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Anti-inflammatory Drugs May Exacerbate Coronavirus Infection

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Over-the-counter anti-inflammatory drugs, such as ibuprofen, should be avoided if you have coronavirus symptoms because they could worsen the condition, warns French authorities.

The British Pharmacological Society has responded to concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs), could exacerbate symptoms of the novel coronavirus infection, COVID-19.** [Updated, March 18, 2020]

The World Health Organization on March 18, 2020 released a statement via Twitter, that it "
is aware of concerns on the use of ibuprofen for the treatment of fever for people with COVID-19."

"We [WHO] are consulting with physicians treating the patients & are not aware of reports of any negative effects, beyond the usual ones that limit its use in certain populations." *** [Updated, March 19, 2020]

Globally, according to the latest* World Health Organization WHO Situation Report there are now 153, 517 confirmed cases of COVID-19 and 5735 deaths. As the number of cases continues to rise, health authorities are issuing advice to the general public on how to avoid catching and spreading COVID-19, as well as guidance on what to do if you believe you may have already become infected.

“The taking of anti-inflammatories [ibuprofen, cortisone …] could be a factor in aggravating the infection. In case of fever, take paracetamol.” – France’s health minister, Olivier Véran – a qualified doctor and neurologist – tweeted, on March 14, 2020.

Véran warned that for patients taking anti-inflammatory drugs for other illnesses, they should consult with their healthcare professional considering this new guidance: “If you are already taking anti-inflammatory drugs, ask your doctor’s advice,” explained Véran.

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Speaking to FranceInfo, a French news source, Alexandre Bleibtreu, an expert in infectious, parasitic and tropical diseases, from the Pitié-Salpêtrière Hospital in Paris described why these drugs should be avoided if possible: "Anti-inflammatory drugs have an immunosuppressive effect" – i.e. they inhibit the activity of the immune system – "which promotes infections. They have a “booster” effect,"

“Paracetamol does not act on the same pathways as the anti-inflammatory drugs and therefore does not present the same risks,” continued Bleibtreu. "The only side effects are in the case of liver pathologies and exceeding the recommended doses."

What are other experts saying?

There have been numerous expert comments made in response to the guidelines issued by the French Health Minister.

"In the UK, paracetamol would generally be preferred over non-steroidal anti-inflammatory drugs ("NSAIDS") such as ibuprofen to relieve symptoms caused by infection such as fever,” said Tom Wingfield from the Liverpool School of Tropical Medicine.

Wingfield continued: “This is because, when taken according to the manufacturer's and/or a health professional's instructions in terms of timing and maximum dosage, it is less likely to cause side effects. Side effects associated with NSAIDs such as ibuprofen, especially if taken regularly for a prolonged period, are stomach irritation and stress on the kidneys, which can be more severe in people who already have stomach or kidney issues.”

“It is not clear from the French Minister's comments whether the advice given is generic "good practice" guidance or specifically related to data emerging from cases of COVID-19 but this might become clear in due course. It should also be noted that, in the UK, we would not commonly use cortisone to relieve infection-related symptoms such as fever," cautioned Wingfield.

Unravelling the situation with steroids

According to a press release, issued by the University of Edinburgh in February, steroids should be avoided when treating patients with COVID-19. This advice is based on the systematic review of observational studies of corticosteroids administered during the outbreaks of severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. These studies indicated that for patients with SARS, treated with corticosteroids, there was no survival benefit, but there was possible harm and delayed viral clearance. In the case of MERS patients, corticosteroids caused delayed lower respiratory tract (LRT) clearance of MERS-CoV.

In relation to the current coronavirus, guidance from the WHO for dealing with the clinical management of severe acute respiratory infection is to avoid use of corticosteroids unless indicated for another reason.

"During this current coronavirus outbreak clinicians are faced with some tough decisions on how to treat people who have been infected. After looking carefully at what evidence is available, we would advise that steroids should not be used for treatment of lung injury caused by this new virus. If steroids are used, it should be as part of a clinical trial so that we can find out if they are helping or harming patients." – J. Kenneth Baillie, lead author of the commentary article and Academic Consultant in Critical Care Medicine, University of Edinburgh.

Rupert Beale, Group Leader in Cell Biology of Infection at The Francis Crick Institute explained that: “Patients taking cortisone or other steroids should not stop them except on advice from their doctor.” The Society for Endocrinology recently issued coronavirus guidance for patients prescribed steroids, such as hydrocortisone, for pituitary or adrenal deficiency.

COVID-19 and “at-risk” groups

According to evidence currently available, more severe forms of the illness are more common among specific risk groups such as the elderly, patients with chronic or immunocompromising conditions, and pregnant women. The European Centre for Disease Prevention and Control has created a number of leaflets designed to provide basic information in the novel coronavirus, its transmission, prevention tips, and specific advice for various at risk groups.

Charlotte Warren-Gash, associate professor of Epidemiology, London School of Hygiene and Tropical Medicine provided expert comment on the use on the use of NSAIDS in at risk groups: “Most deaths from COVID-19 have been among older people and those with underlying health conditions such as cardiovascular disease. We already know that non-steroidal anti-inflammatory drugs (NSAIDs) should be prescribed with caution for people who have underlying health conditions. In England, NICE recommends prescribing the lowest dose for the shortest duration to prevent adverse effects such as gastrointestinal bleeding and cardiovascular or kidney problems.”

Warren-Gash continued: “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. In the meantime, for treating symptoms such as fever and sore throat, it seems sensible to stick to paracetamol as first choice.”

*Situation Report 55, Coronavirus disease 2019 (COVID-19). Date: March 15, 2020. Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports [Last Accessed: March 16, 2020]

** The article has been updated to include comment from the The British Pharmacological Society, and their President, Prof Sir Munir Pirmohamed, regarding the use of non-steroidal anti-inflammatory drugs (NSAIDs), to treat symptoms of the novel coronavirus infection, COVID-19:

"As COVID-19 is a new disease, evidence about it is still emerging. On 17 March 2020, the NHS updated its advice to include:

  • There is currently no strong evidence that ibuprofen can make COVID-19 worse
  • However, until we have more information, people should take paracetamol to treat the symptoms of coronavirus, unless they have been told by their doctor that paracetamol is not suitable for them.

“The NHS has updated its advice to recommend paracetamol rather than ibuprofen to treat some of the symptoms of COVID-19. There is no consistent evidence to suggest that ibuprofen worsens the disease, but we support the cautious approach as more evidence is collected."

“Clinical pharmacologists are experts in interpreting the overall balance of risks and benefits of using medicines. Our members are among those working to evaluate and interpret the emerging evidence to support the safe and effective use of medicines during the COVID-19 pandemic."

“Stopping or changing medicines for chronic health conditions without appropriate advice can be harmful. Now more than ever, people can look after their own health and support the NHS by following both official guidance and that of their doctor."

*** The article has been updated to include comment from the World Health Organization.