COVID-19 and Avoiding Ibuprofen. How Good Is the Evidence?

Abstract

Ibuprofen is an over-the-counter medication that is used widely for the treatment of pain and fever during COVID-19 pandemic. A concern was raised regarding the safety of ibuprofen use because of its role in increasing ACE2 levels within the Renin-Angiotensin-Aldosterone system. ACE2 is the coreceptor for the entry of SARS-CoV-2 into cells, and so, a potential increased risk of contracting COVID-19 disease and/or worsening of COVID-19 infection was feared with ibuprofen use. However, available data from limited studies show administration of recombinant ACE2 improves lung damage caused by respiratory viruses, suggesting ibuprofen use may be beneficial in COVID-19 disease. At this time, there is no supporting evidence to discourage the use of ibuprofen.

Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study

“…The PockDrug-Server was used applying the Fpocket method. reported to be concentration dependent and may require up to 0.500 M [24]. Additionally, it has been pointed out that in the case of NSAIDs the molecular docking values can be much closer to the selectivity through energy terms, but not to the IC 50 , and it has been indicated that for these compounds the molecular docking represents the descriptor most important for drug-protein interactions [82].…”

“…However, this statement, although it contributes to the described use of NSAIDs for the empirical treatment and prevention of COVID-19 [93], requires its experimental demonstration because our predictions cannot guarantee a pharmacologically and clinically relevant interaction. Therefore, more studies are needed, especially given the real controversy that exists regarding the use of these drugs against COVID-19 [19][20][21][22][23][24][25][26][27]. Especially because to date, only one theoretical report of a binding of ligand at the interface of the RBD-ACE2 complex is known [49,50], but this binding is in a different region than the one found in this work, in our work the binding of Ibuprofen occurs in an allosteric region.…”

“…In fact, the use of NSAIDs such as Ibuprofen is highly controversial because it has been reported that in animal models it can mediate the overexpression of the angiotensinconverting enzyme 2 (ACE2) essential for viral recognition and it has been speculated that this could increase the risk of COVID-19 [19][20][21][22][23]. However, in various investigations in patients with COVID-19, the use of Ibuprofen has not been associated with worse clinical outcomes, compared to other NSAIDs such as Acetaminophen [24][25][26]. On the contrary, it has been described that the chronic use of this type of NSAIDs could even protect against the occurrence and severity of COVID-19 [26,27].…”

Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?

“…Several studies are accumulating and reappraising the importance of NSAIDs in COVID-19 management (Bruce et al, 2020;Kutti Sridharan et al, 2020;Smart and Fawkes, 2020;Zolk et al, 2020); interestingly two in silico screenings independently identified the COX-II inhibitor celecoxib as a potential anti-SARS-CoV-2 drug, and a very recent study still under peer review reports its beneficial effects plus famotidine in hospitalized patients (Tomera et al, 2020).…”

Does Ibuprofen Worsen COVID-19?

“…At this point, there exist no scientific data to support an increased risk of SARS-CoV-2 infection or COVID-19 severity with ibuprofen. As for chloroquine [45], it is certainly time for a properly conducted study of the potential risks and benefits of ibuprofen in COVID-19 [46,47].…”