O que é TRATAMENTO PRECOCE para COVID? Existe evidências científicas da eficiência?
Tratamento precoce como próprio nome já indica significa acompanhamento médico intenso, regular e o mais rápido possível, idealmente na FASE 1 da doença (primeiros 5 dias).
COVID é uma grave patologia inflamatória que gera diversas alterações metabólicas que podem necessitar de ajustes rápidos e inclusão de novos fármacos em um período muito curto.
A conotação política e a disputa de poder tem levado veículos de comunicação adotar posicionamentos parciais, onde apenas uma parte do todo é ouvida. Diversas sociedades médicas também se pronunciam contrariamente a um tratamento que aborda os cuidados do paciente desde o início da doença com as melhores evidências científicas do momento. A alegação é que tratamento precoce falta de evidência científica abaixo colocaremos nosso ponto de vista sobre isso.
Um antiparasitário aprovado pela FDA, anteriormente demonstrado ter atividade antiviral de amplo espectro in vitro , é um inibidor do vírus causador (SARS-CoV-2), com uma única adição ao Vero-hSLAM células 2 horas após a infecção com SARS-CoV-2 capaz de efetuar uma redução de ~ 5.000 vezes no RNA viral às 48 h.
A ivermectina é um agente antiparasitário de amplo espectro aprovado pela FDA que, nos últimos anos, juntamente com outros grupos, demonstramos ter atividade antiviral contra uma ampla gama de vírus in vitro . Originalmente identificada como um inibidor da interação entre a proteína integrase (IN) do vírus da imunodeficiência humana-1 (HIV-1) humana e o heterodímero α / β1 da importina (IMP) responsável pela importação nuclear de IN , a ivermectina já confirmou a inibição da enzima nuclear IN importação e replicação do HIV-1 . Outras ações da ivermectina foram relatadas , mas a ivermectina demonstrou inibir a importação nuclear de hospedeiro e proteínas virais, incluindo a proteína não estrutural do antígeno tumoral do vírus símio SV40 (T-ag) e do vírus da dengue (DENV) 5 . É importante ressaltar que foi demonstrado que limita a infecção por vírus de RNA como DENV 1-4 , vírus do Nilo Ocidental , vírus da encefalite equina venezuelana (VEEV) e gripe , com esta atividade de amplo espectro que se acredita ser devida à dependência muitos vírus de RNA diferentes no IMPα / β1 durante a infecção . A ivermectina também demonstrou ser eficaz contra o vírus do pseudo-vírus da DNA (PRV) in vitro e in vivo, com o tratamento com ivermectina demonstrando aumentar a sobrevida em camundongos.
A ivermectina, portanto, merece uma investigação mais aprofundada quanto a possíveis benefícios em humanos, porém devido o quadro caótico da pandemia pode ser umas das ferramentas para ser usada com acompanhamento médico adequado.
A vitamina D parece interagir com o sistema imunológico através de sua ação sobre a regulação e a diferenciação de células como linfócitos, macrófagos e células natural killer (NK), além de interferir na produção de citocinas in vivo e in vitro. Entre os efeitos imunomoduladores demonstrados destacam-se: diminuição da produção de interleucina-2 (IL-2), do interferongama (INFγ) e do fator de necrose tumoral (TNF); inibição da expressão de IL-6 e inibição da secreção e produção de autoanticorpos pelos linfócitos B.
A vitamina D pode ser apenas um marcador de gravidade em pacientes gravemente enfermos. No entanto, a literatura relata vários mecanismos fisiológicos dependentes da vitamina D, sugerindo que a deficiência de 25 (OH) D pode estar implicada na patogênese da disfunção e mortalidade de órgãos em pacientes críticos, talvez mediada por seus efeitos na imunidade e no sistema cardiovascular.
Tem um papel claramente estabelecido na resposta imune a infecções virais:
- Diminuição na produção de radicais livres.
- Inibição da polimerase do RNA da SARS-CoV-2.
- Diminuição de atividade da enzima conversora de angiotensina 2 (ACE2), que é um receptor para SARS COV-2.
O zinco é um conhecido inibidor da replicação do coronavírus. Os ensaios clínicos com pastilhas de zinco no resfriado comum demonstraram reduções modestas na duração e /ou gravidade dos sintomas.
A hidroxicloroquina (HCQ) é uma droga antimalárica / anti-inflamatória que prejudica a entrada do vírus na célula, além de facilitar a entrada do zinco intracelularmente para bloquear a polimerase de RNA dependente de RNA do SARS-CoV-2, que é a enzima central da replicação do vírus.
Os estudos retrospectivos e ensaios randomizados atualmente concluídos geralmente mostraram estes resultados: 1) quando iniciados no final do curso hospitalar e por curtos períodos de tempo, os antimaláricos parecem ser ineficazes, 2) quando iniciados mais cedo no curso hospitalar, e em pacientes ambulatoriais, os antimaláricos podem reduzir a progressão da doença, prevenir a hospitalização e estão associados à redução da mortalidade.
Diferentemente do que se propaga nas mídias políticas, a hidroxicloroquina apresenta um perfil de segurança muito bem estabelecido, sendo vendida há décadas nos balcões das farmácias até mesmo sem receita médica.
A azitromicina é um antibiótico da classe dos macrolídeos comumente usado que possui propriedades antivirais atribuídas principalmente à redução da transferência endossômica de vírions (transporte do vírus para dentro da célula), bem como aos efeitos antiinflamatórios estabelecidos. Tem sido comumente usado em estudos COVID-19 inicialmente com base em relatórios franceses que demonstram durações marcadamente reduzidas de eliminação viral, menos hospitalizações e combinação de mortalidade reduzida com HCQ em comparação com aqueles não tratados.
A doxiciclina é outro antibiótico comum com múltiplos efeitos intracelulares que podem reduzira replicação viral, o dano celular e a expressão de fatores inflamatórios. Esse medicamento não tem efeito na condução cardíaca e tem a principal ressalva de distúrbios gastrointestinais e esofagite. Assim como a azitromicina, a doxiciclina tem a vantagem de oferecer cobertura antibacteriana para infecção bacteriana superposta no trato respiratório superior. A doxiciclina pode ser útil com HCQ para pacientes nos quais a combinação HCQ-azitromicina não é desejada.
Favipiravir, um inibidor seletivo oral da RNA polimerase dependente de RNA – enzima intracelular que permite a replicação viral, está aprovado para uso ambulatorial no COVID-19 na Rússia, Índia e outros países fora dos Estados Unidos. Já foi usado anteriormente para o tratamento de algumas infecções potencialmente fatais, como o vírus Ebola, o vírus de Lassa e a raiva. Sua eficácia terapêutica foi comprovada nessas doenças. Assim como os antimaláricos e antibióticos, o favipiravir não tem estudos randomizados em grande escala concluídos até o momento, devido ao curto período de tempo da pandemia.
As manifestações de COVID-19 que levam à hospitalização e que podem levar à falha do sistema de múltiplos órgãos são atribuídas a uma tempestade de citocinas. O perfil característico de um paciente gravemente doente com COVID-19 inclui leucocitose com neutropenia relativa. É possível acompanhar ambulatorialmente estes pacientes, com monitorização diária do hemograma e PCR (Proteina C reativa) e desta forma identificar a a evolução do paciente para a fase inflamatória, permitindo a administração de imunomoduladores a fim de evitar a tempestade de citocinas que de fato é a causa da hospitalização, ventilação mecânica e óbito destes pacientes.
No COVID-19, alguns dos primeiros achados respiratórios são congestão nasal, tosse e chiado no peito. Essas características são devidas ao excesso de inflamação e ativação de citocinas.
O uso precoce de corticosteroides é uma intervenção racional para pacientes que adentram a fase inflamatória da doença, portanto quanto mais precoce o seu uso, lembrando que não é para ser utilizado na fase de replicação viral, maior a possibilidade de controle do processo inflamatório. Este manejo só é possível com o acompanhamento clinico do paciente. Aquela velha máxima do fique em casa e só vá para o hospital quando piora e, contradita a boa medicina e a perspicácia clínica do bom cuidado médico.
O estudo RECOVERY randomizou 6425 pacientes hospitalizados com COVID-19 em uma proporção de 2: 1 para dexametasona 6 mg via oral e endovenosa diariamente por até 10 dias e descobriu que a dexametasona reduziu a mortalidade (HR = 0,65, IC 95% 0,51-0,82, P <0,001).
A colchicina é uma droga antimitótica não esteroidal que bloqueia a metáfase impedindo a formação do inflamassoma além das moléculas de adesão inflamatórias.
O ensaio clínico aberto randomizado GRECCO-19 em 105 pacientes hospitalizados com COVID-19 descobriu que a colchicina foi associada a uma redução nos níveis de dímero D e melhores resultados clínicos, diminuição dos sintomas.
Vários estudos descreveram taxas aumentadas de macro e micro trombose patológica. Pacientes com COVID-19 descreveram peso no peito associado à dessaturação que sugere a possibilidade de trombose pulmonar. Isto apoia o raciocínio fisiopatológico do comprometimento endotelial como causa desta terrível complicação. Assim a avaliação dos pacientes com comorbidades, com alto risco para a doença enseja a prescrição profilática destas medicações antes da complicação tardia da doença.
Assim a aspirina 81 mg por dia pode ser administrada como um agente antiplaquetário e anti-inflamatório inicial. O uso adicional de heparina subcutânea de baixo peso molecular ou com novos fármacos anticoagulantes de curta ação em esquemas de dosagem semelhantes àqueles usados em trombo profilaxia ambulatorial.
Em um estudo retrospectivo de 2773 pacientes internados com COVID-19, 28% receberam terapia anticoagulante dentro de 2 dias de admissão e, apesar de ser usado em casos mais graves, a administração de anticoagulante foi associada a uma redução de 11 a 18% na mortalidade.
O tratamento do COVID é complexo, multifatorial e quando bem conduzido, com criterioso acompanhamento clínico, o não abandono do paciente com COVID-19, pode reduzir significativamente a morbi-mortalidade e a demanda por recursos caros e atualmente escassos, como unidades de terapia intensiva (UTI).
5/12 News FLCCC Public Statement (News) news FLCCC Alliance Statement on the Irregular Actions of Public Health Agencies and the Widespread Disinformation Campaign Against Ivermectin
Analysis of the ivermectin recommendations from WHO and others, and a call to action for all citizens, scientists, and media to counter false information. Whistleblowers can submit anonymous reports and images at the bottom of this page.
5/10 Early Faisal et al., The Professional Medical Journal, doi:10.29309/TPMJ/2021.28.05.5867 (Peer Reviewed) no recov., ↓68.4%, p=0.005 Potential use of azithromycin alone and in combination with ivermectin in fighting against the symptoms of COVID-19
RCT 100 outpatients in Pakistan, 50 treated with ivermectin, showing faster recovery with ivermectin. All patients received AZ, zinc, vitamin C, vitamin D, and paracetemol. Details of randomization were not provided. No mortality or hospi..
5/5 In Vitro Zatloukal et al. (News) (In Vitro) news News report on In Vitro results from the research institute of Prof. Zatloukal
News report on In Vitro results from the research institute of Prof. Zatloukal, showing that "ivermectin was able to reduce virus replication by a factor of 1,000 even at low concentrations".
5/5 In Silico Qureshi et al., Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1906750 (Peer Reviewed) Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with new implications
In Silico study showing inhibition of importin-α1 by ivermectin, which disrupts SARS-CoV-2 replication.
5/4 Meta Karale et al., medRxiv, doi:10.1101/2021.04.30.21256415 (Preprint) (meta analysis) meta-analysis A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients
Systematic review and meta analysis with 30 studies included in quantitative analysis, showing mortality OR 0.39 [0.22-0.70]. Subgroup analysis of trials with severity data showed mortality OR 0.10 [0.03-0.33] for mild/moderate cases.
5/3 Early Merino et al., SocArXiv Papers, doi:10.31235/osf.io/r93g4 (Preprint) hosp., ↓74.4%, p<0.001 Ivermectin and the odds of hospitalization due to COVID-19: evidence from a quasi-experimental analysis based on a public intervention in Mexico City
Analysis of Mexico City's use of an ivermectin-based medical kit, showing significantly lower hospitalization with use. Authors use logistic-regression models with matched observations, including adjustments for age, sex, COVID severity, ..
4/30 Review Kory et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001377 (Review) (Peer Reviewed) (meta analysis) review Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Review of ivermectin trials and epidemiological data, concluding that ivermectin is effective for prophylaxis and treatment, and should be globally and systematically deployed in the prevention and treatment of COVID-19.
4/19 Review DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2021-001655 (Review) (Peer Reviewed) review Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors
Review suggesting that the effectiveness of ivermectin in the cytokine storm phase of COVID-19 may be, at least in part, an anti-inflammatory effect mediated by increased activation of glycine receptors on leukocytes and possibly vascular..
4/17 Early Loue et al., J. Infectious Diseases and Epidemiology, doi:10.23937/2474-3658/1510202 (Peer Reviewed) death, ↓70.0%, p=0.34 Ivermectin and COVID-19 in Care Home: Case Report
Small quasi-randomized (patient choice) study with 25 PCR+ patients in a nursing home offered ivermectin, of which 10 chose to be treated. The mean age was 83.5 in the treatment group and 81.8 in the control group. There was lower mortali..
4/16 PrEPPEP Morgenstern et al., medRxiv, doi:10.1101/2021.04.10.21255248 (Preprint) hosp., ↓80.0%, p=0.50 Retrospective cohort study of Ivermectin as a SARS-CoV-2 pre-exposure prophylactic method in Healthcare Workers
Propensity matched retrospective prophylaxis study of healthcare workers in the Dominican Republic showing significantly lower cases with treatment, and no hospitalization with treatment (versus 2 in the PSM matched control group). The ca..
4/14 PrEPPEP Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed) severe case, ↓49.8%, p=0.01 Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin ..
4/10 In Silico Bello et al., Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1911857 (Peer Reviewed) Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets
In Silico analysis finding that the in vitro activity of ivermectin may explained by acting as an inhibitor of importin-α, dimeric 3CLpro, and Nsp9.
4/3 Review Turkia, M., Research Gate (Review) (Preprint) review A timeline of ivermectin-related events in the COVID-19 pandemic
An extensive timeline of ivermectin-related events from April 2020 to March 2021 including studies, news, health authority decisions, biased news coverage, and censorship. The author concludes that in a broader historical perspective, th..
4/1 Early Mourya et al., Int. J. Health and Clinical Research (Peer Reviewed) viral+, ↓89.4%, p<0.0001 Comparative Analytical Study of Two Different Drug Regimens in Treatment of Covid 19 Positive Patients in Index Medical College Hospital and Research Center, Indore, India
Retrospective 100 patients in India with 50 treated with ivermectin, and SOC for all patients including HCQ+AZ, showing much higher viral clearance with ivermectin. Baseline clinical status was worse in the control group. Time of testing ..
3/30 Review Wehbe et al., Front. Immunol., doi:10.3389/fimmu.2021.663586 (Review) (Peer Reviewed) review Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities
Review of how ivermectin was identified for use in COVID-19, mechanisms of action, and selected clinical trials.
3/30 Early Chahla et al., Research Square, doi:10.21203/rs.3.rs-495945/v1 (original preprint 3/30) (Preprint) no disch., ↓86.9%, p=0.004 Cluster Randomised Trials - Ivermectin Repurposing For COVID-19 Treatment Of Outpatients With Mild Disease In Primary Health Care Centers
Cluster RCT outpatients in Argentina showing signficantly faster recovery with ivermectin. There were no deaths. Cluster RCT where outpatients in Tucumán were assigned to the ivermectin group and outpatients from San Miguel de Tucumán and..
3/29 Meta Kow et al., Pharmacological Reports, doi:10.1007/s43440-021-00245-z (Peer Reviewed) (meta analysis) meta-analysis The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis
Small meta analysis of 6 RCTs showing mortality OR 0.21 [0.11-0.42]. Authors do not include two more recent RCTs with mortality results, 10 other studies with mortality results, and a total of 42 other studies including other outcomes. Au..
3/26 PrEPPEP Tanioka et al., medRxiv, doi:10.1101/2021.03.26.21254377 (Preprint) death, ↓88.2%, p=0.002 Why COVID-19 is not so spread in Africa: How does Ivermectin affect it?
Retrospective study of the 31 onchocerciasis-endemic countries using the community-directed treatment with ivermectin (CDTI) and the 22 non-endemic countries in Africa, showing significantly lower mortality per capita in the countries us..
3/25 In Silico Udofia et al., Network Modeling Analysis in Health Informatics and Bioinformatics, doi:10.1007/s13721-021-00299-2 (Peer Reviewed) In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV
In Silico analysis finding that ivermectin had the highest binding energy against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2.
3/25 In Silico Choudhury et al., Future Medicine, doi:10.2217/fvl-2020-0342 (Peer Reviewed)Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach
In Silico analysis finding that ivermectin has high binding affinity for the SARS-CoV-2 viral spike protein, main protease, replicase, and human TMPRSS2 receptors.
3/25 Late Huvemek Press Release (Preprint) no improv., ↓31.6%, p=0.28 Kovid-19 - Huvemek® Phase 2 clinical trial
Phase 2 results from a multicenter RCT of hospitalized patients in Bulgaria showing faster viral clearance, greater clinical improvement, and improved biomarkers with treatment. Ivermectin was taken on an empty stomach, potentially reduci..
3/24 Review Yagisawa et al., The Japanese Journal of Antibiotics, 74-1, Mar 2021 (Review) (Peer Reviewed) review Global trends in clinical studies of ivermectin in COVID-19
Review of ivermectin for COVID-19. Authors note that Kitasato University's project was expanded in response to the results of Caly et al. which had left questions regarding in vivo therapeutic levels, and the results of those studies were..
3/21 Early Emmerich et al., Int. J. Environ. Res. Public Health, doi:10.3390/ijerph18073371 (Peer Reviewed) Comparisons between the Neighboring States of Amazonas and Pará in Brazil in the Second Wave of COVID-19 Outbreak and a Possible Role of Early Ambulatory Treatment
Comparison between the two largest neighboring states in Brazil, Amazonas and Pará, showing more than 5 times lower mortality in Pará during the second wave when the Pará government supported early treatment and Amazonas did not, compared..
3/18 Late Del Franco et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1008 (Peer Reviewed) Ivermectin in Long-Covid Patients: A Retrospective Study
Retrospective 856 patients previously admitted to hospital for COVID-19 in Argentina, finding that ivermectin improved recovery from "long covid" symptoms.
3/12 Early Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) recov. time, ↓5.6%, p=0.87 Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and ..
3/11 Meta Nardelli et al., Signa Vitae, doi:10.22514/sv.2021.043 (Peer Reviewed) (meta analysis) death, ↓79.5%, p<0.0001 Crying wolf in time of Corona: the strange case of ivermectin and hydroxychloroquine. Is the fear of failure withholding potential life-saving treatment from clinical use?
Meta analysis of RCT mortality results showing RR 0.19, p < 0.00001.
3/11 Meta Scheim et al., OSF Preprints (Preprint) (meta analysis) meta-analysis Ivermectin sales in Valle del Cauca, Colombia, patterns of AEs, and other background re López-Medina et al. 2021
Analysis of several issues with López-Medina et al. including the atypical adverse effects in the control arm and population use of ivermectin.
3/11 Meta Bryant et al., Research Square, doi:10.21203/rs.3.rs-317485/v1 (OSF preprints 3/11) (Preprint) (meta analysis) death, ↓68.0%, p=0.006 Ivermectin for prevention and treatment of COVID-19 infection: a systematic review and meta-analysis
Systematic review and meta analysis of 21 RCTs finding mortality RR 0.32 [0.14-0.72], and prophylaxis case RR 0.14 [0.09-0.21].
3/11 Meta Scheim et al., OSF Preprints (Preprint) (meta analysis) meta-analysis Protocol violations in López-Medina et al.: 38 switched ivermectin (IVM) and placebo doses, failure of blinding, widespread IVM sales OTC in Cali, and nearly identical AEs for the IVM and control groups
Report on protocol violations in López-Medina et al.
3/10 In Vitro Yesilbag et al., Virus Research, doi:10.1016/j.virusres.2021.198384 (Peer Reviewed) (In Vitro) in vitro Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro
In Vitro study showing that ivermectin can inhibit infection of bovine respiratory disease viral agents BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM and in a dose-dependent manner.
3/9 Late Pott-Junior et al., Toxicology Reports, doi:10.1016/j.toxrep.2021.03.003 (Peer Reviewed) ventilation, ↓85.2%, p=0.25 Use of ivermectin in the treatment of Covid-19: a pilot trial
Small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe and re..
3/8 Early Chamie-Quintero et al., OSF Preprints (Preprint) Ivermectin for COVID-19 in Peru: 14-fold reduction in nationwide excess deaths, p=.002 for effect by state, then 13-fold increase after ivermectin use restricted
Analysis of ivermectin use in Peru concluding that ivermectin most likely caused a 14 times reduction in excess deaths in Peru, prior to a 13 times increase after reversal of ivermectin use. Authors conclude that the results strongly sugg..
3/8 Late Guzman et al., medRxiv, doi:10.1101/2021.03.04.21252084 (Preprint) Factors associated with increased mortality in critically ill COVID-19 patients in a Mexican public hospital: the other faces of health system oversaturation
Retrospective 196 critically ill patients in Mexico. Patients overlap with the existing RCT by Beltran-Gonzalez (NCT04391127). This preprint shows a larger treated population and greater (non-statistically significant) improvement with iv..
3/8 Late Galan et al., Pathogens and Global Health, doi:10.1080/20477724.2021.1890887 (Peer Reviewed) Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection
RCT 168 very late stage severe condition hospitalized patients comparing CQ, HCQ, and ivermectin not showing significant differences. Authors were unable to add a control arm due to ethical issues. Authors claim that "the mortality ..
3/5 Safety Descotes, J., ImmunoSafe Consultance (Preprint) safety analysis Medical Safety of Ivermectin
Safety analysis of >350 articles showing that ivermectin has an excellent safety profile. The author notes that "no severe adverse event has been reported in dozens of completed or ongoing studies involving thousands of participants..
3/4 Early López-Medina et al., JAMA, doi:10.1001/jama.2021.3071 (Peer Reviewed) death, ↓66.8%, p=0.50 Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial
An open letter, signed by >100 physicians, concluding this study is fatally flawed can be found at . Phone survey based RCT with low risk patients, 200 ivermectin and 198 control, showing lower mortality, lower disease progression, lo..
3/1 In Silico Saha et al., Structural Chemistry, doi:10.1007/s11224-021-01776-0 (preprint 3/1) (Peer Reviewed) The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2
In SIlico analysis predicting that ivermectin has a large binding affinity for the SARS-CoV-2 spike protein. Three different computer modeling techniques show that ivermectin can inhibit SARS-CoV-2 entrance via hACE2.
2/23 Late Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Peer Reviewed) death, ↓14.4%, p=1.00 Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 36 low dose ivermectin and 37 control patients not finding significant differences. NCT04391127.
2/20 News BIRD Meeting 20th February 2021 (News) news BIRD Meeting 20th February 2021
The British Ivermectin Recommendation Development (BIRD) panel, with dozens of multi-national scientists & doctors, issued sweeping recommendations for the immediate global use of ivermectin.
2/16 Early Elalfy et al., J. Med. Virol., doi:10.1002/jmv.26880 (Peer Reviewed) viral+, ↓86.9%, p<0.0001 Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1
Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.
2/15 PrEPPEP Behera et al., Research Square, doi:10.21203/rs.3.rs-208785/v1 (Preprint) cases, ↓83.0%, p<0.001 Prophylactic role of ivermectin in SARS-CoV-2 infection among healthcare workers
Prospective prophylaxis study with 3,532 healthcare workers, 2,199 receiving two-dose ivermectin prophylaxis, showing adjusted relative risk of confirmed COVID-19 with treatment 0.17 [0.12-0.23] p<0.001. 186 patients took only the first ..
2/12 Early Schwartz, E., International Ivermectin for Covid Conference, April 24-25, 2021 (Preprint) hosp., ↓70.2%, p=0.34 Ivermectin vs. placebo treatment in non-hospitalized patients with COVID-19 - a double blind, randomized controlled trial
Double blind RCT for mild-moderate COVID-19 outpatients in Israel showing significantly faster reduction in viral load with treatment, and lower hospitalization with treatment. The one treatment hospitalization was a few hours after treat..
2/10 Late Lima-Morales (Peer Reviewed) death, ↓77.7%, p<0.001 Effectiveness of a multidrug therapy consisting of ivermectin, azithromycin, montelukast and acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico
Prospective trial of 768 COVID-19 outpatients in Mexico, 481 treated with ivermectin, AZ, montelukast, and aspirin, and 287 control patients with various treatments, showing significantly lower mortality and hospitalization, and significa..
2/2 Early Mohan et al., Research Square, doi:10.21203/rs.3.rs-191648/v1 (Preprint) no recov., ↓62.5%, p=0.27 Ivermectin in mild and moderate COVID-19 (RIVET-COV): a randomized, placebo-controlled trial
RCT in India with low risk patients, comparing 24mg ivermectin, 12mg ivermectin, and placebo showing non-statistically significant improvements in recovery and PCR+ status (day 5 both arms, day 7 24mg only) with treatment, and showing gre..
1/29 Meta Cobos-Campos et al., Clin. Res. Trials, 2021, doi:10.15761/CRT.1000333 (Peer Reviewed) (meta analysis) meta-analysis Potential use of ivermectin for the treatment and profilaxis of SARS-CoV-2 infection: Efficacy of ivermectin for SARS-CoV-2
Review finding that there appears to be sufficient evidence to recommend ivermectin for the treatment of COVID-19, especially in the early stages of the disease.
1/27 Meta Castaneda-Sabogal et al., medRxiv, doi:10.1101/2021.01.26.21250420 (Preprint) (meta analysis) meta-analysis Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis
Student-written meta analysis of a very small subset of studies exhibiting very high bias and significant flaws. Some of the problems: - As of the publication date, there are 35 studies, authors include only 4. (They list 5, but two are ..
1/25 In Silico Eweas et al., Frontiers in Microbiology, doi:10.3389/fmicb.2020.592908 (Peer Reviewed) Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2
Molecular docking analysis showing that ivermectin efficiently binds to the viral S protein as well as the human cell surface receptors ACE-2 and TMPRSS2; therefore, it might be involved in inhibiting the entry of the virus into the host ..
1/23 Animal Errecalde et al., Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017 (Peer Reviewed) animal study Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
Animal study of a novel spray formulation of ivermectin, showing an advantage of the spray formulation in terms of fast attainment of high and persistent ivermectin concentrations in nasopharyngeal tissue.
1/21 Early Chamie-Quintero et al., Preprint, doi:10.2139/ssrn.3765018 (Preprint) Sharp Reductions in COVID-19 Case Fatalities and Excess Deaths in Peru in Close Time Conjunction, State-By-State, with Ivermectin Treatments
Analysis of ivermectin usage within states in Peru showing sharp reductions in COVID-19 deaths corresponding to the usage of ivermectin treatment.
1/20 In Vitro Mody et al., Communications Biology, doi:10.1038/s42003-020-01577-x (Peer Reviewed) (In Vitro) in vitro Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents
Computational molecular modeling screening and in vitro analysis for inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme, showing that ivermectin blocked more than 85% of 3CLpro activity of SARS-CoV-2. Antiviral activity of ivermectin..
1/19 Late Shahbaznejad et al., Clinical Therapeutics, doi:10.1016/j.clinthera.2021.04.007 (partial results available 1/19) (Peer Reviewed) death, ↑197.1%, p=1.00 Effect of ivermectin on COVID-19: A multicenter double-blind randomized controlled clinical trial
RCT in Iran showing shorter time to recovery and shorter hospitalization time with ivermectin. There were no adverse effects. There was one death in the treatment group, the patient was in critical condition at baseline and died within 24..
1/19 Meta Hill et al., Research Square, doi:10.21203/rs.3.rs-148845/v1 (Preprint) (meta analysis) death, ↓75.0%, p=0.0002 Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection
Meta analysis of 18 ivermectin RCTs with 2,282 patients showing faster viral clearance (dose and duration dependent), improved clinical recovery, and lower hospitalization and mortality. In six RCTs of moderate or severe infection, there ..
1/16 Early Raad et al., ChiCTR2000033627 (Preprint) hosp., ↓85.7%, p=0.24 In vivo use of ivermectin (IVR) for treatment for corona virus infected patients (COVID-19): a randomized controlled trial
RCT in Lebanon showing significantly lower viral load at day 3, and lower hospitalization. Results are from: 
1/16 Early Bukhari et al., medRxiv, doi:10.1101/2021.02.02.21250840 (results 1/16) (Preprint) viral+, ↓82.4%, p<0.0001 Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease
RCT of relatively low risk hospitalized patients with 50 ivermectin and 50 control patients showing significantly faster viral clearance with treatment. 9 patients in the treatment arm were lost to followup compared with 5 in the control ..
1/13 Early, Late, PrEP, PEP Kory et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.643369 (Review) (Peer Reviewed) review Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19. This paper was censored by the journal after acceptance [..
1/12 Late Okumuş et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06104-9 (preprint 1/12) (Peer Reviewed) death, ↓33.3%, p=0.55 Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Severe COVID-19 Patients
Small RCT for severe COVID-19 comparing the addition of ivermectin to SOC (low dose HCQ+AZ+favipiravir), with 30 treatment and 30 control patients in Turkey, showing lower mortality and faster clinical recovery. Authors also investigate t..
1/11 PrEPPEP Chahla et al., medRxiv, doi:10.1101/2021.03.26.21254398 (Preprint) cases, ↓95.2%, p=0.002 A randomized trial - intensive treatment based in ivermectin and iota-carrageenan as pre-exposure prophylaxis for COVID-19 in healthcare agents
Prophylaxis RCT for ivermectin and iota-carrageenan in Argentina, 117 healthcare workers treated with ivermectin and iota-carrageenan, and 117 controls, showing significantly lower cases with treatment. There were no moderate/severe cases..
1/11 N/A Bousquet-Melou et al., Preprint, doi:10.22541/au.161047848.80388481/v1 (Preprint) dosing study Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients
Animal dosing study with an obese dog model concluding that ivermectin maintenance doses should be based on lean body weight and not the total body weight in obese subjects, while the loading dose should be based on the total body weight.
1/10 Review Formiga et al., J. Control Release, doi:10.1016/j.jconrel.2020.10.009 (Review) (Peer Reviewed)review Ivermectin: an award-winning drug with expected antiviral activity against COVID-19
Review hypothesizing that micro- and nanotechnology-based formulations of ivermectin for the pulmonary delivery of ivermectin may be beneficial for use with COVID-19.
1/9 Early Kirti et al., medRxiv, doi:10.1101/2021.01.05.21249310 (Preprint) death, ↓88.7%, p=0.12 Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized placebo-controlled trial
RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 ..
1/8 Early Chamie, J. (News) news COVID-19 in Mexico
Comparison of COVID-19 death rates in Mexico showing that the only state using ivermectin has a dramatically lower rate.
1/6 Early Babalola et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcab035 (preprint 1/6) (Peer Reviewed) viral+, ↓63.9%, p=0.11 Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos
Small RCT comparing ivermectin 6mg & 12mg q84hr with lopinavir/ritonavir, showing a statistically significant and dose dependent effect of ivermectin on reducing the time to PCR-.
1/6 PrEPPEP Hirsch et al., Microbiology & Infectious Diseases (Peer Reviewed) Ivermectin as Prophylaxis Against COVID-19 Retrospective Cases Evaluation
Report on ivermectin prophylaxis for healthcare workers in a hospital in Argentina, showing 0 cases in the 162 participants. Dosage was 0.2mg/kg weekly for eight weeks, followed by 4 months rest.
1/3 Early, Late, PrEP, PEP Lawrie et al., Preprint (Preprint) (meta analysis) death, ↓83.0%, p<0.0001 Ivermectin reduces the risk of death from COVID-19 – a rapid review and meta-analysis in support of the recommendation of the Front Line COVID-19 Critical Care Alliance
Meta analysis confirming the effectiveness of ivermectin for COVID-19, showing ivermectin treatment mortality relative risk RR 0.17 [0.18-0.35] and prophylaxis cases RR 0.12 [0.08-0.18].
12/31 Late Wijaya et al., Cermin Dunia Kedokteran, 47:7 (Peer Reviewed) Ivermectin as a Potential Therapeutic Agent for COVID-19 – case studies
Case report on 3 confirmed cases of COVID-19 with significant clinical and radiological improvement after a single dose of ivermectin.
12/31 Animal Madrid et al., Heliyon, doi:10.1016/j.heliyon.2020.e05820 (Peer Reviewed) animal study Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation
In vivo analysis of the safety of high dose ivermectin with a Corydoras fish animal model.
12/30 Review McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) review Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may ..
12/30 Early Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 (Peer Reviewed) Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection
Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region. At least two of z..
12/27 Meta Hill, A., Preprint (Preprint) (meta analysis) meta-analysis Meta-analysis of clinical trials of ivermectin to treat COVID-19 infection
WHO-funded meta analysis showing ivermectin treatment mortality relative risk RR 0.17 [0.08-0.35] for RCTs and RR 0.28 [0.13-0.62] for RCTs and observational studies, and confirming a dose-response effect.
12/24 In Vitro Jeffreys et al., bioRxiv, doi:10.1101/2020.12.23.424232 (Preprint) (In Vitro) in vitroRemdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2
In Vitro study showing enhanced antiviral activity of ivermectin and remdesivir in combination.
12/20 PrEPPEP Vallejos et al., Trials, doi:10.1186/s13063-020-04813-1 (Preprint) cases, ↓73.4%, p<0.0001 Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): a structured summary of a study protocol for a randomized controlled trial
Report on ivermectin prophylaxis in a hospital in Argentina showing lower cases for healthcare workers taking ivermectin. Preliminary results from: .
12/18 Early, Late, PrEP, PEP Kory et al., FLCCC Alliance (Preprint) (meta analysis) death, ↓69.0%, p<0.0001 Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19.
12/15 PrEPPEP Alam et al., European Journal ofMedical and Health Sciences, doi:10.24018/ejmed.2020.2.6.599 (Peer Reviewed) cases, ↓90.6%, p<0.0001 Ivermectin as Pre-exposure Prophylaxis for COVID-19 among Healthcare Providers in a Selected Tertiary Hospital in Dhaka – An Observational Study
91% reduction in COVID-19 cases with ivermectin prophylaxis. 118 healthcare workers in Bangladesh, 58 receiving ivermectin 12mg monthly, showing RR 0.094, p < 0.0001.
12/15 Early Afsar et al., SSRN (Preprint) symptoms, ↓92.2%, p=0.04 Ivermectin Use Associated with Reduced Duration of COVID-19 Febrile Illness in a Community Setting
Small 95 patient study in Pakistan adding ivermectin to standard of care (HCQ+AZ) for outpatients with mild/moderate suspected COVID-19, showing faster resolution of fever with ivermectin. The low dose HCQ used in this study may not reac..
12/11 Early Hussain et al., International Journal of Molecular and Immuno Oncology, doi:10.25259/IJMIO_30_2020 (Peer Reviewed) Outcome of ivermectin and doxycycline in cancer patients with COVID-19: A positive experience in Bangladesh
Small case study of ivermectin + doxycycline with 8 cancer patients, with all patients becoming PCR- by day 6 when tested again.
12/7 Early Chaccour et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720 (preprint 12/7) (Peer Reviewed) symp. prob., ↓52.9%, p<0.05 The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial
Tiny RCT for early treatment of mild COVID-19 in low risk patients, with 12 400mcg/kg single dose ivermectin patients and 12 control patients, showing significantly faster viral load reduction and symptom improvement with ivermectin. Ave..
12/4 Meta Kalfas et al., medRxiv, doi:10.1101/2020.11.30.20236570 (Preprint) meta-analysis The therapeutic potential of ivermectin for COVID-19: a systematic review of mechanisms and evidence
Review of ivermectin mechanisms and 8 trials, showing positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression, and decreased duration of hospital admission in patients across all stages of c..
12/4 In Vitro Surnar et al., ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179 (Peer Reviewed) (In Vitro) in vitro Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19
In Vitro analysis of ivermectin with orally administrable nanoparticles showing efficacy for decreasing expression of the viral spike protein and ACE2. Inhibition of nuclear transport activities mediated through proteins such as importin ..
12/2 Early Ahmed et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.191 (Peer Reviewed) symptoms, ↓85.0%, p=0.09 A five day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
Small 72 patient RCT of ivermectin and ivermectin + doxycycline showing faster recovery with ivermectin. Ivermectin group: 12mg daily for 5 days Ivermectin + doxycycline: 12mg ivermectin single dose, 200mg doxycycline + 100mg bid 4 days
12/2 Early Chamie, J. (News) news The effect of using ivermectin to control COVID-19 in Chiapas
After starting to distribute ivermectin in drug kits in July, the Mexican state of Chiapas has seen a dramatic divergence from other states with much lower mortality [1, 2].
12/1 Early Alonso et al., (Preprint) death, ↓91.8%, p=0.009 COVID-19: Uso de ivermectina
Observational study in Argentina showing significantly lower mortality in the 60 days after adopting ivermectin compared to the 60 days before, relative risk RR 0.082, p=0.003.
11/28 PrEPPEP Bernigaud et al., Annals of Dermatology and Venereology, doi:10.1016/j.annder.2020.09.231 (Peer Reviewed) death, ↓99.4%, p=0.08 Ivermectin benefit: from scabies to COVID-19, an example of serendipity
69 residents of a French care home, median age 90, were treated with ivermectin for a scabies outbreak. 3,062 residents in 45 nearby comparable homes were used as controls. 7 of 69 treated patients had probable or certain COVID-19, with ..
11/28 PrEPPEP Hellwig et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106248 (Peer Reviewed) cases, ↓78.0%, p<0.02 A COVID-19 Prophylaxis? Lower incidence associated with prophylactic administration of Ivermectin
Analysis of COVID-19 cases vs. widespread prophylactic use of ivermectin for parasitic infections showing significantly lower incidence of COVID-19 cases.
11/24 Late Niaee et al., Research Square, doi:10.21203/rs.3.rs-109670/v1 (Preprint) death, ↓81.8%, p=0.001 Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial
82% lower mortality with ivermectin. RCT with 180 hospitalized patients showing reduced mortality and hospital stay with ivermectin, with a wide margin of safety. All patients received SOC including low dose HCQ.
11/22 Animal de Melo et al., bioRxiv, doi:10.1101/2020.11.21.392639 (Preprint) animal study Anti-COVID-19 efficacy of ivermectin in the golden hamster
Hamster study finding significantly lower COVID-19 pathology although not finding lower viral load at the dosage used. Ivermectin dramatically reduced the Il-6/Il-10 ratio in lung tissue, which may account for the more favorable clinical ..
11/18 Late Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223 (Preprint) death, ↓99.1%, p=0.04 Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience
Retrospective 976 hospitalized patients with 34 treated with ivermectin showing ivermectin mortality relative risk RR 0.13, p = 0.04.
11/17 PrEPPEP Carvallo et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1007 (Peer Reviewed) cases, ↓99.9%, p<0.0001 Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel
Prophylaxis study using ivermectin and iota-carrageenan showing 0 of 788 cases from treated healthcare workers, compared to 237 of 407 control. The authors later reported that carrageenan is not necessary in this protocol .
11/14 Late Spoorthi et al., IAIM, 2020, 7:10, 177-182 (Peer Reviewed) recov. time, ↓21.1%, p=0.03Utility of Ivermectin and Doxycycline combination for the treatment of SARSCoV-2
100 patient prospective trial of ivermectin + doxycycline showing reduced time to symptom resolution and shorter hospital stay with treatment.
11/13 PrEPPEP Elgazzar et al., Research Square, doi:10.21203/rs.3.rs-100956/v2 (Preprint) cases, ↓80.0%, p=0.03 Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic
RCT for prophylaxis with ivermectin showing a significant reduction in cases with treatment. Relative risk of COVID-19 case RR 0.2, p = 0.03 This paper also reports a treatment study .
11/13 Late Elgazzar et al., Research Square, doi:10.21203/rs.3.rs-100956/v2 (Preprint) death, ↓91.7%, p<0.0001 Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic
RCT comparing ivermectin + SOC vs. HCQ + SOC, showing a significant reduction in mortality with ivermectin. Mortality relative risk: RR 0.11, p = 0.12 (mild/moderate cases) RR 0.1, p < 0.001 (severe cases) The HCQ dose is relatively low..
11/11 Late Camprubí et al., PLoS ONE, 15:11, doi:10.1371/journal.pone.0242184 (Peer Reviewed) ventilation, ↓40.0%, p=0.67 Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients
Tiny 26 patients retrospective study of ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses. All patients received HCQ whi..
11/11 Early Krolewiecki et al., SSRN (Preprint) Antiviral Effect of High-Dose Ivermectin in Adults with COVID-19: A Pilot Randomised, Controlled, Open Label, Multicentre Trial
Viral load RCT finding a concentration dependent antiviral activity of oral high dose ivermectin at a dosing regimen that is well tolerated. There was no significant difference in viral load reduction between groups overall, but a signif..
11/10 Review Turkia, M., ResearchGate (Review) (Preprint) review FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review
Review suggesting that ivermectin should be used based on existing data suggesting significant benefits, and that waiting for additional data may result in significant harm.
11/4 Early Cadegiani et al., medRxiv, doi:10.1101/2020.10.31.20223883 (Preprint) death, ↓78.3%, p=0.50 Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, ev..
11/3 Early, Late Morgenstern et al., J. Clinical Trials (preprint 11/3) (Peer Reviewed) The Use of Compassionate Ivermectin in the Management of SymptomaticOutpatients and Hospitalized Patients with Clinical Diagnosis of Covid-19 at theCentro Medico Bournigal and at the Centro Medico Punta Cana, GrupoRescue, Dominican Republic, from May 1 to August 10, 2020
Retrospective 3,099 outpatients treated with ivermectin in an ER. Of 2,706 treated on an outpatient basis, 18 were subsequently hospitalized, 2 in the ICU, and there was one death (0.04%). The average treatment delay for patients treated..
11/3 PrEPPEP Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) cases, ↓53.8%, p<0.0001 Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, ..
11/2 Animal Arévalo et al., Scientific Reports, doi:10.1038/s41598-021-86679-0 (preprint 11/2/20) (Peer Reviewed) animal study Ivermectin reduces in vivo coronavirus infection in a mouse experimental model
Mouse study showing ivermectin reducing MHV viral load and disease. MHV is a type 2 family RNA coronavirus similar to SARS-CoV2.
10/31 PrEPPEP Chang et al., ResearchGate (Preprint) COVID-19: Effectiveness of pre-exposure prophylaxis with ivermectin in exposed persons
Pre-exposure prophylaxis study with 129 people split into high/low exposure groups, with each group split into different dosing regimens, showing higher effectivess with more frequent doses. High-exposure group: every 7 days dosing: 0 o..
10/31 Early Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed) hosp., ↑13.9%, p=0.45 Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
Retrospective 717 patients in Brazil showing OR 1.17 [0.72-1.90] for ivermectin. This paper focuses on HCQ, event counts for ivermectin are not provided. With significant correlation between the variables used, including overlap in the pr..
10/26 Late Hashim et al., medRxiv, doi:10.1101/2020.10.26.20219345 (Preprint) death, ↓66.7%, p=0.27 Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-19 patients in Baghdad, Iraq
RCT 70 ivermectin+doxycycline patients and 70 control patients showing reduced time to recovery and reduced mortality with treatment. Greater success was seen when ivermectin+doxycycline was administered earlier.
10/22 PrEPPEP Guerrero et al., Colombia Médica, doi:10.25100/cm.v51i4.4613 (Peer Reviewed) COVID-19: The Ivermectin African Enigma
Study of African Programme for Onchocerciasis Control (APOC) countries, which used ivermectin, with non-APOC countries in Africa, showing 28% lower mortality for APOC countries, relative risk RR = 0.72 [0.67-0.78]. See also  and the au..
10/19 PrEPPEP Carvallo et al., NCT04425850 (Preprint) cases, ↓96.3%, p<0.0001 Usefulness of Topic Ivermectin and Carrageenan to Prevent Contagion of Covid 19 (IVERCAR)
Prophylaxis study using ivermectin and carrageenan showing 0 of 131 cases from treated healthcare workers, compared to 11 of 98 control. The effect is likely to be primarily due to ivermectin - the author has later reported that carragee..
10/13 Early Chaccour et al., Scientific Reports, doi:10.1038/s41598-020-74084-y (Peer Reviewed) animal study Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats
Study showing that nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats. Authors note that additional experiments are required to assess the safety of this formulation in larger animals.
10/13 Late Rajter et al., Chest, doi:10.1016/j.chest.2020.10.009 (Peer Reviewed) death, ↓46.0%, p=0.04 Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID-19 (ICON study)
Retrospective 280 hospitalized patients showing lower mortality with ivermectin (13.3% vs 24.5%), propensity matched odds ratio OR 0.47 [0.22-0.99], p=0.045.
10/9 Early Mahmud et al., Journal of International Medical Research, doi:10.5061/dryad.qjq2bvqf6 (preprint 10/9/20) (Peer Reviewed) death, ↓85.7%, p=0.25 Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial
RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are n..
10/8 Theory Francés-Monerris et al., ChemRxiv, doi:10.26434/chemrxiv.12782258.v1 (Preprint) (Theory) theory Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent
In silico study showing that ivermectin is capable of interfering in different key steps of the SARS-CoV-2 replication cycle.
10/8 Late Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint) death, ↓17.1%, p=0.01 Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10..
9/30 Late Chachar et al., International Journal of Sciences, 9:31-35, doi:10.18483/ijSci.2378 (Peer Reviewed) no recov., ↓10.0%, p=0.50 Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients
Small RCT with 25 ivermectin and 25 control patients, not finding a significant difference in recovery at day 7.
9/24 Late Khan et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.08.007 (Letter) death, ↓87.0%, p<0.05 Ivermectin treatment may improve the prognosis of patients with COVID-19
Retrospective 115 ivermectin patients and 133 control patients showing significantly lower death and faster viral clearance. Some potential issues and the authors' response can be found in [1, 2].
9/22 In Vitro Li et al., J. Cellular Physiology, doi:10.1002/jcp.30055 (Peer Reviewed) (In Vitro) in vitroQuantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment
In Vitro study showing Ivermectin is a safe wide-spectrum antiviral against SARS-CoV-2, human papillomavirus (HPV), Epstein–Barr virus (EBV), and HIV. Authors note that the combination of ivermectin and other drugs might result in more f..
9/15 Early Carvallo et al., medRxiv, doi:10.1101/2020.09.10.20191619 (Preprint) death, ↓87.9%, p=0.05 Safety and Efficacy of the combined use of ivermectin, dexamethasone, enoxaparin and aspirin against COVID-19
Prospective trial of ivermectin, dexamethasone, enoxaparin, and aspirin. There was one death from 167 patients for 0.59% mortality, compared to an estimated overall mortality rate in Argentina of 2.1%. For moderate to severe cases needi..
9/15 Review Jans et al., Cells 2020, 9:9, 2100, doi:10.3390/cells9092100 (Review) (Letter) reviewIvermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?
Review of ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2. Cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, V..
9/6 Review DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2020-001350 (Review) (Peer Reviewed) review Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19
Review suggesting that ivermectin may be useful for late stage COVID-19. Authors note that ivermectin, in doses at or modestly above the standard clinical dose, may have important clinical potential for managing disorders associated with ..
9/3 Late Podder et al., IMC J. Med. Science, 14:2, July 2020 (Peer Reviewed) recov. time, ↓16.1%, p=0.34 Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study
Small RCT with 32 ivermectin patients and 30 control patients. The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days vs. 6.33 ± 4.23 days in the control arm, p > 0.05. Negative PCR results were not signific..
8/31 Late Kishoria et al., Paripex - Indian Journal of Research, doi:10.36106/paripex/4801859 (Peer Reviewed) no disch., ↑7.5%, p=1.00 Ivermectin as adjuvant to hydroxychloroquine in patients resistant to standard treatment for SARS-CoV-2: results of an open-label randomized clinical study
Small RCT of hospitalized patients in India with 19 ivermectin patients and 13 control patients, with all receiving SOC including HCQ, showing no significant differences. The patient population is biased because the study recruited patien..
8/28 PrEPPEP Shouman et al., Journal of Clinical and Diagnostic Research, doi:10.7860/JCDR/2020/46795.0000 (Peer Reviewed) symp. case, ↓91.3%, p<0.001 Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt: A Randomised Clinical Trial
PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group, adjusted odds ratio OR 0.087, p ..
8/15 Early Espitia-Hernandez et al., Biomedical Research, 31:5 (Peer Reviewed) viral+, ↓97.2%, p<0.0001 Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study
Small study with 28 patients treated with ivermectin + AZ + cholecalciferol and 7 control patients. All treated patients were PCR- at day 10 while all control patients remained PCR+. The mean duration of symptoms was 3 days in the treatm..
8/14 Late Bhattacharya et al., Int. J. Scientific Research, doi:10.36106/ijsr/7232245 (Peer Reviewed) Observational Study on Clinical Features, Treatment and Outcome of COVID 19 in a tertiary care Centre in India- a retrospective case series
Retrospective 148 hospitalized patients showing triple therapy with ivermectin + atorvastatin + N-acetylcysteine resulted in a 1.35% case fatality rate which was well below the national average.
7/31 Review Vora et al., Indian Journal of Tuberculosis, doi:10.1016/j.ijtb.2020.07.031 (Review) (Peer Reviewed) review White paper on Ivermectin as a potential therapy for COVID-19
Panel review of ivermectin reporting that "ivermectin in the dose of 12mg BD alone or in combination with other therapy for 5–7 days may be considered as safe therapeutic option for mild moderate or severe cases of Covid-19 infection..
7/31 Late Chang et al., ResearchGate (Preprint) Post-acute or prolonged COVID-19: ivermectin treatment for patients with persistent symptoms or post-acute symptoms
Report on 33 patients with persistent or post-acute symptoms treated with ivermectin, showing a high rate of clinical improvement.
7/31 Theory Chang et al., ResearchGate, doi:10.13140/RG.2.2.34561.48483/2 (Preprint) (Theory) theoryCOVID-19: Post-exposure prophylaxis with ivermectin in contacts. At Homes, Places of Work, Nursing Homes, Prisons, and Others
Proposed PEP protocol based on ivermectin.
7/31 Late Alam et al., Journal of Bangladesh College of Physicians and Surgeons, doi:10.3329/jbcps.v38i0.47512 (Peer Reviewed) A Case Series of 100 COVID-19 Positive Patients Treated with Combination of Ivermectin and Doxycycline
Case study of 100 patients treated with ivermectin and doxycycline, with no ICU admission, deaths, or serious side effects reported.
7/31 Late Rahman et al., J. Bangladesh Coll. Phys. Surg. 38, 5-9, doi:10.3329/jbcps.v38i0 (Peer Reviewed) Comparison of Viral Clearance between Ivermectin with Doxycycline and Hydroxychloroquine with Azithromycin in COVID-19 Patients
Comparison of 200 patients treated with ivermectin + doxycycline and 200 treated with HCQ + AZ. The HCQ + AZ group had more severe cases at baseline. Viral clearance was faster with ivermectin + doxycycline. Ivermectin dose is given all o..
7/14 Early Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 (Peer Reviewed) hosp., ↓80.6%, p=0.23 A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients
Small 116 patient RCT with low-risk patients comparing ivermectin+doxycycline and HCQ+AZ, showing lower hospitalization, higher viral clearance, and faster symptom resolution and viral clearance with ivermectin+doxycycline. Mid-recovery r..
7/8 Late Gorial et al., medRxiv, doi:10.1101/2020.07.07.20145979 (Preprint) death, ↓71.0%, p=1.00 Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial)
Small trial of hospitalized patients with 16 of 87 patients being treated with ivermectin showing a significantly lower mean hospital stay with ivermectin: 7.62 vs. 13.22 days, p=0.00005. 0 of 16 ivermectin patients died vs. 2 of 71 cont..
6/19 Theory Lehrer et al., In Vivo, 34:5, 3023-3026, doi:10.21873/invivo.12134 (Theory) theoryIvermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2
In silico analysis showing ivermectin docking which may interfere with the attachment of the spike to the human cell membrane.
6/16 Early Ramos et al., Preprint (Preprint) Intervención de la Ivermectina Pre-Hospitalaria para la Modificación de la Evolución del Covid19. Estudio realizado en Perú
Prospective study of 63 outpatients in Peru treated with ivermectin, reporting significant improvement within 24 hours.
6/12 Review Heidary et al., The Journal of Antibiotics, 73, 593–602, doi:10.1038/s41429-020-0336-z (Review) (Peer Reviewed) review Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen
Review of the antimicrobial, antiviral, and anti-cancer properties of ivermectin. Antiviral effects have been reported for Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki For..
5/2 Early Chang, G., Research Gate, doi:10.13140/RG.2.2.34689.48482/7 (Preprint) Inclusión de la ivermectina en la primera línea de acción terapéutica para COVID-19
Peru observational case study of 7 patients treated with ivermectin, showing improvement and resolution of fever within 48 hours, and 100% recovery.
4/21 Review Bray et al., Antiviral Res., doi:10.1016/j.antiviral.2020.104805 (Review) (Preprint) reviewIvermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses
Responses to Caly et al., and the author's reply. The original authors note that "ivermectin's key direct target in mammalian cells is a not a viral component, but a host protein important in intracellular transport; the fact that it..
4/3 In Vitro Caly et al., Antiviral Research, doi:10.1016/j.antiviral.2020.104787 (Peer Reviewed) (In Vitro) in vitro The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
In Vitro study showing that ivermectin is an inhibitor of SARS-CoV-2, with a single addition to Vero-hSLAM cells 2h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48h. Note that this was a proof of con..
2013 N/A Guzzo et al., J. Clinical Pharmacology, doi:10.1177/009127002237994 (Peer Reviewed) safety analysis Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects
Safety study concluding that ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-appr
5/17 Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis - not included in study count) meta-analysis v110 HCQ for COVID-19: real-time meta analysis of 245 studies
• 100% of the 29 early treatment studies report a positive effect (13 statistically significant in isolation). • Random effects meta-analysis with pooled effects using the most s..
5/17 PrEP Syed et al., medRxiv, doi:10.1101/2021.05.17.21257012 (Preprint) symp. case, ↑59.7%, p=0.41 Pre-Exposure Prophylaxis with Various Doses of Hdroxychloroquine among high-risk COVID 19 Healthcare Personnel: CHEER randomized controlled trial
Small PrEP RCT of low risk patients, showing no significant differences. Authors report that there was no hospitalization, ICU care or death from COVID-19, however table 3 shows events marked "requiring hospitalization". NCT0435..
5/16 PrEP Rojas-Serrano et al., medRxiv, doi:10.1101/2021.05.14.21257059 (Preprint) symp. case, ↓82.0%, p=0.12 Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial
Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, p = 0.12. NCT04318015. If the trial is continued and the same event rate is observed, statistical significance will be reached aft..
5/12 Early Drancourt et al., Viruses, doi:10.3390/v13050890 (Peer Reviewed) SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment
Retrospective 3,737 patients in France, showing lower risk of persistent viral shedding with HCQ+AZ treatment.
5/10 Late Sammartino et al., PLOS One, doi:10.1371/journal.pone.0251262 (Peer Reviewed) death, ↑240.0%, p=0.002 Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis
Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar..
5/1 Late De Rosa et al., J. Clin. Med., doi:10.3390/jcm10091951 (Peer Reviewed) death, ↓35.0%, p=0.003 Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry
Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum..
4/30 Late Bosaeed et al., SSRN (Peer Reviewed) death, ↓3.7%, p=0.91 Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT): An Open-Label, Multicentre, Randomised, Controlled Trial
RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of e..
4/29 Late Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 (Peer Reviewed) death, ↓19.5%, p=0.09 Decreased In-Hospital Mortality Associated with Aspirin Administration in Hospitalized Patients Due to Severe COVID-19
Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.
4/28 Late Kokturk et al., Respiratory Medicine, doi:10.1016/j.rmed.2021.106433 (Peer Reviewed) death, ↑3.8%, p=0.97 The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients
Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment.
4/27 Late Réa-Neto et al., Scientific Reports, doi:10.1038/s41598-021-88509-9 (Peer Reviewed) death, ↑57.0%, p=0.20 An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients
Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247.
4/26 Late Mohandas et al., (Peer Reviewed) death, ↑81.0%, p=0.007 Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective study
Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatm..
4/23 Late Toya et al., SSRN (Preprint) A Cross-Country Analysis of the Determinants of COVID-19 Fatalities
Country based analysis finding lower mortality with the use of HCQ.
4/22 Late Reis et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.6468 (Peer Reviewed) death, ↓66.0%, p=1.00 Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19 The TOGETHER Randomized Clinical Trial
Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients bei..
4/15 PrEP Alzahrani et al., Rheumatology International , doi:10.1007/s00296-021-04857-9 (Peer Reviewed) death, ↓58.8%, p=1.00 Clinical characteristics and outcome of COVID-19 in patients with rheumatic diseases
Retrospective 47 rheumatic disease patients not finding significant differences with HCQ.
4/15 PrEP Alegiani et al., Rheumatology, doi:10.1093/rheumatology/keab348 (Peer Reviewed) death, ↑8.0%, p=0.64 Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDs in Italy
Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ signif..
4/14 PEP Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed) severe case, ↓35.1%, p=0.14 Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin ..
4/6 Early Mokhtari et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.107636 (Peer Reviewed) death, ↓69.7%, p<0.0001 Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting
Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment.
4/5 Safety Edington et al., European Journal of Internal Medicine, doi:10.1016/j.ejim.2021.03.028 (Peer Reviewed) (not included in the study count) safety analysis Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis
Safety analysis of CQ and HCQ covering 46 RCTs with 23,132 patients, showing no mortality attributed to CQ/HCQ. Authors conclude that the data reinforces that CQ and HCQ have a good safety profile though caution is advised when using high..
3/31 Late Alghamdi et al., Antibiotics, doi:10.3390/antibiotics10040365 (Peer Reviewed) death, ↑6.9%, p=0.88 Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia
Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely.
3/26 Safety Faruqui et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_2294_20 (Peer Reviewed) safety analysis Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis
Retrospective 1303 health care workers finding that HCQ prophylaxis was well tolerated. 20% reported an adverse event, mostly gastrointestinal. 1.5% received treatment for adverse effects, with none requiring hospitalization.
3/24 PrEP Dev et al., Transactions of The Royal Society of Tropical Medicine and Hygiene, doi:10.1093/trstmh/trab047 (Peer Reviewed) cases, ↓26.0%, p=0.003 Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case–control study
Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no m..
3/23 Late Barry et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.03.058 (Peer Reviewed) death, ↓98.9%, p=0.60 Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients in a MERS-CoV Referral Hospital during the Peak of the Pandemic
605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).
3/17 Late Stewart et al., PLoS ONE, doi:10.1371/journal.pone.0248128 (Peer Reviewed) death, ↑18.0%, p=0.27 COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients
Collection of seven retrospective database analyses in the USA, showing higher mortality with treatment (not statistically significant). Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confo..
3/17 In Vitro Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741 (Preprint) (In Vitro) in vitro Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein
Microscopy/spectroscopy study showing that HCQ binds to both N-terminal domain and C-terminal domain of SARS-CoV-2 nucleocapsid protein to inhibit their interactions with nucleic acids and disrupt NA-induced liquid-liquid phase separation..
3/12 Early Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) recov. time, ↓2.4%, p=0.96 Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and ..
3/9 PrEP Vivanco-Hidalgo et al., Eurosurveillance, doi:/10.2807/1560-7917.ES.2021.26.9.2001202 (Peer Reviewed) hosp., ↑46.0%, p=0.10 Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020
Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 fo..
3/8 Late Martin-Vicente et al., medRxiv, doi:10.1101/2021.03.08.21253121 (Preprint) death, ↓59.3%, p=0.41 Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients
Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment.
3/4 Late Salvador et al., Cureus, doi:10.7759/cureus.13687 (Peer Reviewed) death, ↓32.9%, p=0.007 Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19
Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely.
3/2 PrEP Pham et al., Rheumatology Advances in Practice, 10.1093/rap/rkab014 (Peer Reviewed) death, ↓19.7%, p=0.77 Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases
Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mention..
2/28 Early Thakar et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_3665_20 (Peer Reviewed) Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial
Small RCT for CQ nasal drops suggesting efficacy in preventing infection, while no significant difference was seen for patients that already had mild COVID-19.
2/28 PrEP Bhandari et al., International Journal of Medicine and Public Health, doi:10.5530/ijmedph.2021.1.4 (Peer Reviewed) A Preventive Study on Hydroxychloroquine Prophylaxis against COVID-19 in Health Care Workers at a Tertiary Care Center in North India
Retrospective 4,239 healthcare workers using HCQ prophylaxis showing no mortality, 8 mild symptomatic cases, and 85 asymptomatic cases, with the cases occuring mostly in the first week.
2/26 Early Amaravadi et al., medRxiv, doi:10.1101/2021.02.22.21252228 (Preprint) no recov., ↓60.0%, p=0.13 Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial
Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm). There was no..
2/26 Late Tanriverdi et al., Turkish Journal of Medical Sciences, doi:doi:10.3906/sag-2005-82 (Peer Reviewed) Hydroxychloroquine plus azithromycin and early hospital admission are beneficial in COVID-19 patients: Turkish experience with real-life data
Retrospective 83 hospitalized patients in Turkey confirming that earlier treatment is better, and showing that the addition of AZ to HCQ reduced hospitalization time.
2/26 Early Giraud-Gatineau et al., Research Square, doi:rs.3.rs-251817/v1 (Preprint) The Need for Early Management in Patients With COVID-19
Review of early treatment of COVID-19 at IHU Méditerranée Infection in France, including HCQ+AZ treatment, comparing outcomes to those for all of France. Age-standardized mortality was lower with early treatment for all periods of the epi..
2/23 Late Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Peer Reviewed) death, ↓62.6%, p=0.27 Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127.
2/20 PrEP Bae et al., Viruses 2021, doi:10.3390/v13020329 (Peer Reviewed) cases, ↓30.3%, p=0.17 Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea
Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.
2/19 Late Lamback et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549 (Peer Reviewed) death, ↓8.9%, p=0.83 Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19
Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became ..
2/18 Late Awad et al., American Journal of Health-System Pharmacy, doi:10.1093/ajhp/zxab056 (Peer Reviewed) death, ↑19.1%, p=0.60 Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection
This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, IC..
2/11 Late Lora-Tamayo et al., J. Infection, doi:10.1016/j.jinf.2021.02.011 (Peer Reviewed) death, ↓50.5%, p<0.0001 Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study
Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality.
2/10 Early, Late Desai et al., J. Clinical Medicine, doi:10.3390/jcm10040686 (Peer Reviewed) The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults
Retrospective 143 COVID-19 hospitalized patients >65yo, showing adjusted OR for antiviral treatment starting within 6 days of 0.44 [0.2-0.9], p = 0.02, compared to treatment started later.
2/9 Meta Lounnas e al., Archives of Microbiology & Immunology, doi: (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Revisiting a Meta-analysis Shows that Hydroxychloroquine with Azithromycin may be Efficient in Covid-19 patients
Analysis of the Fiolet meta analysis and correction of bias evaluation, showing HCQ RR 0.45 [0.31-0.59], and HCQ+AZ RR 0.34 [0.06-0.61].
2/9 Late Purwati et al., Biochemistry Research International, doi:10.1155/2021/6685921 (Peer Reviewed) viral+, ↓66.3%, p<0.0001 A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections
RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 ap..
2/5 PrEP Fitzgerald et al., medRxiv, doi:10.1101/2021.02.03.21251069 (Preprint) cases, ↓8.5%, p=0.52Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases
Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity ..
2/5 Late Hernandez-Cardenas et al., medRxiv, doi:10.1101/2021.02.01.21250371 (Preprint) death, ↓12.0%, p=0.66 Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial
Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no signficant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03]. Table 4 shows differen..
2/5 Late Ouedraogo et al., Revue des Maladies Respiratoires, doi:10.1016/j.rmr.2021.02.001 (Peer Reviewed) death, ↓33.0%, p=0.38 Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso
Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (p=0.001) and mortality (p=0.38) with HCQ.
2/1 Review Alexander et al., medRxiv, doi:10.1101/2021.01.28.21250706 (Review) (Preprint) (not included in the study count) review Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents
Review of studies on treatment of COVID-19 for nursing home residents, concluding that there is a large >60% mortality risk reduction associated with multidrug treatment using two or more intracellular anti-infectives (HCQ and either AZM ..
2/1 Late Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306 (Peer Reviewed) death, ↓18.4%, p=0.64 COVID-19: A Single-Center ICU Experience of the First Wave in the Philippines
Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.
1/31 PrEP Naderi et al., Immunopathologia Persa, doi:10.34172/ipp.2021.29 (Peer Reviewed) Prophylactic effects of hydroxychloroquine on the incidence of COVID-19 in patients with rheumatic arthritis: an observational cohort study
Prospective observational study of 215 RA patients treated with HCQ showing 9 cases, 1 hospitalization (without ICU/intubation), and no mortality.
1/31 Late Roig et al., Revista Espanola de Quimioterapia, doi:10.37201/req/130.2020 (Peer Reviewed) death, ↓15.6%, p=0.76 Clinical and pharmacological data in COVID-19 hospitalized nonagenarian patients
Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.
1/27 PrEP Trefond et al., SSRM, doi:10.2139/ssrn.3754815 (Preprint) death, ↑16.6%, p=0.80 Impact of hydroxychloroquine used as DMARD on SARS CoV-2 tests and COVID-19 evolution
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extre..
1/26 Safety Eftekhar et al., medRxiv, doi:10.1101/2021.01.16.21249941 (Preprint) safety analysisHydroxychloroquine and azithromycin: As a double edge sword for COVID-19?
Retrospective 172 hospitalized patients, 83% treated and HCQ+AZ and 17% with HCQ, not finding a significant difference in QTc prolongation, but recommending careful monitoring for the use of HCQ+AZ; especially in males, patients with high..
1/25 Early Dabbous et al., Archives of Virology, doi:10.1007/s00705-021-04956-9 (Peer Reviewed) Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study
RCT with 44 favipiravir patients and 48 CQ patients, showing non-statistically significant lower mortality, ventilation, and hospitalization time with favipiravir.
1/25 In Silico Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979 (Peer Reviewed) Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19
Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 Mpro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds.
1/24 Early Zelenko, Z., Preprint (Preprint) Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing
Report on the use of nebulized HCQ showing much more rapid improvement compared to tablets, with 95% of patients experiencing improved breathing within 1 hour. Author notes that the effectiveness of HCQ is time and dose dependent, with a ..
1/23 PrEP Cifuentes et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2020.10.012 (Peer Reviewed) Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine
Retrospective 3,817 chronic HCQ patients showing 4.4% COVID-19 positive rate, 1.3% severe. There is no comparison with a control group. Authors note that there was a 3.6% incidence among 2,032,863 patients in one of the regions (Castilla ..
1/18 Late Li et al., Science China Life Sciences, doi:10.1007/s11427-020-1871-4 (Peer Reviewed) no disch., ↓50.0%, p=0.08 Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19
Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note..
1/12 Late Li et al., Research Square, doi:10.21203/rs.3.rs-119202/v1 (Preprint) viral- time, ↑40.0%, p=0.06 Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis
Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death ho..
1/10 PrEP Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098 (Peer Reviewed) death, ↓25.1%, p=0.77 Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis
Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically sign..
1/8 Late Yegerov et al., medRxiv, doi:10.1101/2021.01.06.20249091 (Peer Reviewed) death, ↓95.3%, p=1.00 Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort Study
Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant.
1/7 In Silico Baildya et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891 (Peer Reviewed) (not included in the study count) Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies
Molecular docking study of 16 drugs showing CQ had the highest binding affinity with ACE2, and molecular dynamics study of the docked CQ-ACE2 structure. Authors conclude that CQ binds reasonably strongly with ACE2 and the stable ACE2-CQ m..
1/6 Theory Noureddine et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334 (Peer Reviewed) (Theory) theory Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations
In silico analysis of hydroxychloroquine and hydroxychloroquine sulfate predicting that hydroxychloroquine sulfate is more stable and effective for COVID-19.
1/4 Safety Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106236 (Peer Reviewed) (not included in the study count) safety analysisSafety profile of hydroxychloroquine and azithromycin combined treatment in COVID-19 patients
Report on the safety of HCQ+AZ with 3,737 COVID-19 patients. 138 had contraindications and treatment was discontinued in 12 cases due to QTc prolongation. There were no cases of torsade de pointe or sudden death.
1/2 Late Sarfaraz et al., medRxiv, doi:10.1101/2020.12.28.20248920 (Preprint) death, ↑45.0%, p=0.07 Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan
Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely.
1/1 Late Lotfy et al., Turk. Thorac. J., doi:10.5152/TurkThoracJ.2021.20180 (Peer Reviewed) death, ↑24.8%, p=0.76 Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational Study
Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confou..
1/1 Late Sands et al., International Journal of Infectious Diseases, doi:/10.1016/j.ijid.2020.12.060 (Peer Reviewed) death, ↑69.9%, p=0.01 No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19
Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in t..
12/31 Review Matada et al., Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2020.115973 (Review) (Peer Reviewed) review A comprehensive review on the biological interest of quinoline and its derivatives
Review of quinolone and derivatives, natural and drug sources, and biological activity.
12/31 Late Psevdos et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.721 (Peer Reviewed) death, ↑63.5%, p=0.52 Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York
Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was su..
12/31 Late Texeira et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.560 (Peer Reviewed) death, ↑79.3%, p=0.10 Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast
Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was s..
12/31 Late Vernaz et al., Swiss Medical Weekly, doi:10.4414/smw.2020.20446 (Peer Reviewed) death, ↓15.3%, p=0.71 Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs
Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity wi..
12/30 Review McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) (not included in the study count) review Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may ..
12/30 Early Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 (Peer Reviewed) Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection
Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region. At least two of z..
12/29 Late Güner et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.12.017 (Peer Reviewed) ICU, ↓77.3%, p=0.16 Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine plus Favipiravir
Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir.
12/28 PrEP Cordtz et al., Rheumatology, doi:10.1093/rheumatology/keaa897 (Peer Reviewed) hosp., ↓24.0%, p=0.67 Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark
Retrospective 58,052 rheumatic disease patients in Denmark showing that RA patients have a higher risk of COVID-19 hospitalization in general. HCQ treated patients show lower risk, although this is not statistically significant with only ..
12/24 Late Chari et al., Blood, doi:10.1182/blood.2020008150 (Peer Reviewed) death, ↓33.1%, p=0.17 Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set
Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material).
12/23 Early Su et al., BioScience Trends, doi:10.5582/bst.2020.03340 (Peer Reviewed) progression, ↓84.9%, p=0.006 Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China
85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006.
12/23 Late Taccone et al., The Lancet Regional Health - Europe, doi:10.1016/j.lanepe.2020.100019 (Peer Reviewed) death, ↓24.7%, p=0.0004 The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium
Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92].
12/22 Late Cangiano et al., Aging, doi:10.18632/aging.202307 (Peer Reviewed) death, ↓73.4%, p=0.03 Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests
73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, p = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the..
12/19 PrEP Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 (Peer Reviewed) progression, ↑251.0%, p=0.11 Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
Retrospective database analysis with 17 existing users of HCQ and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and autho..
12/18 Late Matangila et al., PLoS ONE, doi:10.1371/journal.pone.0244272 (Peer Reviewed) death, ↓54.9%, p=0.21 Clinical characteristics of COVID-19 patients hospitalized at Clinique Ngaliema, a public hospital in Kinshasa, in the Democratic Republic of Congo: A retrospective cohort study
55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 [0.03-2.2].
12/16 Late Signes-Costa et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.11.012 (Peer Reviewed) death, ↓47.0%, p=0.0005 Prevalence and 30-day mortality in hospitalized patients with COVID-19 and prior lung diseases
47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53, p < 0..
12/16 PrEP Gönenli et al., Research Square, doi:0.21203/rs.3.rs-107937/v1 (Preprint) progression, ↓29.7%, p=0.77 Prophylactic use of Hydroxychloroquine among Physicians working in Pandemic Hospitals
Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, p = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, p = 0.58, which may be due ..
12/14 Late Sofian et al., Wiener Medizinische Wochenschrift, doi:10.1007/s10354-020-00793-8 (Peer Reviewed) SARS-CoV 2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms
Report on a series of 10 patients experiencing prolonged COVID-19 symptoms that were given HCQ 250mg bid for 5 days, with resolution of symptoms in all cases, and patients reporting they felt much better 2 days after treatment initiation.
12/14 Late Orioli et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.12.020 (Peer Reviewed) death, ↓12.7%, p=1.00 Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic center in Belgium
Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, p = 1.0.
12/14 Late Naseem et al., medRxiv, doi:10.1101/2020.12.13.20247254 (Preprint) death, ↓33.3%, p=0.34 Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network
Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, p = 0.34.
12/14 Late Tan et al., Virus Research, doi:10.1016/j.virusres.2020.198262 (Peer Reviewed) hosp. time, ↓35.2%, p=0.04 A retrospective comparison of drugs against COVID-19
Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ.
12/11 Late Bielza et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.12.003 (Peer Reviewed) death, ↓21.5%, p=0.09 Clinical characteristics, frailty and mortality of residents with COVID-19 in nursing homes of a region of Madrid
Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, p = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Med..
12/11 Early Sogut et al., The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2020.12.014 (Peer Reviewed) (not included in the study count) safety analysis Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study
Safety study of 152 outpatients concluding that HCQ is safe for COVID-19, was well tolerated, and was not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation.
12/11 PrEP Jung et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.12.003 (Peer Reviewed) death, ↓59.3%, p=1.00 Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: A population-based cohort study
Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information ..
12/10 Late Alqassieh et al., F1000Research, Preprint (Preprint) hosp. time, ↓18.2%, p=0.11 Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan
Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, p = 0.11.
12/10 News Italian Council of State (News) (not included in the study count) news Consiglio di Stato, sì all'uso dell'idrossiclorachina per la cura del Covid
Consiglio di Stato ruling in Italy re-establishes the right of Italian MDs to prescribe HCQ, which was suspended after the retracted Lancet study.
12/9 Late Johnston et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773 (preprint 12/9) (Peer Reviewed) hosp., ↓29.9%, p=0.73 Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial
Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a..
12/9 Early Agusti et al., Enfermedades Infecciosas y Microbiología Clínica, doi:10.1016/j.eimc.2020.10.023 (Peer Reviewed) progression, ↓68.4%, p=0.21 Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: prospective, non-randomized trial
Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, p = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths. Prospect..
12/9 Late Guglielmetti et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.11.012 (Peer Reviewed) death, ↓35.0%, p=0.22 Severe COVID-19 pneumonia in Piacenza, Italy – a cohort study of the first pandemic wave
Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 [0.33–1.30].
12/7 PEP Barnabas et al., Annals of Internal Medicine, doi:10.7326/M20-6519 (Peer Reviewed) hosp., ↑3.7%, p=1.00 Hydroxychloroquine for Post-exposure Prophylaxis to Prevent Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Trial
Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people wi..
12/4 Late Ozturk et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa271 (Peer Reviewed) death, ↓43.9%, p=0.14 Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey
Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by indication.
12/4 Late Modrák et al., medRxiv, doi:10.1101/2020.12.03.20239863 (Preprint) death, ↓59.0%, p=0.04 Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis
Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication.
12/4 Late Peng et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa288 (Peer Reviewed) progression, ↓10.8%, p=0.63 Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China
Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ.
12/2 PEP Wiseman et al., medRxiv, doi:10.1101/2020.11.29.20235218 (Preprint) (meta analysis - not included in study count) cases, ↓42.0%, p=0.04 Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data
6th independent analysis showing efficacy from the Boulware PEP trial. This prospective analysis corrects an error in the NEJM paper where shipping delays are omitted (still not corrected). 42% reduction in COVID-19 (9.6% vs. 16.5%), RR..
12/1 Late Capsoni et al., Research Square, doi:10.21203/rs.3.rs-113418/v1 (Preprint) ventilation, ↓40.0%, p=0.30 CPAP Treatment In COVID-19 Patients: A Retrospective Observational Study In The Emergency Department
Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ.
11/30 Late Abdulrahman et al., medRxiv, doi:10.1101/2020.11.25.20234914 (Preprint) death, ↓16.7%, p=1.00 The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort
Retrospective medical record analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity - 17.5% of HCQ patients requ..
11/29 Late Abd-Elsalam et al., Biological Trace Element Research, doi:10.1007/s12011-020-02512-1 (Peer Reviewed) Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial
191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. Clinical recovery at 28 days was 79.2% in the zinc group and 77.9% control, p = 0.969. Mechanical ventilation was used with 4 patients..
11/28 Late Lambermont et al., Critical Care Explorations, doi:10.1097/CCE.0000000000000305 (Peer Reviewed) death, ↓32.3%, p=0.46 Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study
Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not sp..
11/28 N/A Ruiz et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247 (Peer Reviewed) dosing study Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19
HCQ lung pharmacokinetic study confirming that lung concentrations can be much higher than plasma. The median lung epithelial lining fluid concentration was 38 times higher than plasma concentrations. 22 COVID-19 patients, median age 59...
11/28 Late Rodriguez-Gonzalez et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106249 (Peer Reviewed) death, ↓22.8%, p=0.26 COVID-19 in hospitalized patients in Spain: a cohort study in Madrid
Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication.
11/27 Late van Halem et al., BMC Infect Dis., doi:10.1186/s12879-020-05605-3 (Peer Reviewed) death, ↓31.6%, p=0.05 Risk factors for mortality in hospitalized patients with COVID-19 at the start of the pandemic in Belgium: a retrospective cohort study
Retrospective 319 hospitalized patients in Belgium showing lower mortality with HCQ, although not reported to be statistically significant.
11/24 Late Abbas et al., Int. J. Clin. Pract., doi:10.1111/ijcp.13856 (Peer Reviewed) Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A Natural Clinical Trial
Prospective study of 161 hospitalized patients in Iraq showing HCQ+AZ appears to help recovery. Most mortality was in patients that were already in critical condition on admission and died before treatment could be effective.
11/23 Late Qin et al., Thrombosis Research, doi:10.1016/j.thromres.2020.11.020 (Peer Reviewed) death, ↓34.3%, p=0.61 Low molecular weight heparin and 28-day mortality among patients with coronavirus disease 2019: A cohort study in the early epidemic era
Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, p = 0.61.
11/21 PrEP Revollo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa477 (Peer Reviewed) cases, ↓23.0%, p=0.52 Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in healthcare workers
Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing ..
11/20 Early Omrani et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100645 (Peer Reviewed) hosp., ↓12.5%, p=1.00 Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19
Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients; that positive PCR may simply reflect detection of inactive (non-infec..
11/19 Late Falcone et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563 (Peer Reviewed) death, ↓65.0%, p=0.20 Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study
Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk: RR 0.35, p = 0.2, pr..
11/18 Late Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223 (Preprint) death, ↓65.4%, p<0.0001 Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience
Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, p < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have received H..
11/17 Late Boari et al, Biosci. Rep., doi:10.1042/BSR20203455 (Peer Reviewed) death, ↓54.5%, p<0.001 Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study
Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, p<0.001. Data is in the supplementary appendix.
11/13 Late Sheshah et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108538 (Peer Reviewed) death, ↓80.0%, p<0.001 Prevalence of Diabetes, Management and Outcomes among Covid-19 Adult Patients Admitted in a Specialized Tertiary Hospital in Riyadh, Saudi Arabia
Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, p < 0.001.
11/12 Early Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed) hosp., ↓93.8%, p=0.01 Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33..
11/12 PEP Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed) cases, ↓92.7%, p=0.01 Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This..
11/12 N/A Tchounga et al., Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2020.113761 (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic
Analysis of fake CQ tablets finding: - no CQ in six samples, substituted with metronidazole (at sub-therapeutic levels) or paracetamol. - trace levels of paracetamol and chloramphenicol in four and two samples respectively. - CQ levels t..
11/11 Late Águila-Gordo et al., Revista Española de Geriatría y Gerontología, doi:10.1016/j.regg.2020.09.006 (Peer Reviewed) death, ↓67.0%, p=0.10 Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19
67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, p = 0.1.
11/9 Late Khamis et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.008 (Peer Reviewed) Randomized Controlled Open Label Trial on the Use of Favipiravir Combined with Inhaled Interferon beta-1b in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia
Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences.
11/9 Late Rodriguez et al., Medicina Intensiva, doi:10.1016/j.medine.2020.05.005 (Peer Reviewed) death, ↓59.0%, p=0.23 Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic
Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, p=0.23.
11/9 Late Self et al., JAMA, doi:10.1001/jama.2020.22240 (Peer Reviewed) death, ↑6.2%, p=0.84 Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial
Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients not showing a significant difference, 28 day mortality adjusted odds ratio aOR 0.93 [0.48-1.85]. For the subgroup not on supplemental..
11/9 Late Brown et al., Annals of the American Thoracic Society, doi:10.1513/AnnalsATS.202008-940OC (Peer Reviewed) Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial
Small early terminated very late stage (86% on oxygen, 44% enrolled in the ICU) RCT comparing HCQ vs. AZ, not finding a significant difference between the two treatments. There is no comparison with a control group. HCQ patients not in th..
11/9 Late Núñez-Gil et al., Intern. Emerg. Med., doi:10.1007/s11739-020-02543-5 (Peer Reviewed) death, ↓7.9%, p=0.005 Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry
Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, p=0.005.
11/6 PrEP Mathai et al., J. Marine Medical Society, doi:10.4103/jmms.jmms_115_20 (Peer Reviewed) cases, ↓89.5%, p<0.0001 Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience
90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers.
11/6 PrEP Datta et al., Journal of Vaccines & Vaccination, S6:1000002 (Peer Reviewed) No Role of HCQ in COVID-19 Prophylaxis: A Survey amongst Indian Doctors
Survey of Indian doctors not finding a significant effect of HCQ prophylaxis, p = 0.54. We do not know the actual results for this study - the numbers for prophylaxis in Table 1 appear to be incorrect. They do not match the total using H..
11/6 PEP Dhibar et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106224 (Peer Reviewed) cases, ↓41.0%, p=0.03 Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study
41% reduction in cases with HCQ PEP. Prospective open label trial with 132 HCQ patients and 185 control patients showing RR 0.59, p=0.03. 50% reduction in PCR+ cases, 44% reduction in symptomatic cases. No serious adverse events. Relati..
11/5 Late Maldonado et al., Nefrología, doi:10.1016/j.nefro.2020.09.002 (Peer Reviewed) death, ↓90.9%, p=0.17 COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic
Small retrospective 12 dialysis patients, 1/11 deaths with HCQ and 1/1 without HCQ.
11/5 Late Rodriguez-Nava et al., Mayo Clinic Proceedings: Innovations, Quality & Outcomes (Peer Reviewed) death, ↑6.3%, p=0.77 Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort study
Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, p = 0.77. Confounding by indication likely.
11/4 Late Salazar et al., The American Journal of Pathology, doi:10.1016/j.ajpath.2020.10.008 (Peer Reviewed) death, ↑37.0%, p=0.28 Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG
Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, p = 0.28. Confounding by indication is likely.
11/4 Early Cadegiani et al., medRxiv, doi:10.1101/2020.10.31.20223883 (Preprint) death, ↓81.2%, p=0.21 Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, ev..
11/3 PrEP Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) cases, ↓27.9%, p=0.29 Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, ..
11/2 Late López et al., Annals of Pediatrics, doi:10.1016/j.anpedi.2020.10.017 (Peer Reviewed) progression, ↓64.3%, p=0.02 Telemedicine follow-ups for COVID-19: experience in a tertiary hospital
Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (p=0.023), less progression (p=0.016), and fewer return visits to the ER (p=0.017).
10/31 Early Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed) hosp., ↓64.0%, p=0.0008 Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, p=0.00081, for HCQ versus no medication, and OR 0.45, p=0.0065, for HCQ vs. anything else.
10/30 Late Tehrani et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.071 (Peer Reviewed) death, ↓13.4%, p=0.63 Risk factors for mortality in adult COVID-19 patients; frailty predicts fatal outcome in older patients
Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, p=0.63. Confounding by indication is likely.
10/27 PrEP Arleo et al., medRxiv, doi:10.1101/2020.10.26.20219154 (Preprint) death, ↓50.0%, p=0.67 Clinical Course and Outcomes of coronavirus disease 2019 (COVID-19) in Rheumatic Disease Patients on Immunosuppression: A case Cohort Study at a Single Center with a Significantly Diverse Population
Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ.
10/27 Late Choi et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.062 (Peer Reviewed) viral- time, ↑22.0%, p<0.0001 Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study
Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose not to..
10/26 Late Frontera et al., Research Square, doi:10.21203/rs.3.rs-94509/v1 (Preprint) death, ↓37.0%, p=0.01 Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc.
10/26 Early Derwand et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106214 (preprint 7/3) (Peer Reviewed) death, ↓79.4%, p=0.12 COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study
79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. No cardiac side effects. Retrospective 518 patients (141 treated, 377 control).
10/24 PrEP Goenka et al., SSRN, doi:10.2139/ssrn.3689618 (Preprint) IgG+, ↓87.2%, p=0.03 Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India
Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6 weeks.
10/23 Late Coll et al., American Journal of Transplantation, doi:10.1111/ajt.16369 (Peer Reviewed) death, ↓45.6%, p<0.0001 Covid‐19 in transplant recipients: the spanish experience
Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, p<0.0001.
10/21 Late Lano et al., Clinical Kidney Journal, 13:5, October 2020, 878–888, doi:10.1093/ckj/sfaa199 (Peer Reviewed) death, ↓33.1%, p=0.28 Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort
33% lower mortality with HCQ+AZ, p=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, p=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment).
10/21 Late Dubee et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.03.005 (preprint 10/21) (Peer Reviewed) death, ↓46.0%, p=0.21 Hydroxychloroquine in mild-to-moderate COVID-19: a placebo-controlled double blind trial
Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 [0.21-1.42] combined mortality/intubation at 28 days relative risk RR 0.74 [0.33-1.70] If not stoppe..
10/21 Late Ñamendys-Silva et al., Heart & Lung, doi:10.1016/j.hrtlng.2020.10.013 (Peer Reviewed) death, ↓32.3%, p=0.18 Outcomes of patients with COVID-19 in the Intensive Care Unit in Mexico: A multicenter observational study
Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, p = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, p = 0.02 HCQ+AZ or CQ vs..
10/20 Early, Late IHU Marseille (Preprint) (meta analysis - not included in study count) meta-analysisMeta-analysis on chloroquine derivatives and COVID-19 mortality
Updated meta analysis of 41 studies showing CQ/HCQ OR 0.57, p<0.0001 from clinical studies. For big data studies authors find inconsistent results and OR 0.83, p=0.0014, and for all studies combined OR 0.72, p<0.0001.
10/20 Late Solh et al., medRxiv, doi:10.1101/2020.10.16.20214130 (Preprint) death, ↑18.0%, p=0.17 Clinical course and outcome of COVID-19 acute respiratory distress syndrome: data from a national repository
Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be us..
10/17 Early Mohana et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.031 (preprint 8/17) (Peer Reviewed) (not included in the study count) safety analysis Hydroxychloroquine Safety Outcome within Approved Therapeutic Protocol for COVID-19 Outpatients in Saudi Arabia
Safety study of 2,733 patients in Saudi Arabia showing HCQ in mild to moderate cases in an outpatient setting, within the protocol recommendation and inclusion/exclusion criteria, is safe, highly tolerable, and has minimal side effects. N..
10/15 Late Guisado-Vasco (Peer Reviewed) death, ↓20.3%, p=0.36 Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort)
Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 [0.022-0.381], p = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 [0.38-1.41], p = 0.36 (558 patients)...
10/15 Late SOLIDARITY Trial Consortium, NEJM, doi:10.1056/NEJMoa2023184 (preprint 10/15) (Peer Reviewed) death, ↑19.0%, p=0.23 Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19 [0.89-1.59], p=0.23. HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10 d..
10/12 Late Annie et al., Pharmacotherapy, doi:10.1002/phar.2467 (Peer Reviewed) death, ↓4.3%, p=0.83 Hydroxychloroquine in hospitalized COVID‐19 patients: Real world experience assessing mortality
Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 [0.62-1.46] for HCQ, and 1.24 [0.70-2.22] for HCQ+AZ. Confounding by indication likely.
10/11 Late Sili et al., medRxiv, doi:10.1101/2020.10.09.20209775 (Preprint) (not included in the study count) Factors associated with progression to critical illness in 28 days among COVID-19 patients: results from a tertiary care hospital in Istanbul, Turkey
Analysis of hospitalized patients in Turkey showing HCQ was given to 99.2% of patients and the incidence of critical illness was lower than most studies. Authors note "whether HCQ administration lowered the rates of critical illness ..
10/8 Late Aparisi et al., medRxiv, doi:10.1101/2020.10.06.20207092 (Preprint) death, ↓63.0%, p=0.008 Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19
Retrospective 654 hospitalized patients focused on low-density lipoprotein cholesterol levels, also showing results for HCQ with 605 HCQ patients, unadjusted 30 day mortality relative risk RR 0.37, p = 0.008.
10/8 Late Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint) death, ↓18.1%, p<0.0001 Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10..
10/6 Late Ader et al., medRxiv, doi:10.1101/2021.01.08.20248149 (news 10/6) (Preprint) death, ↓6.4%, p=1.00 Antiviral drugs in hospitalized patients with COVID-19 - the DisCoVeRy trial
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline in the HCQ group.
10/5 Late Mori et al., Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2020.09.003 (Peer Reviewed) Triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia
Small case study of 5 patients in Japan showing improvement with HCQ+AZ+ciclesonide.
10/5 Early, Late Prodromos et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100776 (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Hydroxychloroquine is effective, and consistently so used early, for Covid-19: A systematic review
Meta analysis of 43 studies: "HCQ was found consistently effective against COVID-19 when used early, in the outpatient setting. It was found overall effective also including inpatient studies. No unbiased study found worse outcomes w..
10/2 Late Nachega et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-1240 (Peer Reviewed) death, ↓27.6%, p=0.17 Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo
Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65% to 84%. Mortality cox regression adjusted hazard ratio aHR 0.26, p < 0.001 Risk of no improvement adj..
10/1 Late Almazrou et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2020.09.019 (Peer Reviewed) ventilation, ↓65.0%, p=0.16 Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study
Retrospective 161 hospitalized patients in Saudi Arabia showing lower ventilation and ICU admission with HCQ, but not statistically significant with the small sample sizes.
10/1 PrEP, PEP Garcia-Albeniz et al., medRxiv, doi:10.1101/2020.09.29.20203869 (Preprint) (meta analysis - not included in study count) cases, ↓22.0%, p=0.04 Brief communication: A meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19
Combination of the four underpowered prophylaxis RCTs to date showing statistically significant results, RR 0.78 [0.61-0.99]. The actual effect of HCQ is likely to be higher for several reasons: the trials did not adjust for losses to fo..
9/30 PEP Polat et al., Medical Journal of Bakirkoy, 16:3, 280-6, doi:10.5222/BMJ.2020.50469 (Peer Reviewed) cases, ↓57.0%, p=0.03 Hydroxychloroquine Use on Healthcare Workers Exposed to COVID-19 -A Pandemic Hospital Experience
Small prophylaxis study of 208 healthcare workers in Turkey, 138 with high risk exposure received HCQ, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative risk RR 0.43, p = 0.026...
9/30 Late Ayerbe et al., Internal and Emergency Medicine, doi:0.1007/s11739-020-02505-x (Peer Reviewed) death, ↓52.2%, p<0.001 The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients
2075 hospital patients in Spain showing HCQ reduces mortality 52%, odds ratio OR 0.39, p<0.001, after adjustment for age, gender, temperature > 37 °C, and saturation of oxygen < 90% treatment with azithromycin, steroids, heparin, tocilizu..
9/30 PrEP, PEP, Early Ladapo et al., medRxiv, doi:10.1101/2020.09.30.20204693 (Preprint) (meta analysis - not included in study count) cases/death/hosp., ↓24.0%, p=0.03 Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis
Meta analysis of prophylactic and early treatment RCTs, 24% reduction in cases, hospitalization or death with HCQ, RR 0.76, p=0.025. No serious adverse cardiac events were reported. 5,577 patients. The Boulware study provides a breakdown..
9/30 PrEP Abella et al., JAMA Internal Medicine, doi:doi:10.1001/jamainternmed.2020.6319 (Peer Reviewed) cases, ↓5.0%, p=1.00 Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 - 3.64]. There was no hospitalization or death, no significant difference..
9/29 Late Lammers et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.09.1460 (Peer Reviewed) death/ICU, ↓32.0%, p=0.02 Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients
Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HCQ treatment starting on the first day of admission. Weighted propensity score adjusted hazard r..
9/29 Late Dabbous et al., Research Square, doi:10.21203/rs.3.rs-83677/v1 (Preprint) A Randomized Controlled Study Of Favipiravir Vs Hydroxychloroquine In COVID-19 Management: What Have We Learned So Far?
Small RCT comparing HCQ and favipiravir, with 50 patients in each arm, finding that 55.1% of HCQ patients were PCR negative on day 7 compared to 48% for favipiravir, p = 0.7. There was no comparison with a control group.
9/28 PEP Luco, J., Trends Med, doi:10.15761/TiM.1000268 (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Hydroxychloroquine as post-exposure prophylaxis for Covid-19: Why simple data analysis can lead to the wrong conclusions from well-designed studies
Reanalysis of Boulware et al. PEP trial data showing statistically significant improvements with HCQ.
9/24 Early, Late Gasperetti et al., EP Europace, doi:10.1093/europace/euaa216 (Peer Reviewed) (not included in the study count) safety analysis Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings
Safety study of 649 patients finding that HCQ administration is safe for short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attrib..
9/24 Late Shoaibi et al., medRxiv, doi:10.1101/2020.09.23.20199463 (Preprint) death, ↓15.4%, p<0.001 Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients
Retrospective database analysis focused on Famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, p<0.001 (13.6% vs. 16.1%).
9/23 Late Ulrich et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa446 (Peer Reviewed) death, ↑6.0%, p=1.00 Treating Covid-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients
Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable - 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients,..
9/22 Late Serrano et al., Ann. Oncol., 2020, Sep, 31, S1026, doi:10.1016/j.annonc.2020.08.1830 (Peer Reviewed) death, ↓43.0%, p=0.14 COVID-19 and lung cancer: What do we know?
Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, p = 0.145.
9/21 PrEP Gentry et al., Lancet Rheumatology, doi:10.1016/S2665-9913(20)30305-2 (Peer Reviewed) death, ↓91.3%, p=0.10 Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study
Retrospective patients with rheumatologic conditions showing zero of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 propensity matched control patients (not statistically significant). The average age of HCQ patients is slight..
9/21 PrEP Rajasingham et al., medRxiv, doi:10.1101/2020.09.18.20197327 (Peer Reviewed) cases, ↓27.0%, p=0.12 Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial
PrEP RCT showing HR 0.73, p = 0.12. Trial halted after 47% enrollment, p < 0.05 will be reached at ~75% enrollment if similar results continue. Trial halted due to low enrollment. US prescriptions only stopped briefly, resuming in June, ..
9/21 PrEP Grau-Pujol et al., Research Square, doi:10.21203/rs.3.rs-72132/v1 (Preprint) cases, ↓67.9%, p=0.47 Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: initial results of a double-blind, placebo-controlled randomized clinical trial
Small PrEP RCT showing that PrEP with HCQ is safe at the dosage used. No deaths, hospitalizations, or serious adverse events. With only one case (in the placebo arm), efficacy was not evaluated. The abstract appears to have a typo and do..
9/21 Early Lofgren et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa500 (preprint 9/21) (Peer Reviewed) (not included in the study count) safety analysis Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19
Analysis of 2,795 outpatients not showing significant safety concerns with HCQ. No deaths were related to HCQ. There was one serious event requiring hospitalization, identical to the frequency with placebo.
9/18 Late Axfors et al., Nature, doi:10.1038/s41467-021-22446-z (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
Meta analysis assigning 89% weight to the RECOVERY and SOLIDARITY trials, producing the same result. These trials used excessively high non-patient-customized dosage in very sick late stage patients, results are not generalizable to typic..
9/16 N/A Karatza et al., Xenobiotica (Peer Reviewed) (not included in the study count) dosing study Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations
Analysis of HCQ dosing, suggesting that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instan..
9/15 Late Ashinyo et al., Pan African Medical Journal, 37:1, doi:10.11604/pamj.supp.2020.37.1.25718 (Peer Reviewed) hosp. time, ↓33.0%, p=0.03 Clinical characteristics, treatment regimen and duration of hospitalization among COVID-19 patients in Ghana: a retrospective cohort study
Retrospective 307 hospital patients in Ghana showing 33% reduction in hospitalization time with HCQ, 29% reduction with HCQ+AZ, and 37% reduction with CQ+AZ.
9/14 Late Lauriola et al., Clinical and Translational Science, doi:10.1111/cts.12860 (Peer Reviewed) death, ↓73.5%, p<0.001 Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in COVID‐19 patients
Retrospective 377 patients, 73% reduction in mortality with HCQ+AZ, adjusted hazard ratio HR 0.27 [0.17-0.41]. Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders.
9/13 Early Sulaiman et al., medRxiv, doi:10.1101/2020.09.09.20184143 (Preprint) death, ↓63.7%, p=0.01 The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study
Observational prospective 5,541 patients, adjusted HCQ mortality odds ratio OR 0.36, p = 0.012. Adjusted hospitalization OR 0.57, p < 0.001. Zinc supplementation was used in all cases. Early treatment in ambulatory fever clinics in Saudi ..
9/12 Late Heberto et al., IJC Heart & Vasculature, doi:10.1016/j.ijcha.2020.100638 (Peer Reviewed) death, ↓53.6%, p=0.04 Implications of myocardial injury in Mexican hospitalized patients with coronavirus disease 2019 (COVID-19)
Observational prospective 254 hospitalized patients, HCQ+AZ mortality odds ratio OR 0.36, p = 0.04. Ventilation OR 0.20, p = 0.008.
9/9 Late Alamdari et al., Tohoku J. Exp. Med., 2020, 252, 73-84, doi:10.1620/tjem.252.73 (Peer Reviewed) death, ↓55.0%, p=0.03 Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran
Retrospective 459 patients in Iran 93% using HCQ, showing HCQ mortality RR 0.45, p = 0.028. HCQ was the only antiviral that showed a significant difference. Small number of control patients and subject to confounding by indication. Averag..
9/9 Early, Late Kirenga et al., BMJ Open Respiratory Research, doi:10.1136/bmjresp-2020-000646 (Peer Reviewed) recov. time, ↓25.6%, p=0.20 Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda
Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (p = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a ..
9/9 PrEP Rentsch et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30378-7 (preprint 9/9, https://www.medrxiv.org/content/10.1101/2020.09.04.20187781v1) (Peer Reviewed) death, ↑3.0%, p=0.83 Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform
Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 [0.80-1.33] (HR 0.78 before adjustments). 70 patients with HCQ prescriptions ..
9/9 PrEP Laplana et al., PLOS ONE, doi:10.1371/journal.pone.0243598 (Peer Reviewed) cases, ↑56.0%, p=0.24 Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients
Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence...
9/7 Review IHU, Expert Review of Clinical Immunology (Review) (Peer Reviewed) (not included in the study count) review Natural history and therapeutic options for COVID-19
Review of the current state of knowledge regarding the natural history of and therapeutic options for COVID-19. Treatment with an oral combination of hydroxychloroquine, azithromycin and zinc may represent the best current therapeutic op..
9/5 Late Synolaki et al., medRxiv, doi:10.1101/2020.09.05.20184655 (Preprint) death, ↓23.6%, p=0.27 The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality
Retrospective 117 patients, 58 HCQ showing lower mortality for HCQ patients. Version 1 of this paper stated: "HCQ, AZ, [and ...] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores..
9/4 Late Furtado et al., The Lancet, doi:10.1016/S0140-6736(20)31862-6 (Peer Reviewed) Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial
Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. No significant difference was found, OR 1.36, p=0.11. One notable result is that even within this extremely late stage population, results sugge..
9/2 In Vitro Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333 (Peer Reviewed) (In Vitro) (not included in the study count) in vitro Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus
In Vitro study providing novel insights into the molecular mechanism of CQ/HCQ treatment, showing that CQ and HCQ both inhibit the entrance of 2019-nCoV into cells by blocking the binding of the virus with ACE2.
9/2 Early Heras et al., European Geriatric Medicine, doi:10.1007/s41999-020-00432-w (preprint 9/2) (Peer Reviewed) death, ↓95.6%, p=0.004 COVID-19 mortality risk factors in older people in a long-term care center
Retrospective 100 elderly nursing home patients, HCQ+AZ mortality 11.4% vs. control 61.9%, RR 0.18, p<0.001. Median age 85. COVID-19 confirmed. 70% treated with HCQ+AZ. Details of differences between groups are not provided, and no adjus..
9/2 PrEP de la Iglesia et al., medRxiv, doi:10.1101/2020.08.31.20185314 (Preprint) hosp., ↑50.0%, p=1.00 Hydroxicloroquine for pre-exposure prophyylaxis for SARS-CoV-2
Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differences between groups. Other research..
9/1 Review Hecel et al., Pharmaceuticals, 13:9, 228, doi:10.3390/ph13090228 (Review) (Peer Reviewed) (not included in the study count) review Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19?
Review of zinc as an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and zinc ionophores including CQ/HCQ, showing the latest evidence for zinc and CQ/HCQ having antiviral, and in particular anticoronaviral action.
9/1 Early Elbazidi et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100749 (Peer Reviewed) Pandemic and social changes, political fate
Analysis of US states and countries. Country analysis shows a significant correlation between the dates of decisions to adopt/decline HCQ, and corresponding trend changes in CFR. US state analysis shows a significant correlation between C..
8/30 Late Albani et al., J, Clinical Medicine, doi:10.3390/jcm9092800 (Peer Reviewed) death, ↓18.4%, p=0.05 Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19
Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ.
8/29 Late Castillo et al., Journal of Steroid Biochemistry and Molecular Biology, 203, October 2020, doi:10.1016/j.jsbmb.2020.105751 (Peer Reviewed) Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study
RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions. All patients received standard care including HCQ+AZ. Significantly lower ICU admission wi..
8/28 Late Fried et al., Clinical Infectious Disease, doi:10.1093/cid/ciaa1268 (Peer Reviewed) death, ↑27.0%, p<0.001 Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States
Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality ..
8/27 PrEP Ferri at al., Clinical Rheumatology, doi:0.1007/s10067-020-05334-7 (Peer Reviewed) cases, ↓63.0%, p=0.01 COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series
Analysis of 1641 systemic autoimmune disease patients showing csDMARD (HCQ etc.) RR 0.37, p=0.015. csDMARDs include HCQ, CQ, and several other drugs, so the effect of HCQ/CQ alone could be higher. This study also confirms that the risk ..
8/26 Late Fiolet et al., Clinical Microbiology and Infection (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis
Meta analysis of late stage studies (and one early treatment study with only 2 deaths), showing HCQ RR 0.83 [0.65-1.06], before exclusions RR 0.80 [0.65-1.0]. Authors claim "HCQ alone is not effective", but the result directly ..
8/25 Early Ip et al., BMC Infectious Diseases, doi:10.1186/s12879-021-05773-w (preprint 8/25) (Peer Reviewed) death, ↓54.5%, p=0.43 Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study
Retrospective 1,274 outpatients, 47% reduction in hospitalization with HCQ with propensity matching, HCQ OR 0.53 [0.29-0.95]. Sensitivity analyses revealed similar associations. Adverse events were not increased (2% QTc prolongation even..
8/25 Late Di Castelnuovo et al., European J. Internal Medicine, doi:10.1016/j.ejim.2020.08.019 (Peer Reviewed) death, ↓30.0%, p<0.0001 Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study
Retrospective 3,451 hospitalized patients, 30% reduction in mortality with HCQ after propensity adjustment, HR 0.70 [0.59 - 0.84].
8/24 Late Catteau et al., Int. J. Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106144 (Peer Reviewed) death, ↓32.0%, p<0.0001 Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants
Retrospective 8,075 hospitalized patients, 4,542 low-dose HCQ, 3,533 control. 35% lower mortality for HCQ (17.7% vs. 27.1%), adjusted HR 0.68 [0.62–0.76]. Low-dose HCQ monotherapy was independently associated with lower mortality in hospi..
8/23 Late Pasquini et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa321 (Peer Reviewed) death, ↓16.4%, p=0.34 Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU
Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment.
8/21 Early Ly et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106219 (preprint 8/21) (Peer Reviewed) death, ↓55.6%, p=0.02 Pattern of SARS-CoV-2 infection among dependant elderly residents living in retirement homes in Marseille, France, March-June 2020
Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, p=0.02. 1690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant..
8/21 N/A Lane et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30276-9 (Peer Reviewed) (not included in the study count) safety analysis Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study
Retrospective study of RA patients using HCQ vs. sulfasalazine (another DMARD). HCQ treatment showed no increased risk in the short term (up to 30 days) among patients with RA. Long term use was associated with excess cardiovascular morta..
8/21 Late Gonzalez et al., medRxiv, doi:10.1101/2020.08.18.20172874 (Preprint) death, ↓26.6%, p=0.06 The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals
Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential conf..
8/20 Late Dubernet et al., J. Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.08.001 (Peer Reviewed) ICU, ↓87.6%, p=0.008 A comprehensive strategy for the early treatment of COVID-19 with azithromycin/hydroxychloroquine and/or corticosteroids: results of a retrospective observational study in the French overseas department of Reunion Island
Retrospective analysis of 36 hospitalized patients showing HCQ/AZ associated with lower ICU admission, p=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumonia that were treated wit..
8/20 Early Prodromos, C., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100747 (Peer Reviewed) (not included in the study count) safety analysis Hydroxychloroquine is protective to the heart, not harmful: A systematic review
Review concluding that HCQ/AZ does not cause Torsade de Pointes or related deaths, HCQ decreases cardiac events, and HCQ should not be restricted in use for COVID-19 patients because of fear of cardiac mortality.
8/18 Late Pinato et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0773 (Peer Reviewed) death, ↓59.0%, p<0.0001 Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients
Restrospective 890 cancer patients with COVID-19, adjusted mortality HR for HCQ/CQ 0.41, p<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Analysis with Cox proportional hazard model. Poten..
8/15 Late Peters et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.10.004 (preprint 8/15) (Peer Reviewed) death, ↑9.0%, p=0.57 Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine
Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ or dexamethasone. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals..
8/14 Late Abd-Elsalam et al., American Journal of Tropical Medicine and Hygiene, 10.4269/ajtmh.20-0873 (Peer Reviewed) death, ↑20.0%, p=1.00 Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study
Small RCT in Egypt with 97/97 HCQ/control patients, showing 58% more recovery @28days for HCQ (53.6% HCQ, 34% control), p=0.009 (0.06 in the paper refers to the 5 combined recovery/death/ICU values). No significant difference in ventilat..
8/13 Late Roomi et al., J. Medical Internet Research, doi:10.2196/21758 (Peer Reviewed) death, ↑37.7%, p=0.54 Efficacy of hydroxychloroquine and tocilizumab in patients with COVID-19: A single-center retrospective chart review
Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication.
8/11 In Silico Tarek et al., European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6 (Peer Reviewed) Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention
In Silico analysis of HCQ treatment showing concluding that HCQ may affect viral clearance if administered early enough when the virus is still confined to the pharyngeal cavity; HCQ's effects against SARS-CoV-2 might be exerted more thro..
8/11 Early Bakhshaliyev et al., J. Electrocardiology, doi:10.1016/j.jelectrocard.2020.08.008 (Peer Reviewed) (not included in the study count) safety analysis The effect of 5-day course of hydroxychloroquine and azithromycin combination on QT interval in non-ICU COVID19(+) patient
Safety study of 109 patients showing 5 days of HCQ+AZ did not lead to clinically significant QT prolongation or other conduction delays compared to baseline ECG in non-ICU patients.
8/11 Late Saleemi et al., medRxiv, doi:10.1101/2020.08.05.20151027 (Preprint) viral- time, ↑21.0%, p<0.05 Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience
Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidi..
8/8 Late Lopez et al., Int. J. Antimicrob. Agents, doi:/j.ijantimicag.2020.106136 (Peer Reviewed) Effects of Hydroxychloroquine on Covid-19 in Intensive Care Unit Patients: Preliminary Results
Small retrospective study of 29 ICU patients comparing those with HCQ plasma concentration within target to those with a concentration below the target value, with no significant differences found. Mortality in the on-target group was 0% ..
8/6 PrEP Salvarani et al., Arthritis & Rheumatology, doi:10.1002/art.41475 (Peer Reviewed) cases, ↓6.0%, p=0.75 Susceptibility to COVID‐19 in Patients Treated With Antimalarials: A Population‐Based Study in Emilia‐Romagna, Northern Italy
Comparison of CQ/HCQ users with the general population in a region of Italy, showing no significant difference in the probability of COVID-19. CQ/HCQ users were mostly systemic autoimmune disease patients and authors do not adjust for th..
8/6 Review McCullough et al., The American Journal of Medicine, doi:10.1016/j.amjmed.2020.07.003 (Review) (Peer Reviewed) (not included in the study count) review Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection
Review of pathophysiological principles related to early outpatient treatment and therapeutic approaches including reduction of reinoculation, combination antiviral therapy, immunomodulation, antiplatelet/antithrombotic therapy, and admin..
8/6 PEP, Early, Late Watanabe et al., Open Letter (Letter) (meta analysis - not included in study count) meta-analysis Concerns regarding the misinterpretation of statistical hypothesis testing in clinical trials for COVID-19
Open letter signed by 38 professors and doctors regarding misinterpretation of statistics in HCQ RCTs. Authors note  that data from RCTs for early treatment in outpatients to date actually show favorable effects, especially in high-ri..
8/5 PrEP Singer et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218500 (Letter) cases, ↑9.0%, p=0.62 Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis
Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity informat..
8/5 Late Kalligeros et al., Journal of Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.07.018 (Peer Reviewed) death, ↑67.0%, p=0.57 Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study
Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely.
8/4 Late Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint) progression, ↓5.0%, p=1.00 Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial
Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ ..
8/3 Late Berenguer et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.07.024 (Peer Reviewed) death, ↓61.9%, p<0.0001 Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain
Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix).
8/3 Late Yu et al., Science China Life Sciences, 2020 Aug 3, doi:10.1007/s11427-020-1782-1 (Letter) progression, ↓82.5%, p=0.05 Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs
Retrospective 2,882 patients in China, median age 62, 278 receiving HCQ, median 10 days post hospitalization, showing that HCQ treatment can reduce systemic inflammation and inhibit the cytokine storm, thus protecting multiple organs from..
8/2 Late Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 (Peer Reviewed) int./hosp., ↓55.0%, p=0.04 Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time
Retrospective of 132 hospitalized patients. HCQ+AZ(52)/AZ(28) significantly reduced death/ICU, HR=0.45, p=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay from admiss..
8/2 In Vitro Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count) in vitro A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity
In vitro study presenting a new theory on SARS-CoV-2 infection and why HCQ/CQ provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and treatment delay, and confirms the importance ..
8/1 Early Bernabeu-Wittel et al., J. Gerontol. A Biol. Sci. Med. Sci., doi:10.1093/gerona/glaa192 (Peer Reviewed) death, ↓59.0%, p=0.03 Effectiveness of a On-Site Medicalization Program for Nursing Homes with COVID-19 Outbreaks
Retrospective 272 nursing home residents showing significantly improved survival after establishing a treatment program including HCQ with or without lopinavir/ritonavir and with the addition of adjuvant and antimicrobial treatments depen..
7/31 Mazzitelli et al., Travel Medicine and Infectious Disease, 37, doi:10.1016/j.tmaid.2020.101826 (Letter) (not included in the study count) Apparent inefficacy of hydroxychloroquine combined with azithromycin on SARS-CoV-2 clearance in an incident cohort of geriatric patients with COVID-19
Report on HCQ+AZ use in 41 elderly high-risk patients. 29 of 30 patients with treatment >= 5 days survived. Only 10% were PCR negative after one week, however the Ct value is not specified.
7/29 Late D'Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter) death, ↓34.0%, p=0.12 Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?
HCQ+AZ adjusted death HR 0.44, p=0.009. Propensity scores include baseline COVID-19 disease severity, age, gender, number of comorbidities, cardio-vascular disease, duration of symptoms, date of admission, baseline plasma CRP. IPW censori..
7/28 Late BaŞaran et al., Turk. J. Med. Sci., doi:10.3906/sag-2006-173 (Peer Reviewed) Outcome of Non-Critical COVID-19 Patients with Early Hospitalization and Early Antiviral Treatment Outside the ICU
Observational study of 174 hospitalized patients in Turkey, median age 45.4, 23 treated with HCQ, 113 with HCQ+AZ, and 32 with regimens including favipiravir. 75% reduction in the median time to clinical improvement for HCQ+AZ vs. FAV, RR..
7/26 PEP Mitjà et al., NEJM, doi:10.1056/NEJMoa2021801 (preprint 7/26) (Peer Reviewed) death, ↓51.7%, p=0.27 A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease
Death rate reduced from 0.6% to 0.4%, RR 0.68, not statistically significant due to low incidence (8 control cases, 5 treatment cases). For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - ..
7/24 PrEP Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint) cases, ↓51.0%, p=0.02 Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital
Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this stu..
7/23 Late Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa2019014 (Peer Reviewed) death, ↓16.0%, p=0.77 Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot de..
7/22 In Vitro Ou et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009212 (preprint 7/22) (Peer Reviewed) (In Vitro) in vitro Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2
In Vitro analysis showing that HCQ efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of HCQ and a TMPRSS2 inhibitor prevents SARS-CoV-2 infection more potently than either drug alone.
7/22 In Vitro Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count) in vitro Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2
The title of this paper does not appear to match the results. Fig. 1b @100uM shows CQ results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, p=0.05, after 24 hours (we do not see the supplementary data at this time so..
7/22 Late Rivera et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0941 (Peer Reviewed) death, ↑2.4%, p=0.90 Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study
Retrospective cancer patients, showing adjusted OR 1.03 [0.62-1.73] for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indicatio..
7/22 Late Kelly et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.14482 (Peer Reviewed) death, ↑143.0%, p=0.03 Clinical outcomes and adverse events in patients hospitalised with COVID‐19, treated with off‐label hydroxychloroquine and azithromycin
Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounde..
7/21 Late Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960 (Preprint) death, ↓17.0%, p<0.0001 Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid
HCQ HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative effect.
7/20 PrEP Desbois et al., Research Square, doi:10.21203/rs.3.rs-41653/v1 (Preprint) cases, ↓16.9%, p=1.00 Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis
Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, p=1.0.
7/20 Early Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis”
Updated meta analysis including 7 new studies of high-risk outpatients, for a total of 12 studies, all showing significant benefit.
7/18 PEP Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in study count) meta-analysis Efficacy of Hydroxychloroquine as Prophylaxis for Covid-19
Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HCQ is effective when used early, p<0.01. The effectiveness found is especially notable considering the limitations of the study. Treatm..
7/19 Late McGrail et al., medRxiv, doi:10.1101/2020.07.17.20156521 (Preprint) death, ↑70.0%, p=0.69 COVID-19 Case Series at UnityPoint Health St. Luke’s Hospital in Cedar Rapids, IA
HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the tre..
7/17 Late Lyngbakken et al., Nature Communications, doi:10.1038/s41467-020-19056-6 (Peer Reviewed) death, ↓3.7%, p=1.00 A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics
Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HCQ was 0.24 [0.03-0.46] RNA copies/mL/24h, and 0.14 [-0.10-0.37] for the control group (71% faster with HCQ but not statistically signi..
7/16 Early Hong et al., Infect. Chemother., 2020, doi:10.3947/ic.2020.52.e43 (Peer Reviewed) viral+, ↓64.9%, p=0.001 Early Hydroxychloroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication
HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administrat..
7/16 Early Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed) hosp./death, ↓36.7%, p=0.58 Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial
~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ showing lower hospitalization/death and faster recovery, but not reaching statistical significance. There was one hospitalized control death and one non-hospitalized HC..
7/16 Early Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed) hosp., ↓16.0%, p=0.64 Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
This paper has conflicting values, table S2 shows 12 control hospitalizations, while table 2 shows 11. The original report for this paper had more conflicting values, with values reported in Table 2 and the abstract corresponding to 12 co..
7/15 Late Gupta et al., JAMA Intern. Med., doi:10.1001/jamainternmed.2020.3596 (Peer Reviewed) death, ↑6.0%, p=0.41 Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US
Analysis of 2215 intensive care unit patients showing no significant differences with this very late stage use of HCQ. HCQ+AZ mortality relative risk RR 0.96, p=0.53, HCQ and HCQ+AZ combined RR 1.06, p=0.409.
7/15 N/A Kavanagh et al., Med. Hypotheses, doi:10.1016/j.mehy.2020.110110 (Peer Reviewed) dosing study Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19
Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the..
7/14 Late Trullàs et al., Research Square, doi:10.21203/rs.3.rs-39421/v1 (Preprint) death, ↓35.6%, p=0.12 High in-hospital mortality due to COVID-19 in a community hospital in Spain: a prospective observational study
Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ.
7/14 Early Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 (Peer Reviewed) A Randomized Trial of Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients
Small 116 patient RCT comparing ivermectin+doxycycline and HCQ+AZ, not showing a significant difference in time to PCR negative or symptom resolution. Time to symptomatic recovery was 5.93 days for ivermectin+doxycycline vs. 6.99 days for..
7/11 Late Lecronier et al., Critical Care, 24:418, 2020, doi:10.1186/s13054-020-03117-9 (Peer Reviewed)death, ↓42.0%, p=0.24 Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences..
7/10 Late Cravedi et al., American Journal of Transplantation, doi:10.1111/ajt.16185 (Peer Reviewed) death, ↑53.0%, p=0.17 COVID‐19 and kidney transplantation: Results from the TANGO International Transplant Consortium
Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, p = 0.17. Subject to confounding by indication.
7/10 Late Chen et al., PLoS ONE, doi:10.1371/journal.pone.0242763 (Peer Reviewed) viral+, ↓24.0%, p=0.71 A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19)
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76..
7/9 Late Rivera-Izquierdo et al., Medicina Clínica, doi:10.1016/j.medcli.2020.06.025 (Peer Reviewed) death, ↓19.0%, p=0.75 Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad
Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazard ratio aHR 0.81 [0.24-2.76].
7/9 Early, Late Raoult et al., Preprint (Preprint) (meta analysis - not included in study count) meta-analysis Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial: Response to David Spencer (Elsevier)
Updated meta analysis showing significant reductions in mortality and viral shedding. Mortality OR 0.53 [0.4-0.71] for clinical studies, 0.92 big data studies, 18,211 patients. Persistent viral shedding OR 0.47 [0.28-0.79], 4,540 patients.
7/8 N/A Marzolini et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01177-20 (Peer Reviewed) (not included in the study count) dosing study Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations
Study of Lopinivar and HCQ plasma concentrations and CRP levels in late stage (treatment initiation median 8 days from onset) COVID-19 patients. The median HCQ plasma concentration was 171 ng/ml, which authors suggest indicates that HCQ l..
7/8 N/A Li et al., Cell Death & Disease volume 11, doi:10.1038/s41419-020-2721-8 (Review) (Peer Reviewed) (not included in the study count) review Is hydroxychloroquine beneficial for COVID-19 patients?
Review of the anti-inflammatory, antiviral, and protective vascular effects of CQ and HCQ, noting that HCQ may be preferable for COVID-19 due to fewer side effects.
7/7 Review Goldstein, L., Preprint, July 7, 2020 (Review) (Preprint) (not included in the study count) review Hydroxychloroquine-based COVID-19 Treatment, A Systematic Review of Clinical Evidence and Expert Opinion from Physicians’ Surveys
85% of globally surveyed physicians recognized HCQ as at least partially effective in treating COVID-19, according to Sermo W3. More than half of the surveyed US physicians would take the drug or give it to family members early or even be..
7/7 Late An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint) viral+, ↓3.0%, p=0.92 Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. "It is notable th..
7/3 PrEP Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7 (Peer Reviewed) cases, ↓91.0%, p=0.04 COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study
Rheumatic disease patients on HCQ had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythematosus, infection in othe..
7/1 Late Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed) death, ↓51.3%, p=0.009 Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, p=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HCQ group average age is 5 years younger and the percenta..
7/1 N/A Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count) safety analysis Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR positive SARS-CoV-2 infection including drug induced changes in the corrected QT interval (QTc)
In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but occur at an incidence higher than expected in a general pediatric population. Comorbidities are not more common in patients wit..
6/30 Late Martinez-Lopez et al., Blood Cancer Journal, doi:10.1038/s41408-020-00372-5 (Peer Reviewed) death, ↓33.0%, p=0.20 Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality
Retrospective 167 multiple myeloma patients in Spain.
6/30 Late Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z (Peer Reviewed) death, ↓47.0%, p<0.0001 Risk Factors for Mortality in Patients with COVID-19 in New York City
HCQ decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City.
6/30 Late Komissarov et al., medRxiv, doi:10.1101/2020.06.30.20143289 (Preprint) viral load, ↑25.0%, p=0.45 Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19
Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with sign..
6/29 Late Sosa-García et al., Cir Cir. 2020, 88:5, 569-575, doi:10.24875/CIRU.20000675 (Peer Reviewed) death, ↑10.5%, p=1.00 Experience in the management of severe COVID-19 patients in an intensive care unit
Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, p = 1.0.
6/29 PrEP Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed) cases, ↓47.1%, p<0.0001 Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection
Chronic treatment with HCQ provides protection against COVID, odds ratio 0.51 (0.37-0.70). The actual benefit is likely to be larger becasue research shows that the risk of COVID-19 for systemic autoimmune disease patients is much highe..
6/29 N/A Mfeukeu-Kuate et al. (Preprint) (not included in the study count) safety analysisElectrocardiographic safety of daily Hydroxychloroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon
No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HCQ+AZ. 51 relatively young patients 39 +/- 11.
6/25 PrEP Gendebien et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218244 (Letter) cases, ↓3.9%, p=0.93 Systematic analysis of COVID-19 infection and symptoms in a systemic lupus erythematosus population: correlation with disease characteristics, hydroxychloroquine use and immunosuppressive treatments
Small study of 152 SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reported for..
6/25 Early Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed) death, ↓59.0%, p=0.05 Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis
Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients.
6/23 Late Bousquet et al., Aging, 12:12, 11306-11313, doi:10.18632/aging.103583 (Peer Reviewed) death, ↓42.8%, p=0.15 ADL-dependency, D-Dimers, LDH and absence of anticoagulation are independently associated with one-month mortality in older inpatients with Covid-19
Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, p = 0.15.
6/22 Safety Isaksen et al., medRxiv, doi:10.1101/2020.06.19.20135475 (Preprint) safety analysisChloroquine, but not hydroxychlorquine, prolongs the QT interval in a primary care population
Safety analysis in patients without COVID-19, finding a small increase in QTc associated with use of CQ, but not HCQ. Authors also study mortality (n=3,368), with HCQ hazard ratio 0.67 [0.43-1.05].
6/22 Late Fontana et al., Clinical Kidney Journal, 13:3, 334–339, doi:10.1093/ckj/sfaa084 (Peer Reviewed) death, ↓50.0%, p=0.53 SARS-CoV-2 infection in dialysis patients in northern Italy: a single-centre experience
Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, p = 0.53.
6/22 Early Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint) viral- time, ↓72.0%, p=0.01 Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study
Significantly faster clinical recovery and shorter time to RNA negative (from 7.0 days to 2.0 days (HCQ), p=0.01. 67 patients with mild/moderate cases.
6/21 Late Faíco-Filho et al., Braz J Microbiol, doi:10.1007/s42770-020-00395-x (preprint 6/21) (Peer Reviewed) viral rate, ↓80.8%, p=0.40 No benefit of hydroxychloroquine on SARS-CoV-2 viral load reduction in non-critical hospitalized patients with COVID-19
Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results show faster recovery wi..
6/19 PrEP SMSH Sawai Man Singh Hospital, India (News) (not included in the study count) news HCQ beneficial as preventive drug: SMS doctors told ICMR
PrEP with 4,300 very high risk healthcare workers in a hospital with up to 500+ COVID patients at a time, only 1% cases, all recovered.
6/19 Late NIH, study not available yet (News) (not included in the study count) news NIH halts clinical trial of hydroxychloroquine
NIH halts late stage trial reporting no harm and no benefit. 470 patients.
6/19 Late Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint) death, ↑5.0%, p=0.74 Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France
Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Oth..
6/19 N/A Kaptein et al., bioRxiv, doi:10.1101/2020.06.19.159053 (Peer Reviewed) (not included in the study count) animal study Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacks activity
Animal study with Syrian hamsters, showing treatment of SARS-CoV-2-infected hamsters with favipiravir or HCQ (with and without AZ). Treatment with HCQ alone resulted in a very modest reduction of 0.3 log10 viral RNA copies/mg lung, and no..
6/18 Late Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed) death, ↓11.0%, p=0.88 Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital
Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.
6/17 Early Capucci et al., J. Cardiovasc. Med. 21, 922–923, doi:10.2459/JCM.0000000000001061 (Peer Reviewed) Low hospitalization rate without severe arrhythmias: a prospective survey on 350 patients early home treated with hydroxychloroquine during COVID-19 pandemic
Prospective analysis of early treatment of 350 patients in Italy (without waiting for PCR results), showing low hospitalization rates and no serious adverse events. From 274 patients treated with HCQ, 16 required hospitalization (5.8%). ..
6/17 Late Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 (Peer Reviewed) Hydroxychloroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China
30 hospitalized patients. Early use of HCQ is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization.
6/17 Late Luo et al., Annals of Oncology, 31:10, 1386-1396, doi:10.1016/j.annonc.2020.06.007 (Peer Reviewed) death, ↑2.2%, p=0.99 COVID-19 in patients with lung cancer
Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, p = 0.99.
6/16 Late Kim et al., Korean J Intern Med, doi:10.3904/kjim.2020.224 (Peer Reviewed) Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019
Small retrospective study of hospitalized patients with 31 lopinavir-ritonavir and 34 HCQ patients, HCQ 400mg once per day, finding no significant difference in clinical response, but more rapid viral clearance with lopinavir-ritonavir.
6/16 PrEP WHIP COVID-19 (News) (not included in the study count) news Henry Ford Health System still moving forward with hydroxychloroquine study
Ongoing WHIP COVID-19 HCQ PrEP study reports analyzing their data and seeing a significantly improved outcome in a group of COVID-19 patients who received HCQ. For more details on the study see .
6/16 PrEP Huang et al., Annals of the Rheumatic Diseases 2020:79, 1163-1169, doi:10.1136/annrheumdis-2020-217425 (Peer Reviewed) hosp., ↓80.0%, p<0.001 Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study
Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%–10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization.
6/12 Theory Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count) theory Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy
Theory paper, not included in the study count or percentages. Proposes a new mechanism supporting the synergistic interaction between HCQ+AZ.
6/12 Late Giacomelli et al., Journal of Medical Virology, doi:10.1002/jmv.26407 (preprint 6/12) (Peer Reviewed) Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study
Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". Th..
6/10 Late Wang et al., medRxiv, doi:10.1101/2020.06.11.20128926 (Peer Reviewed) death, ↓5.8%, p=0.63 Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System
Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, p = 0.82, and HCQ+AZ OR 0.94, p = 0.63
6/10 Early Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint) A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.
80 moderate cases, HCQ+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy.
6/9 Early Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed) Beneficial effect of Hydroxychloroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an observational study
68 very high risk nursing home residents, median age 86, HCQ+AZ early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7 died, significantly less than other nursing homes in France and the same as the median death for the same ..
6/9 PrEP Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint) cases, ↓80.7%, p=0.001 Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers
HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects.
6/6 Review Roussel et al., New Microbes and New Infections, Volume 38, doi:10.1016/j.nmni.2020.100710 (Review) (Peer Reviewed) (not included in the study count) review Influence of conflicts of interest on public positions in the COVID-19 era, the case of Gilead Sciences
Shows a correlation (Spearman test, p = 0.017) between the amount received from Gilead Sciences and public opposition to the use of HCQ in France.
6/6 Early, Late Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world
[H]CQ effective and reduces mortality by a factor 3. Meta analysis of 20 studies.
6/5 Late RECOVERY Collaborative Group, NEJM, doi:10.1056/NEJMoa2022926 (press release 6/5) (Preprint) death, ↑9.0%, p=0.15 Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial
RECOVERY trial finds no significant benefit for very late stage very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) [1, 2]. The overall dosage used is only 23% less than the high dosage tha..
6/3 PEP Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed) cases, ↓17.0%, p=0.35 A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
COVID-19 cases are reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. PEP delayed treatment RCT. For..
6/1 N/A Al-Kofahi et al., Clin. Pharmacol. Ther., Jun 1, 2020, doi:10.1002/cpt.1874 (Peer Reviewed) (not included in the study count) dosing study Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness
Analysis of HCQ dosing regimens, recommending: PrEP: 800mg loading dose followed by 400mg 2 or 3 times weekly to maintain weekly troughs above EC50 in >50% of patients at steady-state. PEP: 800mg loading dose followed in 6 hours by 600m..
5/31 Early Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed) death, ↓61.4%, p=1.00 Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19
Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HCQ+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched patients.
5/28 Late Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint) Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon
HCQ+AZ potentially explains 94.7% success in treating a fairly complex cohort.
5/28 PrEP Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed) cases, ↓66.8%, p<0.001 Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19
4+ doses of HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists.
5/28 Late Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed) viral- time, ↓67.0%, p<0.0001 Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19
197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.
5/27 Late Goldman et al., NEJM, doi:10.1056/NEJMoa2015301 (Peer Reviewed) death, ↓22.3%, p=0.46 Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, p = 0.46.
5/28 Late Kuderer et al., Lancet, June 20, 2020, doi:10.1016/S0140-6736(20)31187-9 (preprint 5/28) (Peer Reviewed) death, ↑134.2%, p<0.0001 Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study
Retrospective 928 cancer patients, showing HCQ OR 1.06 [0.51-2.20]. HCQ+AZ OR 2.93 [1.79-4.79]. The relative risks of different therapies suggest that the results are overly affected by confounding by indication. Authors note: HCQ+AZ migh..
5/28 PrEP Gianfrancesco et al., Annals of the Rheumatic Diseases, 79:7, 859-866, doi:10.1136/annrheumdis-2020-217871 (Peer Reviewed) hosp., ↓3.3%, p=0.82 Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry
Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 [0.57-1.57], p=0.82 after adjustments.
5/27 Early Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis - not included in study count) meta-analysis Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis
Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy.
5/25 Late Ip et al., PLoS ONE, doi:10.1371/journal.pone.0237693 (Peer Reviewed) death, ↓1.0%, p=0.93 Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study
Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HCQ alone (HR, 1.02 ..
5/24 Late Hraiech et al., Ann. Intensive Care, doi:10.1186/s13613-020-00678-4 (Peer Reviewed) death, ↓64.7%, p=0.21 Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome
Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS.
5/22 PEP, PrEP ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) advisory Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection
Healthcare workers on HCQ prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HCQ prophylaxis to asymptomatic household contacts of cases and frontline workers. Degree of benefit not quantified.
5/22 Late Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed) (not included in the study count) retracted Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted.
5/19 Late Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint) death, ↓5.0%, p=0.72 Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network
EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indic..
5/18 Late Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint) hosp. time, ↓51.0%, p=0.01Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea
Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HCQ+antibiotic. Preprint withdrawn pending peer review.
5/18 Early Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint) Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
54 patients in long term care facilities. 6% death with HCQ+AZ compared to 22% using a naive indirect comparison.
5/16 PrEP Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint) hosp., ↓25.5%, p=1.00 Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy
Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. ..
5/15 Late Yu et al., Science China Life Sciences, 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed) death, ↓60.5%, p=0.002 Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19
Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ, RR 0.395, p=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL to 5.2 pg/mL (p<0.05) at the end of the treat..
5/14 Late Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed) death, ↑20.0%, p=0.75 Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions . None of the 15 patients receiving HCQ+AZ were transferred to intensive care..
5/13 Late Okour et al., Journal of Pharmacokinetics and Pharmacodynamics, May 13, 2020, doi:10.1007/s10928-020-09689-x (Peer Reviewed) Hydroxychloroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome
Odds of PCR-positive decrease by 53% for each unit increase in HCQ log-concentration. Similarly, the odds decrease by 61%, and by 12% for each day increase, and for azithromycin co-treatment, respectively. Computes the minimum HCQ concent..
5/12 PrEP Cassione et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217717 (Letter) cases, ↑49.6%, p=0.59 COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine
Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications o..
5/11 Late Shabrawishi et al., medRxix, doi:10.1101/2020.05.08.20095679 (Preprint) viral+, ↓14.7%, p=0.66 Negative nasopharyngeal SARS-CoV-2 PCR conversion in response to different therapeutic interventions
Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, p = 0.65. The treatment group had significantly more severe illness and significantly ..
5/11 Late Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed) death, ↑35.0%, p=0.31 Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
Restrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al.  point out serious limitations that they say should be corrected on the record: patients receiving HCQ wit..
5/10 Late Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed) death, ↓42.9%, p=0.12 A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection
Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HCQ but p=0.12, OR 0.44 [0.16–1.24].
5/8 Ex Vivo Grassin-Delyle et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa546 (Peer Reviewed) (Ex Vivo) (not included in the study count) ex vivo Chloroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants
On human lung parenchymal explants, CQ concentration clinically achievable in the lung (100 µM) inhibited the lipopolysaccharide-induced release of TNF-ɑ (by 76%), IL-6 (by 68%), CCL2 (by 72%), and CCL3 (by 67%). In addition to antiviral ..
5/8 Late Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed) Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients
Retrospective 932 patients. Addition of Zinc to HCQ+AZ reduces mortality / transfer to hospice, ICU admission, and the need for ventilation. Reduction in mortality or transfer to hospice adjusted odds ratio OR 0.56, p = 0.002; increase i..
5/7 PrEP Konig et al., Ann