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Graphical abstract Early use of NSAIDs including ibuprofen blocks the diffuse inflammation produced by SARS CoV-2 thus might prevent COVID-19 complications, whereas early use of glucocorticoids might encourage the development of COVID-19 complications.

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Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P < 0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen.

Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2); ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019 (COVID-19). Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2 soonest. The author recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author recommends more trials for interferons to be tested against SARS CoV-2 especially in severe and critical cases.

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.

In this manuscript, we discuss the expectations versus the real-world results of four repurposed COVID-19 drugs: tocilizumab, remdesivir, favipiravir, and dexamethasone from a clinical and pharmacovigilant point of view. We suggest that though the results of two-phase III double-blind clinical trials have been less than expected, tocilizumab has a real remaining potential to treat selected critical cases of COVID-19 beyond clinical trials until more data are revealed. On the contrary, remdesivir, though its FDA approval, and favipiravir are least likely to benefit COVID-19 patients. Moreover, we recommend that the RECOVERY dexamethasone should only be considered for critical hospitalized COVID-19 patients and we urge physicians in developing countries to avoid using it in mild-moderate COVID-19 cases. Finally, we recommend considering a personalized risk-benefit ratio before a decision is made using any of these drugs.

During the COVID-19 pandemic, a correspondence, published at the Lancet Respiratory Medicine, that linked angiotensinconverting enzyme inhibitors, angiotensin receptor blockers and ibuprofen to a higher risk of SARS CoV-2 infection and complications, has influenced, when adopted by official health authorities, the practical management of COVID-19 with regard to non-steroidal anti-inflammatory drugs that were avoided in all COVID-19 management protocols all over the world. This manuscript discusses, from a pharmacological point of view, the points of weakness in the mentioned correspondence and it also lists some important contradictory review articles as well as clinical results that refuted its claims. The author chose to argue against each claim represented in the mentioned correspondence to confirm that ACEIs, ARBs and NSAIDs including ibuprofen should not be considered hazardous to be administered for COVID-19 patients and to warn against any future adoption of such unproved claims. Keywords COVID-19 • SARS CoV-2 • Aceis • Arbs • Ibuprofen Abbreviations ACEIs Angiotensin-converting enzyme inhibitors ARBs Angiotensin receptor blockers SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 COVID-19 Coronavirus disease 2019 D. Rainsford; Editor in Chief and Dr. Phil Berry; Deputy Editor of Inflammopharmacology for their highly valuable remarks as well as their timely and highly professional management of this manuscript. The author has tried since March 2020 to publish the main body of this manuscript and only on June 2020 a preprint has been published after a dozen of rejections without peer review (Kelleni M 2020, June 2,) and only Inflammopharmacology has accepted to peer review it. Funding None.