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More people with fever and body aches are turning to nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce symptoms, but the drugs have come under new scrutiny as researchers work to find out if they are a safe way to get relief from COVID-19 vaccine pain or symptoms of the disease.
Early in the pandemic, French health officials warned that NSAIDs, such as ibuprofen, could exacerbate coronavirus infection, and recommended switching to acetaminophen instead.
The National Health Service in the United Kingdom followed a similar recommendation for acetaminophen.
But the European Medicines Agency took a different approach, reporting “without any scientific evidence” that COVID-19 NSAIDs could make it worse. The U.S. Food and Drug Administration chose not to stand.
The debate sparked a debate on social media, with different opinions from around the world. He encouraged Craig Wilen, MD, PhD, of Yale University School of Medicine in New Haven, Connecticut, and his team to study the impact of NSAIDs on COVID-19 infection and immune response. Their results were published online Jan. 20 in the Iris Virology.
“I was deeply concerned that frequency-based decisions were not driving the conversation,” Wilen said. “Millions of people are taking NSAIDs every day and clinical decisions should not be made about them. they care about hypotheses. “
One theory is that NSAIDs alter infectious susceptibility by altering enzyme 2 converted angiotensin (ACE2). The drugs could also alter the cell entry receptor for SARS-CoV-2, alter virus reproduction, or even alter the immune response.
British researchers, also questioning the safety of NSAIDs in patients with COVID-19, entered National Health Service records to study two large groups of patients, some of whom were in pain relief. .
“We were looking at the controversy and the lack of evidence and wanted to contribute,” said lead researcher Angel Wong, PhD, of the London School of Hygiene and Tropical Medicine. Medscape Medical News.
And with nearly 11 million NSAID prescriptions dispensed in primary care in England alone in the last 12 months, the inconsistency was worrying.
The team compared COVID-19-related deaths in two groups: one group of more than 700,000 people taking NSAIDs, including patients with rheumatoid arthritis and osteoarthritis; and another of nearly 3.5 million non-pharmacists.
NSAIDs work by inhibiting the enzyme cyclooxygenase (COX) -1 and COX-2 in the body, which are essential for the generation of prostaglandins. These lipid molecules play a role in inflammation and are inhibited by NSAIDs.
The researchers found no evidence of a harmful effect of NSAIDs on COVID-19-related deaths; their results were published online January 21 in the History of rheumatic diseases.
The results, they point out, are in line with a study from Denmark that also showed no evidence of a higher risk for COVID-19 side effects with NSAID use.
“It’s encouraging,” Wong said, “that patients can continue with treatment safely.”
More new evidence
Wilen’s team found that SARS-CoV-2 infection induced COX-2 expression in human and mouse cells. However, overdose of COX-2 by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 expression, viral entry, or viral replication.
In their mouse model of SARS-CoV-2 infection, the researchers found that NSAIDs inhibited the production of proinflammatory cytokines and neutralized antibodies. The findings suggest that NSAIDs affect COVID-19 results by disrupting the inflammatory response and production of immune antibodies, rather than altering infectious vulnerability or viral reproduction.
Understanding the effect of NSAIDs on cytokine production is crucial, Wilen pointed out, because they may be protective early in COVID-19 but pathologic at later stages.
Timing is crucial in the case of other immunomodulatory drugs. For example, dexamethasone reduces mortality in COVID-19 patients on respiratory support but may harm those with milder infection.
There is still a lot to learn, Wilen acknowledged. “We may be seeing something similar going on with NSAIDs, where the timing of treatment is important.”
Allison Shelley is executive editor for Medscape Medical News reporting on COVID-19 pandemic. For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube