Uncertainty Surrounds Use of OTC Anti-Inflammatory Drugs in Patients With COVID-19

Authorities in France have warned that widely used OTC anti-inflammatory drugs may worsen the novel coronavirus known as COVID-19, which prompted a prominent physician to say that more evidence is needed on the subject.

Olivier Véran, MD, France’s health minister and a neurologist, said in a tweet on Saturday that anti-inflammatories may be a factor in aggravating the infection and, in the case of a fever, individuals should take paracetamol.¹ “If you have taken an anti-inflammatory medicine [such as ibuprofen and cortisone or have doubts about your medication use,] consult with your health care provider,” Véran wrote in the tweet.¹

According to The Local France, the country recently tightened the sale of ibuprofen and paracetamol due to the potential dangers associated with the drugs, as these medications are currently only available with a prescription. The restriction affects nearly 36 different brands of paracetamol, including doliprane, Efferalgan, Dafalgan, and 46 kinds of ibuprofen, including Advil and Nurofen.²

In response to Véran’s tweet, French media outlet Le Figaro, wrote that anti-inflammatories can aggravate existing infections, leading to complications.

“Inflammation is a normal response from body to infection and [is] an alert signal. By masking the response of the immune system, taking anti-inflammatories can not only impair the body’s response but also hide the signs of how serious it can be. This can delay the diagnosis and therefore, treatment,” wrote Soline Roy for Le Figaro.^3-4

Roy wrote that the same risks are also observed with cortisone and patients who receive cortico-therapy should be aware of increased risks associated with infection. Anne Pierre Jonville Béra, a specialist at the center of pharmacovigilance in Tours, France, added, “animal testing has shown that taking ibuprofen encourages the growth of certain bacteria.”³

Additionally, Ian Jones, professor and virologist at the University of Reading, told the Science Media Centre that the advice relates to ibuprofen’s anti-inflammatory properties, in that it can potentially weaken the immune system and thereby slow down the recovery process.

“In addition, it is likely, based on the substantial literature around [severe acute respiratory syndrome I] (SARS I) and the similarities this new virus (SARS-CoV-2) has to SARS I, that the virus reduces a key enzyme which part-regulates the water and salt concentration in the blood and could be part of the pneumonia seen in extreme cases. Ibuprofen aggravates this while paracetamol does not. It is recommended that people use paracetamol to reduce temperature if you are feverish,” Jones, told the Science Media Centre.⁵

According to CNN, Véran’s recommendation came on the same day that the French government reported that “grave adverse effects” were linked to the use of non-steroidal anti-inflammatory drugs (NSAIDs). This family of medications has “been identified with patients affected by COVID-19, in potential or confirmed cases.”⁶

However, Muge Cevik, MD, MSc, MRCP, a researcher at the University of St. Andrews Infection and Global Health Division, noted that there is no evidence of a link between NSAIDs and worse outcomes in patients with COVID-19.⁷ Cevik tweeted, “there’s no scientific evidence I am aware of that ibuprofen [causes worse] outcomes in #COVID19."

Other experts suggested that Veran's advice is in line with France’s general guidance on anti-inflammatory painkillers, such as ibuprofen, even if their specific connection to the coronavirus is not clear, according to CNN.⁶

"There is a good reason to avoid ibuprofen as it may exacerbate acute kidney injury brought on by any severe illness, including severe COVID-19 disease. There isn't yet any widely accepted additional reason to avoid it for COVID-19," Rupert Beale, a group leader in Cell Biology of Infection at the UK's Francis Crick Institute, said to the Science Media Centre.⁵

Experts agree that ibuprofen is generally prescribed with caution to older adults with underlying health conditions, a specific patient population at risk for COVID-19.

"Most deaths from COVID-19 have been among older people and those with underlying health conditions, such as cardiovascular disease. We already know that NSAIDs should be prescribed with caution for people who have underlying health conditions," Charlotte Warren-Gash, associate professor of Epidemiology at the London School of Hygiene and Tropical Medicine, told Science Media Centre.⁵

The National Institute for Health and Care Excellence (NHS) recommends prescribing the lowest dose of ibuprofen for the shortest duration to patients with underlying conditions to prevent adverse events, including cardiovascular or kidney problems. The NHS additionally advises using ibuprofen over paracetamol for inflammatory problems such as arthritis, but warns against taking it for long periods.⁶

"For COVID-19, research is needed into the effects of specific NSAIDs among people with different underlying health conditions, which takes into account the severity of infection," Warren-Gash told Science Media Centre.⁵ "In the meantime, for treating symptoms such as fever and sore throat, it seems sensible to stick to paracetamol as first choice."

Véran announced on Friday that the number of COVID-19 cases in the county had increased by 800 in 24 hours. There were 3661 confirmed cases that had led to 79 deaths at that time. Of those diagnosed with the disease, 154 people were in intensive care, however, the number of infected patients undergoing treatment is being consistently updated.⁸

In his daily briefing, Véran said that the evolution and spread of the virus was “rapid and real,” but that 98% of those who had been tested positive with COVID-19 had recovered.⁸

Reference

• Olivier Véran (@olivierveran). Twitter. Published March 14, 2020. https://twitter.com/olivierveran/status/1238776545398923264. Accessed March 16, 2020.
• France tightens (further) rules on sale of paracetamol and ibuprofen. The Local France. Published January 13, 2020. https://www.thelocal.fr/20200113/france-could-tughed-rules-on-sales-of-paracetemol-and-ibuprofen. Accessed March 16, 2020.
• Coronavirus: French health minister issues warning over anti-inflammatories. The Local France. Published March 14, 2020. https://www.thelocal.fr/20200314/coronavirus-french-health-minister-issues-warning-over-anti-flammatories. Accessed March 16, 2020.
• Roy, Soline. Coronavirus: alerte sur l’ibuprofène et autres anti-inflammatoires. Le Figaro. Published March 14, 2020. https://www.lefigaro.fr/sciences/coronavirus-alerte-sur-l-ibuprofene-et-autres-anti-inflammatoires-20200314. Accessed March 16, 2020.
• Expert reaction to reports that the French Health Minister recommended use of paracetamol for fever from COVID-19 rather than ibuprofen or cortisone. Science Media Center. Published March 16, 2020. https://www.sciencemediacentre.org/expert-reaction-to-reports-that-the-french-health-minister-recommended-use-of-paracetamol-for-fever-from-covid-19-rather-than-ibuprofen-or-cortisone/. Accessed March 16, 2020.
• Picheta, Rob. France says ibuprofen may aggravate coronavirus. Experts say more evidence is needed. CNN Health. Published March 16, 2020. https://www.cnn.com/2020/03/16/health/coronavirus-ibuprofen-french-health-minister-scn-intl-scli/index.html. Accessed March 16, 2020.
• Dr. Muge Cevik (@mugecevik). Twitter. Published March 14, 2020. https://twitter.com/mugecevik/status/1238857584204972032. Accessed March 16, 2020.
• Willsher, Kim. Anti-inflammatories may aggravate Covid-19, France advises. The Guardian website. Published March 14, 2020. https://www.theguardian.com/world/2020/mar/14/anti-inflammatory-drugs-may-aggravate-coronavirus-infection. Accessed March 16, 2020.