Ibuprofen use and clinical outcomes in COVID-19 patients

Abstract

Objective: It was recently suggested that ibuprofen might increase the risk for severe and fatal coronavirus disease 2019 and should therefore be avoided in this patient population. We aimed to evaluate whether ibuprofen use in individuals with COVID-19 was associated with more severe disease, compared with individuals using paracetamol or no antipyretics. Methods: In a retrospective cohort study of patients with COVID-19 from Shamir Medical Centre, Israel, we monitored any use of ibuprofen from a week before diagnosis of COVID-19 throughout the disease. Primary outcomes were mortality and the need for respiratory support, including oxygen administration and mechanical ventilation. Results: The study included 403 confirmed cases of COVID-19, with a median age of 45 years. Of the entire cohort, 44 patients (11%) needed respiratory support and 12 (3%) died. One hundred and seventynine (44%) patients had fever, with 32% using paracetamol and 22% using ibuprofen, for symptom-relief. In the ibuprofen group, 3 (3.4%) patients died, whereas in the non-ibuprofen group, 9 (2.8%) patients died (p 0.95). Nine (10.3%) patients from the ibuprofen group needed respiratory support, compared with 35 (11%) from the non-ibuprofen group (p 1). When compared with exclusive paracetamol users, no differences were observed in mortality rates or the need for respiratory support among patients using ibuprofen. Conclusions: In this cohort of COVID-19 patients, ibuprofen use was not associated with worse clinical outcomes, compared with paracetamol or no antipyretic.

Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19

“…Therefore, the findings of these studies may not be applicable to COVID-19. However, very recently Rinott et al [21] published a retrospective cohort study of 403 cases of COVID-19 patients, recruiting those who used "any medication containing ibuprofen, paracetamol or dipyrone starting a week before diagnosis of COVID-19". Their conclusions therefore address the issue of acute use of NSAIDs and found no significant association between ibuprofen usage and clinical outcomes (including mortality) when comparing the NSAID group with cohorts using paracetamol or no antipyretic.…”

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

“…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].…”

Early use of non-steroidal anti-inflammatory drugs in COVID-19 might reverse pathogenesis, prevent complications and improve clinical outcomes

“…Other researchers have also criticized the theoretical basis upon which ibuprofen was avoided in COVID-19 [ 40 , 41 ] and the claims against other drugs mentioned with ibuprofen in that contradictory hypothesis are similarly being revoked [ 42 ]. Notably, ibuprofen has been previously hypothesized to be hazardous in another medical argument and later on that hypothesis was proven incorrect [ 43 ] and recently a clinical study has shown that ibuprofen use was not associated with worse clinical outcomes, compared with paracetamol or no antipyretic [ 44 ]. Similarly, Use of NSAIDs was not associated with 30-day mortality, hospitalization or complications in Danish individuals who tested positive for SARS-CoV-2 [ 45 ].…”