Source: Sante Cool
PROFESSOR PERRONNE DISCOVERS THE SAME RESULTS FROM HYDROXYCHLOROQUINE AS DIDIER RAOULT. HERE IS THE STUDY AND THE RESULTS.
The Pr Perronne discovers the same results of hydroxychloroquine as Didier Raoult . We conducted a single-center and retrospective study, from March 5 to April 25, 2020, on adults admitted to our medical services at a higher university hospital, namely the Raymond Poincaré Hospital (AP-HP), Garches, France.
We included all adults admitted to medicine for COVID-19 infection confirmed by SARS-CoV-2 RT-PCR and / or a compatible lung scanner. The exclusion criteria were: i) patients directly admitted to the ICU; ii) patients discharged from the intensive care unit to a medical ward; iii) opposition to the collection of data expressed by the patient.
The following data was collected from the patient’s medical records:
– Patient characteristics: age, sex, diabetes, cardiovascular risk factors, smoking, obesity, chronic lung disease, Charlson comorbidity index (CHF) ,
– Characteristics of the infection: time between symptom onset and admission, presence of superinfection, C-reactive protein (CRP) and white blood cell count (WBC) on admission, percentage of lung lesions at scan if necessary, positive PCR amplifying the beta-coronavirus E gene and the SARS-CoV-2 RdRp gene on a nasopharyngeal swab or sputum,
– Treatment characteristics: requiring ICU support with invasive ventilation and associated therapeutic strategies (e.g. oxygen, anti-infective agents),
– The endpoint was defined as an unfavorable result assessed by the requirement of transfer to an intensive care unit for invasive ventilation and / or death within 30 days,
– The patients were followed until discharge from the hospital. After their discharge, the patients were followed for 30 days by telemedicine via the French platform covidom ,
– Derived variables: moderate lymphocytopenia was based on a number of lymphocytes with a threshold of 1000 / mm3 and high systemic inflammation was defined as a threshold of CRP ≥ 100 mg / L.
All the patients requiring oxygen systematically received a beta-lactam for at least 5 days, preferably using ceftriaxone or cefotaxime to treat possible superinfection.
The patients were eligible for an anti-infectious agent supposedly effective against COVID-19 (HCQ, AZI, lopinavir-ritonavir), regardless of laboratory abnormalities and taking into account the following indications: i) patient with clinical pneumonia confirmed by SARS-CoV PCR -2, requiring oxygen therapy (regardless of CT scan results); ii) high suspicion of COVID-19 pneumonia based on clinical presentation and / or lung CT scan showing ground glass opacity affecting ≥ 10% of the whole parenchyma.
Patients were classified as receiving an anti-infective agent after receiving at least one dose . Patients who received lopinavir-ritonavir were not assigned to any treatment group, as this antiviral drug has shown no benefit for the treatment of COVID-19.
Prior to the start of HCQ or AZI, patients routinely had an electrocardiogram (ECG) to assess the QT interval corrected using the Framingham formula, and monitored twice a week throughout treatment, as well as serum potassium levels. A day 1 loading dose of 800 mg / day was given followed by a maintenance dose of 400 mg / day up to 600 mg / day in obesity (body mass index (BMI)> 30 ) for a total of 10 days. In addition, 500 mg of azithromycin was prescribed on the first day, followed by 250 mg for 4 days.
Patients have been informed that HCQ and lopinavir-ritonavir were currently off-label for the treatment of COVID-19 pneumonia until March 25, 2020 in France, where ministerial order # 2020-314 authorized the prescription hospital of HCQ in particular indication. If they refused the prescription of HCQ or if the latter was contraindicated (by ECG or drug interactions), this was noted in their medical file and the patients did not receive HCQ.
RESULT: PR PERRONNE DISCOVERS THE SAME RESULTS FOR HYDROXYCHLOROQUINE AS DIDIER RAOULT
Our study shows that the unfavorable outcome (transfer to an intensive care unit and / or death) decreased over time during the management of the first wave of the epidemic and was associated with an increase in performing a lung scan and prescribing anti-infective agents despite an increased need for oxygen therapy on admission. This suggests that the medical care of patients with COVID-19 has improved over time in our hospital.
Due to the lockdown, it appears that patients were admitted later in the second period than in the first period of the outbreak and this could explain why they needed more oxygen therapy initially. We suggest that in the event of a second wave, it might be relevant to introduce telemedicine monitoring of vital signs, including home pulse oximetry. Indeed, home oxygen therapy, as offered by the French platform covidom in patients discharged from hospital during the first wave of the epidemic was interesting.
Our models, adjusted for lymphocyte count or CRP, showed that patients receiving AZI combined or not with HCQ were respectively 2.2 and 2.4 times less likely to have an unfavorable outcome than patients without treatment (p = 0.04). . This finding suggests that the number of lymphocytes which is already known to be closely related to the severity of COVID-19 disease could also be a predictor of the anti-infective therapeutic response. Indeed, patients with a lymphocyte count ≥ 1000 / mm3 could be early stage COVID-19 patients., arguing for the earlier initiation of anti-infective agents, as previously demonstrated with oseltamivir treatment in patients with severe pandemic influenza A 2009 (H1N1) . However, we did not study whether there was a relationship between the number of lymphocytes and the time between the onset of first symptoms and admission, as this variable is declarative and therefore unreliable. Similarly, AZI with or without HCQ has been shown to be of interest in hospitalized patients with elevated systemic inflammation (CRP level ≥ 100 mg / L), known as a “ cytokine storm ”. This is an argument arguing for a possible immunomodulatory effect of the treatment as previously described by Zhao et al ..
Our results are consistent with a recent study conducted in the United States by Arshad et al. who concluded in a retrospective multicentre observational study that treatment with HCQ alone and in combination with AZI was associated with a reduction in mortality associated with COVID-19 in hospitalized patients. Another study plan published by Lagier et al. , partly composed of outpatients, revealed a favorable outcome and a decrease in virologic excretion using the combination HCQ with AZI in a large sample (n> 3000), in a majority of patients with mild lymphocytopenia (≥ 1000 / mm3). Finally, Mahevas et al. observed 15/15 favorable results in a subgroup of patients receiving HCQ with AZI.
Interestingly, our study focuses on the potential benefit of treatment with azithromycin not combined or not according to certain biological parameters. Indeed, the potential antiviral activity of azithromycin is consistent with previous in vitro studies concerning SARS-CoV-2 or H1N1-pdm09 and a randomized clinical trial in the prevention of respiratory infections in children . In addition, a recent publication highlighted the role of azithromycin against COVID-19 via the CD147 receptor in the stem cell . Additionally, a study published in JAMA by Rosenberg et al. highlighted a potential trend towards decrease in mortality in patients receiving azithromycin compared to HCQ or standard of care , although not statistically significant (p = 0.14). Additionally, the authors discussed that the speed with which patients entered the intensive care unit (within 48 hours) may have underestimated the effectiveness of treatment. Also, since azithromycin is commonly prescribed for bronchitis and authorized in outpatient care, a study conducted with general practitioners could be relevant to assess the early indication of this monotherapy for the treatment of COVID-19 in fragile outpatients.
Furthermore, our experience does not report any serious side effects from this combination therapy as long as we take the necessary precautions and perform a follow-up ECG using a conventional dose of HCQ as proposed by Borba et al ..
Our study has several limitations. The first limitation is the single-center nature of the study, describing the experience of a single center whose results might not be generalizable. However, it was performed in a hospital specializing for decades in the treatment of infectious diseases, intensive care and rehabilitation. Since the start of the COVID-19 epidemic, an entire building has been completely dedicated to admitting only COVID-19 positive patients. At the height of the epidemic, we had a maximum capacity of 85 beds in the medical room and 32 beds in the ICU.
In addition, we observed a better favorable evolution over time linked to an increase in the number of pulmonary CT scans performed (not recommended at the start of the epidemic in our hospital) and therefore a more relevant prescription of anti-infectives. Nevertheless, we cannot exclude that other confounding factors may have played a role, as we were facing an unpredictable epidemic, which prompted constant updating of the ICU admission guidelines, including recommending to keep patients longer in medical wards with high oxygen flow (> 6L / min) during the second period of the epidemic. Nevertheless, the delays between admission and transfer to intensive care were similar between the 2 periods, which minimizes this confounding factor.
Additionally, given the inherent limitation of a descriptive study with a limited sample size (n = 132), we were unable to infer causality in the association between the use of AZI ± HCQ and improved prognosis in COVID-19 patients .
In conclusion, Pr Perronne discovers the same results of hydroxychloroquine as Didier Raoult. Many factors could be involved in improving care, including the implementation of a routine pulmonary scanner, better management of oxygen therapy in the medical room and possibly anti-infective agents. Indeed, our study suggests that AZI ± HCQ might have impacted the outcome of COVID-19 in a subpopulation of patients (lymphocyte count ≥ 1000 / mm3 or CRP ≥ 100 mg / L), raising the question. the optimal timing of therapeutic interventions. A larger, randomized controlled study is needed to explore the profiles of patients responding to this therapy and to confirm the potential value of laboratory parameters for the initiation of treatment.
The results of the study can be found HERE