NSAIDs/nitazoxanide/azithromycin repurposed for COVID-19: potential mitigation of the cytokine storm interleukin-6 amplifier via immunomodulatory effects

ABSTRACT

Introduction

Mediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach.

Areas covered

We analyze selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the results that suggested a potential survival benefit of low-dose aspirin and colchicine when used for COVID-19.

Expert opinion

Nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that are unfortunately currently at best of second choice after paracetamol, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their anti-inflammatory and immunomodulatory properties. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials.

GRAPHICAL ABSTRACT

KEYWORDS:

• COVID-19
• Interferons
• nitazoxanide
• azithromycin
• NSAIDS
• ibuprofen
• Diclofenac
• IL-6 amplifier
• NF-kB
• monocytic immunological dysrhythmia

Acknowledgments

This humble work is dedicated to a noble professor, immunologist, Prof. Toshio Hirano (National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan). Apart from IL-6 discovery, without his devout, brilliant, and relentless research most of our knowledge about IL-6 and IL-6 Amp would not become as lucid and readily available as it is. I wish also to express my deepest gratitude to Expert Review of Anti-infective Therapy and to the commissioning editor; Ms. Felicity Poole as highly constructive comments that came from four honorable anonymous peer reviewers have significantly improved the quality of knowledge represented in this manuscript and no words would perfectly convey my utmost respect and gratitude.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.