The ibuprofen COVID-19 paradox

With the surge of information surrounding COVID-19 released in the news this year, an interesting concern arose regarding ibuprofen’s use in patients with COVID-19. In March of 2020, French authorities were the first to investigate anecdotal reports of severe COVID-19 infection in patients who had taken ibuprofen.

The initial concern involved the ACE-2 receptor. The theoretical concern was that NSAIDs (nonsteroidal anti-inflammatory drugs) such as ibuprofen might upregulate this receptor (a known target for cell penetration of the COVID-19 virus), leading to a more severe infection. When this information initially hit the news, many health care providers started recommending acetaminophen instead of NSAIDs to patients with suspected COVID-19 infection. Although well-intentioned, it appears now this idea was misguided.  New research shows that Ibuprofen does not show any correlation with the worsening severity of COVID-19 infection.  A cohort study using Danish health registry data published in September 2020 showed no increase risk in adverse outcomes or 30-day mortality in patients with COVID-19 who used NSAIDs.

Although this link between Ibuprofen and worsening COVID-19 infection has not been demonstrated in the current published data, there likely was some anecdotal evidence to suggest a worsening of symptoms in patients with COVID-19 who used Ibuprofen. It’s possible that the anecdotal reports are not due to the ACE-2 receptor theory but instead, reducing the natural fever response caused a decrease in the immune response, leading to a more severe COVID-19 infection.

In the Danish study published in PLOS Medicine, patients were divided into NSAID users and non-NSAID users. There was no data to track the use of other antipyretics like acetaminophen for symptomatic care, indicating that patients in the control group were likely also treating their fevers, just with non-NSAID medications. Given the ambiguity of these studies, the possible negative effects of using antipyretics in patients with COVID-19 infection is worth further consideration.

It is well known that fevers help to fight infection. For millions of years, humans have evolved with fever as a protective response to infection. Fevers reduce the ability of viruses to replicate in the body and increase immune function through various complex pathways. This begs the question, why do providers routinely recommend treatment of fevers with antipyretic medication?

Fevers rarely cause complications in otherwise healthy patients with viral infections. Ironically this symptomatic care often makes patients feel better temporarily could unknowingly worsen COVID-19 infection outcomes in patients. While the ibuprofen concern regarding COVID-19 has been apparently debunked, it still leaves the larger question yet to be investigated: Could antipyretics be contributing to worse outcomes in patients with COVID-19?

Amy G. Schade is a physician assistant.

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