COVID-19 studies for: C19 studies:  HC QHC Q Vitamin DVitamin D IvermectinIVM LY-CoVLY REGN-COV2REGN RemdesivirRMD
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@CovidAnalysis
Global HC Q/C Q studies
October 21, 2020
@CovidAnalysis
Early treatmentEarly
↓64%
146 HCQ studies
86 peer reviewed

Early treatment of COVID-19 with HCQ shows high efficacy
100% of early treatment studies are positive. 64% is the median improvement.
Late treatmentLate
↓25%
62% of late treatment studies are positive.
 
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Restrict:    All    Early    Late    PrEP    PEP
10/21
Inconc.
INCONC.
 Late
Debee et al., medRxiv, doi:10.1101/2020.10.19.20214940 (Preprint)		 death, ↓46.0%, p=0.21 A placebo-controlled double blind trial of hydroxych loroquine in mild-to-moderate COVID-19
Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality (~ potential lives saved with global HC Q). mortality at 28 days relative risk RR 0...
10/20
Meta
META
 Early, Late
IHU Marseille (Preprint) (meta analysis - not included in study count)		 Meta-analysis on ch loroquine derivatives and COVID-19 mortality
Updated meta analysis of 41 studies showing C Q/HC Q OR 0.57, p<0.0001 from clinical studies (~ potential lives saved with global HC ..
10/20
Negative
NEGATIVE
 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. No results are provided for HC Q for progression to ARDS.
10/17
Safety
SAFETY
 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)		 Hydroxych loroquine Safety Outcome within Approved Therapeutic Protocol for COVID-19 Outpatients in Saudi Arabia
Safety study of 2,733 patients in Saudi Arabia showing HC Q in mild to moderate cases in an outpatient setting, within the protocol recommendation and inclusion/exclusion criteria, is safe, highly tolerable, and has ..
10/15
Positive
POSITIVE
 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 HC Q 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..
10/15
Negative
NEGATIVE
 Late
SOLIDARITY Trial Consortium, medRxiv, doi:10.1101/2020.10.15.20209817 (Preprint)		 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) HC Q patients, mortality relative risk RR 1.19 [0.89-1.59], p=0.23. HC Q dosage very high as in RECOVERY, 1...
10/12
Inconc.
INCONC.
 Late
Annie et al., Pharmacotherapy, doi:10.1002/phar.2467 (Peer Reviewed)		 death, ↓4.3%, p=0.83 Hydroxych loroquine 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 HC Q, and 1.24 [0.70-2.22] for HC Q+AZ. Confounding by indication likely.
10/11
Inconc.
INCONC.
 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 HC Q was given to 99.2% of patients and the incidence of critical illness was lower than most studies. Authors note "whether HC Q adminis..
10/8
Positive
POSITIVE
 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 HC Q with 605 HC Q patients, unadjusted 30 day mortality relative risk RR ..
10/8
Negative
NEGATIVE
 Late
Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint)		 death, ↑84.0%, p=0.02 Real-World Effectiveness of hydroxych loroquine, 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 HC Q/C Q+AZ, 200 received HC Q/C Q, 203 received ivermectin, 1600 received AZ, 358 receive..
10/6
Inconc.
INCONC.
 Late
DISCOVERY Trial (Preprint)		 death, ↓31.1%, p=0.35 DISCOVERY Trial Preliminary Results
Early terminated DISCOVERY trial shows improvements in mortality and day 29 7-point ordinal scale with HC Q. Mortality improvements are seen at both day 15 and day 29 in the graph. Details are not given but based on..
10/5
Meta
META
 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)		 Hydroxych loroquine is effective, and consistently so used early, for Covid-19: A systematic review
Meta analysis of 43 studies: "HC Q 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..
10/2
Positive
POSITIVE
 Late
Nachega et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-1240 (Peer Reviewed)		 death, ↓27.6%, p=0.17 Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo
Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65% to 84%. Mortality cox regression adjusted hazard ratio aHR 0.26, p < 0.001 Risk of no improvement adj..
10/1
Positive
POSITIVE
 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 Hydroxych loroquine 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 HC Q, but not statistically significant with the small sample sizes.
10/1
Meta
META
 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 hydroxych loroquine 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 HC Q is likely to be higher for several reasons: the trials did not ..
9/30
Positive
POSITIVE
 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 Hydroxych loroquine 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 HC Q, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative r..
9/30
Positive
POSITIVE
 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 hydroxych loroquine and hospital mortality in COVID-19 patients
2075 hospital patients in Spain showing HC Q reduces mortality 52% (~ potential lives saved with global HC Q), odds ratio OR 0.39, p<0.001, after adjustmen..
9/30
Meta
META
 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 Hydroxych loroquine 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 HC Q, RR 0.76, p=0.025. No serious adverse cardiac events were reported. 5,577 patients. The Boulware stu..
9/30
Inconc.
INCONC.
 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 Hydroxych loroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
Very small early-terminated underpowered PrEP RCT with 64/61 HC Q/control patients and only 8 infections, HC Q infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 - 3.64]. There was no hospi..
9/29
Positive
POSITIVE
 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
Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HC Q treatment starting on the first day of admission. Weighted propensity ..
9/29
Inconc.
INCONC.
 Late
Dabbous et al., Research Square, doi:10.21203/rs.3.rs-83677/v1 (Preprint)		 A Randomized Controlled Study Of Favipiravir Vs Hydroxych loroquine In COVID-19 Management: What Have We Learned So Far?
Small RCT comparing HC Q and favipiravir, with 50 patients in each arm, finding that 55.1% of HC Q patients were PCR negative on day 7 compared to 48% for favipiravir, p = 0.7. There was no comp..
9/28
Meta
META
 PEP
Luco, J., ResearchGate, doi:10.13140/RG.2.2.24214.98880 (Preprint) (meta analysis - not included in study count)		 Hydroxych loroquine 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 HC Q.
9/27
Meta
META
 PEP
Wiseman et al., medRxiv, doi:10.1101/2020.08.19.20178376 (Preprint) (meta analysis - not included in study count)		 cases, ↓65.0%, p=0.04 Treatment and prevention of early disease before and after exposure to COVID-19 using hydroxych loroquine: A protocol for exploratory re-analysis of age and time
Analysis of Boulware et al. data showing 65% reduction in cases for treatment within 3 days, RR 0.35, p=0.044. Authors were able to obtain data on the shipping delay for participants which adds up to 3.5 days to the treatment time, so fo..
9/24
Safety
SAFETY
 Early, Late
Gasperetti et al., EP Europace, doi:10.1093/europace/euaa216 (Peer Reviewed) (not included in the study count)		 Arrhythmic safety of hydroxych loroquine in COVID-19 patients from different clinical settings
Safety study of 649 patients finding that HC Q 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..
9/24
Positive
POSITIVE
 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 HC Q users, with unadjusted mortality RR 0.85, p<0.001 (13.6% vs. 16.1%).
9/23
Negative
NEGATIVE
 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 Hydroxych loroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients
Small RCT on very late stage use of HC Q, with 48% on oxygen at baseline. 67 HC Q patients, 61 control. Baseline states were not comparable - 82% more HC Q patients had th..
9/22
Positive
POSITIVE
 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 HC Q+AZ, showing HC Q+AZ mortality relative risk RR 0.57, p = 0.145.
9/21
Inconc.
INCONC.
 PrEP
Gentry et al., Lancet Rheumatology, doi:10.1016/S2665-9913(20)30305-2 (Peer Reviewed)		 death, ↓86.7%, p=0.10 Long-term hydroxych loroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study
Retrospective patients with rheumatologic conditions showing zero mortality with HC Q, odds ratio OR 0.13, p=0.10. 0 of 10,703 COVID-19 deaths for HC Q patients versus 7 of 21,406 for control pa..
9/21
Inconc.
INCONC.
 PrEP
Rajasingham et al., medRxiv, doi:10.1101/2020.09.18.20197327 (Peer Reviewed)		 cases, ↓27.0%, p=0.12 Hydroxych loroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial
PrEP RCT showing HR 0.73, p = 0.12. Trial halted after 47% enrollment, p < 0.05 will be reached at ~75% enrollment if similar results continue. Trial halted due to low enrollment. US prescriptions only stopped briefly, resuming in June, ..
9/21
Inconc.
INCONC.
 PrEP
Grau-Pujol et al., Research Square, doi:10.21203/rs.3.rs-72132/v1 (Preprint)		 cases, ↓70.2%, p=0.47 Pre-exposure prophylaxis with hydroxych loroquine for COVID-19: initial results of a double-blind, placebo-controlled randomized clinical trial
Small PrEP RCT showing that PrEP with HC Q is safe at the dosage used. No deaths, hospitalizations, or serious adverse events. With only one case (in the placebo arm), efficacy was not evaluated.
9/21
Safety
SAFETY
 Early
Lofgren et al., medRxiv, doi:10.1101/2020.07.16.20155531 (Preprint) (not included in the study count)		 Safety of Hydroxych loroquine among Outpatient Clinical Trial Participants for COVID-19
Analysis of 2,795 outpatients not showing significant safety concerns with HC Q. No deaths were related to HC Q. There was one serious event requiring hospitalization, identical to the frequency..
9/18
Meta
META
 Late
Axfors et al., medRxiv, doi:10.1101/2020.09.16.20194571 (Preprint) (meta analysis - not included in study count)		 Mortality outcomes with hydroxych loroquine and ch loroquine in COVID-19: an international collaborative meta-analysis of randomized trials
Meta analysis assigning 87% weight to the RECOVERY trial, producing the same result. The RECOVERY trial used excessively high non-patient-customized dosage in very sick late stage patients and the result is not generalizable to typical do..
9/16
Dosing
DOSING
 N/A
Karatza et al., Xenobiotica (Peer Reviewed) (not included in the study count)		 Optimization of hydroxych loroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations
Analysis of HC Q 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 adver..
9/15
Positive
POSITIVE
 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 HC Q, 29% reduction with HC Q+AZ, and 37% reduction with C Q+AZ.
9/14
Positive
POSITIVE
 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 hydroxych loroquine and azithromycin on mortality in COVID‐19 patients
Retrospective 377 patients, 73% reduction in mortality with HC Q+AZ, adjusted hazard ratio HR 0.27 [0.17-0.41]. Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders.
9/13
Positive
POSITIVE
 Early
Sulaiman et al., medRxiv, doi:10.1101/2020.09.09.20184143 (Preprint)		 death, ↓63.7%, p=0.01 The Effect of Early Hydroxych loroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study
Observational prospective 5,541 patients, adjusted HC Q 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 ..
9/12
Positive
POSITIVE
 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, HC Q+AZ mortality odds ratio OR 0.36, p = 0.04. Ventilation OR 0.20, p = 0.008.
9/9
Positive
POSITIVE
 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 HC Q, showing HC Q mortality RR 0.45, p = 0.028. HC Q was the only antiviral that showed a significant difference. Small number..
9/9
Inconc.
INCONC.
 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 HC Q and 27 control, showing 25.6% faster recovery with HC Q, 6.4 vs. 8.6 days (p = 0.20). There was no ICU admission, mechanical ventilation, or death. Tr..
9/9
Negative
NEGATIVE
 PrEP
Rentsch et al., medRxiv, doi:10.1101/2020.09.04.20187781 (Preprint)		 death, ↑3.0%, p=0.83 Hydroxych loroquine for prevention of COVID-19 mortality: a population-based cohort study
Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HC Q prescriptions in the prior 6 months, HC Q HR 1.03 [0.80-1.33] (HR 0.78 before adju..
9/9
Inconc.
INCONC.
 PrEP
Laplana et al., medRxiv, doi:10.1101/2020.09.03.20158121 (Preprint)		 cases, ↑56.0%, p=0.24 Lack of protective effect of ch loroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients
Survey of 319 autoimmune disease patients taking C Q/HC Q with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted..
9/7
Review
REVIEW
 Review
IHU, Expert Review of Clinical Immunology (Review) (Peer Reviewed) (not included in the study count)		 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 hydroxych loroquine, azithromycin and zinc may represent the best..
9/5
Positive
POSITIVE
 Late
Synolaki et al., medRxiv, doi:10.1101/2020.09.05.20184655 (Preprint)		 Activin/Follistatin-axis deregulation is independently associated with COVID-19 in-hospital mortality
Retrospective 117 patients, 58 HC Q. HC Q, AZ, and other treatments were found to be independently associated with survival when treatment commenced early.
9/4
Inconc.
INCONC.
 Late
Furtado et al., The Lancet, doi:10.1016/S0140-6736(20)31862-6 (Peer Reviewed)		 Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial
Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. No significant difference was found, OR 1.36, p=0.11. One notable result is that even within this extremely late stage population, results sugge..
9/2
In Vitro
IN VITRO
 In Vitro
Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333 (Peer Reviewed) (In Vitro) (not included in the study count)		 Ch loroquine and hydroxych loroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus
In Vitro study providing novel insights into the molecular mechanism of C Q/HC Q treatment, showing that C Q and HC Q both inhibit the entrance of 201..
9/2
Positive
POSITIVE
 Early
Heras et al., Research Square, doi:10.21203/rs.3.rs-70219/v1 (Preprint)		 death, ↓92.1%, p<0.001 COVID-19 mortality risk factors in older people in a long-term care center
Retrospective 100 elderly nursing home patients, HC Q+AZ mortality 11.4% vs. control 61.9%, RR 0.18, p<0.001. Median age 85. COVID-19 confirmed. 70% treated with HC Q+AZ. Details of differences..
9/2
Inconc.
INCONC.
 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 HC Q, 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 ..
9/1
Review
REVIEW
 Review
Hecel et al., Pharmaceuticals, 13:9, 228, doi:10.3390/ph13090228 (Review) (Peer Reviewed) (not included in the study count)		 Zinc(II)—The Overlooked Éminence Grise of Ch loroquine’s Fight against COVID-19?
Review of zinc as an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and zinc ionophores including C Q/HC Q, showing the latest evidence for zinc and C Q/HC
9/1
Positive
POSITIVE
 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 HC Q, and corresponding trend changes in CFR. US state analysis shows a significan..
8/29
Inconc.
INCONC.
 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 HC Q+AZ. Significantly..
8/28
Inconc.
INCONC.
 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 HC Q. Strong evidence for confounding by indication and compassionate use of HC Q. 24.9% of HC Q patients were o..
8/27
Positive
POSITIVE
 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 (HC Q etc.) RR 0.37, p=0.015. csDMARDs include HC Q, C Q, and several other drugs, so the effect of H..
8/26
Meta
META
 Late
Fiolet et al., Clinical Microbiology and Infection (Peer Reviewed) (meta analysis - not included in study count)		 Effect of hydroxych loroquine 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 HC Q RR 0.83 [0.65-1.06], before exclusions RR 0.80 [0.65-1.0]. Authors claim "HC Q alone is..
8/25
Positive
POSITIVE
 Early
Ip et al., medRxiv, doi:10.1101/2020.08.20.20178772 (Preprint)		 hosp., ↓45.9%, p=0.03 Hydroxych loroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study
Retrospective 1,274 outpatients, 47% reduction in hospitalization with HC Q with propensity matching, HC Q OR 0.53 [0.29-0.95]. Sensitivity analyses revealed similar associations. Adverse event..
8/25
Positive
POSITIVE
 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 hydroxych loroquine 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 HC Q after propensity adjustment, HR 0.70 [0.59 - 0.84].
8/24
Positive
POSITIVE
 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 Hydroxych loroquine 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 HC Q, 3,533 control. 35% lower mortality for HC Q (17.7% vs. 27.1%), adjusted HR 0.68 [0.62–0.76]. Low-dose HC Q m..
8/21
Positive
POSITIVE
 Early
Ly et al., Preprint, 2020 (Preprint)		 death, ↓53.5%, p=0.03 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, HC Q+AZ >= 3 days mortality OR 0.39, p=0.026. 1690 elderly residents (mean age 83), 226 infected residents, 116 treated with HC Q+AZ >= 3 days. Detec..
8/21
Safety
SAFETY
 N/A
Lane et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30276-9 (Peer Reviewed) (not included in the study count)		 Risk of hydroxych loroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study
Retrospective study of RA patients using HC Q vs. sulfasalazine (another DMARD). HC Q treatment showed no increased risk in the short term (up to 30 days) among patients with RA. Long term use w..
8/21
Positive
POSITIVE
 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 HC Q (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model i..
8/20
Positive
POSITIVE
 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/hydroxych loroquine and/or corticosteroids: results of a retrospective observational study in the French overseas department of Reunion Island
Retrospective analysis of 36 hospitalized patients showing HC Q/AZ associated with lower ICU admission, p=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumoni..
8/20
Safety
SAFETY
 Early
Prodromos, C., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100747 (Peer Reviewed) (not included in the study count)		 Hydroxych loroquine is protective to the heart, not harmful: A systematic review
Review concluding that HC Q/AZ does not cause Torsade de Pointes or related deaths, HC Q decreases cardiac events, and HC Q should not be restricted in use for COVID-19 pat..
8/18
Positive
POSITIVE
 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 HC Q/C Q 0.41, p<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Anal..
8/15
Negative
NEGATIVE
 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)ch loroquine
Retrospective study of HC Q use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HC Q/C Q or dexamethasone. Late stage (admitted to ho..
8/14
Inconc.
INCONC.
 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 Hydroxych loroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study
Small RCT in Egypt with 97/97 HC Q/control patients, showing 58% more recovery @28days for HC Q (53.6% HC Q, 34% control), p=0.009 (0.06 in the paper refers to the 5 combin..
8/13
Negative
NEGATIVE
 Late
Roomi et al., J. Medical Internet Research, doi:10.2196/21758 (Peer Reviewed)		 death, ↑37.7%, p=0.54 Efficacy of hydroxych loroquine and tocilizumab in patients with COVID-19: A single-center retrospective chart review
Retrospective 176 hospitalized patients (144 HC Q, 32 control) showing no significant differences with HC Q or TCZ. Confounding by indication.
8/11
Safety
SAFETY
 Early
Bakhshaliyev et al., J. Electrocardiology, doi:10.1016/j.jelectrocard.2020.08.008 (Peer Reviewed) (not included in the study count)		 The effect of 5-day course of hydroxych loroquine and azithromycin combination on QT interval in non-ICU COVID19(+) patient
Safety study of 109 patients showing 5 days of HC Q+AZ did not lead to clinically significant QT prolongation or other conduction delays compared to baseline ECG in non-ICU patients.
8/11
Negative
NEGATIVE
 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 Hydroxych loroquine and Azithromycin - A real world experience
Retrospective 65 HC Q+AZ, 20 control patients, showing median time to negative PCR of 23 days for HC Q+AZ vs. 19 days for control. Confounding by indication. 100% of non-HC
8/8
Inconc.
INCONC.
 Late
Lopez et al., Int. J. Antimicrob. Agents, doi:/j.ijantimicag.2020.106136 (Peer Reviewed)		 Effects of Hydroxych loroquine on Covid-19 in Intensive Care Unit Patients: Preliminary Results
Small retrospective study of 29 ICU patients comparing those with HC Q plasma concentration within target to those with a concentration below the target value, with no significant differences found. Mortality in the ..
8/6
Review
REVIEW
 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)		 Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection
Review of pathophysiological principles related to early outpatient treatment and therapeutic approaches including reduction of reinoculation, combination antiviral therapy, immunomodulation, antiplatelet/antithrombotic therapy, and admin..
8/6
Meta
META
 PEP, Early, Late
Watanabe et al., Open Letter (Letter) (meta analysis - not included in study count)		 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 HC Q RCTs. Authors note [1] that data from RCTs for early treatment in outpatients to date actually show favorable effects..
8/5
Negative
NEGATIVE
 PrEP
Singer et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218500 (Letter)		 cases, ↑9.0%, p=0.62 Hydroxych loroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis
Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HC Q, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortali..
8/4
Inconc.
INCONC.
 Late
Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint)		 progression, ↓5.0%, p=1.00 Clearing the fog: Is HC Q 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 HC
8/3
Positive
POSITIVE
 Late
Yu et al., Science China Life Sciences, 2020 Aug 3, doi:10.1007/s11427-020-1782-1 (Letter)		 Beneficial effects exerted by hydroxych loroquine in treating COVID-19 patients via protecting multiple organs
Retrospective 2,882 patients in China, median age 62, 278 receiving HC Q, median 10 days post hospitalization, showing that HC Q treatment can reduce systemic inflammation and inhibit the cytoki..
8/2
Positive
POSITIVE
 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. HC Q+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...
8/2
In Vitro
IN VITRO
 In Vitro
Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count)		 A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Ch loroquine Activity
In vitro study presenting a new theory on SARS-CoV-2 infection and why HC Q/C Q provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and..
7/29
Positive
POSITIVE
 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 Hydroxych loroquine in COVID-19 disease: A done and dusted situation?
HC Q+AZ adjusted death HR 0.44, p=0.009. Propensity scores include baseline COVID-19 disease severity, age, gender, number of comorbidities, cardio-vascular disease, duration of symptoms, date of admission, baseline ..
7/28
Inconc.
INCONC.
 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 HC Q, 113 with HC Q+AZ, and 32 with regimens including favipiravir. 75% reduction in the median time ..
7/26
Inconc.
INCONC.
 PEP
Mitjà et al., medRxiv, doi:10.1101/2020.07.20.20157651 (Preprint)		 death, ↓32.0%, p=0.58 A Cluster-Randomized Trial of Hydroxych loroquine as Prevention of Covid-19 Transmission and Disease
Death rate reduced from 0.6% to 0.4%, RR 0.68, not statistically significant due to low incidence (8 control cases, 5 treatment cases). For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - ..
7/24
Positive
POSITIVE
 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 HC Q prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis wa..
7/23
Negative
NEGATIVE
 Late
Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa201901 (Peer Reviewed)		 death, ↓16.0%, p=0.77 Hydroxych loroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot de..
7/22
In Vitro
IN VITRO
 In Vitro
Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count)		 Ch loroquine 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 C Q results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, p=0.05, after 24 hours (we do not see the supplementa..
7/22
Negative
NEGATIVE
 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 HC Q. The study reports the number of HC Q+AZ patients but they do not provide results for HC Q+AZ (..
7/22
Negative
NEGATIVE
 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 hydroxych loroquine and azithromycin
Retrospective 82 hospitalized patients HC Q/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HC Q/AZ patients were more severely i..
7/21
Positive
POSITIVE
 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
HC Q HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative ..
7/20
Meta
META
 Early
Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis - not included in study count)		 Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis”
Updated meta analysis including 7 new studies of high-risk outpatients, for a total of 12 studies, all showing significant benefit.
7/18
Meta
META
 PEP
Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in study count)		 Efficacy of Hydroxych loroquine as Prophylaxis for Covid-19
Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HC Q is effective when used early, p<0.01. The effectiveness found is especially notable considering the limitatio..
7/19
Inconc.
INCONC.
 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
HC Q+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HC Q patients survived and 92% of HC Q+AZ patients. Patients not receiving eithe..
7/17
Inconc.
INCONC.
 Late
Lyngbakken et al., Research Square, doi:10.21203/rs.3.rs-44055/v1 (Peer Reviewed)		 viral- time, ↓71.0%, p=0.51 A pragmatic randomized controlled trial reports lack of efficacy of hydroxych loroquine on coronavirus disease 2019 viral kinetics
Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HC Q 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 HC
7/16
Positive
POSITIVE
 Early
Hong et al., Infect. Chemother., 2020, doi:10.3947/ic.2020.52.e43 (Peer Reviewed)		 viral+, ↓64.9%, p=0.001 Early Hydroxych loroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication
HC Q 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..
7/16
Inconc.
INCONC.
 Early
Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed)		 no recov., ↓20.0%, p=0.21 Hydroxych loroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial
~70 to 140 hour (inc. shipping) delayed outpatient treatment with HC Q reduced combined hospitalization/death by 50%, p=0.29 (5 HC Q cases, 10 control cases), and reduced hospitalization by 60%,..
7/16
Inconc.
INCONC.
 Early
Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed)		 hosp., ↓25.0%, p=0.64 Hydroxych loroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
This paper has inconsistent data - some of the values reported in Table 2 and the abstract correspond to 12 control hospitalizations, while others correspond to 11 control hospitalizations. There was a 25% reduction in hospitalization an..
7/15
Negative
NEGATIVE
 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 HC Q. HC Q+AZ mortality relative risk RR 0.96, p=0.53, HC ..
7/14
Inconc.
INCONC.
 Early
Chowdhury et al., Research Square, doi:10.21203/rs.3.rs-38896/v1 (Preprint)		 A Randomized Trial of Ivermectin-Doxycycline and Hydroxych loroquine-Azithromycin therapy on COVID19 patients
Small 116 patient RCT comparing Ivermectin-Doxycycline and HC Q+AZ, not showing a significant difference in time to PCR negative or symptom resolution. Time to symptomatic recovery was 5.93 days for Ivermectin-Doxycy..
7/11
Negative
NEGATIVE
 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 hydroxych loroquine, 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 HC Q. 28 day mortality 24% (HC Q) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample s..
7/10
Negative
NEGATIVE
 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 HC Q mortality HR 1.53, p = 0.17. Subject to confounding by indication.
7/10
Inconc.
INCONC.
 Late
Chen et al., medRxiv, doi:10.1101/2020.07.08.20148841v1 (Preprint)		 viral+, ↓24.0%, p=0.71 A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxych loroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19)
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76..
7/9
Meta
META
 Early, Late
Raoult et al., Preprint (Preprint) (meta analysis - not included in study count)		 Hydroxych loroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial: Response to David Spencer (Elsevier)
Updated meta analysis showing significant reductions in mortality and viral shedding. Mortality OR 0.53 [0.4-0.71] for clinical studies, 0.92 big data studies, 18,211 patients. Persistent viral shedding OR 0.47 [0.28-0.79], 4,540 patients.
7/8
Review
REVIEW
 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)		 Is hydroxych loroquine beneficial for COVID-19 patients?
Review of the anti-inflammatory, antiviral, and protective vascular effects of C Q and HC Q, noting that HC Q may be preferable for COVID-19 due to fewer side effects.
7/7
Review
REVIEW
 Review
Goldstein, L., Preprint, July 7, 2020 (Review) (Preprint) (not included in the study count)		 Hydroxych loroquine-based COVID-19 Treatment, A Systematic Review of Clinical Evidence and Expert Opinion from Physicians’ Surveys
85% of globally surveyed physicians recognized HC Q 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 m..
7/7
Negative
NEGATIVE
 Late
An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint)		 viral+, ↓3.0%, p=0.92 Treatment Response to Hydroxych loroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
Retrospective of hospitalized patients with 31 HC Q patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. ..
7/3
Positive
POSITIVE
 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 HC Q had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythemat..
7/3
Positive
POSITIVE
 Early
Scholz et al., Preprints 2020, 2020070025, doi:10.20944/preprints202007.0025.v1 (Preprint)		 death, ↓79.4%, p=0.13 COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxych loroquine and Azithromycin: A Retrospective Case Series Study
Early treatment with HC Q+AZ+Z results in 84% lower hospitalization and 80% lower death - hospitalization OR 0.16 (p<0.001), death OR 0.2 (p=0.16). No cardiac side effects. Retrospective 518 patients (141 treated, 37..
7/1
Positive
POSITIVE
 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 Hydroxych loroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
HC Q decreases mortality from 26.4% to 13.5% (HC Q) or 20.1% (HC Q+AZ). Propensity matched HC Q HR 0.487, p=0.009. Michigan 2,541 patients retrospecti..
7/1
Safety
SAFETY
 N/A
Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count)		 Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR positive SARS-CoV-2 infection including drug induced changes in the corrected QT interval (QTc)
In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but occur at an incidence higher than expected in a general pediatric population. Comorbidities are not more common in patients wit..
6/30
Positive
POSITIVE
 Late
Martinez-Lopez et al., (Preprint)		 death, ↓33.0%, p=0.20 Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality
Retrospective 167 multiple myeloma patients in Spain
6/30
Positive
POSITIVE
 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
HC Q decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City.
6/30
Negative
NEGATIVE
 Late
Komissarov et al., medRxiv, doi:10.1101/2020.06.30.20143289 (Preprint)		 Hydroxych loroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19
Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with sign..
6/29
Positive
POSITIVE
 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 hydroxych loroquine and SARS-CoV-2 infection
Chronic treatment with HC Q 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..
6/29
Safety
SAFETY
 N/A
Mfeukeu-Kuate et al. (Preprint) (not included in the study count)		 Electrocardiographic safety of daily Hydroxych loroquine 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 HC Q+AZ. 51 relatively young patients 39 +/- 11.
6/25
Inconc.
INCONC.
 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, hydroxych loroquine use and immunosuppressive treatments
Small study of 152 SLE patients taking HC Q 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 infec..
6/25
Positive
POSITIVE
 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 hydroxych loroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis
Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients.
6/23
Positive
POSITIVE
 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 HC Q mortality OR 0.49, p = 0.15.
6/22
Positive
POSITIVE
 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 HC Q mortality RR 0.50, p = 0.53.
6/22
Positive
POSITIVE
 Early
Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint)		 viral- time, ↓72.0%, p=0.01 Efficacy and safety of ch loroquine or hydroxych loroquine 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 (HC Q), p=0.01. 67 patients with mild/moderate cases.
6/21
Inconc.
INCONC.
 Late
Faico-Filho et al., medRxiv, doi:10.1101/2020.06.16.20133066 (Preprint)		 Effect of hydroxych loroquine on SARS-CoV-2 viral load in patients with COVID-19
Viral load comparison for 34 HC Q and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results sh..
6/19
Positive
(news)
POSITIVE
 PrEP
SMSH Sawai Man Singh Hospital, India (News) (not included in the study count)		 HC Q beneficial as preventive drug: SMS doctors told ICMR
PrEP with 4,300 very high risk healthcare workers in a hospital with up to 500+ COVID patients at a time, only 1% cases, all recovered.
6/19
Negative
(news)
NEGATIVE
 Late
NIH, study not available yet (News) (not included in the study count)		 NIH halts clinical trial of hydroxych loroquine
NIH halts late stage trial reporting no harm and no benefit. 470 patients.
6/19
Positive
POSITIVE
 Late
Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint)		 death, ↑5.0%, p=0.74 Hydroxych loroquine 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 HC Q and HC Q+AZ. No significant effect is seen on 28-day mortality, however many more control ..
6/18
Inconc.
INCONC.
 Late
Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed)		 death, ↓11.0%, p=0.88 Compassionate use of hydroxych loroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital
Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.
6/17
Positive
POSITIVE
 Late
Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 (Peer Reviewed)		 Hydroxych loroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China
30 hospitalized patients. Early use of HC Q is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization.
6/17
Inconc.
INCONC.
 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 HC Q, mortality OR 1.03, p = 0.99.
6/16
Inconc.
INCONC.
 Late
Kim et al., Korean J Intern Med, doi:10.3904/kjim.2020.224 (Peer Reviewed)		 Lopinavir-ritonavir versus hydroxych loroquine 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 HC Q patients, HC Q 400mg once per day, finding no significant difference in clinical response, but more rap..
6/16
Positive
(news)
POSITIVE
 PrEP
WHIP COVID-19 (News) (not included in the study count)		 Henry Ford Health System still moving forward with hydroxych loroquine study
Ongoing WHIP COVID-19 HC Q PrEP study reports analyzing their data and seeing a significantly improved outcome in a group of COVID-19 patients who received HC Q. For more details on the study se..
6/16
Positive
POSITIVE
 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 C Q/HC
6/12
Theory
THEORY
 Theory
Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count)		 Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxych loroquine-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 HC Q+AZ.
6/12
Negative
NEGATIVE
 Late
Giacomelli et al., Journal of Medical Virology, doi:10.1002/jmv.26407 (preprint 6/12) (Peer Reviewed)		 Early administration of lopinavir/ritonavir plus hydroxych loroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study
Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". Th..
6/10
Inconc.
INCONC.
 Late
Wang et al., medRxiv, doi:10.1101/2020.06.11.20128926 (Peer Reviewed)		 death, ↓5.8%, p=0.63 Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System
Database analysis of 7,592 patients in NYC, showing adjusted HC Q mortality odds ratio OR 0.96, p = 0.82, and HC Q+AZ OR 0.94, p = 0.63
6/10
Positive
POSITIVE
 Early
Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint)		 A short therapeutic regimen based on hydroxych loroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.
80 moderate cases, HC Q+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy.
6/9
Positive
POSITIVE
 Early
Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed)		 Beneficial effect of Hydroxych loroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an observational study
68 very high risk nursing home residents, median age 86, HC Q+AZ early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7 died, significantly less than other nursing homes in France and the same as the med..
6/9
Positive
POSITIVE
 PrEP
Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint)		 cases, ↓80.7%, p=0.001 Pre exposure Hydroxych loroquine use is associated with reduced COVID19 risk in healthcare workers
HC Q reduced cases from 38% to 7%. 106 people. No serious adverse effects.
6/6
Meta
META
 Early, Late
Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer Reviewed) (meta analysis - not included in study count)		 Clinical Efficacy of Ch loroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world
[H]C Q effective and reduces mortality by a factor 3. Meta analysis of 20 studies.
6/5
Negative
NEGATIVE
 Late
RECOVERY Collaborative Group, NEJM, doi:10.1056/NEJMoa2022926 (press release 6/5) (Preprint)		 death, ↑9.0%, p=0.15 Effect of Hydroxych loroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial
RECOVERY trial finds no significant benefit for very late stage very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) [1, 2]. The overall dosage used is only 23% less than the high dosage tha..
6/3
Positive
(see notes)
POSITIVE
 PEP
Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed)		 cases, ↓17.0%, p=0.35 A Randomized Trial of Hydroxych loroquine as Postexposure Prophylaxis for Covid-19
COVID-19 cases are reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. PEP delayed treatment RCT. Cur..
6/1
Dosing
DOSING
 N/A
Al-Kofahi et al., Clin. Pharmacol. Ther., Jun 1, 2020, doi:10.1002/cpt.1874 (Peer Reviewed) (not included in the study count)		 Finding the Dose for Hydroxych loroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness
Analysis of HC Q dosing regimens, recommending: PrEP: 800mg loading dose followed by 400mg 2 or 3 times weekly to maintain weekly troughs above EC50 in >50% of patients at steady-state. PEP: 800mg loading dose foll..
5/31
Positive
POSITIVE
 Early
Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed)		 death, ↓43.0%, p=0.73 Azithromycin and Hydroxych loroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19
Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HC Q+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched pa..
5/28
Positive
POSITIVE
 Late
Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint)		 Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxych loroquine and azithromycin in Lebanon
HC Q+AZ potentially explains 94.7% success in treating a fairly complex cohort.
5/28
Positive
POSITIVE
 PrEP
Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed)		 cases, ↓66.8%, p<0.001 Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19
4+ doses of HC Q associated with a significant decline in the odds of getting infected, dose-response relationship exists.
5/28
Positive
POSITIVE
 Late
Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed)		 viral- time, ↓67.0%, p<0.0001 Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of ch loroquine for the treatment of COVID-19
197 C Q patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.
5/27
Inconc.
INCONC.
 Late
Goldman et al., NEJM, doi:10.1056/NEJMoa2015301 (Peer Reviewed)		 death, ↓22.3%, p=0.46 Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
Study focused on remdesivir but with results for HC Q in the supplementary appendix, showing 9% death with HC Q versus 12% control, unadjusted relative risk uRR 0.78, p = 0.46.
5/28
Negative
NEGATIVE
 Late
Kuderer et al., Lancet, June 20, 2020, doi:10.1016/S0140-6736(20)31187-9 (preprint 5/28) (Peer Reviewed)		 death, ↑134.2%, p<0.0001 Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study
Retrospective 928 cancer patients, showing HC Q OR 1.06 [0.51-2.20]. HC Q+AZ OR 2.93 [1.79-4.79]. The relative risks of different therapies suggest that the results are overly affected by confou..
5/28
Inconc.
INCONC.
 PrEP
Gianfrancesco et al., Annals of the Rheumatic Diseases, 79:7, 859-866, doi:10.1136/annrheumdis-2020-217871 (Peer Reviewed)		 hosp., ↓3.3%, p=0.82 Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry
Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 [0.57-1.57], p=0.82 after adjustments.
5/27
Meta
META
 Early
Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis - not included in study count)		 Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis
Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy.
5/25
Negative
NEGATIVE
 Late
Ip et al., medRxiv, doi:10.1101/2020.05.21.20109207 (Preprint)		 death, ↓1.0%, p=0.93 Hydroxych loroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study
Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HC Q during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]..
5/22
Positive
(advisory)
POSITIVE
 PEP, PrEP
ICMR, Indian Council of Medical Research (Advisory) (not included in the study count)		 Revised advisory on the use of Hydroxych loroquine (HC Q) as prophylaxis for SARS-CoV-2 infection
Healthcare workers on HC Q prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HC Q prophylaxis to asymptomatic household contacts of cases and fron..
5/22
Retracted
RETRACTED
 Late
Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed) (not included in the study count)		 Hydroxych loroquine or ch loroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted.
5/19
Negative
NEGATIVE
 Late
Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint)		 death, ↓5.0%, p=0.72 Outcomes of Hydroxych loroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network
EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indic..
5/18
Positive
POSITIVE
 Late
Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint)		 hosp. time, ↓51.0%, p=0.01 Treatment Response to Hydroxych loroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea
Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HC Q+antibiotic. Preprint withdrawn pending peer review.
5/18
Positive
POSITIVE
 Early
Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint)		 Doxycycline and Hydroxych loroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
54 patients in long term care facilities. 6% death with HC Q+AZ compared to 22% using a naive indirect comparison.
5/16
Inconc.
INCONC.
 PrEP
Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint)		 hosp., ↓25.5%, p=1.00 Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxych loroquine therapy
Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HC Q 0.5-4.0%, no-HC Q 0.4-2.7%). Confirmed cases were 1 HC
5/15
Positive
POSITIVE
 Late
Yu et al., Science China Life Sciences, 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed)		 death, ↓60.5%, p=0.002 Low Dose of Hydroxych loroquine Reduces Fatality of Critically Ill Patients With COVID-19
Retrospective, 550 critically ill patients. 19% fatality for HC Q versus 47% for non-HC Q, RR 0.395, p=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL..
5/14
Negative
NEGATIVE
 Late
Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed)		 death, ↑20.0%, p=0.75 Clinical efficacy of hydroxych loroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions [1]. None of the 15 patients receiving HC ..
5/13
Positive
POSITIVE
 Late
Okour et al., Journal of Pharmacokinetics and Pharmacodynamics, May 13, 2020, doi:10.1007/s10928-020-09689-x (Peer Reviewed)		 Hydroxych loroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome
Odds of PCR-positive decrease by 53% for each unit increase in HC Q log-concentration. Similarly, the odds decrease by 61%, and by 12% for each day increase, and for azithromycin co-treatment, respectively. Computes ..
5/12
Inconc.
INCONC.
 PrEP
Cassione et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217717 (Letter)		 cases, ↑49.6%, p=0.59 COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine
Survey of 165 SLE patients, 127 on HC Q. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for co..
5/11
Inconc.
INCONC.
 Late
Shabrawishi et al., medRxix, doi:10.1101/2020.05.08.20095679 (Preprint)		 viral+, ↓14.7%, p=0.66 Negative nasopharyngeal SARS-CoV-2 PCR conversion in response to different therapeutic interventions
Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, p = 0.65. The treatment group had significantly more severe illness and significantly ..
5/11
Negative
NEGATIVE
 Late
Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed)		 death, ↑35.0%, p=0.31 Association of Treatment With Hydroxych loroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
Restrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. [1] point out serious limitations that they say should be corrected on the record: patients receiving HC
5/10
Positive
POSITIVE
 Late
Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed)		 death, ↓42.9%, p=0.12 A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection
Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HC Q but p=0.12, OR 0.44 [0.16–1.24].
5/8
Ex Vivo
EX VIVO
 Ex Vivo
Grassin-Delyle et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa546 (Peer Reviewed) (Ex Vivo) (not included in the study count)		 Ch loroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants
On human lung parenchymal explants, C Q concentration clinically achievable in the lung (100 µM) inhibited the lipopolysaccharide-induced release of TNF-ɑ (by 76%), IL-6 (by 68%), CCL2 (by 72%), and CCL3 (by 67%). In..
5/8
Positive
POSITIVE
 Late
Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed)		 Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients
Retrospective 932 patients. Addition of Zinc to HC Q+AZ reduces mortality / transfer to hospice, ICU admission, and the need for ventilation. Reduction in mortality or transfer to hospice adjusted odds ratio OR 0.56..
5/7
Inconc.
INCONC.
 PrEP
Konig et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217690 (Letter)		 hosp., ↓3.0%, p=0.88 Baseline use of hydroxych loroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19
Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), p=ns. Authors suggest that the dosage use..
5/7
Theory
THEORY
 Theory
Derendorf, H., Int. J. Antimicrobial Agents, 7 May 2020, doi:10.1016/j.ijantimicag.2020.106007 (Peer Reviewed) (Theory) (not included in the study count)		 Excessive lysosomal ion-trapping of hydroxych loroquine and azithromycin
Discusses pharmacokinetic properties of HC Q+AZ as a potential underlying mechanism of the observed antiviral effects.
5/7
Inconc.
INCONC.
 Late
Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer Reviewed)		 int./death, ↑4.0%, p=0.76 Observational Study of Hydroxych loroquine in Hospitalized Patients with Covid-19
There appears to be a major error in this paper. Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). This is not possible. Even if all propensity matched co..
5/7
Positive
(news)
POSITIVE
 N/A
Sermo (News) (not included in the study count)		 Sermo reports: COVID-19 treatment trends over 6 weeks and 33,700 interviews: Usage, efficacy and safety perceptions of most-used therapies
HC Q used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians.
5/6
Animal
ANIMAL
 N/A
Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count)		 Hydroxych loroquine use against SARS-CoV-2 infection in non-human primates
Monkey study which reports no effect of HC Q or HC Q+AZ. However, there are several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and control monkey..
5/5
Positive
POSITIVE
 Late
Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint)		 death, ↓55.1%, p=0.002 Early Hydroxych loroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study
166 patients hospitalised with COVID-19, HC Q increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients were in relatively serious condition.
5/5
Positive
POSITIVE
 Early, Late
Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 (Peer Reviewed)		 Early Treatment of COVID-19 Patients With Hydroxych loroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille, France
Retrospective 1061 patients. HC Q+AZ safe and results in a low fatality rate.
5/5
Inconc.
INCONC.
 PrEP
Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed)		 cases, ↓8.1%, p=0.88 Continuous Hydroxych loroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis
Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HC Q patient cases. Only considers people tested at a time when primarily symptomatic cases..
5/5
Positive
POSITIVE
 PrEP
Mitchell et al., SSRN, doi:10.2139/ssrn.3586954 (Preprint)		 death, ↓99.0%, p<0.0001 Markedly Lower Rates of Coronavirus Infection and Fatality in Malaria-Endemic Regions – A Clue As to Treatment?
Analysis of COVID-19 amongst 2.4B people shows a wide counterintuitive disparity between well-developed and less-developed countries, with more affluent countries about one hundred times more likely to be infected and die due to COVID-19...
5/4
Inconc.
INCONC.
 PrEP
Huh et al., medRxiv, doi:10.1101/2020.05.04.20089904 (Preprint)		 cases, ↑47.7%, p=0.09 Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea
Database analysis of many drugs and COVID-19 cases, with 23 cases taking HC Q, and 251 control patients not taking HC Q, showing OR 1.07, p=0.77, and in multivariable analysis OR 1.48, p=0.086. ..
5/1
Safety
SAFETY
 N/A
Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in the study count)		 Risk of QT Interval Prolongation Associated With Use of Hydroxych loroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)
Study of 90 hospitalized patients given HC Q, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HC Q, and 442ms for HC Q+AZ. Medi..
5/1
Safety
SAFETY
 N/A
Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in the study count)		 Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxych loroquine Alone or in Combination With Azithromycin in an Intensive Care Unit
Study of 40 very serious condition ICU patients, 75% required invasive mechanical ventilation, 63% received vasoactive drugs, 50% received other treatments favoring QT prolongation. HC Q with or w/o AZ was given to 4..
5/2
Positive
(news)
POSITIVE
 Late
Seydi (News) (not included in the study count)		 Coronavirus: a study in Senegal confirms the effectiveness of hydroxych loroquine
Preliminary results of Senegal trial with 181 patients showing faster recovery with HC Q, and even faster recovery with HC Q+AZ.
4/30
Positive
POSITIVE
 Early
Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed)		 Efficacy of ch loroquine and hydroxych loroquine in the treatment of COVID-19
Analysis of COVID-19 and malaria, finding that COVID-19 is highly pandemic in countries where malaria is least pandemic, and vice versa, suggesting that C Q/HC Q (widely used for malaria) are pr..
4/27
Positive
POSITIVE
 Late
Sánchez-Álvarez et al., Nefrología, doi:10.1016/j.nefroe.2020.04.002 (Peer Reviewed)		 death, ↓45.9%, p=0.005 Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN)
Analysis of 868 patients on renal replacement therapy. Statistically significant reduction in mortality with HC Q for patients on dialysis (OR 0.47, p=0.005). No statistically significant change was found for transp..
4/29
Safety
SAFETY
 N/A
Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed)		 The Effect of Ch loroquine, Hydroxych loroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection
201 hospitalized patients. No serious side effects of HC Q. No instances of Torsade de pointes, or arrhythmogenic death were reported. They report that although use of these medications resulted in QT prolongation, c..
4/25
In Vitro
IN VITRO
 In Vitro
Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (Peer Reviewed) (In Vitro) (not included in the study count)		 In vitro testing of combined hydroxych loroquine and azithromycin on SARS-CoV-2 shows synergistic effect
HC Q and AZ has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.
4/24
Inconc.
INCONC.
 Early
Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint)		 death, ↓67.5%, p=0.15 COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes
Small limited trial with 100 patients concluding that HC Q improved clinical outcome, OR 0.016 [0.002-0.11] in regression analysis.
4/21
Positive
POSITIVE
 Early
Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint)		 death, ↓85.0%, p<0.001 Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths
Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using [H]C Q, showing dramatically lower death in [H]C Q countries. This paper does not at..
4/21
Negative
NEGATIVE
 Late
Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed)		 death, ↑31.0%, p=0.28 Outcomes of hydroxych loroquine usage in United States veterans hospitalized with Covid-19
Retrospective 368 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HC Q or HC Q+AZ, or for death with HC
4/17
Positive
POSITIVE
 PEP
Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 (Peer Reviewed)		 Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals?
Post exposure prophylaxis of 211 high-risk people after major exposure event in a long term care hospital, showing no positive cases after 14 days.
4/16
Negative
NEGATIVE
 Late
Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed)		 Ch loroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)
Comparison of typical C Q dosage with high dosage C Q (600mg C Q twice daily for 10 days), showing higher mortality with high dosage, OR 2.8 [0.9 - 8.5] when controlled by ..
4/15
Positive
POSITIVE
 Early, Late
Esper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint)		 hosp., ↓64.0%, p=0.02 Empirical treatment with hydroxych loroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine
636 patients. HC Q+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
4/15
Theory
THEORY
 Theory
Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Peer Reviewed) (Theory) (not included in the study count)		 Hyperglycemia, hydroxych loroquine, and the COVID‐19 pandemic
Theory on the effectiveness of HC Q. HC Q has been shown to block the polarization of macrophages to an M1 inflammatory subtype and is predicted to interfere with glycosylation of a number of pr..
4/14
Negative
NEGATIVE
 Late
Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed)		 viral+, ↓21.5%, p=0.51 Hydroxych loroquine in patients with COVID-19: an open-label, randomized, controlled trial
150 patients very late stage RCT showing no significant difference. Treatment very late, average 16.6 days after symptom onset. Data favorable to HC Q was deleted in the second version, see analysis [1]. "[HC..
4/13
Review
REVIEW
 Late
Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Review) (Peer Reviewed) (not included in the study count)		 Update on Use of Ch loroquine/Hydroxych loroquine to Treat Coronavirus Disease 2019 (COVID-19)
Increasing evidence from completed clinical studies shows C Q and HC Q effective (HC Q more effective).
4/12
Negative
NEGATIVE
 Late
Barbosa et al., Preprint (Preprint)		 death, ↑147.0%, p=0.58 Clinical outcomes of hydroxych loroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study
Small retrospective study with 63 patients (32 treated with HC Q), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been publish..
4/11
Positive
POSITIVE
 Early
Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed)		 Clinical and microbiological effect of a combination of hydroxych loroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study
Pilot study suggesting improvement with HC Q+AZ and recommending further study. 80 patients with relatively mild cases, no control group, and no attempt to analyze confounding factors.
4/10
Meta
META
 Late
Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in study count)		 Quantifying treatment effects of hydroxych loroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020)
Secondary analysis of Gautret et al. showing "modest to no impact of HC Q treatment, with more significant effects from [HC Q+AZ]".
4/3
Theory
THEORY
 Theory
Fantini et al., Int J Antimicrob Agents, 55:5, doi:10.1016/j.ijantimicag.2020.105960 (Peer Reviewed) (Theory) (not included in the study count)		 Structural and molecular modelling studies reveal a new mechanism of action of ch loroquine and hydroxych loroquine against SARS-CoV-2 infection
In-silico analysis confirming the antiviral properties of C Q, showing a new mechanism of action of C Q, and showing that HC Q is more potent than C Q.
4/1
Positive
POSITIVE
 Early
Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed)		 no recov., ↓90.9%, p=0.09 Treating COVID-19 with Ch loroquine
22 patients. All C Q patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for C Q vs. 6.5 days for Lopinavir/Rotinavir.
3/31
Positive
POSITIVE
 Late
Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint)		 pneumonia, ↓57.0%, p=0.04 Efficacy of hydroxych loroquine in patients with COVID-19: results of a randomized clinical trial
62 patients. RCT showing significantly faster recovery with HC Q. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% ..
3/31
In Vitro
IN VITRO
 In Vitro
Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31) (Peer Reviewed) (In Vitro) (not included in the study count)		 Combined Prophylactic and Therapeutic Use Maximizes Hydroxych loroquine Anti-SARS-CoV-2 Effects in vitro
In vitro study, not included in the study count or percentages, showing greater inhibition for combined pre and post-exposure treatment for Vero E6 and Caco-2 cells.
3/28
Negative
NEGATIVE
 Late
Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter)		 No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxych loroquine and azithromycin in patients with severe COVID-19 infection
11 patients with severe cases. No evidence of benefit for HC Q.
3/26
Positive
POSITIVE
 Late
Zhong Nanshan (钟南山) (Preprint)		 viral+, ↓80.0%, p<0.0001 Efficacy and safety of ch loroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial
197 patients. C Q effective. Day 10 viral RNA negative 91.4% HC Q versus 57.4% control. Median time to negative test 3 days versus 9 days for control.
3/24
Theory
THEORY
 Theory
Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory) (not included in the study count)		 Is Hydroxych loroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19?
C Q and HC Q inhibit replication at early stages of infection, no similar effect reported for other drugs which are only able to interfere after cell infection. Large volume of existing data on ..
3/23
Theory
THEORY
 Theory
Hu et al., Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Peer Reviewed) (Theory) (not included in the study count)		 Insights from nanomedicine into ch loroquine efficacy against COVID-19
C Q is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.
3/21
Positive
(advisory)
POSITIVE
 PrEP
ICMR, Indian Council of Medical Research (Advisory) (not included in the study count)		 Advisory on the use of hydroxy-ch loroquine as prophylaxis for SARS-CoV-2 infection
Recommends HC Q for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo.
3/20
Positive
(news)
POSITIVE
 Late
Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count)		 Shanghai Experience of COVID-19 Management
Clinical studies of HC Q with 184 cases and 21 hospitals show HC Q is effective.
3/18
In Vitro
IN VITRO
 In Vitro
Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not included in the study count)		 Hydroxych loroquine, a less toxic derivative of ch loroquine, is effective in inhibiting SARS-CoV-2 infection in vitro
HC Q effective in vitro and less toxic than C Q. In addition to direct antiviral activity, HC Q is a safe and successful anti-inflammatory agent that has been used extensiv..
3/17
Inconc.
INCONC.
 Early
Gautret et al., Int. J. of Antimicrobial Agents, 17 March 2020, doi:10.1016/j.ijantimicag.2020.105949 (Peer Reviewed)		 viral+, ↓66.0%, p=0.001 Hydroxych loroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial
HC Q was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues [1, 2, 3]. Despite the limitations, t..
3/17
Review
REVIEW
 N/A
Sahraei et al., Int. J. Antimicrobial Agents, April 2020, 55:4, doi:10.1016/j.ijantimicag.2020.105945 (Review) (Peer Reviewed) (not included in the study count)		 Aminoquinolines against coronavirus disease 2019 (COVID-19): ch loroquine or hydroxych loroquine
Discussion of mechanisms of action, C Q vs. HC Q, early studies, safety.
3/13
Review
REVIEW
 N/A
Todaro and Rigano (Review) (Preprint) (not included in the study count)		 An Effective Treatment for Coronavirus (COVID-19)
Discussion of existing research, treatment guidelines, and mechanisms of action for C Q and HC Q, recommending use.
3/12
Theory
THEORY
 Theory
Devaux et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not included in the study count)		 New insights on the antiviral effects of ch loroquine against coronavirus: what to expect for COVID-19?
Discusses mechanisms of C Q interference with the SARS-CoV-2 replication cycle.
3/10
Meta
META
 N/A
Cortegiani et al., J. Crit. Care, June 2020, 57:279-283, doi:10.1016/j.jcrc.2020.03.005, Epub Mar 10, 2020 (Peer Reviewed) (meta analysis - not included in study count)		 A Systematic Review on the Efficacy and Safety of Ch loroquine for the Treatment of COVID-19
Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI.
3/9
In Vitro
IN VITRO
 N/A
Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (Peer Reviewed) (not included in the study count)		 In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxych loroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
HC Q is more potent than C Q in vitro for inhibiting SARS-CoV-2. Simulates HC Q concentration in lung fluid and provides dosing recommendations.
3/6
Negative
NEGATIVE
 Late
Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed)		 progression, ↓29.0%, p=0.57 A pilot study of hydroxych loroquine in treatment of patients with common coronavirus disease-19 (COVID-19)
30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HC Q but not statistically significant. One HC Q patient developed to ..
3/4
Review
REVIEW
 Late
Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Review) (Peer Reviewed) (not included in the study count)		 Ch loroquine and Hydroxych loroquine as Available Weapons to Fight COVID-19
Recommending C Q and HC Q for COVID-19 based on 20 clinical studies in China and a strong rationale for use.
2/20
Positive
POSITIVE
 Late
Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed)		 Expert Consensus on Ch loroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia
Early trials in China show C Q results in shorter hospital stays and improved patient outcomes.
2/19
Positive
POSITIVE
 Late
Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047 (Peer Reviewed)		 Breakthrough: Ch loroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies
Results from 15 clinical trials in China showing C Q is effective.
2/17
Positive
(news)
POSITIVE
 Late
Sun Yanrong, deputy head of the China National Center for Biotechnology Development (News) (not included in the study count)		 Antimalarial drug confirmed effective on COVID-19
HC Q under clinical trials in >10 hospitals in China and has shown fairly good efficacy.
2/11
Positive
POSITIVE
 Late
Xia et al., ChiCTR2000029741 (Preprint)		 viral+, ↓37.5%, p=0.17 Efficacy of Ch loroquine and Lopinavir/ Ritonavir in mild/general novel coronavirus (CoVID-19) infections: a prospective, open-label, multicenter randomized controlled clinical study
Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative co..
2/4
In Vitro
IN VITRO
 In Vitro
Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (Peer Reviewed) (In Vitro) (not included in the study count)		 Remdesivir and ch loroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
In vitro study, not included in the study count or percentages. Remdesivir and C Q potently blocked virus infection in vitro.
2017
Dosing
DOSING
 N/A
Chhonker et al., Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences, 22 Nov 2017, 1072:320-327 doi:10.1016/j.jchromb.2017.11.026 (Peer Reviewed) (not included in the study count)		 Simultaneous quantitation of hydroxych loroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies
Presents a method for quantification of HC Q in mouse blood and tissues. They show a lung concentration significantly higher than other organs, and about 30 times the blood concentration.
2014
Animal
ANIMAL
 Animal
Browning, D., Pharmacology of Ch loroquine and Hydroxych loroquine, 2014, 35-63, doi:10.1007/978-1-4939-0597-3_2 (Peer Reviewed) (not included in the study count)		 Pharmacology of Ch loroquine and Hydroxych loroquine
Review of the pharmacology of C Q and HC Q. Some notable points: - HC Q and C Q are equipotent but C Q is more toxic, the thera..
2014
In Vitro
IN VITRO
 In Vitro
de Wilde et al., Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8, 4875-4884, doi:10.1128/AAC.03011-14 (Peer Reviewed) (In Vitro) (not included in the study count)		 Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture
C Q inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range.
2012
Animal
ANIMAL
 Animal
Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count)		 Anti-malaria drug ch loroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model
C Q, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus.
2009
Animal
ANIMAL
 Animal
Keyaerts et al., Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the study count)		 Antiviral Activity of Ch loroquine against Human Coronavirus OC43 Infection in Newborn Mice
C Q inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with C Q acquired transplacentally or via maternal milk. The highest survi..
2008
In Vitro
IN VITRO
 In Vitro
Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (Peer Reviewed) (In Vitro) (not included in the study count)		 Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by ch loroquine: Involvement of p38 MAPK and ERK
C Q significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. C Q affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracell..
2006
In Vitro
IN VITRO
 In Vitro
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (Peer Reviewed) (In Vitro) (not included in the study count)		 New insights into the antiviral effects of ch loroquine
Update to 2003 paper, not included in the study count or percentages. Hypothesis of C Q inhibiting SARS replication has been confirmed in two in-vitro studies. C Q affected an early stage of SAR..
2005
In Vitro
IN VITRO
 In Vitro
Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count)		 Ch loroquine is a potent inhibitor of SARS coronavirus infection and spread
In vitro study, SARS-CoV-1, not included in the study count or percentages. C Q has strong antiviral effects on SARS CoV infection when cells treated either before or after exposure, suggesting prophylactic and treat..
2004
In Vitro
IN VITRO
 In Vitro
Keyaerts et al., Biochem. Biophys. Res. Comm., 323:1, 8 October 2004, doi:10.1016/j.bbrc.2004.08.085 (Peer Reviewed) (In Vitro) (not included in the study count)		 In vitro inhibition of severe acute respiratory syndrome coronavirus by ch loroquine
In vitro study, SARS-CoV-1, not included in the study count or percentages. IC50 of C Q for antiviral activity (8.8) is significantly lower than cytostatic activity CC50 (261.3), selectivity index of 30. IC50 for inh..
2003
Theory
THEORY
 Theory
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count)		 Effects of ch loroquine on viral infections: an old drug against today's diseases
Not included in the study count or percentages. Discussion/review noting that C Q exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coron..
1918
Inconc.
INCONC.
 N/A
Burrows, E., Medical Record, 97:6, 235, Feb 7, 1920 (Peer Reviewed) (not included in the study count)		 A confirmatory report upon the abortive action of quinine dihydrochloride
Quinine was found to be effective for the Spanish Flu in 1918.
1890
Inconc.
(news)
INCONC.
 N/A
Le Grelot (News) (not included in the study count)		 Quinine use for the Russian influenze pandemic if 1889-1890
Quinine and antipyrine, a bitherapy for defying death during the Russian influenza pandemic of 1889-1890 (around 40,000 deaths in France at the beginning of 1890).
1889
Inconc.
(news)
INCONC.
 N/A
Edwin Wiley Grove (News) (not included in the study count)		 Laxative Bromo Quinine
Quinine has been used for respiratory infections since 1889. Not included in the study count or percentages, just as an interesting observation.

Note: In Vitro, Ex Vivo, Meta, Theory, Safety, Review, News, and Retracted items are not included in the percentages and study count. There is a total of 224 items. Positive/negative effects vary in degree and certainty, please read the papers or descriptions thereof for more details. Every study has some limitations when considered in isolation (for example confounding factors; sub-optimal treatment regimens; dosing regimens that may be too low, too high, or insufficiently account for the long half-life of HC ; large treatment delays; small sample sizes; lack of focus on severity; reliance on Internet surveys; and patient characteristics very different from the most at-risk population).

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