Azithromycin for COVID-19: More Than Just an Antimicrobial?
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EDITORIAL
Azithromycin for COVID‑19: More Than Just an Antimicrobial? Nathalie Bleyzac1 · Sylvain Goutelle1,2 · Laurent Bourguignon1,2 · Michel Tod1,2
© Springer Nature Switzerland AG 2020
The COVID-19 infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue worldwide, as no vaccines or drugs for prevention and treatment have been approved so far, except remdesivir that has been recently authorized for use in the USA and Japan [1]. Many clinical studies are ongoing. Most of them evaluate established antiviral drugs such as lopinavir/ritonavir, and chloroquine (CQ) or its derivative hydroxychloroquine (HCQ), which have shown in vitro antiviral activity against SARS-CoV-2 [2]. Because SARS coronavirus infections are known to induce inflammation and subsequent tissue damage in the lungs in moderate-to-severe cases [3], using immunomodulating drugs could provide a benefit in the treatment of COVID-19. Drugs with the most relevant immunomodulatory profile remain to be found. We believe the antibacterial macrolide azithromycin (AZM) has a special and interesting profile in this search for drug therapy for COVID-19. We discuss below the arguments for this claim. It has been shown that AZM has significant antiviral properties. In contrast with CQ or HCQ, its antiviral activity has been shown in vitro and/or in vivo on a large panel of viruses: Ebola, Zika, respiratory syncytial virus, influenzae H1N1 virus, enterovirus, and rhinovirus [4–13]. Its activity against respiratory syncytial virus has been demonstrated in a randomized study in infants [10]. Azithromycin exhibited a synergistic antiviral effect against SARS-CoV-2 when combined with HCQ both in vitro [11] and in a clinical setting [13]. Of note, the pre-print version of the article from Andreani et al. [14] also reported a significant antiviral effect of AZM alone on SARS-CoV-2. The mechanisms of the antiviral effect of AZM support a large-spectrum antiviral * Sylvain Goutelle sylvain.goutelle@chu‑lyon.fr 1
Service de Pharmacie, Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital Pierre Garraud, 136 rue du Commandant Charcot, 69005 Lyon, France
Univ Lyon, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon & UMR CNRS 5558, Laboratoire de Biométrie et Biologie Evolutive, Lyon, France
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activity. Azithromycin appears to decrease the virus entry into cells [2, 8]. In addition, it can enhance the immune response against viruses by several actions. Azithromycin up-regulates the production of type I and III interferons (especially interferon-β and interferon-λ), and genes involved in virus recognition such as MDA5 and RIG-I [7, 12, 13, 15, 16]. These mechanisms are universally involved in the innate response against infectious agents, and potentially against SARS-CoV-2. The immunomodulation properties of AZM are the rationale of its use against inflammatory manifestations leading to interstitial lung disease [17, 18]. SARS-CoV-2 has been shown to exacerbate the inflammatory response of its hos
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