aged 1 month-18 years, who were followed up with a definite/probable diagnosis of COVID-19, who were treated in the Pediatric Infection Clinic, were included in the study. The demographic features, clinical characteristics, and laboratory findings of the patients were retrospectively analyzed from their electronic medical records. Results: Eighty (42.1%) of the patients were laboratory confirmed (Polymerase chain reaction positive in nasopharyngeal swab). Mean age was 72 (2-216 months) and 102 (53.7%) patients were female. Family contact history was present in 115 (60.5%) patients. The patients were classified as asymptomatic (5.8%), mild (73.2%), moderate (18.4%), and severe/critical (2.6%) according to the severity of the disease. The most common symptoms were cough (71.1%) and fever (51.1%). Hydroxychloroquine alone or in combination was the most commonly used agent. Conclusion: In our study, in which we examined the pediatric COVID-19 patients, most of the patients had a mild clinical course, but there were applications with different clinical pictures such as acute appendicitis. Therefore, COVID-19 infection, which is still very unknown, will continue to surprise us with both changing treatment protocols and clinical presentations such as multisystem inflammatory syndrome in children.

14.
J Family Med Prim Care ; 11(4): 1514-1518, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35516670

RESUMO

Objective: The use of hydroxychloroquine (HCQ) for COVID-19 treatment and prophylaxis raised issues concerning its cardiac safety owing to the possibility of QT prolongation and arrhythmias. There was no study on long-term electrocardiographic telemetry monitoring of patients taking HCQ. We planned a continuous electrocardiographic Holter telemetry of these patients for 7 days. Material and Methods: Health care workers taking HCQ as pre exposure prophylaxis and patients on HCQ were monitored using seven day Holter electrocardiographic telemetry with continuous beat to beat analysis. Telemetry can instantly convey any arrhythmic event or significant QT prolongation to the medical faculty. Results: Twenty-five participants with a mean age of 42.4 ± 14.1 years were included in the study; 40% were females. Twenty percent of participants needed to stop HCQ. Four patients developed QT prolongation >500 ms and needed to stop HCQ, one patient had accelerated idioventricular rhythm and stopped treatment, and one had short episodes of atrial fibrillation. No malignant arrhythmia or ventricular arrhythmia, or torsade de pointis were noted. No episode of significant conduction disturbance and arrhythmic death was noted. Baseline mean QTc was 423.96 ± 32.18 ms, mean QTc corrected at 24 h was 438.93 ± 37.95, mean QTc was 451.879 ± 37.99 at 48 h, and change in baseline mean QTc to max QTc was 30.74 ± 21.75 ms at 48 h. All those who developed QTc prolongation >500 ms were greater than 50 years of age. Conclusion: Ambulatory telemetry ECG monitoring detects early QT prolongation, and stopping drugs prevents malignant arrhythmias. HCQ seems to have less risk of QT prolongation in young, healthy individuals.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35526987

RESUMO

At the beginning of the COVID-19 pandemic, worldwide attempts were made to identify potential drugs effective against the COVID-19. Hydroxychloroquine was among the first receiving attention. However, following its use in therapy, it has been shown that hydroxychloroquine was not only ineffective but probably, due to its known side effects, even responsible of increased mortality of patients. The objective of this study was to review the safety profile of hydroxychloroquine used off-label for the treatment of COVID-19. We analyze the reports of suspected adverse drug reactions (ADRs) collected in EudraVigilance, the European database of ADR reports. We collected 2266 reports for 2019 and 6525 for 2020. The most reported ADRs during 2020 were those relating to cardiac, hepatic, renal toxicity such as QT prolongation with 400 cases in 2020 (of which, 345 cases-9.97%-with COVID-19 as a therapeutic indication) versus 1 case only in 2019 (0.01%), long QT syndrome: 38 cases in 2020 (36 as COVID-19 treatment) versus 0 in 2019, hepatitis: 13 cases in 2019 (0.11%) and 132 in 2020, and 32 cases (24, 0.69%) of acute kidney injury in 2020 and only 3 cases in 2019. Moreover, some important vision-related ADRs also increased significantly during 2020, such as retinal toxicity with 92 cases in 2020 versus 7 in 2019. Even though with its intrinsic limitations, our results may be added to the most recent scientific evidence to confirm the unfavorable risk profile of hydroxychloroquine in its off-label use in the treatment of COVID-19 disease.

16.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554750

RESUMO

Although blood-heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVI-19, the mechanism is unclear. The goal of this project is to determine the mechanism BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase-9 (MMP-9) during CHF. MMP-9 degrades connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte, and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP-9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP-9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial-myocyte coupling. To determine this, CHF was created by aorta-vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling-induced mitochondrial-myocyte, and endothelial-myocyte contractions were measured. Microvascular leakage was measured using FITC-albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP-9 activation, endocardial endothelial leakage, endothelial-myocyte (E-M) uncoupling, dyssynchronous mitochondrial fusion-fission (Mfn2/Drp1 ratio) and mito-myocyte uncoupling in AVF heart failure were found to be rampant however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID-19 in human subjects.

17.
J Pharm Technol ; 38(2): 75-87, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571345

RESUMO

Background: Understanding medication use patterns for patients with COVID-19 will provide needed insight into the evolution of COVID-19 treatment over the course of the SARS-CoV-2 pandemic and aid clinical management considerations. Objectives: To systematically determine most frequently used medications among COVID-19 patients overall and by hospitalization status. Secondary objective was use measurement of medications considered potential therapeutic options. Methods: Retrospective cohort study was performed using data from the University of California COVID Research Data Set (UC CORDS) patients between March 10, 2020, and December 31, 2020. Main outcomes were percentages of patients prescribed medications, overall, by age group, and by comorbidity based on hospitalization status for COVID-19 patients. Use percentage by month of COVID-19 diagnosis was measured. Cumulative count of potential therapeutic options was measured over time. Results: Dataset included 22 896 unique patients with COVID-19 (mean [SD] age, 42.4 [20.4] years; 12 154 [53%] women). Most frequently used medications in patients overall were acetaminophen (21.2%), albuterol (14.9%), ondansetron (13.9%), and enoxaparin (10.8%). Dexamethasone use increased from fewer than 50 total hospitalized patients through April who had received the medication, to more than 500 patients by mid-August. Cumulative count of enoxaparin users was the largest throughout the study period. Conclusion and Relevance: In this retrospective cohort study, across age and comorbidity groups, predominant utilization was for supportive care therapy. Dexamethasone and remdesivir experienced large increases in use. Conversely, hydroxychloroquine and azithromycin use markedly dropped. Medication utilization rapidly shifted toward more evidence-concordant treatment of patients with COVID-19 as rigorous study findings emerged.

18.
Expert Opin Drug Saf ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35574687

RESUMO

BACKGROUND: The use of hydroxychloroquine (HCQ) in the first COVID-19 epidemic wave raised concerns about its safety. RESEARCH DESIGN AND METHODS: All the adverse reactions (ADR) suspected to be induced by HCQ and submitted to the Spanish Pharmacovigilance Database were studied. A disproportionality analysis was performed to determine adverse effects reported with non-Covid and Covid patients. To explore potential drug-drug interactions, Omega (Ω) statistics was calculated. RESULTS: More severe cases were reported when used in COVID-19. Main differences in frequency were observed in hepatobiliary, skin, gastrointestinal, eye, nervous system and heart ADRs. During the COVID-19 pandemic, high disproportionality in reports was found for Torsade de Pointes/QT prolongation with a ROR (-ROR) of 132.8 (76.7); severe hepatotoxicity, 18.7 (14.7); dyslipidaemias, 12.1 (6.1); shock, 9.5 (6.9) and ischaemic colitis, 8.9 (2.6). Myopathies, haemolytic disorders and suicidal behaviour increased their disproportionality during the pandemic. Disproportionality was observed for neoplasms, haematopoietic cytopaenias and interstitial lung disease in the pre-COVID-19 period. Potential interactions were showed between HCQ and azithromycin, ceftriaxone, lopinavir and tocilizumab. CONCLUSIONS: The way in which HCQ has been used during the Covid-19 pandemic has resulted in a change in the profile of spontaneous reporting HCQ-related ADR in Spain. Of particular concern during the pandemic were arrhythmias, hepatotoxicity, severe skin reactions and suicide risk, but not ocular disorders. Some of the new ADRs identified will require more detailed analyses.

19.
BMJ ; 377: e069400, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35537738

RESUMO

OBJECTIVE: To systematically identify, match, and compare treatment effects and study demographics from individual or meta-analysed observational studies and randomized controlled trials (RCTs) evaluating the same covid-19 treatments, comparators, and outcomes. DESIGN: Meta-epidemiological study. DATA SOURCES: National Institutes of Health Covid-19 Treatment Guidelines, a living review and network meta-analysis published in The BMJ, a living systematic review with meta-analysis and trial sequential analysis in PLOS Medicine (The LIVING Project), and the Epistemonikos "Living OVerview of Evidence" (L·OVE) evidence database. ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES: RCTs in The BMJ's living review that directly compared any of the three most frequently studied therapeutic interventions for covid-19 across all data sources (that is, hydroxychloroquine, lopinavir-ritonavir, or dexamethasone) for any safety and efficacy outcomes. Observational studies that evaluated the same interventions, comparisons, and outcomes that were reported in The BMJ's living review. DATA EXTRACTION AND SYNTHESIS: Safety and efficacy outcomes from observational studies were identified and treatment effects for dichotomous (odds ratios) or continuous (mean differences or ratios of means) outcomes were calculated and, when possible, meta-analyzed to match the treatment effects from individual RCTs or meta-analyses of RCTs reported in The BMJ's living review with the same interventions, comparisons, and outcomes (that is, matched pairs). The analysis compared the distribution of study demographics and the agreement between treatment effects from matched pairs. Matched pairs were in agreement if both observational and RCT treatment effects were significantly increasing or decreasing (P<0.05) or if both treatment effects were not significant (P≥0.05). RESULTS: 17 new, independent meta-analyses of observational studies were conducted that compared hydroxychloroquine, lopinavir-ritonavir, or dexamethasone with an active or placebo comparator for any safety or efficacy outcomes in covid-19 treatment. These studies were matched and compared with 17 meta-analyses of RCTs reported in The BMJ's living review. 10 additional matched pairs with only one observational study and/or one RCT were identified. Across all 27 matched pairs, 22 had adequate reporting of demographical and clinical data for all individual studies. All 22 matched pairs had studies with overlapping distributions of sex, age, and disease severity. Overall, 21 (78%) of the 27 matched pairs had treatment effects that were in agreement. Among the 17 matched pairs consisting of meta-analyses of observational studies and meta-analyses of RCTs, 14 (82%) were in agreement; seven (70%) of the 10 matched pairs consisting of at least one observational study or one RCT were in agreement. The 18 matched pairs with treatment effects for dichotomous outcomes had a higher proportion of agreement (n=16, 89%) than did the nine matched pairs with treatment effects for continuous outcomes (n=5, 56%). CONCLUSIONS: Meta-analyses of observational studies and RCTs evaluating treatments for covid-19 have summary treatment effects that are generally in agreement. Although our evaluation is limited to three covid-19 treatments, these findings suggest that meta-analyzed evidence from observational studies might complement, but should not replace, evidence collected from RCTs.

20.
Osong Public Health Res Perspect ; 13(2): 84-100, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35538681

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNAbased vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.

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