ANALYSIS : The clinical studies for treatment against the Covid-19 are numerous. We make it a point on the French studies to this day. This article is a little technical, but it allows to have an overview of the various studies. The summary tries to keep a level of detail acceptable to allow the reader to make a tour of the horizon.
Hydroxychloroquine and azithromycin as a treatment against the Covid 19 University Hospital Institute Méditerranée Infection, Marseille – France
24 French patients (age 51.2 years ± 18.7 ) Covid-19 CONFIRMED have been included in a single protocol of arms of the beginning of March to the 16th march e to receive 600mg of hydroxychloroquine per day, and their viral load in the swabs naso – pharyngeal has been tested as an outpatient procedure in a hospital setting.
According to their clinical presentation, azithromycin was added to the treatment. Untreated patients from a different centre and the cases rejecting the protocol were included as negative controls. The presence and the absence of virus at day 6 after the inclusion were considered as the main criterion of the study.
Six patients were asymptomatic, 22 had symptoms of upper respiratory tract infection and eight had symptoms of lower respiratory tract infection.
Study clinical and microbiological effects of the combination of the’hyrdoxychloroquine and the’azithromycine on 80 patients COVID-19 with a follow-up of six days. Study observation
- 80 patients with COVID-19 confirmed
- Only 1 death, ill very advanced, 86 years
All patients who received treatment with hydroxychloroquine and azithromycin for at least three days and who were followed for at least six days were included in this analysis.
The median age of the patients was 52 years (18 to 88 years) with a sex-ratio H / F of 1.1. 57.5% of these patients had at least one chronic condition that is known to be a risk factor for the severe form of COVID-19 (hypertension, diabetes, and respiratory diseases).
The time between the onset of symptoms and hospitalization was on average of five days, the longest being 17 days. 53.8% of the patients had symptoms LRTI (infection of the lower respiratory tract), and 41.2% of symptoms of URTI (upper respiratory tract infection).
Only 15% of the patients were febrile. Four patients were asymptomatic carriers. The majority of the patients had a score NEWS bottom (92%) and 53.8% of the patients had LDCT (ct chest low dose ) compatible with pneumonia.
For all other patients of this cohort of 80 people, the combination of hydroxychloroquine and azithromycin resulted in a clinical improvement that seemed to be superior compared to the results of other patients, as described in the literature.
Etude retrospective on 1061 patients in Marseille (Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin):
- 1061 patients included in this analysis ( mean age 43,6 years – extreme 14-95 years of age)
- 91,7% of good clinical results and a healing virological in 10 days.
- With 4.3% of patients with a viral load higher at diagnosis (p <0.001) had their viral load eliminated at day 15.
- With 4.3% of patients had poor clinical outcomes, and 8 died (0.75 per cent) (74-95 years).
All the deaths are due to respiratory failure and not cardiac toxicity.
Study on patients Covid 19, early diagnosis and management : on 3737 patients. (Early diagnosis and management of covid-19 patients: a real-life cohort study of 3,737 patients, Marseille, france (hcq-az)
The largest cohort studied in France by the physicians who treated and followed the patients.
- 65 993 people tested by PCR
- 6 836 patients, or 10.4%, diagnosed Covid-19
- 3 737 included in the cohort whose 3054 treated with HCQ+AZT and 683 by other methods
- 2 065 ct scans at low dose (CT) pointing to lung injury in 581 of 933 (62%) patients, however, clinical symptoms minimal (score NEWS = 0).
Treatment with HCQ-AZ has been associated with a decreased risk of transfer to the intensive care unit or death (HR 0,19 0,12-0,29), a decrease in the risk of hospitalization for ≥ 10 days (odds ratios and 95% CI of 0.37 to 0.26-0.51) and a shorter duration of viral shedding (the time before PCR negative : HR 1,27 1,16-1,39).
Lesions with moderate and severe detected in the ct scans at low dose were associated with poor clinical outcomes. Prolongation of the QTc interval (> 60 ms) was observed in 25 patients (0,67%) leading to discontinuation of treatment in 3 cases. No cases of torsade de pointe or sudden death were not observed.
The beneficial effect of the association Hydroxychloroquine-Azithromycin in the treatment of elderly patients with the Covid-19: results of an observational study. Department of Pharmacy Groupe Hospitalier Le Raincy-Montfermeil – FRANCE
- 68 patients, all older than 65 years and diagnosed PCR-positive for the Covid-19 received the combination of hydroxychloroquine / azithromycin between 27 march and 1 may 2020.
- The average age was 86,4 ± 8,2 years.
27% of deaths in long-term care facilities Source via the official figures of 37 599 positive and 10 384 deaths on the government site.
Azithromycin and Hydroxychloroquine, acceleration of healing of patients with symptoms of mild to moderates COVID-19. Hospital Ténon APHP – INSERM – France
- 88 patients studied
- n = 34 NST (no treatment or symptomatic treatment)
- n= 34 AZM alone
- n = 20 AZM + HCQ
The end point of efficacy was the time to clinical recovery and the end point of safety was the occurrence of cardiovascular events.
The average time of recovery
- NST (no treatment) : 25,8 days
- Azithromycin (AZM): 12,9 days
- AZM+HCQ : 9.2 days
57 patients (19 / group) matched for age, sex and BMI. The statistical difference between NST and AZM was confirmed (p = 0,0149) as well as the difference with AZM + HCQ (p = 0.0002).
No cardiac toxicity was not recorded in any patient. No statistical difference was shown between groups AZM and AZM + HCQ, although the combination therapy has tended to be more effective in patients over 50 years of age, on the basis of an analysis using the Cox model.
APHP -retrospective Study on 4642 patients – Dr. Eric CAUMES is a signatory of the study
Attention this study concluded formally that the hydroxychloroquine or not combined with azithromycin does not really show of efficiency, but in fact the outcome section says virtually the opposite . This result is inverted compared to the direct analysis must be confirmed by an independent evaluation because a statistical treatment very sophisticated (AIPTW) has been used to rebalance the data between the arm and the confounding variables so that results largely in evidence, obtained in the univariate analysis, are surprisingly inverted in relation to the multivariate analysis in a proportion that raises questions about the appropriateness of the analysis AIPTW. This analysis which could be avoided if the arm of reference had been randomly selected with the same basic features as the arm HCQ and even more flagrant than the arm HCQ + AZT (see open-ended questions to the authors at the end of this document).
In spite of the comparison groups not homogenous (patients are much sicker and with more comorbidities such as Diabetes, Obesity, and COPD, one clearly sees that the ALONE results in a scientifically SIGNIFICANT (i.e. p<0.05) of this study show that
Clinical efficacy of hydroxychloroquine in patients with pneumonia covid-19 who need oxygen : a comparative study of observational data from routine care. Hospital Henri Mondor – APHP – Paris – France.
181 patients (18-80 years) all in a state of severe (severe acute respiratory syndrome with the need of oxygen). Significantly more men in the treatment group HCQ and the amounts of C-reactive protein the most important.
- Control group of 89 patients of which 26 patients (29% ) were also taking azithromycin
- Group HCQ 84 patients, of whom 15 patients (18%) were also taking azithromycin
- Group HCQ + azithromycin : 0 deaths and 0 transfer to an intensive care unit in this small
- Control group +azithromycin : 6 admissions to the intensive care unit and 5 deaths
In the unweighted analyses, the survival rate without transfer to the intensive care unit for 21 days : 80% in the treatment group, 75% in the control group (risk ratio 0.8, the 95 % confidence interval 0.4 to 1.5 ).
The other studies that we have been able to observe (meta-analyses and in vitro studies)
Clinical efficacy of the derivatives of chloroquine for the infection to COVIDE-19 : Meta-analysis comparative between the Big Data and the real world, University Hospital Institute Méditerranée Infection, Marseille – FRANCE
Among the clinical studies, 3 of the 4 randomized controlled trials reported a significant beneficial effect. Among the clinical studies, a summary significant beneficial has been observed for the duration of cough (odds ratio (OR), to 0.19, p = 0.00003), the duration of fever (0,11, p = 0.039), clinical cure (0.21, p =. 0495), dead (0.32, p = 4,1×10-6 ) and viral shedding (0.43, p = 0,031).
A trend towards a favourable effect was noted for the outcome “deaths and / or transfer in the ICU” (0.29, p =0,069) with a point estimate that was remarkably similar to that observed for the death (∼0,3).
In vitro trials of hydroxychloroquine combined and azithromycin on the SARS-CoV-2 show a synergistic effect. The synergy between the hydroxychloroquine and azithromycin observed in this article is at concentrations achieved in vivo , and detected in the serum and lung tissue.
The combination of azithromycin and hydroxychloroquine led to a significant inhibition of viral replication to the wells containing hydroxychloroquine to 5 µM in combination with azithromycin to 10 and 5 µM (values of P 0,0003 for A10H5 and 0,0004 for A5H5) with a viral inhibition relative to 97.5% and 99.1%, respectively
Synergistic effects of antiviral of the azithromycin and hydroxychloroquine in the framework of the Covid 19 INSERM – Marseille. There is a molecular mimicry between the azithromycin and the ” ganglioside sugar “
Azithromycin binds to the protein peak of the virus of SARS-CoV-2 and hydroxychloroquine binds to gangliosides . In the presence of azithromycin, the peak of the virus does not reach the gangliosides on the plasma membrane of the host. The simulations MD in this present study indicate that the’hydroxychloroquine and azythromycine can block binding of the SARS-CoV2 to gangliosides via mechanisms that are competitive in a mirror.
Author(s): The Citizens ‘ group for FranceSoir