Macrolides and viral infections: focus on azithromycin in COVID-19 pathology

The emergence of the new disease COVID-19, is posing the challenge of seeking effective therapies. Since the most severe clinical manifestation of COVID-19 appeared to be a severe acute respiratory syndrome, azithromycin has been proposed as a potential treatment. Azithromycin is known to have immunomodulating and antiviral properties. In vitro studies have demonstrated the capacity of azithromycin to reduce production of pro-inflammatory cytokines such as IL-8, IL-6, TNF alpha, reduce oxidative stress and modulate T-helper functions. At the same time there are multiple clinical evidences of the role of azithromycin in acute respiratory distress syndrome and against MERS. Some preliminary evidences have demonstrated controversial results regarding efficacy of azithromycin in combination with hydroxychloroquine in COVID-19. Firstly, a French trial demonstrated 100% of virological negativization of six patients treated with azithromycin plus hydroxychloroquine vs 57.1% of patients treated with only hydroxychloroquine and 12.5% of the control group (p<0.05). On the other hand, another case series revealed no efficacy at all on eleven patients treated with same combination and doses. Furthermore, there are some concerns regarding the association of azithromycin and hydroxychloroquine because of the potential Qt prolongation. In fact, both drugs have this as potential side effect and evidences regarding the safety use of this combination are controversial. Despite the necessity to quickly find solutions for COVID-19, extreme caution must be used in evaluating the risk-benefit balance. However, based on preclinical and clinical evidences and some preliminary results in COVID-19, azithromycin could have a potential in the fight against this new disease.