Azithromycin for COVID-19: Pharmacological Mechanisms, Challenges, and Prospects

The coronavirus disease (COVID)-19 pandemic led to a new challenge in the field of effective treatment methods for this disease. Antiviral and immunomodulatory agents were suggested as potential therapeutic methods in this field. Since the most severe clinical symptoms associated with COVID-19 disease appear to be acute respiratory syndrome, azithromycin has been proposed as a potentially effective drug in this context. We have updated the evidence and selected all relevant items to understand the mechanism of role of azithromycin, clinical efficacy, and their side effects in coronavirus disease-19 treatment on July 20th and updated on March 20th, 2020. A literature search of electronic databases including the Web of Science, PubMed, and Google Scholar was conducted by searching keywords such as "Azithromycin", "COVID-19", and "Combination therapy". The ultimate goal of this review was identifying eligible studies about the pharmacological activities, safety, and effectiveness of azithromycin in treating COVID-19 patients. Immunomodulatory properties of azithromycin include the ability to reduce cytokine production, maintain epithelial cell integrity, or prevent lung fibrosis. The use of azithromycin in some studies was associated with a decrease in mortality and need for ventilation in patients. These properties can be useful during the period of COVID-19 infection, especially in patients with underlying diseases. However, the evidence for the use of azithromycin is still scarce and the quality of the studies is low. In some retrospective studies, azithromycin was mainly evaluated in combination with hydroxychloroquine, which showed no particular advantage. The results of this review showed that azithromycin has appropriate and well-known safety characteristics in the treatment of patients with COVID-19. However, the most appropriate dosage in different stages of the disease and the effect of its combination with other drugs are important questions that should be considered in future clinical trials.