COVID-19 studies:  C19 studies: C19:  IvermectinIVM Vitamin DV.D HC QHC Q Vitamin CV.C ZincZn BHBH FPVFPV FLVFLV PVP-IPI REGNR2 LY-CoVLY RMDRMD
  Meta AnalysisMeta
Global HCQ/CQ studies
March 6, 2021
Database of all HCQ COVID-19 studies. 264 studies, 193 peer reviewed, 215 comparing treatment and control groups. Submit updates/corrections below. HCQ is not effective when used very late with high dosages over a long period (RECOVERY/SOLIDARITY), effectiveness improves with earlier usage and improved dosing. Early treatment consistently shows positive effects. Negative evaluations typically ignore treatment time, often focusing on a subset of late stage studies. In Vitro evidence made some believe that therapeutic levels would not be attained, however that was incorrect, e.g. see [Ruiz].
Restrict:    All    Early    Late    PrEP    PEP
Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis - not included in study count) meta-analysis v81 HCQ is effective for COVID-19 when used early: real-time meta analysis of 215 studies
• HCQ is effective for COVID-19. The probability that an ineffective treatment generated results as positive as the 215 studies to date is estimated to be 1 in 195 quadrillion (p = 0.0000000000000000051). • Early treatment is most succes..
PrEP Pham et al., Rheumatology Advances in Practice, 10.1093/rap/rkab014 (Peer Reviewed) death, ↓19.7%, p=0.77 Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases
Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mention..
Early Amaravadi et al., medRxiv, doi:10.1101/2021.02.22.21252228 (Preprint) no recov., ↓60.0%, p=0.13 Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial
Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm). There was no..
Late Tanriverdi et al., Turkish Journal of Medical Sciences, doi:doi:10.3906/sag-2005-82 (Peer Reviewed) Hydroxychloroquine plus azithromycin and early hospital admission are beneficial in COVID-19 patients: Turkish experience with real-life data
Retrospective 83 hospitalized patients in Turkey confirming that earlier treatment is better, and showing that the addition of AZ to HCQ reduced hospitalization time.
Early Giraud-Gatineau et al., Research Square, (Preprint) The Need for Early Management in Patients With COVID-19
Review of early treatment of COVID-19 at IHU Méditerranée Infection in France, including HCQ+AZ treatment, comparing outcomes to those for all of France. Age-standardized mortality was lower with early treatment for all periods of the epi..
Late Beltran-Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Peer Reviewed) death, ↓62.6%, p=0.27 Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127
PrEP Bae et al., Viruses 2021, doi:10.3390/v13020329 (Peer Reviewed) cases, ↓30.3%, p=0.17 Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea
Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.
Late Lamback et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549 (Peer Reviewed) death, ↓8.9%, p=0.83 Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19
Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became ..
Late Awad et al., American Journal of Health-System Pharmacy, doi:10.1093/ajhp/zxab056 (Peer Reviewed) death, ↑19.1%, p=0.60 Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection
This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, IC..
Late Lora-Tamayo et al., J. Infection, doi:10.1016/j.jinf.2021.02.011 (Peer Reviewed) death, ↓50.5%, p<0.0001 Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study
Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality.
Early, Late Desai et al., J. Clinical Medicine, doi:10.3390/jcm10040686 (Peer Reviewed) The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults
Retrospective 143 COVID-19 hospitalized patients >65yo, showing adjusted OR for antiviral treatment starting within 6 days of 0.44 [0.2-0.9], p = 0.02, compared to treatment started later.
Meta Lounnas e al., Archives of Microbiology & Immunology, doi: (Peer Reviewed) meta-analysis Revisiting a Meta-analysis Shows that Hydroxychloroquine with Azithromycin may be Efficient in Covid-19 patients
Analysis of the Fiolet meta analysis and correction of bias evaluation, showing HCQ RR 0.45 [0.31-0.59], and HCQ+AZ RR 0.34 [0.06-0.61].
Late Purwati et al., Biochemistry Research International, doi:10.1155/2021/6685921 (Peer Reviewed) viral+, ↓66.3%, p<0.0001 A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections
RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 ap..
PrEP Fitzgerald et al., medRxiv, doi:10.1101/2021.02.03.21251069 (Preprint) cases, ↓8.5%, p=0.52 Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases
Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity ..
Late Hernandez-Cardenas et al., medRxiv, doi:10.1101/2021.02.01.21250371 (Preprint) death, ↓12.0%, p=0.66 Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial
Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no signficant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03]. Table 4 shows differen..
Late Ouedraogo et al., Revue des Maladies Respiratoires, doi:10.1016/j.rmr.2021.02.001 (Peer Reviewed) death, ↓33.0%, p=0.38 Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso
Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (p=0.001) and mortality (p=0.38) with HCQ.
Review Alexander et al., medRxiv, doi:10.1101/2021.01.28.21250706 (Review) (Preprint) (not included in the study count) review Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents
Review of studies on treatment of COVID-19 for nursing home residents, concluding that there is a large >60% mortality risk reduction associated with multidrug treatment using two or more intracellular anti-infectives (HCQ and either AZM ..
Late Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306 (Peer Reviewed) death, ↓18.4%, p=0.64 COVID-19: A Single-Center ICU Experience of the First Wave in the Philippines
Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.
Late Roig et al., Revista Espanola de Quimioterapia, doi:10.37201/req/130.2020 (Peer Reviewed) death, ↓15.6%, p=0.76 Clinical and pharmacological data in COVID-19 hospitalized nonagenarian patients
Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.
PrEP Trefond et al., SSRM, doi:10.2139/ssrn.3754815 (Preprint) death, ↑16.6%, p=0.80 Impact of hydroxychloroquine used as DMARD on SARS CoV-2 tests and COVID-19 evolution
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extre..
Safety Eftekhar et al., medRxiv, doi:10.1101/2021.01.16.21249941 (Preprint) safety analysis Hydroxychloroquine and azithromycin: As a double edge sword for COVID-19?
Retrospective 172 hospitalized patients, 83% treated and HCQ+AZ and 17% with HCQ, not finding a significant difference in QTc prolongation, but recommending careful monitoring for the use of HCQ+AZ; especially in males, patients with high..
Early Dabbous et al., Archives of Virology, doi:10.1007/s00705-021-04956-9 (Peer Reviewed) Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study
RCT with 44 favipiravir patients and 48 CQ patients, showing non-statistically significant lower mortality, ventilation, and hospitalization time with favipiravir.
In Silico Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979 (Peer Reviewed) Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19
Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 Mpro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds.
Early Zelenko, Z., Preprint (Preprint) Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing
Report on the use of nebulized HCQ showing much more rapid improvement compared to tablets, with 95% of patients experiencing improved breathing within 1 hour. Author notes that the effectiveness of HCQ is time and dose dependent, with a ..
PrEP Cifuentes et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2020.10.012 (Peer Reviewed) Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine
Retrospective 3,817 chronic HCQ patients showing 4.4% COVID-19 positive rate, 1.3% severe. There is no comparison with a control group. Authors note that there was a 3.6% incidence among 2,032,863 patients in one of the regions (Castilla ..
Late Li et al., Science China Life Sciences, doi:10.1007/s11427-020-1871-4 (Peer Reviewed) no discharge, ↓50.0%, p=0.08 Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19
Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note..
Late Li et al., Research Square, doi:10.21203/ (Preprint) viral- time, ↑40.0%, p=0.06 Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis
Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death ho..
PrEP Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098 (Peer Reviewed) death, ↓25.1%, p=0.77 Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis
Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically sign..
Late Yegerov et al., medRxiv, doi:10.1101/2021.01.06.20249091 (Peer Reviewed) death, ↓95.3%, p=1.00 Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort Study
Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant.
In Silico Baildya et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891 (Peer Reviewed) (not included in the study count) Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies
Molecular docking study of 16 drugs showing CQ had the highest binding affinity with ACE2, and molecular dynamics study of the docked CQ-ACE2 structure. Authors conclude that CQ binds reasonably strongly with ACE2 and the stable ACE2-CQ m..
Theory Noureddine et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334 (Peer Reviewed) (Theory) theory Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations
In silico analysis of hydroxychloroquine and hydroxychloroquine sulfate predicting that hydroxychloroquine sulfate is more stable and effective for COVID-19.
Safety Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106236 (Peer Reviewed) (not included in the study count) safety analysis Safety profile of hydroxychloroquine and azithromycin combined treatment in COVID-19 patients
Report on the safety of HCQ+AZ with 3,737 COVID-19 patients. 138 had contraindications and treatment was discontinued in 12 cases due to QTc prolongation. There were no cases of torsade de pointe or sudden death.
Late Sarfaraz et al., medRxiv, doi:10.1101/2020.12.28.20248920 (Preprint) death, ↑45.0%, p=0.07 Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan
Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely.
Late Lotfy et al., Turk. Thorac. J., doi:10.5152/TurkThoracJ.2021.20180 (Peer Reviewed) death, ↑24.8%, p=0.76 Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational Study
Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confou..
Late Sands et al., International Journal of Infectious Diseases, doi:/10.1016/j.ijid.2020.12.060 (Peer Reviewed) death, ↑69.9%, p=0.01 No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19
Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in t..
Review Matada et al., Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2020.115973 (Review) (Peer Reviewed) review A comprehensive review on the biological interest of quinoline and its derivatives
Review of quinolone and derivatives, natural and drug sources, and biological activity.
Late Psevdos et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.721 (Peer Reviewed) death, ↑63.5%, p=0.52 Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York
Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was su..
Late Texeira et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.560 (Peer Reviewed) death, ↑79.3%, p=0.10 Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast
Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was s..
Late Vernaz et al., Swiss Medical Weekly, doi:10.4414/smw.2020.20446 (Peer Reviewed) death, ↓15.3%, p=0.71 Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs
Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity wi..
Review McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) (not included in the study count) review Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may ..
Early Procter 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..
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.
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 ..
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).
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.
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].
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..
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..
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].
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..
PrEP Gönenli et al., Research Square, doi:0.21203/ (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 ..
Late Sofian et al., Wiener Medizinische Wochenschrift, doi:10.1007/s10354-020-00793-8 (Peer Reviewed) SARS-CoV‑2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms
Report on a series of 10 patients experiencing prolonged COVID-19 symptoms that were given HCQ 250mg bid for 5 days, with resolution of symptoms in all cases, and patients reporting they felt much better 2 days after treatment initiation.
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.
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.
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.
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..
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.
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 ..
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.
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.
Late Johnson et al., SSRN (Preprint) hosp., ↓29.9%, p=0.73 Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial
Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a..
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..
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].
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..
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.
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.
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.
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..
Late Capsoni et al., Research Square, doi:10.21203/ (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.
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..
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 ventilation was used with 4 patients..
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..
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...
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.
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.
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.
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.
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 ..
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..
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..
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..
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)
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.
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..
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..
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..
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.
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.
Late Rodriguez et al., Medicina Intensiva, doi:10.1016/j.medine.2020.05.005 (Peer Reviewed) death, ↓59.0%, p=0.23 Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic
Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, p=0.23.
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..
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..
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.
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.
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..
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..
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.
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.
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.
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..
PrEP Behera et al., PLOS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) cases, ↓27.9%, p=0.29 Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
Retrospective matched case-control 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, ..
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).
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.
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.
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.
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..
Late Frontera et al., Research Square, doi:10.21203/ (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.
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).
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.
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.
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).
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..
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..
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.
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..
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..
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)...
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..
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.
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 ..
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.
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..
Late Ader et al., medRxiv, doi:10.1101/2021.01.08.20248149 (news 10/6) (Preprint) death, ↓6.4%, p=1.00 Antiviral drugs in hospitalized patients with COVID-19 - the DisCoVeRy trial
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline in the HCQ group.
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.
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..
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..
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.
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..
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...
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..
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..
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..
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..
Late Dabbous et al., Research Square, doi:10.21203/ (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.
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.
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..
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%).
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,..
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.
PrEP Gentry et al., Lancet Rheumatology, doi:10.1016/S2665-9913(20)30305-2 (Peer Reviewed) death, ↓91.3%, 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 of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 propensity matched control patients (not statistically significant). The average age of HCQ patients is slight..
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, ..
PrEP Grau-Pujol et al., Research Square, doi:10.21203/ (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. The abstract appears to have a typo and do..
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.
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..
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..
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.
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.
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 ..
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.
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..
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 ..
PrEP Rentsch et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30378-7 (preprint 9/9, (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 ..
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...
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..
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..
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..
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.
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..
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..
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.
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..
Late Albani et al., J, Clinical Medicine, doi:10.3390/jcm9092800 (Peer Reviewed) death, ↓18.4%, p=0.05 Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19
Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ.
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..
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 ..
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 ..
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 ..
Early Ip et al., BMC Infectious Diseases, doi:10.1186/s12879-021-05773-w (preprint 8/25) (Peer Reviewed) death, ↓54.5%, p=0.43 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..
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].
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..
Late Pasquini et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa321 (Peer Reviewed) death, ↓16.4%, p=0.34 Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU
Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment.
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..
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..
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..
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..
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.
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..
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..
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..
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.
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.
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..
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% ..
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..
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..
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..
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.
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 ..
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).
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..
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..
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 ..
Early Bernabeu-Wittel et al., J. Gerontol. A Biol. Sci. Med. Sci., doi:10.1093/gerona/glaa192 (Peer Reviewed) death, ↓59.0%, p=0.03 Effectiveness of a On-Site Medicalization Program for Nursing Homes with COVID-19 Outbreaks
Retrospective 272 nursing home residents showing significantly improved survival after establishing a treatment program including HCQ with or without lopinavir/ritonavir and with the addition of adjuvant and antimicrobial treatments depen..
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.
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..
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..
PEP Mitjà et al., NEJM, doi:10.1056/NEJMoa2021801 (preprint 7/26) (Peer Reviewed) death, ↓51.7%, p=0.27 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 - ..
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..
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..
In Vitro Ou et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009212 (preprint 7/22) (Peer Reviewed) (In Vitro) in vitro Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2
In Vitro analysis showing that HCQ efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of HCQ and a TMPRSS2 inhibitor prevents SARS-CoV-2 infection more potently than either drug alone.
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..
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..
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..
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.
PrEP Desbois et al., Research Square, doi:10.21203/ (Preprint) cases, ↓16.9%, p=1.00 Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis
Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, p=1.0.
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.
PEP Watanabe, M.,, 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..
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..
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..
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..
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..
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..
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.
N/A Kavanagh et al., Med. Hypotheses, doi:10.1016/j.mehy.2020.110110 (Peer Reviewed) dosing study Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19
Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the..
Late Trullàs et al., Research Square, doi:10.21203/ (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.
Early Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 (Peer Reviewed) 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..
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..
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.
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..
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].
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.
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..
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.
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..
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..
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..
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..
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..
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.
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.
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..
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.
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..
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.
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..
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.
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.
Safety Isaksen et al., medRxiv, doi:10.1101/2020.06.19.20135475 (Preprint) safety analysis Chloroquine, but not hydroxychlorquine, prolongs the QT interval in a primary care population
Safety analysis in patients without COVID-19, finding a small increase in QTc associated with use of CQ, but not HCQ. Authors also study mortality (n=3,368), with HCQ hazard ratio 0.67 [0.43-1.05].
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.
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.
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..
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.
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.
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..
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..
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.
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%). ..
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.
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.
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.
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].
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.
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.
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