The estimated number of lives lost from not using HCQ:890,455based on the effectiveness of early treatment.
| Early | ↓66% | 219 HCQ studies 156 peer reviewed Early treatment shows high efficacy |
| 100% of studies report positive effects. 66% improvement from meta analysis, p<0.0001. | ||
| Late | ↓27% | |
| 76% of studies report positive effects. |
Search: Restrict: All Early Late PrEP PEP
| 12/30 | Early | Proctor et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 (Peer Reviewed) | Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection | |
| Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region. At least two of z.. | ||||
| 12/29 | Early, Late, PrEP, PEP | Covid Analysis (Preprint) (meta analysis – not included in study count) | meta-analysis | HCQ is effective for COVID-19 when used early: meta analysis of 185 studies |
| • HCQ is effective for COVID-19. The probability that an ineffective treatment generated results as positive as the 185 studies to date is estimated to be 1 in 8 quadrillion (p = 0.00000000000000012). • Early treatment is most successful.. | ||||
| 12/29 | Late | Güner et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.12.017 (Peer Reviewed) | ICU, ↓77.3%, p=0.16 | Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine plus Favipiravir |
| Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir. | ||||
| 12/28 | PrEP | Cordtz et al., Rheumatology, doi:10.1093/rheumatology/keaa897 (Peer Reviewed) | hosp., ↓24.0%, p=0.67 | Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark |
| Retrospective 58,052 rheumatic disease patients in Denmark showing that RA patients have a higher risk of COVID-19 hospitalization in general. HCQ treated patients show lower risk, although this is not statistically significant with only .. | ||||
| 12/24 | Late | Chari et al., Blood, doi:10.1182/blood.2020008150 (Peer Reviewed) | death, ↓33.1%, p=0.17 | Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set |
| Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material). | ||||
| 12/23 | Early | Su et al., BioScience Trends, doi:10.5582/bst.2020.03340 (Peer Reviewed) | progression, ↓84.9%, p=0.006 | Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China |
| 85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006. | ||||
| 12/23 | Late | Taccone et al., The Lancet Regional Health – Europe, doi:10.1016/j.lanepe.2020.100019 (Peer Reviewed) | death, ↓24.7%, p=0.0004 | The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium |
| Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92]. | ||||
| 12/22 | Late | Cangiano et al., Aging, doi:10.18632/aging.202307 (Peer Reviewed) | death, ↓73.4%, p=0.03 | Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests |
| 73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, p = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the.. | ||||
| 12/19 | PrEP | Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 (Peer Reviewed) | progression, ↑251.0%, p=0.11 | Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea |
| Retrospective database analysis with 17 existing users of HCQ and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and autho.. | ||||
| 12/18 | Late | Matangila et al., PLOS ONE, doi:10.1371/journal.pone.0244272 (Peer Reviewed) | death, ↓54.9%, p=0.21 | Clinical characteristics of COVID-19 patients hospitalized at Clinique Ngaliema, a public hospital in Kinshasa, in the Democratic Republic of Congo: A retrospective cohort study |
| 55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 [0.03-2.2]. | ||||
| 12/16 | Late | Signes-Costa et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.11.012 (Peer Reviewed) | death, ↓47.0%, p=0.0005 | Prevalence and 30-day mortality in hospitalized patients with COVID-19 and prior lung diseases |
| 47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53, p < 0.. | ||||
| 12/16 | PrEP | Gönenli et al., Research Square, doi:0.21203/rs.3.rs-107937/v1 (Preprint) | progression, ↓29.7%, p=0.77 | Prophylactic use of Hydroxychloroquine among Physicians working in Pandemic Hospitals |
| Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, p = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, p = 0.58, which may be due .. | ||||
| 12/14 | Late | Orioli et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.12.020 (Peer Reviewed) | death, ↓12.7%, p=1.00 | Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic center in Belgium |
| Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, p = 1.0. | ||||
| 12/14 | Late | Naseem et al., medRxiv, doi:10.1101/2020.12.13.20247254 (Preprint) | death, ↓33.3%, p=0.34 | Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network |
| Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, p = 0.34. | ||||
| 12/14 | Late | Tan et al., Virus Research, doi:10.1016/j.virusres.2020.198262 (Peer Reviewed) | hosp. time, ↓35.2%, p=0.04 | A retrospective comparison of drugs against COVID-19 |
| Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ. | ||||
| 12/11 | Late | Bielza et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.12.003 (Peer Reviewed) | death, ↓21.5%, p=0.09 | Clinical characteristics, frailty and mortality of residents with COVID-19 in nursing homes of a region of Madrid |
| Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, p = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Med.. | ||||
| 12/11 | Early | Sogut et al., The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2020.12.014 (Peer Reviewed) (not included in the study count) | safety analysis | Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study |
| Safety study of 152 outpatients concluding that HCQ is safe for COVID-19, was well tolerated, and was not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation. | ||||
| 12/11 | PrEP | Jung et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.12.003 (Peer Reviewed) | death, ↓59.3%, p=1.00 | Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: A population-based cohort study |
| Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information .. | ||||
| 12/10 | Late | Alqassieh et al., F1000Research, Preprint (Preprint) | hosp. time, ↓18.2%, p=0.11 | Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan |
| Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, p = 0.11. | ||||
| 12/10 | News | Italian Council of State (News) (not included in the study count) | news | Consiglio di Stato, sì all’uso dell’idrossiclorachina per la cura del Covid |
| Consiglio di Stato ruling in Italy re-establishes the right of Italian MDs to prescribe HCQ, which was suspended after the retracted Lancet study. | ||||
| 12/9 | Early | Agusti et al., Enfermedades Infecciosas y Microbiología Clínica, doi:10.1016/j.eimc.2020.10.023 (Peer Reviewed) | progression, ↓68.4%, p=0.21 | Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: prospective, non-randomized trial |
| Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, p = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths. Prospect.. | ||||
| 12/9 | Late | Guglielmetti et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.11.012 (Peer Reviewed) | death, ↓35.0%, p=0.22 | Severe COVID-19 pneumonia in Piacenza, Italy – a cohort study of the first pandemic wave |
| Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 [0.33–1.30]. | ||||
| 12/7 | PEP | Barnabas et al., Annals of Internal Medicine, doi:10.7326/M20-6519 (Peer Reviewed) | hosp., ↑3.7%, p=1.00 | Hydroxychloroquine for Post-exposure Prophylaxis to Prevent Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Trial |
| Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people wi.. | ||||
| 12/4 | Late | Ozturk et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa271 (Peer Reviewed) | death, ↓43.9%, p=0.14 | Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey |
| Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by indication. | ||||
| 12/4 | Late | Modrák et al., medRxiv, doi:10.1101/2020.12.03.20239863 (Preprint) | death, ↓59.0%, p=0.04 | Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis |
| Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication. | ||||
| 12/4 | Late | Peng et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa288 (Peer Reviewed) | progression, ↓10.8%, p=0.63 | Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China |
| Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ. | ||||
| 12/2 | PEP | Wiseman et al., medRxiv, doi:10.1101/2020.11.29.20235218 (Preprint) (meta analysis – not included in study count) | cases, ↓42.0%, p=0.04 | Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data |
| 6th independent analysis showing efficacy from the Boulware PEP trial. This prospective analysis corrects an error in the NEJM paper where shipping delays are omitted (still not corrected). 42% reduction in COVID-19 (9.6% vs. 16.5%), RR.. | ||||
| 12/1 | Late | Capsoni et al., Research Square, doi:10.21203/rs.3.rs-113418/v1 (Preprint) | ventilation, ↓40.0%, p=0.30 | CPAP Treatment In COVID-19 Patients: A Retrospective Observational Study In The Emergency Department |
| Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ. | ||||
| 11/30 | Late | Abdulrahman et al., medRxiv, doi:10.1101/2020.11.25.20234914 (Preprint) | death, ↓16.7%, p=1.00 | The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort |
| Retrospective medical record analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity – 17.5% of HCQ patients requ.. | ||||
| 11/29 | Late | Abd-Elsalam et al., Biological Trace Element Research, doi:10.1007/s12011-020-02512-1 (Peer Reviewed) | Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial | |
| 191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. Clinical recovery at 28 days was 79.2% in the zinc group and 77.9% control, p = 0.969. Mechanical ventialation was used with 4 patient.. | ||||
| 11/28 | Late | Lambermont et al., Critical Care Explorations, doi:10.1097/CCE.0000000000000305 (Peer Reviewed) | death, ↓32.3%, p=0.46 | Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study |
| Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not sp.. | ||||
| 11/28 | N/A | Ruiz et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247 (Peer Reviewed) | dosing study | Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19 |
| HCQ lung pharmacokinetic study confirming that lung concentrations can be much higher than plasma. The median lung epithelial lining fluid concentration was 38 times higher than plasma concentrations. 22 COVID-19 patients, median age 59… | ||||
| 11/28 | Late | Rodriguez-Gonzalez et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106249 (Peer Reviewed) | death, ↓22.8%, p=0.26 | COVID-19 in hospitalized patients in Spain: a cohort study in Madrid |
| Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication. | ||||
| 11/27 | Late | van Halem et al., BMC Infect Dis., doi:10.1186/s12879-020-05605-3 (Peer Reviewed) | death, ↓31.6%, p=0.05 | Risk factors for mortality in hospitalized patients with COVID-19 at the start of the pandemic in Belgium: a retrospective cohort study |
| Retrospective 319 hospitalized patients in Belgium showing lower mortality with HCQ, although not reported to be statistically significant. | ||||
| 11/24 | Late | Abbas et al., Int. J. Clin. Pract., doi:10.1111/ijcp.13856 (Peer Reviewed) | Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A Natural Clinical Trial | |
| Prospective study of 161 hospitalized patients in Iraq showing HCQ+AZ appears to help recovery. Most mortality was in patients that were already in critical condition on admission and died before treatment could be effective. | ||||
| 11/23 | Late | Qin et al., Thrombosis Research, doi:10.1016/j.thromres.2020.11.020 (Peer Reviewed) | death, ↓34.3%, p=0.61 | Low molecular weight heparin and 28-day mortality among patients with coronavirus disease 2019: A cohort study in the early epidemic era |
| Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, p = 0.61. | ||||
| 11/21 | PrEP | Revollo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa477 (Peer Reviewed) | cases, ↓23.0%, p=0.52 | Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in healthcare workers |
| Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they « identified 69 HCWs receiving HCQ » while providing .. | ||||
| 11/20 | Early | Omrani et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100645 (Peer Reviewed) | hosp., ↓12.5%, p=1.00 | Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19 |
| Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients; that positive PCR may simply reflect detection of inactive (non-infec.. | ||||
| 11/19 | Late | Falcone et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563 (Peer Reviewed) | death, ↓65.0%, p=0.20 | Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study |
| Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk: RR 0.35, p = 0.2, pr.. | ||||
| 11/18 | Late | Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223 (Preprint) | death, ↓65.4%, p<0.0001 | Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience |
| Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, p < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have received H.. | ||||
| 11/17 | Late | Boari et al, Biosci. Rep., doi:10.1042/BSR20203455 (Peer Reviewed) | death, ↓54.5%, p<0.001 | Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study |
| Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, p<0.001. (data is in the supplementary appendix) | ||||
| 11/13 | Late | Sheshah et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108538 (Peer Reviewed) | death, ↓80.0%, p<0.001 | Prevalence of Diabetes, Management and Outcomes among Covid-19 Adult Patients Admitted in a Specialized Tertiary Hospital in Riyadh, Saudi Arabia |
| Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, p < 0.001. | ||||
| 11/12 | Early | Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed) | hosp., ↓93.8%, p=0.01 | Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers |
| 100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33.. | ||||
| 11/12 | PEP | Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed) | cases, ↓92.7%, p=0.01 | Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers |
| 100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This.. | ||||
| 11/12 | N/A | Tchounga et al., Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2020.113761 (Peer Reviewed) (not included in the study count) | meta-analysis | Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic |
| Analysis of fake CQ tablets finding: – no CQ in six samples, substituted with metronidazole (at sub-therapeutic levels) or paracetamol. – trace levels of paracetamol and chloramphenicol in four and two samples respectively. – CQ levels t.. | ||||
| 11/11 | Late | Águila-Gordo et al., Revista Española de Geriatría y Gerontología, doi:10.1016/j.regg.2020.09.006 (Peer Reviewed) | death, ↓67.0%, p=0.10 | Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19 |
| 67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, p = 0.1. | ||||
| 11/9 | Late | Khamis et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.008 (Peer Reviewed) | Randomized Controlled Open Label Trial on the Use of Favipiravir Combined with Inhaled Interferon beta-1b in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia | |
| Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences. | ||||
| 11/9 | Late | Self et al., JAMA, doi:10.1001/jama.2020.22240 (Peer Reviewed) | death, ↓7.0%, p=0.84 | Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial |
| Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients not showing a significant difference, 28 day mortality adjusted odds ratio aOR 0.93 [0.48-1.85]. For the subgroup not on supplemental.. | ||||
| 11/9 | Late | Brown et al., Annals of the American Thoracic Society, doi:10.1513/AnnalsATS.202008-940OC (Peer Reviewed) | Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial | |
| Small early terminated very late stage (86% on oxygen, 44% enrolled in the ICU) RCT comparing HCQ vs. AZ, not finding a significant difference between the two treatments. There is no comparison with a control group. HCQ patients not in th.. | ||||
| 11/9 | Late | Núñez-Gil et al., Intern. Emerg. Med., doi:10.1007/s11739-020-02543-5 (Peer Reviewed) | death, ↓7.9%, p=0.005 | Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry |
| Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, p=0.005. | ||||
| 11/6 | PrEP | Mathai et al., J. Marine Medical Society, doi:10.4103/jmms.jmms_115_20 (Peer Reviewed) | cases, ↓89.5%, p<0.0001 | Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience |
| 90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers. | ||||
| 11/6 | PrEP | Datta et al., Journal of Vaccines & Vaccination, S6:1000002 (Peer Reviewed) | No Role of HCQ in COVID-19 Prophylaxis: A Survey amongst Indian Doctors | |
| Survey of Indian doctors not finding a significant effect of HCQ prophylaxis, p = 0.54. We do not know the actual results for this study – the numbers for prophylaxis in Table 1 appear to be incorrect. They do not match the total using H.. | ||||
| 11/6 | PEP | Dhibar et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106224 (Peer Reviewed) | cases, ↓41.0%, p=0.03 | Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study |
| 41% reduction in cases with HCQ PEP. Prospective open label trial with 132 HCQ patients and 185 control patients showing RR 0.59, p=0.03. 50% reduction in PCR+ cases, 44% reduction in symptomatic cases. No serious adverse events. Relati.. | ||||
| 11/5 | Late | Maldonado et al., Nefrología, doi:10.1016/j.nefro.2020.09.002 (Peer Reviewed) | death, ↓90.9%, p=0.17 | COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic |
| Small retrospective 12 dialysis patients, 1/11 deaths with HCQ and 1/1 without HCQ. | ||||
| 11/5 | Late | Rodriguez-Nava et al., Mayo Clinic Proceedings: Innovations, Quality & Outcomes (Peer Reviewed) | death, ↑6.3%, p=0.77 | Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort study |
| Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, p = 0.77. Confounding by indication likely. | ||||
| 11/4 | Late | Salazar et al., The American Journal of Pathology, doi:10.1016/j.ajpath.2020.10.008 (Peer Reviewed) | death, ↑37.0%, p=0.28 | Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG |
| Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, p = 0.28. Confounding by indication is likely. | ||||
| 11/4 | Early | Cadegiani et al., medRxiv, doi:10.1101/2020.10.31.20223883 (Preprint) | death, ↓81.2%, p=0.21 | Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients |
| Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, ev.. | ||||
| 11/3 | PrEP | Behera et al., medRxiv, doi:10.1101/2020.10.29.20222661v1 (Preprint) | cases, ↓27.9%, p=0.29 | Role of ivermectin in the prevention of COVID-19 infection among healthcare workers in India: A matched case-control study |
| Retrospective prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin O.. | ||||
| 11/2 | Late | López et al., Annals of Pediatrics, doi:10.1016/j.anpedi.2020.10.017 (Peer Reviewed) | progression, ↓64.3%, p=0.02 | Telemedicine follow-ups for COVID-19: experience in a tertiary hospital |
| Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (p=0.023), less progression (p=0.016), and fewer return visits to the ER (p=0.017). | ||||
| 10/31 | Early | Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed) | hosp., ↓64.0%, p=0.0008 | Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis |
| 64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, p=0.00081, for HCQ versus no medication, and OR 0.45, p=0.0065, for HCQ vs. anything else. | ||||
| 10/30 | Late | Tehrani et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.071 (Peer Reviewed) | death, ↓13.4%, p=0.63 | Risk factors for mortality in adult COVID-19 patients; frailty predicts fatal outcome in older patients |
| Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, p=0.63. Confounding by indication is likely. | ||||
| 10/27 | PrEP | Arleo et al., medRxiv, doi:10.1101/2020.10.26.20219154 (Preprint) | death, ↓50.0%, p=0.67 | Clinical Course and Outcomes of coronavirus disease 2019 (COVID-19) in Rheumatic Disease Patients on Immunosuppression: A case Cohort Study at a Single Center with a Significantly Diverse Population |
| Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ. | ||||
| 10/27 | Late | Choi et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.062 (Peer Reviewed) | viral- time, ↑22.0%, p<0.0001 | Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study |
| Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose not to.. | ||||
| 10/26 | Late | Frontera et al., Research Square, doi:10.21203/rs.3.rs-94509/v1 (Preprint) | death, ↓37.0%, p=0.01 | Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study |
| Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc. | ||||
| 10/26 | Early | Derwand et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106214 (preprint 7/3) (Peer Reviewed) | death, ↓79.4%, p=0.12 | COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study |
| 79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. No cardiac side effects. Retrospective 518 patients (141 treated, 377 control). | ||||
| 10/24 | PrEP | Goenka et al., SSRN, doi:10.2139/ssrn.3689618 (Preprint) | IgG+, ↓87.2%, p=0.03 | Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India |
| Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6 weeks. | ||||
| 10/23 | Late | Coll et al., American Journal of Transplantation, doi:10.1111/ajt.16369 (Peer Reviewed) | death, ↓45.6%, p<0.0001 | Covid‐19 in transplant recipients: the spanish experience |
| Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, p<0.0001. | ||||
| 10/21 | Late | Lano et al., Clinical Kidney Journal, 13:5, October 2020, 878–888, doi:10.1093/ckj/sfaa199 (Peer Reviewed) | death, ↓33.1%, p=0.28 | Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort |
| 33% lower mortality with HCQ+AZ, p=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, p=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment). | ||||
| 10/21 | Late | Dubee et al., medRxiv, doi:10.1101/2020.10.19.20214940 (Preprint) | death, ↓46.0%, p=0.21 | A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19 |
| Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 [0.21-1.42] combined mortality/intubation at 28 days relative risk RR 0.74 [0.33-1.70] If not stoppe.. | ||||
| 10/21 | Late | Ñamendys-Silva et al., Heart & Lung, doi:10.1016/j.hrtlng.2020.10.013 (Peer Reviewed) | death, ↓32.3%, p=0.18 | Outcomes of patients with COVID-19 in the Intensive Care Unit in Mexico: A multicenter observational study |
| Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, p = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, p = 0.02 HCQ+AZ or CQ vs.. | ||||
| 10/20 | Early, Late | IHU Marseille (Preprint) (meta analysis – not included in study count) | meta-analysis | Meta-analysis on chloroquine derivatives and COVID-19 mortality |
| Updated meta analysis of 41 studies showing CQ/HCQ OR 0.57, p<0.0001 from clinical studies. For big data studies authors find inconsistent results and OR 0.83, p=0.0014, and for all studies combined OR 0.72, p<0.0001. | ||||
| 10/20 | Late | Solh et al., medRxiv, doi:10.1101/2020.10.16.20214130 (Preprint) | death, ↑18.0%, p=0.17 | Clinical course and outcome of COVID-19 acute respiratory distress syndrome: data from a national repository |
| Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be us.. | ||||
| 10/17 | Early | Mohana et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.031 (preprint 8/17) (Peer Reviewed) (not included in the study count) | safety analysis | Hydroxychloroquine Safety Outcome within Approved Therapeutic Protocol for COVID-19 Outpatients in Saudi Arabia |
| Safety study of 2,733 patients in Saudi Arabia showing HCQ in mild to moderate cases in an outpatient setting, within the protocol recommendation and inclusion/exclusion criteria, is safe, highly tolerable, and has minimal side effects. N.. | ||||
| 10/15 | Late | Guisado-Vasco (Peer Reviewed) | death, ↓20.3%, p=0.36 | Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort) |
| Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 [0.022-0.381], p = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 [0.38-1.41], p = 0.36 (558 patients)… | ||||
| 10/15 | Late | SOLIDARITY Trial Consortium, NEJM, doi:10.1056/NEJMoa2023184 (preprint 10/15) (Peer Reviewed) | death, ↑19.0%, p=0.23 | Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results |
| WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19 [0.89-1.59], p=0.23. HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10 d.. | ||||
| 10/12 | Late | Annie et al., Pharmacotherapy, doi:10.1002/phar.2467 (Peer Reviewed) | death, ↓4.3%, p=0.83 | Hydroxychloroquine in hospitalized COVID‐19 patients: Real world experience assessing mortality |
| Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 [0.62-1.46] for HCQ, and 1.24 [0.70-2.22] for HCQ+AZ. Confounding by indication likely. | ||||
| 10/11 | Late | Sili et al., medRxiv, doi:10.1101/2020.10.09.20209775 (Preprint) (not included in the study count) | Factors associated with progression to critical illness in 28 days among COVID-19 patients: results from a tertiary care hospital in Istanbul, Turkey | |
| Analysis of hospitalized patients in Turkey showing HCQ was given to 99.2% of patients and the incidence of critical illness was lower than most studies. Authors note « whether HCQ administration lowered the rates of critical illness .. | ||||
| 10/8 | Late | Aparisi et al., medRxiv, doi:10.1101/2020.10.06.20207092 (Preprint) | death, ↓63.0%, p=0.008 | Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19 |
| Retrospective 654 hospitalized patients focused on low-density lipoprotein cholesterol levels, also showing results for HCQ with 605 HCQ patients, unadjusted 30 day mortality relative risk RR 0.37, p = 0.008. | ||||
| 10/8 | Late | Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint) | death, ↓18.1%, p<0.0001 | Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru |
| Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10.. | ||||
| 10/6 | Late | DISCOVERY Trial (Preprint) | death, ↓31.1%, p=0.35 | DISCOVERY Trial Preliminary Results |
| Early terminated DISCOVERY trial shows improvements in mortality and day 29 7-point ordinal scale with HCQ. Mortality improvements are seen at both day 15 and day 29 in the graph. Details are not given but based on measuring the pixels o.. | ||||
| 10/5 | Late | Mori et al., Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2020.09.003 (Peer Reviewed) | Triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia | |
| Small case study of 5 patients in Japan showing improvement with HCQ+AZ+ciclesonide. | ||||
| 10/5 | Early, Late | Prodromos et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100776 (Peer Reviewed) (meta analysis – not included in study count) | meta-analysis | Hydroxychloroquine is effective, and consistently so used early, for Covid-19: A systematic review |
| Meta analysis of 43 studies: « HCQ was found consistently effective against COVID-19 when used early, in the outpatient setting. It was found overall effective also including inpatient studies. No unbiased study found worse outcomes w.. | ||||
| 10/2 | Late | Nachega et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-1240 (Peer Reviewed) | death, ↓27.6%, p=0.17 | Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo |
| Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65% to 84%. Mortality cox regression adjusted hazard ratio aHR 0.26, p < 0.001 Risk of no improvement adj.. | ||||
| 10/1 | Late | Almazrou et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2020.09.019 (Peer Reviewed) | ventilation, ↓65.0%, p=0.16 | Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study |
| Retrospective 161 hospitalized patients in Saudi Arabia showing lower ventilation and ICU admission with HCQ, but not statistically significant with the small sample sizes. | ||||
| 10/1 | PrEP, PEP | Garcia-Albeniz et al., medRxiv, doi:10.1101/2020.09.29.20203869 (Preprint) (meta analysis – not included in study count) | cases, ↓22.0%, p=0.04 | Brief communication: A meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19 |
| Combination of the four underpowered prophylaxis RCTs to date showing statistically significant results, RR 0.78 [0.61-0.99]. The actual effect of HCQ is likely to be higher for several reasons: the trials did not adjust for losses to fo.. | ||||
| 9/30 | PEP | Polat et al., Medical Journal of Bakirkoy, 16:3, 280-6, doi:10.5222/BMJ.2020.50469 (Peer Reviewed) | cases, ↓57.0%, p=0.03 | Hydroxychloroquine Use on Healthcare Workers Exposed to COVID-19 -A Pandemic Hospital Experience |
| Small prophylaxis study of 208 healthcare workers in Turkey, 138 with high risk exposure received HCQ, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative risk RR 0.43, p = 0.026… | ||||
| 9/30 | Late | Ayerbe et al., Internal and Emergency Medicine, doi:0.1007/s11739-020-02505-x (Peer Reviewed) | death, ↓52.2%, p<0.001 | The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients |
| 2075 hospital patients in Spain showing HCQ reduces mortality 52%, odds ratio OR 0.39, p<0.001, after adjustment for age, gender, temperature > 37 °C, and saturation of oxygen < 90% treatment with azithromycin, steroids, heparin, tocilizu.. | ||||
| 9/30 | PrEP, PEP, Early | Ladapo et al., medRxiv, doi:10.1101/2020.09.30.20204693 (Preprint) (meta analysis – not included in study count) | cases/death/hosp., ↓24.0%, p=0.03 | Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis |
| Meta analysis of prophylactic and early treatment RCTs, 24% reduction in cases, hospitalization or death with HCQ, RR 0.76, p=0.025. No serious adverse cardiac events were reported. 5,577 patients. The Boulware study provides a breakdown.. | ||||
| 9/30 | PrEP | Abella et al., JAMA Internal Medicine, doi:doi:10.1001/jamainternmed.2020.6319 (Peer Reviewed) | cases, ↓5.0%, p=1.00 | Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers |
| Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 – 3.64]. There was no hospitalization or death, no significant difference.. | ||||
| 9/29 | Late | Lammers et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.09.1460 (Peer Reviewed) | death/ICU, ↓32.0%, p=0.02 | Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients |
| Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HCQ treatment starting on the first day of admission. Weighted propensity score adjusted hazard r.. | ||||
| 9/29 | Late | Dabbous et al., Research Square, doi:10.21203/rs.3.rs-83677/v1 (Preprint) | A Randomized Controlled Study Of Favipiravir Vs Hydroxychloroquine In COVID-19 Management: What Have We Learned So Far? | |
| Small RCT comparing HCQ and favipiravir, with 50 patients in each arm, finding that 55.1% of HCQ patients were PCR negative on day 7 compared to 48% for favipiravir, p = 0.7. There was no comparison with a control group. | ||||
| 9/28 | PEP | Luco, J., ResearchGate, doi:10.13140/RG.2.2.24214.98880 (Preprint) (meta analysis – not included in study count) | meta-analysis | Hydroxychloroquine as Post-Exposure Prophylaxis for Covid-19: Why simple data analysis can lead to the wrong conclusions from well-designed studies |
| Reanalysis of Boulware et al. PEP trial data showing statistically significant improvements with HCQ. | ||||
| 9/24 | Early, Late | Gasperetti et al., EP Europace, doi:10.1093/europace/euaa216 (Peer Reviewed) (not included in the study count) | safety analysis | Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings |
| Safety study of 649 patients finding that HCQ administration is safe for short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attrib.. | ||||
| 9/24 | Late | Shoaibi et al., medRxiv, doi:10.1101/2020.09.23.20199463 (Preprint) | death, ↓15.4%, p<0.001 | Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients |
| Retrospective database analysis focused on Famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, p<0.001 (13.6% vs. 16.1%). | ||||
| 9/23 | Late | Ulrich et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa446 (Peer Reviewed) | death, ↑6.0%, p=1.00 | Treating Covid-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients |
| Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable – 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients,.. | ||||
| 9/22 | Late | Serrano et al., Ann. Oncol., 2020, Sep, 31, S1026, doi:10.1016/j.annonc.2020.08.1830 (Peer Reviewed) | death, ↓43.0%, p=0.14 | COVID-19 and lung cancer: What do we know? |
| Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, p = 0.145. | ||||
| 9/21 | PrEP | Gentry et al., Lancet Rheumatology, doi:10.1016/S2665-9913(20)30305-2 (Peer Reviewed) | death, ↓86.7%, p=0.10 | Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study |
| Retrospective patients with rheumatologic conditions showing zero mortality with HCQ, odds ratio OR 0.13, p=0.10. 0 of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 for control patients. COVID-19 cases OR 0.79, p=0.27. There.. | ||||
| 9/21 | PrEP | Rajasingham et al., medRxiv, doi:10.1101/2020.09.18.20197327 (Peer Reviewed) | cases, ↓27.0%, p=0.12 | Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial |
| PrEP RCT showing HR 0.73, p = 0.12. Trial halted after 47% enrollment, p < 0.05 will be reached at ~75% enrollment if similar results continue. Trial halted due to low enrollment. US prescriptions only stopped briefly, resuming in June, .. | ||||
| 9/21 | PrEP | Grau-Pujol et al., Research Square, doi:10.21203/rs.3.rs-72132/v1 (Preprint) | cases, ↓67.9%, p=0.47 | Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: initial results of a double-blind, placebo-controlled randomized clinical trial |
| Small PrEP RCT showing that PrEP with HCQ is safe at the dosage used. No deaths, hospitalizations, or serious adverse events. With only one case (in the placebo arm), efficacy was not evaluated. | ||||
| 9/21 | Early | Lofgren et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa500 (preprint 9/21) (Peer Reviewed) (not included in the study count) | safety analysis | Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19 |
| Analysis of 2,795 outpatients not showing significant safety concerns with HCQ. No deaths were related to HCQ. There was one serious event requiring hospitalization, identical to the frequency with placebo. | ||||
| 9/18 | Late | Axfors et al., medRxiv, doi:10.1101/2020.09.16.20194571 (Preprint) (meta analysis – not included in study count) | meta-analysis | Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials |
| Meta analysis assigning 87% weight to the RECOVERY trial, producing the same result. The RECOVERY trial used excessively high non-patient-customized dosage in very sick late stage patients and the result is not generalizable to typical do.. | ||||
| 9/16 | N/A | Karatza et al., Xenobiotica (Peer Reviewed) (not included in the study count) | dosing study | Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations |
| Analysis of HCQ dosing, suggesting that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instan.. | ||||
| 9/15 | Late | Ashinyo et al., Pan African Medical Journal, 37:1, doi:10.11604/pamj.supp.2020.37.1.25718 (Peer Reviewed) | hosp. time, ↓33.0%, p=0.03 | Clinical characteristics, treatment regimen and duration of hospitalization among COVID-19 patients in Ghana: a retrospective cohort study |
| Retrospective 307 hospital patients in Ghana showing 33% reduction in hospitalization time with HCQ, 29% reduction with HCQ+AZ, and 37% reduction with CQ+AZ. | ||||
| 9/14 | Late | Lauriola et al., Clinical and Translational Science, doi:10.1111/cts.12860 (Peer Reviewed) | death, ↓73.5%, p<0.001 | Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in COVID‐19 patients |
| Retrospective 377 patients, 73% reduction in mortality with HCQ+AZ, adjusted hazard ratio HR 0.27 [0.17-0.41]. Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders. | ||||
| 9/13 | Early | Sulaiman et al., medRxiv, doi:10.1101/2020.09.09.20184143 (Preprint) | death, ↓63.7%, p=0.01 | The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study |
| Observational prospective 5,541 patients, adjusted HCQ mortality odds ratio OR 0.36, p = 0.012. Adjusted hospitalization OR 0.57, p < 0.001. Zinc supplementation was used in all cases. Early treatment in ambulatory fever clinics in Saudi .. | ||||
| 9/12 | Late | Heberto et al., IJC Heart & Vasculature, doi:10.1016/j.ijcha.2020.100638 (Peer Reviewed) | death, ↓53.6%, p=0.04 | Implications of myocardial injury in Mexican hospitalized patients with coronavirus disease 2019 (COVID-19) |
| Observational prospective 254 hospitalized patients, HCQ+AZ mortality odds ratio OR 0.36, p = 0.04. Ventilation OR 0.20, p = 0.008. | ||||
| 9/9 | Late | Alamdari et al., Tohoku J. Exp. Med., 2020, 252, 73-84, doi:10.1620/tjem.252.73 (Peer Reviewed) | death, ↓55.0%, p=0.03 | Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran |
| Retrospective 459 patients in Iran 93% using HCQ, showing HCQ mortality RR 0.45, p = 0.028. HCQ was the only antiviral that showed a significant difference. Small number of control patients and subject to confounding by indication. Averag.. | ||||
| 9/9 | Early, Late | Kirenga et al., BMJ Open Respiratory Research, doi:10.1136/bmjresp-2020-000646 (Peer Reviewed) | recov. time, ↓25.6%, p=0.20 | Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda |
| Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (p = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a .. | ||||
| 9/9 | PrEP | Rentsch et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30378-7 (preprint 9/9, https://www.medrxiv.org/content/10.1101/2020.09.04.20187781v1) (Peer Reviewed) | death, ↑3.0%, p=0.83 | Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform |
| Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 [0.80-1.33] (HR 0.78 before adjustments). 70 patients with HCQ prescriptions .. | ||||
| 9/9 | PrEP | Laplana et al., PLOS ONE, doi:10.1371/journal.pone.0243598 (Peer Reviewed) | cases, ↑56.0%, p=0.24 | Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients |
| Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence… | ||||
| 9/7 | Review | IHU, Expert Review of Clinical Immunology (Review) (Peer Reviewed) (not included in the study count) | review | Natural history and therapeutic options for COVID-19 |
| Review of the current state of knowledge regarding the natural history of and therapeutic options for COVID-19. Treatment with an oral combination of hydroxychloroquine, azithromycin and zinc may represent the best current therapeutic op.. | ||||
| 9/5 | Late | Synolaki et al., medRxiv, doi:10.1101/2020.09.05.20184655 (Preprint) | death, ↓23.6%, p=0.27 | The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality |
| Retrospective 117 patients, 58 HCQ showing lower mortality for HCQ patients. Version 1 of this paper stated: « HCQ, AZ, [and …] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores.. | ||||
| 9/4 | Late | Furtado et al., The Lancet, doi:10.1016/S0140-6736(20)31862-6 (Peer Reviewed) | Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial | |
| Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. No significant difference was found, OR 1.36, p=0.11. One notable result is that even within this extremely late stage population, results sugge.. | ||||
| 9/2 | In Vitro | Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333 (Peer Reviewed) (In Vitro) (not included in the study count) | in vitro | Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus |
| In Vitro study providing novel insights into the molecular mechanism of CQ/HCQ treatment, showing that CQ and HCQ both inhibit the entrance of 2019-nCoV into cells by blocking the binding of the virus with ACE2. | ||||
| 9/2 | Early | Heras et al., European Geriatric Medicine, doi:10.1007/s41999-020-00432-w (preprint 9/2) (Peer Reviewed) | death, ↓95.6%, p=0.004 | COVID-19 mortality risk factors in older people in a long-term care center |
| Retrospective 100 elderly nursing home patients, HCQ+AZ mortality 11.4% vs. control 61.9%, RR 0.18, p<0.001. Median age 85. COVID-19 confirmed. 70% treated with HCQ+AZ. Details of differences between groups are not provided, and no adjus.. | ||||
| 9/2 | PrEP | de la Iglesia et al., medRxiv, doi:10.1101/2020.08.31.20185314 (Preprint) | hosp., ↑50.0%, p=1.00 | Hydroxicloroquine for pre-exposure prophyylaxis for SARS-CoV-2 |
| Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differences between groups. Other research.. | ||||
| 9/1 | Review | Hecel et al., Pharmaceuticals, 13:9, 228, doi:10.3390/ph13090228 (Review) (Peer Reviewed) (not included in the study count) | review | Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19? |
| Review of zinc as an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and zinc ionophores including CQ/HCQ, showing the latest evidence for zinc and CQ/HCQ having antiviral, and in particular anticoronaviral action. | ||||
| 9/1 | Early | Elbazidi et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100749 (Peer Reviewed) | Pandemic and social changes, political fate | |
| Analysis of US states and countries. Country analysis shows a significant correlation between the dates of decisions to adopt/decline HCQ, and corresponding trend changes in CFR. US state analysis shows a significant correlation between C.. | ||||
| 8/29 | Late | Castillo et al., Journal of Steroid Biochemistry and Molecular Biology, 203, October 2020, doi:10.1016/j.jsbmb.2020.105751 (Peer Reviewed) | Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study | |
| RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions. All patients received standard care including HCQ+AZ. Significantly lower ICU admission wi.. | ||||
| 8/28 | Late | Fried et al., Clinical Infectious Disease, doi:10.1093/cid/ciaa1268 (Peer Reviewed) | death, ↑27.0%, p<0.001 | Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States |
| Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality .. | ||||
| 8/27 | PrEP | Ferri at al., Clinical Rheumatology, doi:0.1007/s10067-020-05334-7 (Peer Reviewed) | cases, ↓63.0%, p=0.01 | COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series |
| Analysis of 1641 systemic autoimmune disease patients showing csDMARD (HCQ etc.) RR 0.37, p=0.015. csDMARDs include HCQ, CQ, and several other drugs, so the effect of HCQ/CQ alone could be higher. This study also confirms that the risk .. | ||||
| 8/26 | Late | Fiolet et al., Clinical Microbiology and Infection (Peer Reviewed) (meta analysis – not included in study count) | meta-analysis | Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis |
| Meta analysis of late stage studies (and one early treatment study with only 2 deaths), showing HCQ RR 0.83 [0.65-1.06], before exclusions RR 0.80 [0.65-1.0]. Authors claim « HCQ alone is not effective », but the result directly .. | ||||
| 8/25 | Early | Ip et al., medRxiv, doi:10.1101/2020.08.20.20178772 (Preprint) | hosp., ↓45.9%, p=0.03 | Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study |
| Retrospective 1,274 outpatients, 47% reduction in hospitalization with HCQ with propensity matching, HCQ OR 0.53 [0.29-0.95]. Sensitivity analyses revealed similar associations. Adverse events were not increased (2% QTc prolongation even.. | ||||
| 8/25 | Late | Di Castelnuovo et al., European J. Internal Medicine, doi:10.1016/j.ejim.2020.08.019 (Peer Reviewed) | death, ↓30.0%, p<0.0001 | Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study |
| Retrospective 3,451 hospitalized patients, 30% reduction in mortality with HCQ after propensity adjustment, HR 0.70 [0.59 – 0.84]. | ||||
| 8/24 | Late | Catteau et al., Int. J. Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106144 (Peer Reviewed) | death, ↓32.0%, p<0.0001 | Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants |
| Retrospective 8,075 hospitalized patients, 4,542 low-dose HCQ, 3,533 control. 35% lower mortality for HCQ (17.7% vs. 27.1%), adjusted HR 0.68 [0.62–0.76]. Low-dose HCQ monotherapy was independently associated with lower mortality in hospi.. | ||||
| 8/21 | Early | Ly et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106219 (preprint 8/21) (Peer Reviewed) | death, ↓55.6%, p=0.02 | Pattern of SARS-CoV-2 infection among dependant elderly residents living in retirement homes in Marseille, France, March-June 2020 |
| Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, p=0.02. 1690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant.. | ||||
| 8/21 | N/A | Lane et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30276-9 (Peer Reviewed) (not included in the study count) | safety analysis | Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study |
| Retrospective study of RA patients using HCQ vs. sulfasalazine (another DMARD). HCQ treatment showed no increased risk in the short term (up to 30 days) among patients with RA. Long term use was associated with excess cardiovascular morta.. | ||||
| 8/21 | Late | Gonzalez et al., medRxiv, doi:10.1101/2020.08.18.20172874 (Preprint) | death, ↓26.6%, p=0.06 | The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals |
| Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential conf.. | ||||
| 8/20 | Late | Dubernet et al., J. Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.08.001 (Peer Reviewed) | ICU, ↓87.6%, p=0.008 | A comprehensive strategy for the early treatment of COVID-19 with azithromycin/hydroxychloroquine and/or corticosteroids: results of a retrospective observational study in the French overseas department of Reunion Island |
| Retrospective analysis of 36 hospitalized patients showing HCQ/AZ associated with lower ICU admission, p=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumonia that were treated wit.. | ||||
| 8/20 | Early | Prodromos, C., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100747 (Peer Reviewed) (not included in the study count) | safety analysis | Hydroxychloroquine is protective to the heart, not harmful: A systematic review |
| Review concluding that HCQ/AZ does not cause Torsade de Pointes or related deaths, HCQ decreases cardiac events, and HCQ should not be restricted in use for COVID-19 patients because of fear of cardiac mortality. | ||||
| 8/18 | Late | Pinato et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0773 (Peer Reviewed) | death, ↓59.0%, p<0.0001 | Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients |
| Restrospective 890 cancer patients with COVID-19, adjusted mortality HR for HCQ/CQ 0.41, p<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Analysis with Cox proportional hazard model. Poten.. | ||||
| 8/15 | Late | Peters et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.10.004 (preprint 8/15) (Peer Reviewed) | death, ↑9.0%, p=0.57 | Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine |
| Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ or dexamethasone. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals.. | ||||
| 8/14 | Late | Abd-Elsalam et al., American Journal of Tropical Medicine and Hygiene, 10.4269/ajtmh.20-0873 (Peer Reviewed) | death, ↑20.0%, p=1.00 | Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study |
| Small RCT in Egypt with 97/97 HCQ/control patients, showing 58% more recovery @28days for HCQ (53.6% HCQ, 34% control), p=0.009 (0.06 in the paper refers to the 5 combined recovery/death/ICU values). No significant difference in ventilat.. | ||||
| 8/13 | Late | Roomi et al., J. Medical Internet Research, doi:10.2196/21758 (Peer Reviewed) | death, ↑37.7%, p=0.54 | Efficacy of hydroxychloroquine and tocilizumab in patients with COVID-19: A single-center retrospective chart review |
| Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication. | ||||
| 8/11 | Early | Bakhshaliyev et al., J. Electrocardiology, doi:10.1016/j.jelectrocard.2020.08.008 (Peer Reviewed) (not included in the study count) | safety analysis | The effect of 5-day course of hydroxychloroquine and azithromycin combination on QT interval in non-ICU COVID19(+) patient |
| Safety study of 109 patients showing 5 days of HCQ+AZ did not lead to clinically significant QT prolongation or other conduction delays compared to baseline ECG in non-ICU patients. | ||||
| 8/11 | Late | Saleemi et al., medRxiv, doi:10.1101/2020.08.05.20151027 (Preprint) | viral- time, ↑21.0%, p<0.05 | Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin – A real world experience |
| Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidi.. | ||||
| 8/8 | Late | Lopez et al., Int. J. Antimicrob. Agents, doi:/j.ijantimicag.2020.106136 (Peer Reviewed) | Effects of Hydroxychloroquine on Covid-19 in Intensive Care Unit Patients: Preliminary Results | |
| Small retrospective study of 29 ICU patients comparing those with HCQ plasma concentration within target to those with a concentration below the target value, with no significant differences found. Mortality in the on-target group was 0% .. | ||||
| 8/6 | Review | McCullough et al., The American Journal of Medicine, doi:10.1016/j.amjmed.2020.07.003 (Review) (Peer Reviewed) (not included in the study count) | review | Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection |
| Review of pathophysiological principles related to early outpatient treatment and therapeutic approaches including reduction of reinoculation, combination antiviral therapy, immunomodulation, antiplatelet/antithrombotic therapy, and admin.. | ||||
| 8/6 | PEP, Early, Late | Watanabe et al., Open Letter (Letter) (meta analysis – not included in study count) | meta-analysis | Concerns regarding the misinterpretation of statistical hypothesis testing in clinical trials for COVID-19 |
| Open letter signed by 38 professors and doctors regarding misinterpretation of statistics in HCQ RCTs. Authors note [1] that data from RCTs for early treatment in outpatients to date actually show favorable effects, especially in high-ri.. | ||||
| 8/5 | PrEP | Singer et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218500 (Letter) | cases, ↑9.0%, p=0.62 | Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis |
| Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity informat.. | ||||
| 8/5 | Late | Kalligeros et al., Journal of Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.07.018 (Peer Reviewed) | death, ↑67.0%, p=0.57 | Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study |
| Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely. | ||||
| 8/4 | Late | Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint) | progression, ↓5.0%, p=1.00 | Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial |
| Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ .. | ||||
| 8/3 | Late | Berenguer et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.07.024 (Peer Reviewed) | death, ↓61.9%, p<0.0001 | Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain |
| Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix). | ||||
| 8/3 | Late | Yu et al., Science China Life Sciences, 2020 Aug 3, doi:10.1007/s11427-020-1782-1 (Letter) | progression, ↓82.5%, p=0.05 | Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs |
| Retrospective 2,882 patients in China, median age 62, 278 receiving HCQ, median 10 days post hospitalization, showing that HCQ treatment can reduce systemic inflammation and inhibit the cytokine storm, thus protecting multiple organs from.. | ||||
| 8/2 | Late | Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 (Peer Reviewed) | int./hosp., ↓55.0%, p=0.04 | Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time |
| Retrospective of 132 hospitalized patients. HCQ+AZ(52)/AZ(28) significantly reduced death/ICU, HR=0.45, p=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay from admiss.. | ||||
| 8/2 | In Vitro | Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count) | in vitro | A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity |
| In vitro study presenting a new theory on SARS-CoV-2 infection and why HCQ/CQ provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and treatment delay, and confirms the importance .. | ||||
| 7/31 | Mazzitelli et al., Travel Medicine and Infectious Disease, 37, doi:10.1016/j.tmaid.2020.101826 (Letter) (not included in the study count) | Apparent inefficacy of hydroxychloroquine combined with azithromycin on SARS-CoV-2 clearance in an incident cohort of geriatric patients with COVID-19 | ||
| Report on HCQ+AZ use in 41 elderly high-risk patients. 29 of 30 patients with treatment >= 5 days survived. Only 10% were PCR negative after one week, however the Ct value is not specified. | ||||
| 7/29 | Late | D’Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter) | death, ↓34.0%, p=0.12 | 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 plasma CRP. IPW censori.. | ||||
| 7/28 | Late | BaŞaran et al., Turk. J. Med. Sci., doi:10.3906/sag-2006-173 (Peer Reviewed) | Outcome of Non-Critical COVID-19 Patients with Early Hospitalization and Early Antiviral Treatment Outside the ICU | |
| Observational study of 174 hospitalized patients in Turkey, median age 45.4, 23 treated with HCQ, 113 with HCQ+AZ, and 32 with regimens including favipiravir. 75% reduction in the median time to clinical improvement for HCQ+AZ vs. FAV, RR.. | ||||
| 7/26 | PEP | Mitjà et al., NEJM, doi:10.1056/NEJMoa2021801 (preprint 7/26) (Peer Reviewed) | death, ↓32.0%, p=0.58 | 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 | PrEP | Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint) | cases, ↓51.0%, p=0.02 | 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 was important in this stu.. | ||||
| 7/23 | Late | Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa2019014 (Peer Reviewed) | death, ↓16.0%, p=0.77 | 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 | Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count) | in vitro | 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 supplementary data at this time so.. | ||||
| 7/22 | Late | Rivera et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0941 (Peer Reviewed) | death, ↑2.4%, p=0.90 | Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study |
| Retrospective cancer patients, showing adjusted OR 1.03 [0.62-1.73] for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indicatio.. | ||||
| 7/22 | Late | Kelly et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.14482 (Peer Reviewed) | death, ↑143.0%, p=0.03 | Clinical outcomes and adverse events in patients hospitalised with COVID‐19, treated with off‐label hydroxychloroquine and azithromycin |
| Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication – authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounde.. | ||||
| 7/21 | Late | Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960 (Preprint) | death, ↓17.0%, p<0.0001 | 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 effect. | ||||
| 7/20 | PrEP | Desbois et al., Research Square, doi:10.21203/rs.3.rs-41653/v1 (Preprint) | Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis | |
| Retrospective 199 sarcoidosis patients showing RR 0.83, p=1.0. | ||||
| 7/20 | Early | Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis – not included in study count) | meta-analysis | 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 | PEP | Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis – not included in study count) | meta-analysis | 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 limitations of the study. Treatm.. | ||||
| 7/19 | Late | McGrail et al., medRxiv, doi:10.1101/2020.07.17.20156521 (Preprint) | death, ↑70.0%, p=0.69 | COVID-19 Case Series at UnityPoint Health St. Luke’s Hospital in Cedar Rapids, IA |
| HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the tre.. | ||||
| 7/17 | Late | Lyngbakken et al., Nature Communications, doi:10.1038/s41467-020-19056-6 (Peer Reviewed) | death, ↓3.7%, p=1.00 | A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics |
| Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HCQ was 0.24 [0.03-0.46] RNA copies/mL/24h, and 0.14 [-0.10-0.37] for the control group (71% faster with HCQ but not statistically signi.. | ||||
| 7/16 | Early | Hong et al., Infect. Chemother., 2020, doi:10.3947/ic.2020.52.e43 (Peer Reviewed) | viral+, ↓64.9%, p=0.001 | Early Hydroxychloroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication |
| HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administrat.. | ||||
| 7/16 | Early | Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed) | hosp., ↓51.7%, p=0.19 | 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%, p=0.17. There was one hospitalized control de.. | ||||
| 7/16 | Early | Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed) | hosp., ↓25.0%, p=0.64 | 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.. | ||||
| 7/15 | Late | Gupta et al., JAMA Intern. Med., doi:10.1001/jamainternmed.2020.3596 (Peer Reviewed) | death, ↑6.0%, p=0.41 | Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US |
| Analysis of 2215 intensive care unit patients showing no significant differences with this very late stage use of HCQ. HCQ+AZ mortality relative risk RR 0.96, p=0.53, HCQ and HCQ+AZ combined RR 1.06, p=0.409. | ||||
| 7/14 | Late | Trullàs et al., Research Square, doi:10.21203/rs.3.rs-39421/v1 (Preprint) | death, ↓35.6%, p=0.12 | High in-hospital mortality due to COVID-19 in a community hospital in Spain: a prospective observational study |
| Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ. | ||||
| 7/14 | Early | Chowdhury et al., Research Square, doi:10.21203/rs.3.rs-38896/v1 (Preprint) | A Randomized Trial of Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients | |
| Small 116 patient RCT comparing Ivermectin-Doxycycline and HCQ+AZ, not showing a significant difference in time to PCR negative or symptom resolution. Time to symptomatic recovery was 5.93 days for Ivermectin-Doxycycline vs. 6.99 days for.. | ||||
| 7/11 | Late | Lecronier et al., Critical Care, 24:418, 2020, doi:10.1186/s13054-020-03117-9 (Peer Reviewed) | death, ↓42.0%, p=0.24 | Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis |
| Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences.. | ||||
| 7/10 | Late | Cravedi et al., American Journal of Transplantation, doi:10.1111/ajt.16185 (Peer Reviewed) | death, ↑53.0%, p=0.17 | COVID‐19 and kidney transplantation: Results from the TANGO International Transplant Consortium |
| Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, p = 0.17. Subject to confounding by indication. | ||||
| 7/10 | Late | Chen et al., PLOS ONE, doi:10.1371/journal.pone.0242763 (Peer Reviewed) | viral+, ↓24.0%, p=0.71 | A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19) |
| 2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76.. | ||||
| 7/9 | Late | Rivera-Izquierdo et al., Medicina Clínica, doi:10.1016/j.medcli.2020.06.025 (Peer Reviewed) | death, ↓19.0%, p=0.75 | Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad |
| Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazard ratio aHR 0.81 [0.24-2.76]. | ||||
| 7/9 | Early, Late | Raoult et al., Preprint (Preprint) (meta analysis – not included in study count) | meta-analysis | 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. | ||||
| 7/8 | N/A | Marzolini et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01177-20 (Peer Reviewed) (not included in the study count) | dosing study | Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations |
| Study of Lopinivar and HCQ plasma concentrations and CRP levels in late stage (treatment initiation median 8 days from onset) COVID-19 patients. The median HCQ plasma concentration was 171 ng/ml, which authors suggest indicates that HCQ l.. | ||||
| 7/8 | N/A | Li et al., Cell Death & Disease volume 11, doi:10.1038/s41419-020-2721-8 (Review) (Peer Reviewed) (not included in the study count) | review | Is hydroxychloroquine beneficial for COVID-19 patients? |
| Review of the anti-inflammatory, antiviral, and protective vascular effects of CQ and HCQ, noting that HCQ may be preferable for COVID-19 due to fewer side effects. | ||||
| 7/7 | Review | Goldstein, L., Preprint, July 7, 2020 (Review) (Preprint) (not included in the study count) | review | Hydroxychloroquine-based COVID-19 Treatment, A Systematic Review of Clinical Evidence and Expert Opinion from Physicians’ Surveys |
| 85% of globally surveyed physicians recognized HCQ as at least partially effective in treating COVID-19, according to Sermo W3. More than half of the surveyed US physicians would take the drug or give it to family members early or even be.. | ||||
| 7/7 | Late | An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint) | viral+, ↓3.0%, p=0.92 | 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. « It is notable th.. | ||||
| 7/3 | PrEP | Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7 (Peer Reviewed) | cases, ↓91.0%, p=0.04 | 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 erythematosus, infection in othe.. | ||||
| 7/1 | Late | Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed) | death, ↓51.3%, p=0.009 | 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 retrospective. Before propensity matching the HCQ group average age is 5 years younger and the percenta.. | ||||
| 7/1 | N/A | Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count) | safety analysis | 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 | Late | Martinez-Lopez et al., Blood Cancer Journal, doi:10.1038/s41408-020-00372-5 (Peer Reviewed) | death, ↓33.0%, p=0.20 | Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality |
| Retrospective 167 multiple myeloma patients in Spain. | ||||
| 6/30 | Late | Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z (Peer Reviewed) | death, ↓47.0%, p<0.0001 | 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. | ||||
| 6/30 | Late | Komissarov et al., medRxiv, doi:10.1101/2020.06.30.20143289 (Preprint) | viral load, ↑25.0%, p=0.45 | Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19 |
| Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with sign.. | ||||
| 6/29 | Late | Sosa-García et al., Cir Cir. 2020, 88:5, 569-575, doi:10.24875/CIRU.20000675 (Peer Reviewed) | death, ↑10.5%, p=1.00 | Experience in the management of severe COVID-19 patients in an intensive care unit |
| Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, p = 1.0. | ||||
| 6/29 | PrEP | Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed) | cases, ↓47.1%, p<0.0001 | 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). The actual benefit is likely to be larger becasue research shows that the risk of COVID-19 for systemic autoimmune disease patients is much highe.. | ||||
| 6/29 | N/A | Mfeukeu-Kuate et al. (Preprint) (not included in the study count) | safety analysis | 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 | PrEP | Gendebien et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218244 (Letter) | cases, ↓3.9%, p=0.93 | Systematic analysis of COVID-19 infection and symptoms in a systemic lupus erythematosus population: correlation with disease characteristics, hydroxychloroquine use and immunosuppressive treatments |
| Small study of 152 SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reported for.. | ||||
| 6/25 | Early | Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed) | death, ↓59.0%, p=0.05 | 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. | ||||
| 6/23 | Late | Bousquet et al., Aging, 12:12, 11306-11313, doi:10.18632/aging.103583 (Peer Reviewed) | death, ↓42.8%, p=0.15 | ADL-dependency, D-Dimers, LDH and absence of anticoagulation are independently associated with one-month mortality in older inpatients with Covid-19 |
| Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, p = 0.15. | ||||
| 6/22 | Late | Fontana et al., Clinical Kidney Journal, 13:3, 334–339, doi:10.1093/ckj/sfaa084 (Peer Reviewed) | death, ↓50.0%, p=0.53 | SARS-CoV-2 infection in dialysis patients in northern Italy: a single-centre experience |
| Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, p = 0.53. | ||||
| 6/22 | Early | Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint) | viral- time, ↓72.0%, p=0.01 | 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. | ||||
| 6/21 | Late | Faíco-Filho et al., Braz J Microbiol, doi:10.1007/s42770-020-00395-x (preprint 6/21) (Peer Reviewed) | viral rate, ↓80.8%, p=0.40 | No benefit of hydroxychloroquine on SARS-CoV-2 viral load reduction in non-critical hospitalized patients with COVID-19 |
| Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results show faster recovery wi.. | ||||
| 6/19 | PrEP | SMSH Sawai Man Singh Hospital, India (News) (not included in the study count) | news | 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 | Late | NIH, study not available yet (News) (not included in the study count) | news | NIH halts clinical trial of hydroxychloroquine |
| NIH halts late stage trial reporting no harm and no benefit. 470 patients. | ||||
| 6/19 | Late | Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint) | death, ↑5.0%, p=0.74 | 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 patients are still in hospital at 28 days. Oth.. | ||||
| 6/19 | N/A | Kaptein et al., bioRxiv, doi:10.1101/2020.06.19.159053 (Peer Reviewed) (not included in the study count) | animal study | Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacks activity |
| Animal study with Syrian hamsters, showing treatment of SARS-CoV-2-infected hamsters with favipiravir or HCQ (with and without AZ). Treatment with HCQ alone resulted in a very modest reduction of 0.3 log10 viral RNA copies/mg lung, and no.. | ||||
| 6/18 | Late | Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed) | death, ↓11.0%, p=0.88 | 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 | Early | Capucci et al., J. Cardiovasc. Med. 21, 922–923, doi:10.2459/JCM.0000000000001061 (Peer Reviewed) | Low hospitalization rate without severe arrhythmias: a prospective survey on 350 patients early home treated with hydroxychloroquine during COVID-19 pandemic | |
| Prospective analysis of early treatment of 350 patients in Italy (without waiting for PCR results), showing low hospitalization rates and no serious adverse events. From 274 patients treated with HCQ, 16 required hospitalization (5.8%). .. | ||||
| 6/17 | 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 | Late | Luo et al., Annals of Oncology, 31:10, 1386-1396, doi:10.1016/j.annonc.2020.06.007 (Peer Reviewed) | death, ↑2.2%, p=0.99 | COVID-19 in patients with lung cancer |
| Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, p = 0.99. | ||||
| 6/16 | Late | Kim et al., Korean J Intern Med, doi:10.3904/kjim.2020.224 (Peer Reviewed) | Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019 | |
| Small retrospective study of hospitalized patients with 31 lopinavir-ritonavir and 34 HCQ patients, HCQ 400mg once per day, finding no significant difference in clinical response, but more rapid viral clearance with lopinavir-ritonavir. | ||||
| 6/16 | PrEP | WHIP COVID-19 (News) (not included in the study count) | news | 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 see [1]. | ||||
| 6/16 | PrEP | Huang et al., Annals of the Rheumatic Diseases 2020:79, 1163-1169, doi:10.1136/annrheumdis-2020-217425 (Peer Reviewed) | hosp., ↓80.0%, p<0.001 | Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study |
| Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%–10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization. | ||||
| 6/12 | Theory | Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count) | theory | 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 | Late | Giacomelli et al., Journal of Medical Virology, doi:10.1002/jmv.26407 (preprint 6/12) (Peer Reviewed) | 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 | Late | Wang et al., medRxiv, doi:10.1101/2020.06.11.20128926 (Peer Reviewed) | death, ↓5.8%, p=0.63 | Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System |
| Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, p = 0.82, and HCQ+AZ OR 0.94, p = 0.63 | ||||
| 6/10 | 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 | Early | 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 median death for the same .. | ||||
| 6/9 | PrEP | Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint) | cases, ↓80.7%, p=0.001 | 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 | Review | Roussel et al., New Microbes and New Infections, Volume 38, doi:10.1016/j.nmni.2020.100710 (Review) (Peer Reviewed) (not included in the study count) | review | Influence of conflicts of interest on public positions in the COVID-19 era, the case of Gilead Sciences |
| Shows a correlation (Spearman test, p = 0.017) between the amount received from Gilead Sciences and public opposition to the use of HCQ in France. | ||||
| 6/6 | Early, Late | Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer Reviewed) (meta analysis – not included in study count) | meta-analysis | 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 | Late | RECOVERY Collaborative Group, NEJM, doi:10.1056/NEJMoa2022926 (press release 6/5) (Preprint) | death, ↑9.0%, p=0.15 | Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial |
| RECOVERY trial finds no significant benefit for very late stage very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) [1, 2]. The overall dosage used is only 23% less than the high dosage tha.. | ||||
| 6/3 | PEP | Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed) | cases, ↓17.0%, p=0.35 | 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. For.. | ||||
| 6/1 | N/A | Al-Kofahi et al., Clin. Pharmacol. Ther., Jun 1, 2020, doi:10.1002/cpt.1874 (Peer Reviewed) (not included in the study count) | dosing study | Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness |
| Analysis of HCQ dosing regimens, recommending: PrEP: 800mg loading dose followed by 400mg 2 or 3 times weekly to maintain weekly troughs above EC50 in >50% of patients at steady-state. PEP: 800mg loading dose followed in 6 hours by 600m.. | ||||
| 5/31 | Early | Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed) | death, ↓61.4%, p=1.00 | 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 patients. | ||||
| 5/28 | 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 | PrEP | Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed) | cases, ↓66.8%, p<0.001 | 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 | Late | Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed) | viral- time, ↓67.0%, p<0.0001 | 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 | Late | Goldman et al., NEJM, doi:10.1056/NEJMoa2015301 (Peer Reviewed) | death, ↓22.3%, p=0.46 | Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 |
| Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, p = 0.46. | ||||
| 5/28 | Late | Kuderer et al., Lancet, June 20, 2020, doi:10.1016/S0140-6736(20)31187-9 (preprint 5/28) (Peer Reviewed) | death, ↑134.2%, p<0.0001 | Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study |
| Retrospective 928 cancer patients, showing HCQ OR 1.06 [0.51-2.20]. HCQ+AZ OR 2.93 [1.79-4.79]. The relative risks of different therapies suggest that the results are overly affected by confounding by indication. Authors note: HCQ+AZ migh.. | ||||
| 5/28 | PrEP | Gianfrancesco et al., Annals of the Rheumatic Diseases, 79:7, 859-866, doi:10.1136/annrheumdis-2020-217871 (Peer Reviewed) | hosp., ↓3.3%, p=0.82 | Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry |
| Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 [0.57-1.57], p=0.82 after adjustments. | ||||
| 5/27 | Early | Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis – not included in study count) | meta-analysis | 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 | Late | Ip et al., PLOS ONE, doi:10.1371/journal.pone.0237693 (Peer Reviewed) | death, ↓1.0%, p=0.93 | 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]), HCQ alone (HR, 1.02 .. | ||||
| 5/22 | PEP, PrEP | ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) | advisory | 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 frontline workers. Degree of benefit not quantified. | ||||
| 5/22 | Late | Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed) (not included in the study count) | retracted | 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. | ||||
| 5/19 | Late | Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint) | death, ↓5.0%, p=0.72 | 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 | Late | Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint) | hosp. time, ↓51.0%, p=0.01 | 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 | 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 | PrEP | Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint) | hosp., ↓25.5%, p=1.00 | 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 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. .. | ||||
| 5/15 | Late | Yu et al., Science China Life Sciences, 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed) | death, ↓60.5%, p=0.002 | 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, RR 0.395, p=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL to 5.2 pg/mL (p<0.05) at the end of the treat.. | ||||
| 5/14 | Late | Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed) | death, ↑20.0%, p=0.75 | 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 [1]. None of the 15 patients receiving HCQ+AZ were transferred to intensive care.. | ||||
| 5/13 | Late | Okour et al., Journal of Pharmacokinetics and Pharmacodynamics, May 13, 2020, doi:10.1007/s10928-020-09689-x (Peer Reviewed) | Hydroxychloroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome | |
| Odds of PCR-positive decrease by 53% for each unit increase in HCQ log-concentration. Similarly, the odds decrease by 61%, and by 12% for each day increase, and for azithromycin co-treatment, respectively. Computes the minimum HCQ concent.. | ||||
| 5/12 | PrEP | Cassione et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217717 (Letter) | cases, ↑49.6%, p=0.59 | COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine |
| Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications o.. | ||||
| 5/11 | Late | Shabrawishi et al., medRxix, doi:10.1101/2020.05.08.20095679 (Preprint) | viral+, ↓14.7%, p=0.66 | Negative nasopharyngeal SARS-CoV-2 PCR conversion in response to different therapeutic interventions |
| Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, p = 0.65. The treatment group had significantly more severe illness and significantly .. | ||||
| 5/11 | Late | Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed) | death, ↑35.0%, p=0.31 | 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. [1] point out serious limitations that they say should be corrected on the record: patients receiving HCQ wit.. | ||||
| 5/10 | 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) | death, ↓42.9%, p=0.12 | 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 | Ex Vivo | Grassin-Delyle et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa546 (Peer Reviewed) (Ex Vivo) (not included in the study count) | ex vivo | Chloroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants |
| On human lung parenchymal explants, CQ concentration clinically achievable in the lung (100 µM) inhibited the lipopolysaccharide-induced release of TNF-ɑ (by 76%), IL-6 (by 68%), CCL2 (by 72%), and CCL3 (by 67%). In addition to antiviral .. | ||||
| 5/8 | Late | Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed) | Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients | |
| Retrospective 932 patients. Addition of Zinc to HCQ+AZ reduces mortality / transfer to hospice, ICU admission, and the need for ventilation. Reduction in mortality or transfer to hospice adjusted odds ratio OR 0.56, p = 0.002; increase i.. | ||||
| 5/7 | PrEP | Konig et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217690 (Letter) | hosp., ↓3.0%, p=0.88 | Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19 |
| Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), p=ns. Authors suggest that the dosage use.. | ||||
| 5/7 | 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) | theory | 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 | Late | Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer Reviewed) | int./death, ↑4.0%, p=0.76 | 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 | N/A | Sermo (News) (not included in the study count) | news | 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 | N/A | Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count) | animal study | 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 several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and control monkeys. 58% reduction in lung lesions: the final d.. | ||||
| 5/5 | Late | Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint) | death, ↓55.1%, p=0.002 | 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 were in relatively serious condition. | ||||
| 5/5 | 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 | PrEP | Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed) | cases, ↓8.1%, p=0.88 | 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 were tested. Other r.. | ||||
| 5/5 | PrEP | Mitchell et al., SSRN, doi:10.2139/ssrn.3586954 (Preprint) | death, ↓99.0%, p<0.0001 | Markedly Lower Rates of Coronavirus Infection and Fatality in Malaria-Endemic Regions – A Clue As to Treatment? |
| Analysis of COVID-19 amongst 2.4B people shows a wide counterintuitive disparity between well-developed and less-developed countries, with more affluent countries about one hundred times more likely to be infected and die due to COVID-19… | ||||
| 5/4 | PrEP | Huh et al., medRxiv, doi:10.1101/2020.05.04.20089904 (Preprint) | cases, ↑47.7%, p=0.09 | Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea |
| Database analysis of many drugs and COVID-19 cases, with 23 cases taking HCQ, and 251 control patients not taking HCQ, showing OR 1.07, p=0.77, and in multivariable analysis OR 1.48, p=0.086. Patients taking HCQ are most likely taking it.. | ||||
| 5/2 | Late | Mallat et al., Medicine (Baltimore), doi:10.1097/MD.0000000000023720 (preprint 5/2) (Peer Reviewed) | viral- time, ↑203.0%, p=0.02 | Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study |
| Very small retrospective analysis of 34 patients finding slower binary PCR viral clearance with HCQ. No information on severity for treatment versus control is provided. No deaths, ICU admission, or mechanical ventilation. Binary PCR does.. | ||||
| 5/1 | N/A | Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in the study count) | safety analysis | 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. Median change for HCQ+AZ ΔQTc of 23ms vs. 5.5ms for HCQ. Other factors su.. | ||||
| 5/1 | N/A | Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in the study count) | safety analysis | 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 45% and 55% respectively.. | ||||
| 5/2 | Late | Seydi (News) (not included in the study count) | news | 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 | 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 protective for COVID-19. This paper also include.. | ||||
| 4/27 | Late | Sánchez-Álvarez et al., Nefrología, doi:10.1016/j.nefroe.2020.04.002 (Peer Reviewed) | death, ↓45.9%, p=0.005 | Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN) |
| Analysis of 868 patients on renal replacement therapy. Statistically significant reduction in mortality with HCQ for patients on dialysis (OR 0.47, p=0.005). No statistically significant change was found for transplant patients (the resu.. | ||||
| 4/29 | N/A | Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed) | safety analysis | 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, clinicians seldom need t.. | ||||
| 4/26 | Late | Auld et al., Critical Care Medicine, doi:10.1097/ccm.0000000000004457 (Peer Reviewed) | death, ↑2.8%, p=1.00 | ICU and ventilator mortality among critically ill adults with COVID-19 |
| Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality. | ||||
| 4/25 | 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 | 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 | Early | Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint) | death, ↓67.5%, p=0.15 | COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes |
| Small limited trial with 100 patients concluding that HCQ improved clinical outcome, OR 0.016 [0.002-0.11] in regression analysis. | ||||
| 4/21 | Early | Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint) | death, ↓85.0%, p<0.001 | 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 attempt to account for population age and other .. | ||||
| 4/21 | Late | Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed) | death, ↓11.0%, p=0.74 | Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19 |
| Retrospective 807 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ, or for death with HCQ+AZ, HR 1.83, p=0.009 for HCQ mortality. The preprint notes tha.. | ||||
| 4/17 | 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 | 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) | |
| Comparison of typical CQ dosage with high dosage CQ (600mg CQ twice daily for 10 days), showing higher mortality with high dosage, OR 2.8 [0.9 – 8.5] when controlled by age in multivariate analysis. Increased incidence of prolonged QT an.. | ||||
| 4/15 | Early, Late | Esper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint) | hosp., ↓64.0%, p=0.02 | 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. | ||||
| 4/15 | Theory | Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Peer Reviewed) (Theory) (not included in the study count) | theory | Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic |
| Theory on the effectiveness of HCQ. HCQ has been shown to block the polarization of macrophages to an M1 inflammatory subtype and is predicted to interfere with glycosylation of a number of proteins involved in the humoral immune response.. | ||||
| 4/14 | Late | Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed) | viral+, ↓21.4%, p=0.51 | Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial |
| 150 patients very late stage RCT showing no significant difference. Treatment very late, average 16.6 days after symptom onset. Data favorable to HCQ was deleted in the second version, see analysis [1]. « [HCQ] accelerate[s] the all.. | ||||
| 4/13 | Late | Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Review) (Peer Reviewed) (not included in the study count) | review | 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 | Late | Barbosa et al., Preprint (Preprint) | death, ↑147.0%, p=0.58 | 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 published several months later. | ||||
| 4/11 | 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. 80 patients with relatively mild cases, no control group, and no attempt to analyze confounding factors. | ||||
| 4/10 | Late | Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis – not included in study count) | meta-analysis | 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] ». | ||||
| 4/3 | Theory | Fantini et al., Int J Antimicrob Agents, 55:5, doi:10.1016/j.ijantimicag.2020.105960 (Peer Reviewed) (Theory) (not included in the study count) | theory | Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection |
| In-silico analysis confirming the antiviral properties of CQ, showing a new mechanism of action of CQ, and showing that HCQ is more potent than CQ. | ||||
| 4/1 | Early | Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed) | no recov., ↓91.7%, p=0.02 | 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 | Late | Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint) | pneumonia, ↓57.0%, p=0.04 | 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% of treated patients and.. | ||||
| 3/31 | 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) | in vitro | 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 | 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 | |
| Report on 11 patients treated with HCQ with no control group. Authors suggest there is no evidence of benefit for HCQ based on PCR+ results for 8/10 patients at day 5-6. Binary PCR evaluation with an unknown Ct. Binary PCR does not distin.. | ||||
| 3/26 | Late | Zhong Nanshan (钟南山) (Preprint) | viral+, ↓80.0%, p<0.0001 | Efficacy and safety of chloroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial |
| 197 patients. CQ effective. Day 10 viral RNA negative 91.4% HCQ versus 57.4% control. Median time to negative test 3 days versus 9 days for control. | ||||
| 3/24 | Theory | Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory) (not included in the study count) | 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 safety. (8/23: we corrected the classification.. | ||||
| 3/23 | 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) | theory | 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 | PrEP | ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) | advisory | 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 | Late | Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count) | news | Shanghai Experience of COVID-19 Management |
| Clinical studies of HCQ with 184 cases and 21 hospitals show HCQ is effective. | ||||
| 3/18 | 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) | in vitro | 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 extensively in autoimmune diseases and can significantly decrease the product.. | ||||
| 3/17 | Early | Gautret et al., Int. J. of Antimicrobial Agents, 17 March 2020, doi:10.1016/j.ijantimicag.2020.105949 (Peer Reviewed) | viral+, ↓66.0%, p=0.001 | Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial |
| HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues [1, 2, 3]. Despite the limitations, this early observational.. | ||||
| 3/17 | N/A | Sahraei et al., Int. J. Antimicrobial Agents, April 2020, 55:4, doi:10.1016/j.ijantimicag.2020.105945 (Review) (Peer Reviewed) (not included in the study count) | review | Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine |
| Discussion of mechanisms of action, CQ vs. HCQ, early studies, safety. | ||||
| 3/13 | N/A | Todaro and Rigano (Review) (Preprint) (not included in the study count) | review | 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 | Devaux et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not included in the study count) | theory | 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 | 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 study count) | meta-analysis | 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 | 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 | 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. See also [1, 2]. | ||||
| 3/6 | Late | Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed) | progression, ↓29.0%, p=0.57 | 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 a severe case. Treatment group 4 years older a.. | ||||
| 3/4 | Late | Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Review) (Peer Reviewed) (not included in the study count) | review | 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 | 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 | 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 | Late | Sun, Y., deputy head of the China National Center for Biotechnology Development (News) (not included in the study count) | news | Antimalarial drug confirmed effective on COVID-19 |
| HCQ under clinical trials in >10 hospitals in China and has shown fairly good efficacy. | ||||
| 2/11 | Late | Xia et al., ChiCTR2000029741 (Preprint) | viral+, ↓37.5%, p=0.17 | Efficacy of Chloroquine and Lopinavir/ Ritonavir in mild/general novel coronavirus (CoVID-19) infections: a prospective, open-label, multicenter randomized controlled clinical study |
| Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative co.. | ||||
| 2/4 | 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) | in vitro | 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. | ||||
| 2017 | N/A | Chhonker et al., Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences, 22 Nov 2017, 1072:320-327 doi:10.1016/j.jchromb.2017.11.026 (Peer Reviewed) (not included in the study count) | dosing study | Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies |
| Presents a method for quantification of HCQ in mouse blood and tissues. They show a lung concentration significantly higher than other organs, and about 30 times the blood concentration. | ||||
| 2014 | Animal | Browning, D., Pharmacology of Chloroquine and Hydroxychloroquine, 2014, 35-63, doi:10.1007/978-1-4939-0597-3_2 (Peer Reviewed) (not included in the study count) | animal study | Pharmacology of Chloroquine and Hydroxychloroquine |
| Review of the pharmacology of CQ and HCQ. Some notable points: – HCQ and CQ are equipotent but CQ is more toxic, the therapeutic ratio is higher for HCQ. – Concentrations in different tissues can vary >10x, in particular the concentratio.. | ||||
| 2014 | 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) | in vitro | 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 | Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count) | animal study | 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 | Keyaerts et al., Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the study count) | animal study | 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 survival rate (98.6%) was found when mother mice we.. | ||||
| 2008 | 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) | in vitro | 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 extracellular signal-regulated kinase (ERK). p38 MAPK i.. | ||||
| 2006 | 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) | in vitro | 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 SARS replication. | ||||
| 2005 | 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) | in vitro | 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 treatment use. Describes thr.. | ||||
| 2004 | 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 | 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 inhibition of SARS-CoV in .. | ||||
| 2003 | Theory | Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count) | theory | 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 coronaviruses. Notes that CQ.. | ||||
| 1918 | N/A | Burrows, E., Medical Record, 97:6, 235, Feb 7, 1920 (Peer Reviewed) (not included in the study count) | A confirmatory report upon the abortive action of quinine dihydrochloride | |
| Quinine was found to be effective for the Spanish Flu in 1918. | ||||
| 1890 | N/A | Le Grelot (News) (not included in the study count) | news | Quinine use for the Russian influenze pandemic if 1889-1890 |
| Quinine and antipyrine, a bitherapy for defying death during the Russian influenza pandemic of 1889-1890 (around 40,000 deaths in France at the beginning of 1890). | ||||
| 1889 | N/A | Edwin Wiley Grove (News) (not included in the study count) | news | Laxative Bromo Quinine |
| Quinine has been used for respiratory infections since 1889. Not included in the study count or percentages, just as an inte |
naufrage/sauvetage 