Ibuprofen could increase risk of coronavirus complications

By Dr. Liji Thomas, MDMar 17 2020

The UK’s National Health Service says that people who have COVID-19 and are self-quarantined should rest and drink plenty of fluids. So far, so good. However, it goes on to advise that they take paracetamol or ibuprofen to keep down fever and pain. This has drawn disagreement from the French Health Minister, Olivier Véran, himself a neurologist. Veran said in a tweet on Saturday, “The taking of anti-inflammatories [ibuprofen, cortisone … ] could be a factor in aggravating the infection. In case of fever, take paracetamol. If you are already taking anti-inflammatory drugs, ask your doctor’s advice.”

⚠️ #COVIDー19 | La prise d'anti-inflammatoires (ibuprofène, cortisone, ...) pourrait être un facteur d'aggravation de l’infection. En cas de fièvre, prenez du paracétamol.
Si vous êtes déjà sous anti-inflammatoires ou en cas de doute, demandez conseil à votre médecin.

— Olivier Véran (@olivierveran) March 14, 2020

Some physicians wonder if this was backed by any sound evidence from COVID-19 in particular, or just an offshoot of studies on the effects of NSAIDs on the immune system, in general.

NSAIDs reduce immune function

This advice is supported by virologist Ian Jones: “There’s good scientific evidence for ibuprofen aggravating the condition or prolonging it. That recommendation needs to be updated.” He gives as a reason the ability of ibuprofen to dampen the immune system, thus delaying recovery. In addition, it could lead to a worsening of pneumonia. He recommends the use of paracetamol to bring down the temperature in case of COVID-19 patients isolating themselves at home if they have a fever.

Similarly, professor Paul Little says the French directive is “sensible”, because, “There is now a sizeable literature from case-control studies in several countries that prolonged illness or the complications of respiratory infections may be more common when non-steroidal anti-inflammatories [NSAIDs] are used.”

Little explains that inflammation is a natural infection-fighting response, meant to enhance the body’s immune ability. However, there is no direct evidence that ibuprofen, in particular, is harmful in patients with COVID-19 specifically. Yet, if there is sufficient ground to suspect that it could be harmful, the NHS advice should be changed, he says.

Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Ibuprofen increases the risk of complications

For instance, one trial by Little and his team, as published in the BMJ, reports that patients with respiratory infections and took ibuprofen rather than paracetamol were at a higher risk for severe illness or complications. Other studies indicate that anti-inflammatory drugs worsen pneumonia.

Ian Jones explains this by pointing out the many common features of SARS and the novel coronavirus, which means this could also inhibit an essential enzyme responsible for electrolyte regulation, leading to fluid accumulation and pneumonia. This action is aggravated by ibuprofen but not paracetamol.

According to the NHS, NSAIDs can cause stomach irritation, gastric ulcers, headaches, dizziness, allergic reactions, and liver and/or kidney problems, if taken over any length of time, according to the NHS.

NSAIDs cause kidney injury

Epidemiologist Charlotte Warren-Gash adds, “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 the infection.” She also recommends taking paracetamol to relieve fever and sore throat unless the need is pressing, and there is no alternative. According to her, NSAIDS can aggravate some kidney and cardiovascular problems.

For her, this provides reasonable grounds to avoid ibuprofen, since these are among the underlying health conditions that increase the chances of death among older people with COVID-19. Even otherwise, she says, people who are already suffering from one or more medical conditions should be prescribed such drugs only with great caution. She cites a 2017 study that reported an increase in the odds of a heart attack when patients with respiratory infection were treated with NSAIDs.

A balanced view

On the other hand, taking ibuprofen will not kill the patient immediately if a pill is taken at a time when there isn’t any paracetamol available, and the person is struggling to sleep, for instance. But in other situations, when the need for paracetamol is not urgent, as with low-grade fever, it would be better to wait until one is able to get paracetamol.

Public Health England defends the NHS guideline on the ground that there isn’t enough evidence to show ibuprofen is harmful in this condition, either increasing the risk of acquiring the infection or worsening it. Also, the proof is lacking that ibuprofen may harm people with respiratory infections.

On the other hand, the PHE statement says, “Currently there is no published scientific evidence that ibuprofen increases the risk of catching Covid-19 or makes the illness worse. There is also no conclusive evidence that taking ibuprofen is harmful to other respiratory infections.”

It goes on to recommend the use of paracetamol or ibuprofen for fever, headache, and other aches provided the dosage advice is followed. The statement also advises, “Patients who have been prescribed NSAIDs for long-term health problems should continue to take them as directed by their healthcare professional.”

Rupert Beale of the Francis Crick Institute also confirms the risk of worsening acute kidney injury by ibuprofen intake but insisted that there was no established reason for COVID-19 patients not to take this medication. Tom Wingfield, of the Liverpool School of Tropical Medicine, says, “In the UK, paracetamol would generally be preferred over non-steroidal anti-inflammatory drugs (NSAID) such as ibuprofen to relieve symptoms caused by infection such as fever. This is because, when taken according to the manufacturer’s instructions in terms of timing and maximum dosage, it is less likely to cause side effects.”

Simultaneously, Irish public health authorities quelled false rumors that four youngsters who had all been on NSAIDs had become very sick with COVID-19. Ireland’s health official Colm Henry said the Whatsapp message purportedly reporting this ‘fact’ among parents’ groups was, in fact, “complete lies and totally untrue.’ He also said that both paracetamol and ibuprofen could be taken together and that there was no evidence supporting the non-use of any medication at present.