Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19

Abstract

The challenge regarding COVID-19 is to prevent complications and fatal evolution. Azithromycin (AZM) and hydroxychloroquine (HCQ) have proven their antiviral effect in vitro. We aimed to assess the efficacy and safety of AZM alone or combined to HCQ, prescribed, at an early stage, in patients with Covid-19, in a primary care setting. Eighty-eight patients received either no or a symptomatic treatment (NST) (n=34) or AZM alone (n=34) or AZM+HCQ (n=20). The efficacy end point was the time to clinical recovery and the safety end point was the occurrence of cardiovascular events. The mean (SD) times to achieve clinical recovery were respectively 25.8 days (11.1), 12.9 days (13.4) and 9.2 days (9.3), showing a statistically significant difference between NST and AZM alone (p<0.0001) or AZM+HCQ (p<0.0001). To improve the evidence level, a case-control analysis was performed on a sample of 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 recorded in any patient. No statistical difference was shown between AZM and AZM+HCQ groups, although the dual therapy tended to be more effective in patients over 50 years, based on an analysis using the cox model. In conclusion, AZM and AZM+HCQ favourably impacted the course of the disease. We need trials, ideally prospective/double blind, to show if a statistical difference can be evidenced with a broader group, and clarify the indications of each treatment depending on initial clinical presentation.

The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients

“…The later study was based on primary care, and reported an association between treatment and lower rates of hospital admissions, as well. Another observational study conducted in primary care, were mortality was not the outcome, showed significantly shorter time to clinical recovery for those treated with HCQ or HCQ plus azithromycin [28]. In our study, the addition of azithromycin to HCQ does not seem to add any clear benefit.…”

Azithromycin in the treatment of COVID-19: a review

“…Guerin et al reported no cardiovascular events [65]. In the study of Barbosa et al the main adverse effect was diarrhea, but 12.9% of patients presented diarrhea before the onset of the treatment [66]. No cardiovascular adverse effects were recorded.…”

“…Other limitations include that the time of treatment initiation from symptom onset was day 1 in 41% of patients, while the rest initiated within 15 days except one in the azithromycin alone group in day 40. Barbosa et al evaluated the need for hospitalization in outpatients treated with combination therapy [66]. Patients with flu-like symptoms were referred to telemedicine service, where combination therapy was offered.…”

“…In the early phase of COVID-19 azithromycin alone or combined with hydroxychloroquine could reduce the need for hospitalization or time to clinical recovery [65,66]. The potential implications of these outcomes are huge, considering the overload of patients to which hospitals have been subjected.…”

The use of pharmacological protocols during the Covid-19 crisis - a déjà vu of the 2009 A/H1N1 pandemic experience

“…A review of research papers published from January to April 2020, conducted by the Association of American Physicians and Surgeons, also concluded that the HCQ-AZ combination, when started immediately after diagnosis, appeared to be a safe and efficient treatment for COVID-19 [32]. As expected in an unfolding public health emergency, evidence has also come from reports of promising outcomes obtained by multiple treating physicians [33][34][35]. As is inherent to observational research, it is certainly not possible to completely account for potential biases and confounding associated with the results of these studies.…”