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75% 66 studies (39 peer reviewed)
COVID deaths: 687,594 Global HCQ studies. PrEP, PEP, and early treatment studies show high effectiveness, while late treatment shows mixed results. 7/29 Positive Late D'Arminio Monforte et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter) Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation? HCQ+AZ adjusted death HR 0.44, p=0.009. Propensity scores include baseline COVID-19 disease severity, age, gender, number of comorbidities, cardio-vascular disease, duration of symptoms, date of admission, baseline .. 7/26 Inconc. PEP Mitjà et al., medRxiv, doi:10.1101/2020.07.20.20157651 (Preprint) A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease Death rate reduced from 0.6% to 0.4%, RR 0.68, not statistically significant due to low incidence (8 control cases, 5 treatment cases). For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - .. 7/24 Positive PrEP Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint) Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis wa.. 7/23 Negative Late Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa201901 (Peer Reviewed) Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19 Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot de.. 7/22 In Vitro In Vitro Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count) Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2 The title of this paper does not appear to match the results. Fig. 1b @100uM shows CQ results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, p=0.05, after 24 hours (we do not see the supplementa.. 7/21 Positive Late Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960 (Preprint) Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid HCQ HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative .. 7/20 Meta
(positive) Early Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis - not included in the study count) Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis” Updated meta analysis including 7 new studies of high-risk outpatients, for a total of 12 studies, all showing significant benefit. 7/18 Meta
(positive) PEP Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in the study count) Efficacy of Hydroxychloroquine as Prophylaxis for Covid-19 Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HCQ is effective when used early, p<0.01. The effectiveness found is especially notable considering the limitatio.. 7/16 Inconc. Early Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed) Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial ~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ reduced combined hospitalization/death by 50%, p=0.29 (5 HCQ cases, 10 control cases), and reduced hospitalization by 60%,.. 7/16 Inconc. Early Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed) Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial This paper has inconsistent data - some of the values reported in Table 2 and the abstract correspond to 12 control hospitalizations, while others correspond to 11 control hospitalizations. There was a 25% reduction in hospitalization an.. 7/9 Meta
(positive) Early, Late Raoult et al., Preprint (Preprint) (meta analysis - not included in the study count) Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial: Response to David Spencer (Elsevier) Updated meta analysis showing significant reductions in mortality and viral shedding. Mortality OR 0.53 [0.4-0.71] for clinical studies, 0.92 big data studies, 18,211 patients. Persistent viral shedding OR 0.47 [0.28-0.79], 4,540 patients. 7/7 Negative Late An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint) Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. .. 7/3 Positive PrEP Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7 (Peer Reviewed) COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study Rheumatic disease patients on HCQ had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythemat.. 7/3 Positive Early Scholz et al., Preprints 2020, 2020070025, doi:10.20944/preprints202007.0025.v1 (Preprint) COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study Early treatment with HCQ+AZ+Z results in 84% lower hospitalization and 80% lower death - hospitalization OR 0.16 (p<0.001), death OR 0.2 (p=0.16). No cardiac side effects. Retrospective 518 patients (141 treated, 37.. 7/1 Positive Late Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed) Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19 HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, p=0.009. Michigan 2,541 patients retrospecti.. 7/1 Safety N/A Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count) Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR positive SARS-CoV-2 infection including drug induced changes in the corrected QT interval (QTc) In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but occur at an incidence higher than expected in a general pediatric population. Comorbidities are not more common in patients wit.. 6/30 Positive Late Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z (Peer Reviewed) Risk Factors for Mortality in Patients with COVID-19 in New York City HCQ decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City. 6/29 Positive PrEP Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed) Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection Chronic treatment with HCQ provides protection against COVID, odds ratio 0.51 (0.37-0.70). Note that patients with SLE, RA, and other autoimmune conditions have a significantly increased susceptibility to and incide.. 6/29 Safety N/A Mfeukeu-Kuate et al. (Preprint) (not included in the study count) Electrocardiographic safety of daily Hydroxychloroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HCQ+AZ. 51 relatively young patients 39 +/- 11. 6/25 Positive Early Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed) Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients. 6/22 In Vitro In Vitro Wang et al., bioRxiv, doi:10.1101/2020.06.22.164665 (Preprint) (In Vitro) (not included in the study count) Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of COVID-19 Spike pseudotype virus In vitro study, not included in the study count or percentages. CQ and HCQ inhibit the entry of COVID-19 spike pseudotype virus using ACE2 high expressed HEK293T cells. 6/22 Positive Early Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint) Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study Significantly faster clinical recovery and shorter time to RNA negative (from 7.0 days to 2.0 days (HCQ), p=0.01. 67 patients with mild/moderate cases. 6/19 Positive
(news) PrEP SMSH Sawai Man Singh Hospital, India (News) (not included in the study count) HCQ beneficial as preventive drug: SMS doctors told ICMR PrEP with 4,300 very high risk healthcare workers in a hospital with up to 500+ COVID patients at a time, only 1% cases, all recovered. 6/19 Negative
(news) Late NIH, study not available yet (News) (not included in the study count) NIH halts clinical trial of hydroxychloroquine NIH halts late stage trial reporting no harm and no benefit. 470 patients. 6/19 Positive Late Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint) Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control .. 6/18 Inconc. Late Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed) Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered. 6/17 Positive Late Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 (Peer Reviewed) Hydroxychloroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China 30 hospitalized patients. Early use of HCQ is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization. 6/17 Negative
(news) Late World Health Organization, study not available yet (News) (not included in the study count) “Solidarity” clinical trial for COVID-19 treatments WHO stopped the Solidarity late stage trial of HCQ reporting no benefit. Later news reported "little or no reduction in mortality" . The study has not been released yet and few details are available. Th.. 6/16 Positive
(news) PrEP WHIP COVID-19 (News) (not included in the study count) Henry Ford Health System still moving forward with hydroxychloroquine study Ongoing WHIP COVID-19 HCQ PrEP study reports analyzing their data and seeing a significantly improved outcome in a group of COVID-19 patients who received HCQ. For more details on the study se.. 6/12 Theory Theory Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count) Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy Theory paper, not included in the study count or percentages. Proposes a new mechanism supporting the synergistic interaction between HCQ+AZ. 6/12 Negative Late Giacomelli et al., medRxiv, doi:10.1101/2020.06.05.20123299 (Preprint) Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". Th.. 6/10 Positive Early Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint) A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications. 80 moderate cases, HCQ+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy. 6/9 Positive Late Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed) Beneficial effect of Hydroxychloroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an observational study 68 very high risk nursing home residents, median age 86, HCQ+AZ early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7 died, significantly less than other nursing homes in France and the same as the med.. 6/9 Positive PrEP Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint) Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects. 6/6 Meta
(positive) Early, Late Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer Reviewed) (meta analysis - not included in the study count) Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world [H]CQ effective and reduces mortality by a factor 3. Meta analysis of 20 studies. 6/5 Negative Late Horby et al., medRxiv, 7/15/2020, doi:10.1101/2020.07.15.20151852 (press release 6/5) (Preprint) Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial RECOVERY trial reports no significant benefit seen for very late stage very sick patients. Results may be due to the unusually high dosage used [1, 2]. Patients were extremely sick (average of 9 days post symptoms, 60% requiring oxygen an.. 6/3 Positive
(see notes) PEP Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed) A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 COVID-19 cases are reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. PEP delayed treatment RCT. Cur.. 5/31 Positive Early Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed) Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19 Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HCQ+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched pa.. 5/29 Positive Late Ayerbe et al., Journal of Thrombosis and Thrombolysis, doi: 10.1007/s11239-020-02162-z (Peer Reviewed) The association between treatment with heparin and survival in patients with Covid-19 2075 hospital patients in Spain. HCQ reduces mortality from 30% to 13%. Not adjusted for age and gender. HCQ group 10% more males and 6 years younger. Study primarily interested in Heparin. 5/28 Positive Late Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint) Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon HCQ+AZ potentially explains 94.7% success in treating a fairly complex cohort. 5/28 Positive PrEP Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed) Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19 4+ doses of HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists. 5/28 Positive Late Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed) Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19 197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events. 5/27 Meta Early Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis - not included in the study count) Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy. 5/25 Negative Late Ip et al., medRxiv, doi:10.1101/2020.05.21.20109207 (Preprint) Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22].. 5/22 Positive
(advisory) PEP, PrEP ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection Healthcare workers on HCQ prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HCQ prophylaxis to asymptomatic household contacts of cases and fron.. 5/22 Retracted Late Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed) Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted. 5/20 Meta
(negative) Late Chacko et al., medRxiv, doi:10.1101/2020.05.14.20101774 (Preprint) (meta analysis - not included in the study count) Hydroxychloroquine in COVID-19: A systematic review and meta-analysis Meta analysis not seeing a significant effect other than time to resolution of chest CT. Limited by heterogeneous nature of studies, baseline severity varied, most studies have a small sample size, endpoints reported at varying times, dos.. 5/19 Negative Late Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint) Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indic.. 5/18 Positive Late Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint) Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HCQ+antibiotic. Preprint withdrawn pending peer review. 5/18 Positive Early Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint) Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities 54 patients in long term care facilities. 6% death with HCQ+AZ compared to 22% using a naive indirect comparison. 5/16 Inconc. PrEP Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint) Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HC 5/15 Positive Late Yu et al., Sci China Life Sci., 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed) Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19 Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ. 5/14 Negative Late Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed) Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions . None of the 15 patients receiving HC<.. 5/11 Positive Late Davido et al., medRxiv, doi:10.1101/2020.05.05.2008875 (Preprint) Hydroxychloroquine plus azithromycin: a potential interest in reducing in hospital morbidity due to COVID-19 pneumonia (HI-ZY-COVID)? Retrospective of 132 hospitalized patients. HCQ+AZ significantly reduces death. Note that due to the controversy, authors withdrew this paper from medRxiv pending peer review. 5/11 Negative Late Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed) Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State Restrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al.  point out serious limitations that they say should be corrected on the record: patients receiving HC 5/10 Positive Late Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed) A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HCQ but p=0.12, OR 0.44 (0.16–1.24). 5/8 Positive Late Carlucci et al., doi:10.1101/2020.05.02.20080036 (Preprint) Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients Observational retrospective. Addition of Zinc to HCQ+AZ reduces mortality. 5/7 Theory Theory Derendorf, H., Int. J. Antimicrobial Agents, 7 May 2020, doi:10.1016/j.ijantimicag.2020.106007 (Peer Reviewed) (Theory) (not included in the study count) Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin Discusses pharmacokinetic properties of HCQ+AZ as a potential underlying mechanism of the observed antiviral effects. 5/7 Inconc. Late Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer Reviewed) Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 There appears to be a major error in this paper. Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). This is not possible. Even if all propensity matched co.. 5/7 Positive
(news) N/A Sermo (News) (not included in the study count) Sermo reports: COVID-19 treatment trends over 6 weeks and 33,700 interviews: Usage, efficacy and safety perceptions of most-used therapies HCQ used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians. 5/6 Animal Animal Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count) Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates Monkey study which reports no effect of HCQ or HCQ+AZ. However, there are actually several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and contr.. 5/5 Positive Late Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint) Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study 166 patients hospitalised with COVID-19, HCQ increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients relatively serious condition. 5/5 Positive Early, Late Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 (Peer Reviewed) Early Treatment of COVID-19 Patients With Hydroxychloroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille, France Retrospective 1061 patients. HCQ+AZ safe and results in a low fatality rate. 5/5 Inconc. PrEP Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed) Continuous Hydroxychloroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases.. 5/1 Safety N/A Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in the study count) Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19) Study of 90 hospitalized patients given HCQ, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HCQ, and 442ms for HCQ+AZ. Medi.. 5/1 Safety N/A Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in the study count) Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit Study of 40 very serious condition ICU patients, 75% required invasive mechanical ventilation, 63% received vasoactive drugs, 50% received other treatments favoring QT prolongation. HCQ with or w/o AZ was given to 4.. 5/2 Positive
(news) Late Seydi (News) (not included in the study count) Coronavirus: a study in Senegal confirms the effectiveness of hydroxychloroquine Preliminary results of Senegal trial with 181 patients showing faster recovery with HCQ, and even faster recovery with HCQ+AZ. 4/30 Positive Early Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed) Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19 Analysis of COVID-19 and malaria, finding that COVID-19 is highly pandemic in countries where malaria is least pandemic, and vice versa, suggesting that CQ/HCQ (widely used for malaria) are pr.. 4/29 Safety N/A Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed) The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection 201 hospitalized patients. No serious side effects of HCQ. No instances of Torsade de pointes, or arrhythmogenic death were reported. They report that although use of these medications resulted in QT prolongation, c.. 4/25 In Vitro In Vitro Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (Peer Reviewed) (In Vitro) (not included in the study count) In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect HCQ and AZ has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung. 4/24 Positive Early Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint) COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes 100 patients. HCQ improved clinical outcome. 4/21 Positive Early Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint) Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using [H]CQ, showing dramatically lower death in [H]CQ countries. This paper does not at.. 4/21 Negative Late Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed) Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19 Retrospective 368 hospitalized patients, no significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ. Study notes HCQ was more likely.. 4/17 Positive PEP Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 (Peer Reviewed) Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals? Post exposure prophylaxis of 211 high-risk people after major exposure event in a long term care hospital, showing no positive cases after 14 days. 4/16 Negative Late Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed) Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study) Increased incidence of prolonged QT and death in high dose treatment arm. Patients >75 only enrolled in high dose arm, age of high dose arm significantly higher than low dose arm (p=0.02). Very sick at baseline, 43% in ICU, 88.9% on respi.. 4/15 Positive Early Esper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint) Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine 636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized. 4/14 Negative Late Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed) Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial 150 patients very late stage RCT. No significant difference. More symptomatic relief with HCQ. No safety concerns of HCQ. Treatment very late, average 16.6 days after symptom onset. Data favor.. 4/13 Positive Late Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Peer Reviewed) Update on Use of Chloroquine/Hydroxychloroquine to Treat Coronavirus Disease 2019 (COVID-19) Increasing evidence from completed clinical studies shows CQ and HCQ effective (HCQ more effective). 4/12 Negative Late Barbosa et al., Preprint (Preprint) Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19 : a quasi-randomized comparative study Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been publishe.. 4/11 Positive Early Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed) Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study Pilot study suggesting improvement with HCQ+AZ and recommending further study. 4/10 Meta
(negative) Late Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in the study count) Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020) Secondary analysis of Gautret et al. showing "modest to no impact of HCQ treatment, with more significant effects from [HCQ+AZ]". 4/1 Positive Late Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed) Treating COVID-19 with Chloroquine 22 patients. All CQ patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for CQ vs. 6.5 days for Lopinavir/Rotinavir. 3/31 Positive Late Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint) Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial 62 patients. RCT showing significantly faster recovery with HCQ. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% .. 3/31 In Vitro In Vitro Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31) (Peer Reviewed) (In Vitro) (not included in the study count) Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro In vitro study, not included in the study count or percentages, showing greater inhibition for combined pre and post-exposure treatment for Vero E6 and Caco-2 cells. 3/28 Negative Late Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter) No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection 11 patients with severe cases. No evidence of benefit for HCQ. 3/26 Positive
(news) Late Zhong Nanshan (钟南山) (News) (not included in the study count) Efficacy and safety of chloroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial 197 patients. HCQ effective. Viral RNA negative in 95.9% versus 79.6% control. Median time to negative tests 3 days versus 9 days for control. 3/24 Theory Theory Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory) Is Hydroxychloroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19? CQ and HCQ inhibit replication at early stages of infection, no similar effect reported for other drugs which are only able to interfere after cell infection. Large volume of existing data on .. 3/23 Theory Theory Hu et al., Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Peer Reviewed) (Theory) (not included in the study count) Insights from nanomedicine into chloroquine efficacy against COVID-19 CQ is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19. 3/21 Positive
(advisory) PrEP ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) Advisory on the use of hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection Recommends HCQ for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo. 3/20 Positive
(news) Late Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count) Shanghai Experience of COVID-19 Management Clinical studies of HCQ with 184 cases and 21 hospitals show HCQ is effective. 3/18 In Vitro In Vitro Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not included in the study count) Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro HCQ effective in vitro and less toxic than CQ. In addition to direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensiv.. 3/17 Positive Early Gautret et al., Int. J. of Antimicrobial Agents, 17 March 2020, doi:10.1016/j.ijantimicag.2020.105949 (Peer Reviewed) Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial HCQ significantly associated with viral load reduction / elimination, enhanced with AZ. 3/17 Review N/A Sahraei et al., Int. J. Antimicrobial Agents, April 2020, 55:4, doi:10.1016/j.ijantimicag.2020.105945 (Peer Reviewed) (not included in the study count) Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine Discussion of mechanisms of action, CQ vs. HCQ, early studies, safety. 3/13 Review N/A Todaro and Rigano (Preprint) (not included in the study count) An Effective Treatment for Coronavirus (COVID-19) Discussion of existing research, treatment guidelines, and mechanisms of action for CQ and HCQ, recommending use. 3/12 Theory Theory Devaux et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not included in the study count) New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Discusses mechanisms of CQ interference with the SARS-CoV-2 replication cycle. 3/10 Meta
(positive) N/A Cortegiani et al., J. Crit. Care, June 2020, 57:279-283, doi:10.1016/j.jcrc.2020.03.005, Epub Mar 10, 2020 (Peer Reviewed) (meta analysis - not included in the study count) A Systematic Review on the Efficacy and Safety of Chloroquine for the Treatment of COVID-19 Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI. 3/9 In Vitro N/A Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (Peer Reviewed) (not included in the study count) 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) HCQ is more potent than CQ in vitro for inhibiting SARS-CoV-2. Simulates HCQ concentration in lung fluid and provides dosing recommendations. 3/6 Negative Late Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed) A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19) 30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HCQ but not statistically significant. One HCQ patient developed to .. 3/4 Positive Late Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Peer Reviewed) Chloroquine and Hydroxychloroquine as Available Weapons to Fight COVID-19 Recommending CQ and HCQ for COVID-19 based on 20 clinical studies in China and a strong rationale for use. 2/20 Positive Late Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed) Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia Early trials in China show CQ results in shorter hospital stays and improved patient outcomes. 2/19 Positive Late Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047 (Peer Reviewed) Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies Results from 15 clinical trials in China showing CQ is effective. 2/17 Positive
(news) Late Sun Yanrong, deputy head of the China National Center for Biotechnology Development (News) (not included in the study count) Antimalarial drug confirmed effective on COVID-19 HCQ under clinical trials in >10 hospitals in China and has shown fairly good efficacy. 2/4 In Vitro In Vitro Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (Peer Reviewed) (In Vitro) (not included in the study count) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro In vitro study, not included in the study count or percentages. Remdesivir and CQ potently blocked virus infection in vitro. 2014 In Vitro In Vitro de Wilde et al., Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8, 4875-4884, doi:10.1128/AAC.03011-14 (Peer Reviewed) (In Vitro) (not included in the study count) Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture CQ inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range. 2012 Animal Animal Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count) Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model CQ, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus. 2009 Animal Animal Keyaerts et al., Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the study count) Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice CQ inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with CQ acquired transplacentally or via maternal milk. The highest survi.. 2008 In Vitro In Vitro Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (Peer Reviewed) (In Vitro) (not included in the study count) Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK CQ significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracell.. 2006 In Vitro In Vitro Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (Peer Reviewed) (In Vitro) (not included in the study count) New insights into the antiviral effects of chloroquine Update to 2003 paper, not included in the study count or percentages. Hypothesis of CQ inhibiting SARS replication has been confirmed in two in-vitro studies. CQ affected an early stage of SAR.. 2005 In Vitro In Vitro Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count) Chloroquine is a potent inhibitor of SARS coronavirus infection and spread In vitro study, SARS-CoV-1, not included in the study count or percentages. CQ has strong antiviral effects on SARS CoV infection when cells treated either before or after exposure, suggesting prophylactic and treat.. 2004 In Vitro In Vitro Keyaerts et al., Biochem. Biophys. Res. Comm., 323:1, 8 October 2004, doi:10.1016/j.bbrc.2004.08.085 (Peer Reviewed) (In Vitro) (not included in the study count) In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine In vitro study, SARS-CoV-1, not included in the study count or percentages. IC50 of CQ for antiviral activity (8.8) is significantly lower than cytostatic activity CC50 (261.3), selectivity index of 30. IC50 for inh.. 2003 Theory Theory Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count) Effects of chloroquine on viral infections: an old drug against today's diseases Not included in the study count or percentages. Discussion/review noting that CQ exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coron.. 1889 Inconc.
(news) N/A Edwin Wiley Grove (News) (not included in the study count) Laxative Bromo Quinine Quinine has been used for respiratory infections since 1889. Not included in the study count or percentages, just as an interesting observation.
Note: In Vitro, Meta, Theory, Safety, Review, News, and Retracted items are not included in the percentages and study count. There is a total of 112 items. Positive/negative effects vary in degree and certainty, please read the papers or descriptions thereof for more details. Every study has some limitations when considered in isolation (for example confounding factors; sub-optimal treatment regimens; dosing regimens that may be too low, too high, or insufficiently account for the long half-life of HCQ; large treatment delays; small sample sizes; lack of focus on severity; reliance on Internet surveys; and patient characteristics very different from the most at-risk population).
Please send us corrections, updates, comments. Please send us any missing papers but check first - almost all submissions to date were already posted. NOTE: If the excuse of mandating masks that "it will not eliminate but greatly reduce the chance to get COVID" is used, why is not the smae reasoning applied to the use of a concoction of HCQ+Zinq+Zithromax? Yet HCQ is banned and masks are not. Science just like law, is never settled. If you question this just ask Einstein.
Testing the Rocker Badge!