ACEIs, ARBs, ibuprofen originally linked to COVID-19: the other side of the mirror

Abstract

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.

Diclofenac potassium/nitazoxanide/azithromycin novel COVID-19 protocol used in adults, children and pregnant patients: could it be the magic bullet?

“…This later suggestion has contradicted the more prevalent approach adopted worldwide that has avoided NSAIDs and, unfortunately, preferred paracetamol that does not possess major peripheral anti-inflammatory effects as compared to NSAIDs 10 . Notably, we have fully explained from a pharmacological point of view the very unfortunate incident that led to the avoidance of the use of ibuprofen in COVID-19 11 , other researchers have also criticized avoiding ibuprofen in COVID-19 12 and ibuprofen use was not shown to be associated with worse COVID-19 clinical outcomes, compared with paracetamol or no antipyretic 13,14 . Moreover, ibuprofen has been shown to be among the drugs that are significantly associated with diminished COVID-19 risk for hospitalization as revealed by an In silico cohort study that examined the electronic health records from individuals 7,360 individuals with COVID-19 positive test results by PCR.…”

Clinical Management of Hypertension, Inflammation and Thrombosis in Hospitalized COVID-19 Patients: Impact on Survival and Concerns

“…Similarly, it is important to acknowledge that, contrary to what has been previously reported, the use of NSAIDs, while not being beneficial, is also not detrimental to COVID-19 patients. These are examples of how misinformation has led to the assumption of facts, something from which we should learn, as was discussed rigorously for precisely these treatment arms [ 55 ].…”

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

“…Alternatively, we have previously published two articles to justify the use of NSAIDs including diclofenac potassium and ibuprofen for early management of COVID-19 [ 32 , 33 ]. We suggested that NSAIDs might prevent, especially when early administered, or reverse COVID-19 associated hyperinflammatory response which is correlated with the immuno-pathologically induced SARS CoV-2 morbidity and mortality [ 5 ] and to prevent the cytokine induced lymphocyte distraction into or away from the lungs that is laboratory manifested through lymphopenia [ 32 ].…”

“…Unfortunately, six months have elapsed until our paper revoking the original claims that led to the current NSAIDs situation has been eventually sent for peer review, accepted and published [ 33 ], yet until today, NSAIDs are avoided in many countries all over the world especially in the developing ones and, even in the most favorable situations, they are considered of second choice to manage COVID-19 after paracetamol that does not possess major peripheral anti-inflammatory effects as compared to NSAIDs [ 50 ].…”