Role of Azithromycin in the Treatment of COVID-19
During December 2019, a disease emerged which arose in the Wuhan city of China and rapidly spread globally and WHO declared it as a pandemic. One research study from China showed that 80% of cases are with disease and death rate are 8% in the patients of old age. France is also facing difficulty in treating the patient due to its fast transmission cause deaths of 4500 people according to a study.
Consequently, there is a need for effective treatment. The drug should not only be able to cure the disease patients but also decline the population transmission by decreasing the viability timing of virus carriage. It also needs to be taken under consideration about the safety of the drug, side effects, adverse effects, posology and interaction with other components .
In the mid of such an outbreak, many drugs are supposed to be the cure for the disease but it is also important to assess benefit-risk. That is why trials are going on for hydroxychloroquine and azithromycin. It is suggested that azithromycin help in reducing the diseases as well as transmission but on the other hand it also has the potential to cause deadly arrhythmia.
Researchers are working together for analyzing the efficacy of heart medication and collecting the data. This group is known as OHDSI (Observational Health Data Science and Informatics) that generates results from daily databases.
Mechanism of action
Azithromycin is an antibacterial agent. It is sub classified under macrolide antimicrobial agents. It mainly works for preventing super infection and such macrolides are used as adjunct therapy as it possesses immunomodulatory activities. It acts by suppressing the inflammatory response and decrease the production of cytokine attributed to respiratory infection. Chemotaxis of neutrophils declined to the lungs due to cytokine inhibition that is interleukin 8. It’s a direct impact on viral clearance is unpredictable .
Structure of Azithromycin Molecule
It also suppresses increase secretion from the mucosa, thereby, reducing the reactive oxygen species generation; enhance the apoptosis process of neutrophils. Moreover, it blocks nuclear transcription factors activation. Thus, it is found to have activity against COVID-19 and prescription recommended .
Some tests performed to assess the efficacy of the drug and its combinations. The open-label test was a non-randomized clinical trial where azithromycin and HCQ were given to six patients. In a preliminary test, it was cleared that it can be given as adjunct therapy. But then all the patients were found to be cured of any kind of viral disease as a comparison to hydroxychloroquine alone .
During retrospective analysis, 136 patients having MERS-CoV were kept on macrolide therapy with other antiviral agents. Macrolide alone did not show a decrease in mortality rate but during sensitivity test patients who got macrolide after 3 days show different results [6, 7].
In prospective review, 11 hospitals we’re taken to study virology and clinical data about that patient who received a combination of HCQ and azithromycin. But the results were shocking because one patient out of five died, 2 admitted in ICU and others stopped taking medication due to prolongation of QT wave.
As we all know COVID-19 is an pandmic whose spread rate is very high, in order to, control it a drug is required which not only cure the disease but also break the chain of transmission by reducing the duration of the viability of microorganism. But a drug needs to be analyzed for its benefits and risk before marketed. But the clinical trial is time-consuming and the requirement of the drug is crucial.
That is why authorities gave acceptance to hydroxychloroquine and azithromycin to be given for the treatment of COVID-19. But still, there is a need to assess the drug for any kind of drug interaction as in case prospective reviews where given combination found to have deadly effects on the patients. The open-label test is also one of the test periods for azithromycin combination.
Azithromycin shows it’s action by limiting cytokine inhibition, neutrophils chemotaxis lessen. Moreover, it enhances apoptosis as well as inhibits the secretion which helps to treat a lung infection. Nuclear transcription factors blockage show its immunomodulatory action. Hence, Azithromycin can be considered to treat the disease but simultaneously it also attributed to some side effects. A clinical trial should speed up and drug dosing maintenance to be done.
- Gautret, P., Raoult, D. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial agents, https://doi.org/10.1016/j.ijantimicag.2020.105949.
- Krumholz, H. (2020). Hydroxychloroquine And Azithromycin For COVID-19: Benefits TBD, Risks Clear. Forbes, https://www.forbes.com/sites/harlankrumholz/2020/04/10/hydroxychloroquine-and-azithromycin-for-covid-19-benefits-tbd-risks-clear/amp/
- Smith, T., Bushek, J. COVID-19 Drug Therapy. Retrieved on 13/4/2020.Elseveir.https://www.elsevier.com/__data/assets/pdf_file/0007/988648/COVID-19-Drug-Therapy_Mar-2020.pdf.
- Gautret, P., Lagier, J., Parola, P., et al. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents, [Epub ahead of print] PMID: 32205204.
- Arabia, Y.M., Deeb, A., Al-Hameed, et al. (2019). Macrolides in critically ill patients with Middle East Respiratory Syndrome. Int J Infect Dis, 81,184-190.
- Zarogoulidis, P., Papanas, N., Kioumis, I. et al. (2012). Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory disease. Eur J Clin Pharmacol, 68, 479-503. PMID: 22105373.
- Molina, J.M., Delaugerre, C., Goff, J.L., et al. (2020). No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19. Med Mal Infect . [Epub ahead of print].