@Gaby was sent this from a friend on FB not sure if you have seen it yet.Copy pasted Most of it, full document attached below.
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.
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)
2019 Novel Coronavirus (2019-nCoV) Information | Mount Sinai - New York 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.
24 March 2020
Pagliano P, Piazza O, De Caro F, Ascione T, Filippelli A. Is Hydroxychloroquine a possible post-exposure prophylaxis drug to limit the transmission to health care workers exposed to COVID19? Clin Infect Dis. 2020 Mar 24.
Is Hydroxychloroquine a possible post-exposure prophylaxis drug to limit the transmission to health care workers exposed to COVID19? - PubMed - NCBI
PMID: 32211764 DOI: 10.1093/cid/ciaa320
Chloroquine and Hydroxychloroquine are able to inhibit replication at early stages of viral
infection. No similar effect on early phases of Coronavirus infection has been reported for other drugs proposed for SARS-CoV-2 treatment, which are able to interfere only after cell infection.
We believe that hydroxychloroquine can be effective in preventing respiratory tract invasion in HCW and that hydroxychloroquine administration as prophylactic agent could be particularly useful for HCW attending to high risk procedures on respiratory tract in COVID-19 patients.
Hydroxychloroquine effectiveness profile, its ability to inhibit lung viral replication for a 10-day period after only a 5- day cycle of therapy, and the large amounts of knowledge in term of safety deriving from its use for malaria prophylaxis and rheumatologic diseases permit to recommend its pre-exposure or post-exposure use for those performing procedures at high risk of viral diffusion in patients with COVID-19 pneumonia.
26 March 2020
A.K. Singh,, A. Singh, A. Shaikh, R. Singh, and A. Misra. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes Metab Syndr. Published online 2020 Mar26. doi: 10.1016/j.dsx.2020.03.011
PMCID: PMC7102587 PMID: 32247211
A systematic review of Hydroxychloroquine and COVID-19
7 April 2020
Belgium Task Force Interim clinical guidelines for patients suspected of / confirmed with COVID-19 infection.
https://epidemio.wivisp.be/ID/Documents/Covid19/COVID19_InterimGuidelines_Treatment_ENG.pdf
Based on pharmacokinetic simulations, the recommended dosing of hydroxychloroquine sulphate is 400mg BID on day 1, followed by 200mg BID on day 2-5.
Because of the long elimination half-life of the drug (32–50 days), the duration of treatment should not exceed 5 days to avoid accumulation of hydroxychloroquine concentrations in plasma and tissues, and associated increased risk of toxicity, and because there is no in vitro evidence that longer courses improve drug activity on SARS-CoV-2.
10 April 2020
Zhaowei Chen, VJijia Hu, Zongwei Zhang, Shan Jiang, Shoumeng Han, Dandan Yan, Ruhong Zhuang, Ben Hu, Zhan Zhang Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial doi:
Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
Evidence regarding the in-vivo use of Hydroxychloroquine is limited. In COVID-19 infection. This study evaluated the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ.
For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.
Clinical Trial ChiCTR2000029559
12 April 2020
Raoult, D. Cohort of 1061 COVID-18 cases treated with HCQ-AZ Combination with 9 day follow-up. IHU Méditerranée Infection, Marseille.
Professor Didier Raoult Releases the Results of a New Hydroxychloroquine Treatment Study on 1061 Patients – COVEXIT.com
A cohort of 1061 COVID-19 patients, treated for at least 3 days with the HCQ-AZ combination and a follow-up of at least 9 days was investigated. Endpoints were death, worsening and viral shedding persistence. From March 3rd to April 9th, 2020, 59,655 specimens from 38,617 patients were tested for COVID-19 by PCR. Of the 3,165 positive patients placed in the care of our institute, 1061 previously unpublished patients met the inclusion criteria for a Hydroxychloroquine –Azithromycin trial.
Mean age was 43.6 years old and 492 were male (46.4%), As in other studies, no cardiac toxicity was observed in this study.
• A good clinical outcome and virological cure was obtained in 973 patients out of a total pf 1061 patients within 10 days (91.7%).
• Mortality was significantly lower in patients who had received > 3 days of HCQ-AZ than in patients treated with other regimens both at IHU and in all Marseille public hospitals (p< 10-2).
A poor outcome was observed for 46 patients (4.3%); -10 were transferred to intensive care units, 5 patients died (0.47%) (74-95 years old), 31 required 10 days of hospitalization or more.
Among this group, 25 patients are now cured and 16 are still hospitalized (98% of patients cured so far).
Table 1. Baseline characteristics according to clinical and virological outcome of 1061 patients treated with HCQ + AZ ≥ 3 days at IHU Méditerranée infection Marseille, France with Day 0 between March 3 and March 31, 2020
13 April 2020
J. Gao, Hu, S., Update on use of Hydroxychloroquine to TREAT coronavirus disease 2019 (COVID-19).
Increasing evidence from completed clinical studies indicates the prospects for the treatment of COVID-19 by Chloroquine and Hydroxychloroquine (indications Hydroxychloroquine is more effective).
• Chloroquine has indicated its efficacy in mild and moderate COVID-19 cases.
• Chloroquine is superior to Lopinavir/ritonavir in improving COVID-19 lung lesions.
• Chloroquine has demonstrated significant efficacy in returning body temperature to normal.
• Hydroxychloroquine seems more effective than Chloroquine in a French study on reducing the amount of virus in the body.
• Hydroxychloroquine helps reduce the duration of cough, reduce the amount of virus in the body and improve negative lung lesions on X-ray.
• We have already commented on the single paper involving 15 patients subjected simultaneously to Interferon-Alpha, arbidol, and lopinavir/ritonavir in the control group.
In general, completed clinical studies have yielded promising results regarding the safety and effectiveness of Chloroquine and Hydroxychloroquine in the TREATMENT of COVID-19
Summary of Bibliography Review
Dependent upon a successful peer review of the data presented in 1,061 COVID-19 patients, treated for at least 3 days with the HCQ-AZ combination in the French Abstract released 12 April 2020, by D. Raoult of the IHU Méditerranée Infection and a successful review of the 10 April 2020 paper by Zhaowei Chen et.al, ……
………….the use of HCQ-AZ combination when started immediately after diagnosis, appears to be a safe an efficient treatment for COVID-19. It appears to halt respiratory disease progression and length of hospital stay in many cases.
Within the context of an expanding COVID-19 pandemic, it is reasonable to propose the EARLY use of Hydroxychloroquine in attempt to reduce the number of COVID patient hospitalization days, and hence provide an increased rate of patient turnover and a more efficient use of limited hospital ventilators.
The finding in the gross data study done on 10 April 2020 showing a slightly prolonged Average Length of Hospital Stay (ALOS) in the population group given HCQ/CQ/Azithromycin, requires further investigation. Azithromycin can show the same cardiac conduction effects as Chloroquine in humans, but there has not been a widespread aversion to its being prescribed. Some 4,000 individuals have now been given what are considered to be COVID doses of Hydroxychloroquine, and not one cardiac conduction problem has been noted.
Opinion
Historical controls are used in many previous studies in medicine. In this respect, the safety of Hydroxychloroquine is well documented. When the safe use of this drug is projected against its apparent effect of decreasing the progression of early cases to ventilator use, it is difficult to understand the reluctance of the authorities in charge of U.S. pandemic management to recommend its use in early COVID-19 cases. The effects of the chloroquines were first outlined 15 years ago by the CDC’s own Special Pathogens Unit.