April 2020. Characteristics of experimental studies included in the updated meta-analysis. For the updated meta-analysis, the quality effects model [42] was employed to pool the estimates (odds ratios), as it is more robust and performs better than the random-effects model [43]. Disease worsening was defined as any form of symptom worsening such as the need for oxygen, dyspnoea, hospitalization in the case of community-based studies. The other 2 reviews, Shamshirian et al., 2020 [55] (103486 participants, 21 studies) and Charko et al., 2020 [54] (4306 participants, 11 studies) found slight but non-significant increases in the risk of mortality with HCQ use, with significant heterogeneity in both meta-analyses. Nicastri E., Petrosillo N., Bartoli T.A., Lepore L., Mondi A., Palmieri F., et al. 1). Graham R.L., Donaldson E.F., Baric R.S. Video, Audio, Photos & Rush Transcript: Amid Ongoing COVID-19 Pandemic, Governor Cuomo Accepts Recommendation of Army Corps of Engineers for Four Temporary Hospital Sites in New York. Low body weight adults should follow the dosing for children. The total number of index studies in the included reviews, after removing duplicate studies was 40. The following search terms were used for the study design; clinical study, clinical trial, trial, RCT, controlled trial, randomized controlled trial, meta-analysis, rapid review, review, systematic reviews. We adjusted for these covariates via exposure propensity scores using stabilized inverse probability treatment weighting. A study by S. Steinlauf et al. Das S., Bhowmick S., Tiwari S., Sen S. An updated systematic review of the therapeutic role of hydroxychloroquine in coronavirus disease-19 (COVID-19). A decade after SARS: strategies for controlling emerging coronaviruses. Gautret P., Lagier J.-C., Parola P. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Since the COVID-19 pandemic is ongoing, and > 7.1 million patients have been infected worldwide, there is an urgent need to generate robust evidence regarding the efficacy and safety of CQ and HCQ in COVID-19. Nine of the reviews [28,30,50,51,[53], [54], [55], [56], [57]] all concluded that there was insufficient evidence to support the use of either CQ or HCQ with or without Azithromycin in the treatment of people with COVID-19. One institution received HCQ shortly after admission, and in the other institution did not receive HCQ until days later when PCR results came through so there was no real control arm and was not published with a submission version of the pdf circulated on the internet. Coronavirus disease 2019 (COVID-19) is a highly transmissible viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, doses used in routine care (e.g. Furuya-Kanamori L., Barendregt J.J., Doi S.A. A new improved graphical and quantitative method for detecting bias in meta-analysis. As a library, NLM provides access to scientific literature. Spallanzani, IRCCS. Azathioprine. Due to the heterogeneous nature of the outcomes assessed in different systematic reviews, meta-analyses and primary studies, we grouped the outcomes into four main groups. The evidence regarding the use of chloroquine or hydroxychloroquine in the treatment of COVID-19 will be reviewed as it becomes available and this statement will be updated accordingly. The I2 statistic measures consistency and is an indication of the variability in the estimates of the effects that are caused by heterogeneity instead of sampling error, and ranges from a 0% (no heterogeneity) to 100% (high heterogeneity). Due to the above reasons and the unprecedented situation and the urgency to curb the COVID-19 pandemic, CQ and HCQ have been approved, on a fast track basis, by the United States Food and Drug Administration and other regulatory bodies, despite the lack of good quality evidence of their efficacy and safety [15,16]. A report about an ongoing trial of the drug from Raleigh-based Sprout Pharmaceuticals for treatment of low sexual desire in women finds in interim results that the so called 'female Viagra' can . Mehra M.R., Desai S.S., Ruschitzka F., Patel A.N. and transmitted securely. The reasons for exclusion of the other experimental studies were as follows; duplicate study (n=1) [61] which used data from Gautret et al., 2020 [20], one study had no full text available [62], one study compared high dose chloroquine to low dose chloroquine [63], and one study included participants who did not have COVID-19 confirmed by PCR [64]. Hydroxychloroquine for early treatment of adults with mild covid-19: a randomized-controlled trial. Location of all primary studies in included reviews. Both CQ and HCQ are weak bases and thought to inhibit this process that the SARS COV-2 virus needs for replication [8]. official website and that any information you provide is encrypted Tang W., Cao Z., Han M., Wang Z., Chen J., Sun W., et al. Ray W.A., Murray K.T., Hall K., Arbogast P.G., Stein C.M. Tableau Foundation Tableau software 2020. Gautret P, Lagier JC, Parola P et al. Removal of the quasi-experimental study, Gautret et al., 2020, did not alter the results of the pooled analysis (RR 1.02 95%CI 0.911.14, I2=0%). Hennessy S., Leonard C.E., Freeman C.P. 1 Hydroxychloroquine, which is better tolerated than chloroquine in humans, exhibits both an antiviral activity against SARS-CoV-2 in vitro and strong immunomodulatory capacit. Research in Social & Administrative Pharmacy, https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports, https://www.fda.gov/media/136535/download, https://www.fda.gov/media/137250/download, https://www.governor.ny.gov/news/video-audio-photos-rush-transcript-amid-ongoing-covid-19-pandemic-governor-cuomo-accepts, https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v2, https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v2, https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-do-not-use-chloroquine-phosphate-intended-fish-treatment-covid-19-humans, Autoimmune diseases during 6 months before index date, Systemic lupus erythematosus and connective tissue disorders, Rheumatoid arthritis and related diseases, Infections during 2 weeks before index date, Drugs with possible risk of QT prolongation, Drugs with conditional risk of QT prolongation, Duration of chloroquine/hydroxychloroquine use, Coronary atherosclerosis and other heart disease, Peripheral and visceral atherosclerosis; aneurysms, Occlusion or stenosis of precerebral arteries, Other and ill-defined cerebrovascular disease, Other hereditary and degenerative nervous system condition, Nervous system disorder (not related to eye/ear). Results of meta-analyses - HCQ and all-cause mortality. The effect of inclusion of the observational studies could have been reduced by using quality-adjusted meta-analysis synthesis, which decreases the weight of the observational studies in the overall estimate. For HCQ alone, two meta-analyses; Yang et al., 2020 [52] (677 participants, 5 studies) and Singh et al., 2020 [50](2042 participants, 10 studies) found a higher risk of mortality with HCQ with odds ratios of 3.0 and 2.2, respectively, with no heterogeneity (I2=0% for both). 1 Mounting research efforts are under way to test and develop effective prophylactics and therapeutics. 6 During pretravel consultations, travel health providers must consider potential interactions between vaccines and medications, including those already taken by the traveler. Further, all the deaths, except one, occurred in the U.S. veterans observational study, and therefore the meta-analysis effectively drew its conclusions from the one big observational study where clinical severity may have influenced allocation of treatment. Epub 2020 Jun 23. 13, While controlled evidence on the risk of the combination use is lacking, a recent analysis of the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) data found a signal for QTc prolongation or Torsades de Pointes associated with azithromycin. Higgins J.P., Thompson S.G., Deeks J.J., Altman D.G. and transmitted securely. The eight experimental studies included in the updated meta-analysis (7 RCTs [22,24,[58], [59], [60],67,68] and 1 quasi-experimental study [20]), had a total of 5279 participants and 1856 on either CQ/HCQ or HCQ with Azithromycin Table 2. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In COVID-19 patients, the transition from the first symptoms of this viral infection to acute respiratory distress syndrome is likely due to uncontrolled cytokine release. Before SARS-COV-2 harbours a spike (S) protein, which is considered a crucial element in the virus replication cycle as it binds to angiotensin-converting enzyme 2 (ACE2) expressed in the lungs of the host cell receptor [9]. Safety was assessed as the occurrence of the known adverse events of CQ or HCQ or Azithromycin. Updated meta-analysis of experimental studies - secondary outcomes. Skipper C.P., Pastick K.A., Engen N.W., Bangdiwala A.S., Abassi M., Lofgren S.M., et al. Treatment plan of chloroquine phosphate in Guangdong Province. Lenzer J. Covid-19: US gives emergency approval to hydroxychloroquine despite lack of evidence. April 2020. The site is secure. There are several mechanisms which have been suggested for the expected effect of the two drugs against viruses in general and SARS-COV-2 in particular. Where there were no available meta-analyses, findings from systematic reviews were compared narratively. Risk of cardiac events among chloroquine/hydroxychloroquine-azithromycin and chloroquine/hydroxychloroquine-amoxicillin users stratified by data sources. Background Since December 2019, the COVID-19 pandemic has changed the concept of medicine. Herbal & Nutritional Supplements. Barbosa J., Kaitis D., Freedman R., Le K., Lin X. Of the two meta-analyses which found a higher risk of mortality, Singh et al., 2020 [50] included three studies with 474 participants from two observational studies [72,73] and the one quasi-experimental study [66] had a weight of 4.6%, in their meta-analysis. Tyagi K., Ghosh A., Nair D., Dutta K., Singh Bhandari P., Ahmed Ansari I., et al. Before The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is currently known to be among one of the most contagious viruses in the history of pathogens [1]. Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2) (Colson et al., 2020; Gao et al., 2020).The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research. A total of ten reviews investigated the risk of adverse events between HCQ or HCQ with Azithromycin groups and control. The findings of this review also shows that HCQ with or without Azithromycin does not have a beneficial effect on other clinical outcomes. For each study, two authors independently extracted data and assessed quality. 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