Non-steroidal Anti-inflammatory Drugs (NSAIDs)
Non-steroidal anti-inflammatory drugs, or NSAIDs, are one of the most commonly prescribed drugs for treating fever, pain, and inflammation. NSAIDs include over-the-counter household names such as ibuprofen, naproxen, and aspirin. Given the widespread use of these medications it is appropriate that researchers have investigated the potential benefits and harms of NSAIDs in patients diagnosed with COVID-19. Thus far, the evidence for using NSAIDs in the context of CoVs are mixed and might not be generalizable to all NSAIDs as reports tended to focus on specific NSAIDs. These studies also focused on the potential for NSAIDs to act as an antiviral, with a potential added benefit of being able to treat inflammatory symptoms. One report showed that the NSAID indomethacin could directly inhibit SARS-CoV replication in Vero cell monolayers in a dose-dependent manner (263). The antiviral properties of naproxen have been described in the context of influenza virus (264, 265) and has prompted the initiation of a clinical trial investigating the efficacy of naproxen as a treatment for critically ill COVID-19 infected patients (NCT04325633).
NSAID therapy should be used with caution as they have been shown to interfere with immune responses and ability to produce antibodies, with ibuprofen having the greatest suppressive effect (266). Furthermore, ibuprofen has been reported to increase the expression of the ACE2 receptor (267) which could facilitate SARS-CoV-2 viral entry. This finding should be considered for any current (NCT04334629) and potential COVID-19 clinical trial assessing ibuprofen therapy. NSAIDs also have been shown to have a direct suppressive effect on NK cell IFN-γ and TNF-α production (268) which may be beneficial for late stage COVID-19 patients.