Hydroxychloroquine has long been used to treat malaria as well as other conditions such as lupus and arthritis. Time to clinical improvementwas not reported as a mean or median(Huang 2020). We judged that 10 out of the 14included trials were at low risk of bias (AbdElsalam 2020; Boulware 2020; Cavalcanti 2020; Chen 2020b; Chen 2020c; Horby 2020; Mitj 2020a; Pan 2020; Skipper 2020; Tang 2020), two were at unclear risk of bias (Davoodi 2020; Mitj 2020b), and two were at high risk of bias for random sequence generation (Chen 2020a;Huang 2020). Hernandez 2020, published in August 2020, is a living systematic review which includes 3 RCTs, 8 cohort studies, and 3 case series. The description of the method of randomisation was inadequate in Davoodi 2020 and Mitj 2020b. Both drugs have been used widely and for many years for the treatment and prevention of malaria (although they are now largely ineffective against falciparum malaria)and in the treatment of rheumatological conditions, such as systemic lupus erythematosus and rheumatoid arthritis (Fiehn2020; Steinhardt 2011). A retrospective cohort study inMichigan, USA comparedfour groups of a total of 2541 patients hospitalized with confirmed COVID19 according to physiciandirectedtreatment assignment: 1202 received HCQ; 147 azithromycinalone; 783 HCQ with azithromycin; and 409 received neither drug (Arshad 2020). In three of the fivetrials reportingchronic heart and lungdisease (including asthma), prevalence for each was < 15% of participants (Cavalcanti 2020; Mitj 2020a; Skipper 2020);Horby 2020reported 26%of participants to have heart disease and 22% chronic lung disease; Pan 2020 reported 21% of participants to have cardiac disease and 12% chronic lung disease or asthma. For time to clinical improvement, we graded the estimate of effect as very low certainty, that is we do not know what effect HCQ has on this outcome. No difference was found in the primary endpoint, which was the incidence of death at 28 days (26.8% hydroxychloroquine vs. 25% usual care, 95% CI 0.96-1.23; p=0.18). Dates of recruitment:11 February to29 February 2020. Hydroxychloroquine has actions, pharmacokinetics and metabolism similar to those of chloroquine. HR is a Specialist Registrar in Clinical Pharmacology in Liverpool, and is employed as a fulltime NHS clinician, and has no conflicts of interest to declare with respect to chloroquine or hydroxychloroquine for the management of COVID19. Methods were reported incompletely, such as the sampling approach for cases and controls from the database of21,402 healthcare workers,of whom 1073has a positive PCR test (Chatterjee 2020). Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. The generic is . Of the 359 total reported, 192 were taking hydroxyurea prior to their COVID-19 diagnosis (53.8 %) (Figure 3). Soon after this, another research group from France reported much poorer clinical and virological outcomes in 11 hospitalized patients treated with both drugs (Molina 2020). Dosing regimens for HCQ varied widely, and are summarized inTable 6. We judged Cavalcanti 2020to be at unclear risk of bias, as it was not blinded, and the primary outcome consisted of an ordinal scale ranking clinical improvement or deterioration. Five, with some overlap (AbdElsalam 2020;Davoodi 2020;Horby 2020;Pan 2020;Skipper 2020), did not report the number of participants experiencing serious adverse events, with Skipper 2020stating: No serious adverse events attributable to the study drug occurred. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. HCQ may make little or no difference to proportion of people having negative PCR for SARSCoV2 on respiratory samples at day 14 from enrolment. Clinical characteristics of Coronavirus Disease 2019 in China. Zang 2020, published in September 2020, includes 3 RCTs, 2 prospective observational studies, and 2 retrospective observational studies. If you take hydroxychloroquine, you should know about its possible drug interactions.Some interactions only need extra monitoring, while others can . We judged the trial to be at low risk for four out of five domains (see Characteristics of included studies), and at high riskof bias forcomparability with individually randomized trials: contamination was possible due to the openlabel design,and the intervention would be expectedto work best when given to all contacts of a case rather than some being randomized to the intervention and some randomized to no intervention, which would preclude comparability with an individually randomized trial. Uptodate lists of ongoing trialscan be found atwww.covid-nma.com, updated daily. Any disagreements were resolved through discussion. Initiation of ventilation (initial on protocol as on 16 October 2020: Time to first receiving ventilation (or intensive care)). Approved as a pharmacy medicine, Sanofi will launch Cialis Together in the second half of the year. The pharmacological cointerventions reported per arm in the treatment trials for comparison 1 (HCQ versus standard care without HCQ or placebo) are shown in Table 7. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection:a randomized clinical trial, Brescia-COVID Respiratory Severity Scale Algorithm. Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, et al. For Objective 3 prevention of COVID19 in people who have been exposed to SARSCoV2, we included one RCT and graded four outcomes (Boulware 2020). Adverse events were reported in 671/1197 (56%) participants in the HCQ clusters versus 77/1300 (6%) participants in the clusters not receiving HCQ; a relative effect estimate was not reported(Mitj 2020b). 30% to 60%: may represent moderate heterogeneity; 50% to 90%: may represent substantial heterogeneity; Time in the illness when treatment started (< 7days, and 7 daysafter symptoms started), Comorbidity, such as cardiovascular disease, diabetes, and immunosuppression, Admitted to hospitalversusreceiving ambulatory/outpatient treatment, Participants initially enrolled into the HCQ arm of, Number of participants admitted to hospital (if receiving ambulatory treatment): this was reported by the three outpatientbased trials(, Number of participants requiring mechanical ventilation: three trials reported this outcome (, Length of hospital admission: this was reported as a mean by, Time to clinical improvement was reported as survival data only by, Obesity:HCQ 40/97 (41%); standard care 35/97 (36%), Morbid obesity: HCQ 21/97 (22%); standard care 24/97 (25%), Smoking: HCQ 35/97 (36%); standard care 25/97 (26%), Liver disease: HCQ 0/97; standard care 2/97 (2%), Renal impairment: HCQ 2/97 (2%); standard care 4/97 (4%), "Comorbidities": HCQ 15/97 (15%); standard care 12/97 (12%). Severity of disease varied between trials. It is used alone or in combination with other anti-arthritic medications to treat rheumatoid arthritis. Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. Two review authors independently examined the search results, assessed studies for eligibility, and extracted data, in order to minimize bias in study selection and data extraction. Interdisciplinary recommendations on the basis of a systematic literature review. We classifiedeach 'Risk of bias' domain as either at high, low, or unclear riskof bias (Higgins 2011). Total 7 days. Time to clinical improvement (for symptomatic patients)and time to negative PCR for SARSCoV2 on respiratory samples werereported as hazard ratios (HRs) and corresponding 95% CIsbyTang 2020. Transmission is common in, though not limited to, households (Pung 2020). No eligible trials were identifiedfor this objective. It's used to reduce fever and inflammation, and the hope has been that it can also . Where reported, hypertension was usually the most common comorbidity, though its prevalence varied widely:from 6% of participants inTang 2020and 11% inSkipper 2020, to 27% inChen 2020aand 39% inCavalcanti 2020. The same group thenpublished twoobservational singlearm cohorts ofpatients treated with HCQ plus azithromycin, reporting benefit of the combination(Gautret 2020b;Million 2020). We assessed Horby 2020as at low risk of bias for selective reporting. Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Methods We recruited antiretroviral-naive patients with viral loads less than 100 000 HIV-1 RNA copies/mLand CD4 counts greater than 150 cells/mL. Low attrition numbers labelled as "lost to follow up", and 2 further participants withdrew consent without explanation. Onward transmission to household contacts from index participants was not assessed. may not increase the risk of serious harmful effects (6 studies; 1004 people). Further details of the trialsare provided in subsectionsfor eachof the review's objectives. Due to the lack of studies at that time, the authors included only two preclinical studies and three commentaries, concluding that although evidence from preclinical studies is promising, there was no evidence to support the efficacy of CQ or HCQ in preventing COVID19. We attempted to identify all relevant trials regardless of language or publication status (published, unpublished, in press, and in progress) up to 15 September 2020. CQ is generally less tolerable than HCQ, and can cause acute poisoning at a lower dose, as has been seen in reports from the USA and Nigeria of members of the public taking CQ without a prescription (CNN 2020; Owens 2020). No placebo was used. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). No significant difference was found for time to clinical improvement (HR 1.01, 95% CI 0.59 to 1.74; 119 participants; 1 RCT; Analysis 1.8) or time to negative PCR for SARSCoV2 on respiratory samples (HR 0.85, 95% CI 0.58 to 1.23; 150 participants; 1 RCT; Analysis 1.9). Dates of recruitment:17 March to 6 May 2020, Permutedblock sequence variably sized blocks, stratified by country, Randomization will be recorded on an electronic log by the pharmacy. number of patients with virological cure. BS is a Clinical Research Fellow for the National Institute for Health Research (NIHR) Global Health Research Group on Brain Infections at the University of Liverpool (No. Elavarasi 2020, published in September 2020, is a systematic review of RCTs, case series, and cohort studies with a comparator arm including 12 nonrandomized studies and 3 RCTs. Monitoring Editor: Cochrane Infectious Diseases Group, This is an open access article under the terms of the. Hoffman M, Kleine-Weber H, Schroeder S, Krger N, Herrier T, Erichsen S, et al. Three of the hospitalbased trials recruited on average betweensix and nine days from onset (Cavalcanti 2020; Chen 2020a; Horby 2020). BS and HR prepared initial drafts of Background and Methods; selected studies; assessed risk of bias; extracted data; synthesized data;and prepared initial drafts of results,'Summary of findings' tables, discussion, and conclusions. The other trials recruited from March until May or June 2020:in Brazil (Cavalcanti 2020);Egypt (AbdElsalam 2020); Iran (Davoodi 2020);Spain (Mitj 2020a);Taiwan (Chen 2020c); the UK (Horby 2020);the USA and Canada (Skipper 2020; around 90% of participants were in the USA); and one trial recruited participants in 30 countries globally(Pan 2020). 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