COVID-19 and NSAIDS: A Narrative Review of Knowns and Unknowns

Abstract

Concern about the appropriate role of nonsteroidal anti-inflammatory drugs (NSAIDs) in COVID-19 speculate that NSAIDs, in particular ibuprofen, may upregulate the entry point for the virus, the angiotensin-converting enzyme (ACE) 2 receptors and increase susceptibility to the virus or worsen symptoms in existing disease. Adverse outcomes with COVID-19 have been linked to cytokine storm but the most effective way to address exaggerated inflammatory response is complex and unclear. The Expert Working Group on the Commission of Human Medicines in the UK and other organizations have stated that there is insufficient evidence to establish a link between ibuprofen and susceptibility to or exacerbation of COVID-19. NSAID use must also be categorized by whether the drugs are relatively low-dose overthe-counter oral products taken occasionally versus higher-dose or parenteral NSAIDs. Even if evidence emerged arguing for or against NSAIDs in this setting, it is unclear if this evidence would apply to all NSAIDs at all doses in all dosing regimens. Paracetamol (acetaminophen) has been proposed as an alternative to NSAIDs but there are issues with liver toxicity at high doses. There are clearly COVID-19 cases where NSAIDs should not be used, but there is no strong evidence that NSAIDs must be avoided in all patients with COVID-19; clinicians must weigh these choices on an individual basis.

Influence of COVID-19 pandemic on decisions for the management of people with inflammatory rheumatic and musculoskeletal diseases: a survey among EULAR countries

“…NSAIDs, which have been concerned to upregulate ACE 2 receptors and to increase the susceptibility to the virus, 40 and glucocorticoids, which might negatively affect virus clearance, 41 should not automatically be stopped in patients with RMDs according to the EULAR task force. 11 Even patients with symptoms of COVID-19 who are chronically treated with glucocorticoids should continue this treatment.…”

Pain Management During the COVID-19 Pandemic

“…NSAIDs are relatively contraindicated in patients with respiratory disorders, as in acute respiratory infections. NSAIDs have also been implicated in acute myocardial infarction and risk of stroke in rare cases [25]. Specific concerns related to COVID-19 and the use of NSAIDs have hypothesized that NSAIDs may upregulate entry through the angiotensin-converting enzyme (ACE) 2 receptors, thereby increasing susceptibility to the virus.…”

“…Specific concerns related to COVID-19 and the use of NSAIDs have hypothesized that NSAIDs may upregulate entry through the angiotensin-converting enzyme (ACE) 2 receptors, thereby increasing susceptibility to the virus. These data are still inconclusive [25]. Selective COX-2 inhibitors (e.g., etoricoxib and celecoxib) COX-2 inhibitors specifically target prostaglandins that mediate pain and inflammation and have less gastric side effects compared to their non-specific NSAID counterparts.…”

“…Even if anti-inflammatory therapy were to be advocated, it is not yet clear which medication therapies provide the most benefit. Similarly, at which point during the disease, at what doses, and for what duration anti-inflammatory therapy should be used is still unknown [25,31].…”

“…-Clinicians must consider a patient's whole picture with the addition of any new medication, and avoid NSAIDs in those patients where NSAIDs are contraindicated, such as those with peptic ulcer disease or renal dysfunction [25]. -Discontinuation of prescribed NSAIDs for chronic pain conditions is not recommended at this time.…”