Sequential CQ / HCQ Research Papers and Reports
January to April 20, 2020
Executive Summary Interpretation of the Data In This Report
The HCQ-AZ combination, when started immediately after diagnosis, appears to be a safe and efficient treatment for COVID-19, with a mortality rate of 0.5%, in elderly patients. It avoids worsening and clears virus persistence and contagious infectivity in most cases.
Sequential CQ / HCQ Research Papers and Reports
January to April 12, 2020
22 August 2005
CDC Special Pathogens Branch
MJ VIncet, E.Bergon, S. Benjannet, BR Erickson, Pierre Rollin, T.G. Ksiazek, NG Seidah,
ST Nichole. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology Journal. (2005) 2: 69
Chloroquine has strong antiviral effects on SARS CoV infection of primate cells in tissue culture. These inhibitory effects are observed when cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic preventative and treatment use. The paper describes three mechanisms by which the drug might work and suggest it may have both a prophylactic and therapeutic role in Coronavirus infections.
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28 January 2020
M. Wang, R. Cao, L. Zhang, X. Yang, J. Liu, M. Xu, Z. Shi, Z. Hu, W. Zhong, G. Xiao
LETTER TO THE EDITOR Cell Research Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research (2020) 0:1–3; https://doi.org/10.1038/s41422-020-0282-0
Tested Remdesivir and Chloroquine in addition to five other drugs were tested in tissue culture against a clinical sample of virus from a COVID-19 patient, Remdesivir and Chloroquine are highly effective in the control of 2019-nCoV infection in vitro. Since these compounds have been used in human patients with a safety track record and shown to be effective against various ailments, we suggest that they should be assessed in human patients suffering from the novel coronavirus disease.
February 13, 2020
Physicians work out treatment guidelines for coronavirus, Korea Biomedical Review http://www.koreabiomed.com/news/articleView.html?idxno=7428
The Korean COVID-19 Central Clinical Task Force, held the sixth video conference and agreed on treatment principles for patients with COVID-19.
* Young with mild symptoms without underlying conditions, doctors can observe them without antiviral treatment.
* If 10 days have passed since the onset of the illness and the symptoms are mild, physicians do not have to start an antiviral medication.
* If patients are old or have underlying conditions with serious symptoms, physicians should consider an antiviral treatment as soon as possible. lopinavir 400mg/ritonavir 100mg (Kaletra two tablets, twice a day) or chloroquine 500mg orally per day. Alternate is hydroxychloroquine 400mg orally per day.
February 18, 2020.
Jianjun Gao, Zhenxue Tian, Xu Yang Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. BioScience Trends Advance Publication, DOI: 10.5582/bst.2020.0104
Thus far, results from more than 100 patients have demonstrated that chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion, and shortening the disease course.
Severe adverse reactions to chloroquine phosphate were not noted in the aforementioned patients. Given these findings, a conference was held on February 15, 2020; participants including experts from government and regulatory authorities and organizers of clinical trials reached an agreement that chloroquine phosphate has potent activity against COVID-19.
27 February 2020
Philippe Colson , Jean-Marc Rolain , Jean-Christophe Lagier , Philippe Brouqui , Didier Raoult , Chloroquine and hydroxychloroquine as available weapons to fight COVID-19, International Journal of Antimicrobial Agents Feb (2020), doi: https://doi.org/10.1016/j.ijantimicag.
2020.105932
following the very recent publication of results showing the in vitro activity of chloroquine against SARS-CoV-2, data have been reported on the efficacy of this drug in patients with SARS-CoV-2-related pneumonia (named COVID-19) at different levels of severity.
Following the in vitro results, 20 clinical studies were launched in several Chinese hospitals.
The first results obtained from more than 100 patients showed the superiority of chloroquine compared with treatment of the control group in terms of reduction of exacerbation of pneumonia, duration of symptoms and delay of viral clearance, all in the absence of severe side effects. This has led in China to include chloroquine in the recommendations regarding the prevention and treatment of COVID-19 pneumonia.
Chinese teams showed that Chloroquine could reduce the length of hospital stay and improve the evolution of COVID-19 pneumonia, leading to recommend the administration of 500 mg of chloroquine twice a day in patients with mild, moderate and severe forms of COVID-19 pneumonia.
4 March 2929
Philippe Colson,a,b Jean-Marc Rolain,a,b Jean-Christophe Lagier,a,b Philippe Brouqui,a,b and Didier Raoult, Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 Mar 4 : 105932. doi: 10.1016/j.ijantimicag.2020.105932 [Epub ahead of print] PMCID: PMC7135139 IPMID: 32145363
A review of the safety and efficiency of CQ and HCQ reviewing more than 20 clinical studies in several Chinese hospitals.
Although only available in letter form, this data caused China to recommend Chloroquine in the National Guidelines for the Treatment of COVID-19.
9 March 2020
X.Yao, F/ Ye2, M. Zhang, C.Cui, R. Lu, H. Li, W. Tan, D. Liu. 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). 2020.. Clin Infect Dis. 2020 Mar 9. pii: ciaa237. doi: 10.1093/cid/ciaa237.
Hydroxychloroquine was found to be more potent than chloroquine at inhibiting SARS-CoV-2 in vitro. Hydroxychloroquine sulfate 400 mg given twice daily for 1 day, followed by 200 mg twice daily for 4 more days is recommended to treat SARS-CoV-2 infection.
9 March 2020
Expert Chinese consensus on Chloroquine Phosphate for New Coronavirus Pneumonia. Diagnosis and Treatment Plan. Chinese Journal of Tuberculosis and Respiratory Diseases. 2020, 43:
A Multicenter Collaboration Group was formed to guide and standardize the use of Chloroquine in Coronavirus pneumonia, standardizing Chloroquine treatment at 500mg 2x day for 10 days. Use of azithromycin was contraindicated.
20 March 2020
Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Giordanengo V, Vieira VE, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20:105949. doi: 10.1016/j.ijantimicag.2020.105949.
Confirmed COVID-19 patients were included in a 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.
Untreated patients from another center were included as negative controls.
20 cases were treated in this study and showed a significant reduction of the viral levels 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.
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,
20 March 2020
Mount Sinai health system treatment guidelines for SARS-CoV-2 infection (COVID-19) https://www.mountsinai.org/health-library/diseases-conditions/2019-novel-coronavirus-2019-ncov Last accessed on 20th March 2020.
Mount Sinai Heath System establishes protocols for dosing and treatment of COVID-19 patients using Chloroquine and Hydroxychloroquine.
27 March 2020
P. Gautret, J.C. Lagier, P. Parola, V.T. Hoang, T. Dupont, S. Honoré, A. Stein, M. Million, B. La Scola, P. Brouqui, Didier Raoul. Hydroxychloroquine-Azithromycin Treatment for COVID-19 Shown to be Effective in an 80-Patient Study
IHU-Méditerranée Infection, Marseille, France March 27, 2020
In 80 patients receiving hydroxychloroquine and azithromycin we noted a clinical improvement in all but one 86 year-old patient who died, and one 74 year still in ICU. A rapid fall of nasopharyngeal viral load tested by qPCR was noted, with Virus cultures from patient respiratory samples turning negative in 97.5% patients at Day 5.
This allowed patients to rapidly be discharged from highly contagious wards with a mean length of stay of five days.
10 March 2020
Cortegiani A., Ingoglia G., Ippolito M., Giarratano A., Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020 Mar 10;(20):30390–30397.
A review was made of six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and these clinical trials done in China.
ChiCTR2000030417 COVID-19 pneumonia (n = 30) Chloroquine phosphate
ChiCTR2000030054 COVID-19 pneumonia (n = 100) HCQ 0.2 g BID × 14 days
ChiCTR20000300