Hydroxychloroquine

[DMDarcs]

Can someone show me a study where this is a verified treatment for COVID-19? They Henry Ford trial seems to have been flawed.

[Eliahad]

I'm pretty sure there isn't one.

[FlameBlade]

More damage than good it does, in general.

[Mike]

Right now, all major news outlets* that mention hydroxychloriquine consistently mention that studies have proven it ineffective in treating coronavirus. Sometimes they also mention that it it can actually be harmful.

*Fox News also mentions these facts, however the last couple times I saw them talk about it, they specifically phrase it as, "The New York Times reports that..." My assumption is that they do this so that they can claim credit for reporting it, but they also ONLY mention NYT as the source, because they know that most of their readers will immediately discount it, because they have no faith in "the failing New York Times".

[DMDarcs]

This is what I was expecting, as nothing I've found shows effectiveness. A Lancet study says that it's actually deadly, but that study has been later described as being flawed as the Henry Ford study was. Thanks Nerd Pride!

[Phoebe]

I get my covid treatment info directly from doctors, epidemiologists, and a PhD who is a review editor for medical journals. They still trust the Lancet results despite the walk back because it was done out of an abundance of caution over not being able to track and verify all of the data they got from other sources. They believe they still have plenty of other data that supports the overall conclusions, and their clinical protocols in the infectious diseases unit do not involve hydroxychloroquine except in certain specific circumstances. For treatment, their attention is focused on drugs Remdesivir, dexamethasone, and NT-17, as well as different therapeutic combinations. People still pushing hydroxychloroquine as a magic drug are 100% full of s*** and not to be trusted on this matter, and that includes most political leaders where I live who are basically too stupid to be responsible for other human beings.

[Ronster]

Before I went out on leave from work I came across a 24 page article. I emailed it to Mike. It is a study done abroad I will include excerpts from it here.

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
Philippe Gautreta,b$, Jean-Christophe Lagiera,c$, Philippe Parolaa,b, Van Thuan Hoanga,b,d, Line Meddeba, Morgane Mailhea, Barbara Doudiera, Johan Courjone,f,g, Valérie Giordanengoh, Vera Esteves Vieiraa, Hervé Tissot Duponta,c, Stéphane Honoréi,j, Philippe Colsona,c, Eric Chabrièrea,c, Bernard La Scolaa,c, Jean-Marc Rolaina,c, Philippe Brouquia,c, Didier Raoulta,c*.
aIHU-Méditerranée Infection, Marseille, France.
bAix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France.
cAix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.
dThai Binh University of Medicine and Pharmacy, Thai Binh, Viet Nam
eInfectiologie, Hôpital de l’Archet, Centre Hospitalier Universitaire de Nice, Nice, France
fUniversité Côte d’Azur, Nice, France
gU1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Virulence Microbienne et Signalisation Inflammatoire, INSERM, Nice, France
hDepartment of Virology, Biological and Pathological Center, Centre Hospitalier Universitaire de Nice, 06200 Nice, France.
iService Pharmacie, Hôpital Timone, AP-HM, Marseille, France
jLaboratoire de Pharmacie Clinique, Aix Marseille Université, Marseille, France.
$equal work
*Corresponding author:
2
Didier Raoult

3
Abstract
Background
Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads.
Patients and methods
French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.
Results
Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms.
Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
Conclusion
4
Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
Key words: 2019-nCoV; SARS-CoV-2; COVID-19; hydroxychloroquine; azithomycin; clinical trial
1. Introduction
In late December 2019, an outbreak of an emerging disease (COVID-19) due to a novel coronavirus (named SARS-CoV-2 latter) started in Wuhan, China and rapidly spread in China and outside [1,2]. The WHO declared the epidemic of COVID-19 as a pandemic on March 12th 2020 [3]. According to a recent Chinese stud, about 80% of patients present with mild disease and the overall case-fatality rate is about 2.3% but reaches 8.0% in patients aged 70 to 79 years and 14.8% in those aged >80 years [4]. However, there is probably an important number of asymptomatic carriers in the population, and thus the mortality rate is probably overestimated. France is now facing the COVID-19 wave with more than 4500 cases, as of March 14th 2020 [5]. Thus, there is an urgent need for an effective treatment to treat symptomatic patients but also to decrease the duration of virus carriage in order to limit the transmission in the community. Among candidate drugs to treat COVID-19, repositioning of old drugs for use as antiviral treatment is an interesting strategy because knowledge on safety profile, side effects, posology and drug interactions are well known [6,7].
A recent paper reported an inhibitor effect of remdesivir (a new antiviral drug) and chloroquine (an old antimalarial drug) on the growth of SARS-CoV-2 in vitro, [8] and an early clinical trial conducted in COVID-19 Chinese patients, showed that chloroquine had a significant effect, both in terms of clinical outcome and viral clearance, when comparing to controls groups [9,10]. Chinese experts recommend that patients diagnosed as mild, moderate and severe cases of COVID-19 pneumonia and without contraindications to chloroquine, be treated with 500 mg chloroquine twice a day for ten days [11].
Hydroxychloroquine (an analogue of chloroquine) has been demonstrated to have an anti-SARS-CoV activity in vitro [12]. Hydroxychloroquine clinical safety profile is better than that of chloroquine (during long-term use) and allows higher daily dose [13] and has fewer
6
concerns about drug-drug interactions [14]. Our team has a very comprehensive experience in successfully treating patients with chronic diseases due to intracellular bacteria (Q fever due to Coxiella burnetii and Whipple’s disease due to Tropheryma whipplei) with long-term hydroxychloroquine treatment (600 mg/day for 12 to 18 months) since more than 20 years. [15,16] We therefore started to conduct a clinical trial aiming at assessing the effect of hydroxychloroquine on SARS-CoV-2-infected patients after approval by the French Ministry of Health. In this report we describe our early results, focusing on virological data in patients receiving hydroxychloroquine as compared to a control group.

2. Study population and Methods
Setting
This ongoing study is coordinated by The Méditerranée Infection University Hospital Institute in Marseille. Patients who were proposed a treatment with hydroxychloroquine were recruited and managed in Marseille centre. Controls without hydroxychloroquine treatment were recruited in Marseille, Nice, Avignon and Briançon centers, all located in South France.
Patients
Hospitalized patients with confirmed COVID-19 were included in this study if they fulfilled two primary criteria: i) age >12 years; ii) PCR documented SARS-CoV-2 carriage in nasopharyngeal sample at admission whatever their clinical status.
Patients were excluded if they had a known allergy to hydroxychloroquine or chloroquine or had another known contraindication to treatment with the study drug, including retinopathy, G6PD deficiency and QT prolongation. Breastfeeding and pregnant patients were excluded based on their declaration and pregnancy test results when required.
Informed consent
Before being included in the study, patients meeting inclusion criteria had to give their consent to participate to the study. Written informed signed consent was obtained from adult participants (> 18 years) or from parents or legal guardians for minors (<18 years). An information document that clearly indicates the risks and the benefits associated with the participation to the study was given to each patient. Patients received information about their clinical status during care regardless of whether they participate in the study or not. Regarding patient identification, a study number was assigned sequentially to included participants, according to the range of patient numbers allocated to each study centre. The study was conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines of good clinical practice, the Helsinki Declaration, and applicable standard operating procedures.
The protocol, appendices and any other relevant documentation were submitted to the French National Agency for Drug Safety (ANSM) (2020-000890-25) and to the French Ethic Committee (CPP Ile de France) (20.02.28.99113) for reviewing and approved on 5th and 6th March, 2020, respectively. This trial is registered with EU Clinical Trials Register, number 2020-000890-25.
Procedure
Patients were seen at baseline for enrolment, initial data collection and treatment at day-0, and again for daily follow-up during 14 days. Each day, patients received a standardized clinical examination and when possible, a nasopharyngeal sample was collected. All clinical data were collected using standardized questionnaires. All patients in Marseille center were proposed oral hydroxychloroquine sulfate 200 mg, three times per day during ten days (in this preliminary phase ,we did not enrolled children in the treatment group based in data indicating that children develop mild symptoms of COVID-19 [4]). Patients who refused the treatmentor had an exclusion criteria, served as controls in Marseille centre. Patients in other centers did not receive hydroxychloroquine and served as controls. Symptomatic treatment and antibiotics as a measure to prevent bacterial super-infection was provided by investigators based on clinical judgment. Hydroxychloroquine was provided by the National Pharmacy of France on nominative demand.
absorption, as for hydroxychloroquine concentration. Considering both concentrations provides an estimation of initial serum hydroxychloroquine concentration.
Culture
9
For all patients, 500 μL of the liquid collected from the nasopharyngeal swab were passed through 0.22-μm pore sized centrifugal filter (Merck millipore, Darmstadt, Germany), then were inoculated in wells of 96-well culture microplates, of which 4 wells contained Vero E6 cells (ATCC CRL-1586) in Minimum Essential Medium culture medium with 4% fetal calf serum and 1% glutamine. After centrifigation at 4,000 g, microplates were incubated at 37°C. Plates were observed daily for evidence of cytopathogenic effect. Presumptive detection of virus in supernatant was done using SU5000 SEM (Hitachi) then confirmed by specific RT-PCR.
Outcome
The primary endpoint was virological clearance at day-6 post-inclusion. Secondary outcomes were virological clearance overtime during the study period, clinical follow-up (body temperature, respiratory rate, long of stay at hospital and mortality), and occurrence of side-effects.
Statistics
Assuming a 50% efficacy of hydroxychloroquine in reducing the viral load at day 7, a 85% power, a type I error rate of 5% and 10% loss to follow-up, we calculated that a total of 48 COVID-19 patients (ie, 24 cases in the hydroxychloroquine group and 24 in the control group) would be required for the analysis (Fleiss with CC). Statistical differences were evaluated by Pearson’s chi-square or Fisher’s exact tests as categorical variables, as appropriate. Means of quantitative data were compared using Student’s t-test. Analyses were performed in Stata version 14.2.
3. Results (detailed results are available in supplementary Table 1)
10
Demographics and clinical presentation
We enrolled 36 out of 42 patients meeting the inclusion criteria in this study that had at least six days of follow-up at the time of the present analysis. A total of 26 patients received hydroxychloroquine and 16 were control patients. Six hydroxychloroquine-treated patients were lost in follow-up during the survey because of early cessation of treatment. Reasons are as follows: three patients were transferred to intensive care unit, including one transferred on day2 post-inclusion who was PCR-positive on day1, one transferred on day3 post-inclusion who was PCR-positive on days1-2 and one transferred on day4 post-inclusion who was PCR-positive on day1 and day3; one patient died on day3 post inclusion and was PCR-negative on day2; one patient decided to leave the hospital on day3 post-inclusion and was PCR-negative on days1-2; finally, one patient stopped the treatment on day3 post-inclusion because of nausea and was PCR-positive on days1-2-3. The results presented here are therefore those of 36 patients (20 hydroxychloroquine-treated patients and 16 control patients). None of the control patients was lost in follow-up. Basic demographics and clinical status are presented in Table 1. Overall, 15 patients were male (41.7%), with a mean age of 45.1 years. The proportion of asymptomatic patients was 16.7%, that of patients with URTI symptoms was 61.1% and that of patients with LRTI symptoms was 22.2%). All patients with LRTI symptoms, had confirmed pneumonia by CTScan. Hydroxychloroquine-treated patients were older than control patients (51.2 years vs. 37.3 years). No significant difference was observed between hydroxychloroquine-treated patients and control patients with regard to gender, clinical status and duration of symptoms prior to inclusion (Table 1). Among hydroxychloroquine-treated patients six patients received azithromycin (500mg on day1 followed by 250mg per day, the next four days) to prevent bacterial super-infection under daily electrocardiogram control. Clinical follow-up and occurrence of side-effects will be described in a further paper at the end of the trial.
11
Hydroxychloroquine dosage
Mean hydroxychloroquine serum concentration was 0.46 μg/ml+0.2 (N=20).
Effect of hydroxychloroquine on viral load
The proportion of patients that had negative PCR results in nasopharyngeal samples significantly differed between treated patients and controls at days 3-4-5 and 6 post-inclusion (Table 2). At day6 post-inclusion, 70% of hydroxychloroquine-treated patients were virologicaly cured comparing with 12.5% in the control group (p= 0.001).
When comparing the effect of hydroxychloroquine treatment as a single drug and the effect of hydroxychloroquine and azithromyc in combination, the proportion of patients that had negative PCR results in nasopharyngeal samples was significantly different between the two groups at days 3-4-5 and 6 post-inclusion (Table 3). At day6 post-inclusion, 100% of patients treated with hydroxychloroquine and azithromycin combination were virologicaly cured comparing with 57.1% in patients treated with hydroxychloroquine only, and 12.5% in the control group (p<0.001). These results are summarized in Figures 1 and 2. Drug effect was significantly higher in patients with symptoms of URTI and LRTI, as compared to asymptomatic patients with p<0.05 (data not show).
Of note, one patient who was still PCR-positive at day6-post inclusion under hydroxychloroquine treatment only, received azithromycin in addition to hydroxychloroquine at day8-post inclusion and cured her infection at day-9 post infection. In contrast, one of the patients under hydroxychloroquine and azithromycin combination who tested negative at day6 post-inclusion was tested positive at low titer at day8 post-inclusion.
Cultures
We could isolate SARS-CoV-2 in 19 out of 25 clinical samples from patients.
12
4. Discussion
For ethical reasons and because our first results are so significant and evident we decide to share our findings with the medical community, given the urgent need for an effective drug against SARS-CoV-2 in the current pandemic context.
We show here that hydroxychloroquine is efficient in clearing viral nasopharyngeal carriage of SARS-CoV-2 in COVID-19 patients in only three to six days, in most patients. A significant difference was observed between hydroxychloroquine-treated patients and controls starting even on day3 post-inclusion. These results are of great importance because a recent paper has shown that the mean duration of viral shedding in patients suffering from COVID-19 in China was 20 days (even 37 days for the longest duration) [19]
Very recently, a Chinese team published results of a study demonstrating that chloroquine and hydroxychloroquine inhibit SARS-CoV-2 in vitro with hydroxychloroquine (EC50=0.72%μM) found to be more potent than chloroquine (EC50=5.47%μM) [14]. These in vitro results corroborate our clinical results. The target values indicated in this paper [14] were reached in our experiments. The safer dose-dependent toxicity profile of hydroxychloroquine in humans, compared to that of chloroquine [13] allows using clinical doses of hydroxychloroquine that will be over its EC50 observed in vitro [14].
Our preliminary results also suggest a synergistic effect of the combination of hydroxychloroquine and azithromycin. Azithromycin has been shown to be active in vitro against Zika and Ebola viruses [20-22] and to prevent severe respiratory tract infections when administrated to patients suffering viral infection [23]. This finding should be further explored to know whether a combination is more effective especially in severe cases. Speculated potential risk of severe QT prolongation induced by the association of the two drugs has not
13
been established yet but should be considered. As for each treatment, the cost benefits of the risk should be evaluated individually. Further studies on this combination are needed, since such combination may both act as an antiviral therapy against SARS-CoV-2 and prevent bacterial super-infections.
The cause of failure for hydroxychloroquine treatment should be investigated by testing the isolated SARS-CoV-2 strains of the non-respondents and analyzing their genome, and by analyzing the host factors that may be associated with the metabolism of hydroxychloroquine. The existence of hydroxychloroquine failure in two patients (mother and son) is more suggestive of the last mechanism of resistance.
Such results are promising and open the possibility of an international strategy to decision-makers to fight this emerging viral infection in real-time even if other strategies and research including vaccine development could be also effective, but only in the future. We therefore recommend that COVID-19 patients be treated with hydroxychloroquine and azithromycin to cure their infection and to limit the transmission of the virus to other people in order to curb the spread of COVID-19 in the world. Further works are also warranted to determine if these compounds could be useful as chemoprophylaxis to prevent the transmission of the virus, especially for healthcare workers. Our study has some limitations including a small sample size, limited long-term outcome follow-up, and dropout of six patients from the study, however in the current context, we believe that our results should be shared with the scientific community.
14
Titles for figures
Figure 1. Percentage of patients with PCR-positive nasopharyngeal samples from inclusion to day6 post-inclusion in COVID-19 patients treated with hydroxychloroquine and in COVID-19 control patients.
Figure 2. Percentage of patients with PCR-positive nasopharyngeal samples from inclusion to day6 post-inclusion in COVID-19 patients treated with hydroxychloroquine only, in COVID-19 patients treated with hydroxychloroquine and azithomycin combination, and in COVID-19 control patients.
Acknowledgements:
We thank Céline Boschi, Stéphanie Branger, Véronique Filosa, Géraldine Gonfier, Nadège Palmero, Magali Richez and all the clinical, technical and paramedical staffs of the hospitalization units and laboratories for their support in this difficult context.
Funding source
This work was supported by the French Government under the « Investissements d’avenir » (Investments for the Future) program managed by the Agence Nationale de la Recherche (ANR, fr: National Agency for Research), (reference: Méditerranée Infection 10-IAHU-03)
References
[1] Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and
15
the challenges. Int J Antimicrob Agents. 2020 Feb 17:105924. doi: 10.1016/j.ijantimicag.2020.105924. [Epub ahead of print]
[2] Wang LS, Wang YR, Ye DW, Liu QQ. A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence”. Int J Antimicrob Agents. 2020 [Epub ahead of print]
[3] WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. [https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020]
[4] Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648. [Epub ahead of print]
[5] Santé Publique France. Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde [https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-et-infections-respiratoires/infection-a-coronavirus/articles/infection-au-nouveau-coronavirus-sars-cov-2-covid-19-france-et-monde]
[6] Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020 Feb 15:105923. doi: 10.1016/j.ijantimicag.2020.105923. [Epub ahead of print]
[7] Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 [Epub ahead of print]
16
[8] Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;10-0282.
[9] Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020 Feb 19. doi: 10.5582/bst.2020.01047. [Epub ahead of print]
[10] Chinese Clinical Trial Registry. http://www.chictr.org.cn/ searchproj.aspx?title=%E6%B0%AF%E5%96%B9&offi cialname=&subjectid=&secondaryid=&applier=&study leader=&ethicalcommitteesanction=&sponsor=&studya ilment=&studyailmentcode=&studytype=0&studystage= 0&studydesign=0&minstudyexecutetime=&maxstudyexe cutetime=&recruitmentstatus=0&gender=0&agreetosign =&secsponsor=&regno=&regstatus=0&country=&prov ince=&city=&institution=&institutionlevel=&measure= &intercode=&sourceofspends=&createyear=0&isupload rf=&whetherpublic=&btngo=btn&verifycode=&page=1.
[11] Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185-188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009.
17
[12] Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D, et al. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem 2006;49:2845-2849.
[13] Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF; American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016 Jun;123(6):1386-94. doi: 10.1016/j.ophtha.2016.01.058. Epub 2016 Mar 16.
[14] Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. pii: ciaa237. doi: 10.1093/cid/ciaa237. [Epub ahead of print]
[15] Raoult D, Houpikian P, Tissot Dupont H, Riss JM, Arditi-Djiane J, Brouqui P. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med. 1999 Jan 25;159(2):167-73.
[16] Lagier JC, Raoult D. Whipple's disease and Tropheryma whipplei infections: when to suspect them and how to diagnose and treat them. Curr Opin Infect Dis. 2018 Dec;31(6):463-470. doi: 10.1097/QCO.0000000000000489. [x] Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185-188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009.
[17] Amrane S, Tissot-Dupont H, Doudier B, Eldin C, Hocquart M, Mailhe M et al. Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot. Travel Med Infect Dis. 2020 [Epub ahead of print].
18
[18] Armstrong N, Richez M, Raoult D, Chabriere E. Simultaneous UHPLC-UV analysis of hydroxychloroquine, minocycline and doxycycline from serum samples for the therapeutic drug monitoring of Q fever and Whipple's disease. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2017: 1060, 166-172.
[19] Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 11. pii: S0140-6736(20)30566-3. doi: 10.1016/S0140-6736(20)30566-3. [Epub ahead of print]
[20] Retallack H, Di Lullo E, Arias C, Knopp KA, Laurie MT, Sandoval-Espinosa C, et al. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14408-14413. Epub 2016 Nov 29.
[21] Madrid PB, Panchal RG, Warren TK, Shurtleff AC, Endsley AN, Green CE, Kolokoltsov A, et al. Evaluation of Ebola Virus Inhibitors for Drug Repurposing. ACS Infect Dis. 2015 Jul 10;1(7):317-26. doi: 10.1021/acsinfecdis.5b00030. Epub 2015 May 11.
[22] Bosseboeuf E, Aubry M, Nhan T, de Pina, JJ, Rolain JM, Raoult D, et al. Azithromycin inhibits the replication of Zika virus. J Antivirals Antiretrovirals. 2018 10(1):6-11. doi: 10.4172/1948-5964.1000173.
[23] Bacharier LB, Guilbert TW, Mauger DT, Boehmer S, Beigelman A, Fitzpatrick AM, et al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: A randomized clinical trial. JAMA. 2015 Nov 17;314(19):2034-2044. doi: 10.1001/jama.2015.13896

[Ronster]

I have the full pdf and will be glad to share it with anyone. my email is ronald(dot)poteet@delta(dot)com if you want to see it with all the graphs and other data. Also, Mike has it...the pdf, not coronavirus.

[Stan]

Overall, it doesn't seem to do much. The above study showed some signal - it was small and not a standard RCT (which was understandable given the attempt to get results quickly). Three large RCTs found no benefit. Though the paper that showed harm has been retracted.

From :
"‘A total of 1542 patients were randomised to hydroxychloroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on hospital stay duration or other outcomes."

I know it sounds bad but I'm jealous about their ability to recruit. I'm on trials that take years to get a hundred patients just because it's not an emergency and their long list of inclusions/exclusions.

[Kyle]

I don't understand the point of the article. Why is this important?

[FlameBlade]

Quickly, the paper linked by Ronster -- one of the flaws: sample size is too small. My impression is, it's a paper that essentially documents trial, but as you add more data, you get more information.

Very much like vaccine trials -- you start small, then you expand to include as much cross-section of the population as possible to determine if there are any serious side effects that makes vaccine useless overall.

When evaluating the statistics, you need to be aware of the what statistics is showing claiming. If the p-value is at .05, then you have 5% chance that maybe it's a false positive or perhaps what some call "high random" -- random values that seems like it is behaving like a real deal, but really, a random value. If you notice, as you add more people, you reduce variance of what tests might be suggesting, and therefore, start to narrow down to a true conclusion.

[Ronster]

[Kyle]

Got it. Thanks.

[Phoebe]

It just boggles my mind that MAGA world thinks the doctors could be saving lives with this wonderful drug, but due to malice or incompetence or political loyalties to Democrats, they have decided to let their patients die needless deaths sans hydroxychloroquine.