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Ibuprofen and COVID-19: What GPs need to know

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Ibuprofen and its association with COVID-19 has been in the news lately. Why?
 
A brief summary of salient points:

• On 14 March, the French Health Minister tweeted that ibuprofen ‘could be a factor in aggravating’ infection in patients with COVID-19
• The World Health Organization (WHO) initially recommended people with COVID-19 avoid taking ibuprofen for symptomatic relief; however, it retracted that advice days later
• There is a hypothesis, mentioned in a paper in The Lancet, that taking ibuprofen may also increase a person’s chance of developing COVID-19 due to its effect on angiotensin converting enzyme 2 (ACE-2) receptors
• GP Dr Evan Ackermann does not believe patients need to cease long-term ibuprofen use in light of that hypothesis
• Respiratory specialist Associate Professor Irving believes it is worth advising patients infected with COVID-19 to avoid ibuprofen and instead use paracetamol for symptomatic relief
• At this stage, Dr Ackermann also advises patients with COVID-19 use paracetamol as a first line instead of ibuprofen
• Both experts believe more research is needed

Where did the issue surrounding ibuprofen and COVID-19 originate?
On 14 March, the French Health Minister Olivier Veran, a neurologist, tweeted that taking anti-inflammatory drugs such as ibuprofen ‘could be a factor in aggravating the infection’.
 
He went on to say, ‘In cases of fever, take paracetamol. If you are already taking anti-inflammatory drugs, ask your doctor’s advice’.
 
That tweet has since been shared more than 43,000 times and has sparked international concern over whether it is safe for patients to take nonsteroidal anti-inflammatory drugs (NSAIDs) if they are infected with COVID-19.
 
There is now widespread concern that taking NSAIDs such as ibuprofen may also increase a person’s chances of contracting the coronavirus.
 
A letter published in The Lancet on 11 March may have ignited that particular concern.
 
That letter explained that human pathogenic coronaviruses bind to their target cells through ACE-2 receptors. It went on to say that ACE-2 ‘can’ be increased by ibuprofen.
 
‘Consequently, the increased expression of ACE-2 would facilitate infection with COVID-19,’ the authors wrote.
 
It must be noted, however, that this is a hypothesis only.
 
The issues regarding the use of ibuprofen and its effect on COVID-19 have intensified as false rumours have also been circulating.
 
For instance, there is a message purporting to be from infectious diseases consultants in the UK, signed by ‘Dr Tim in Cork’, that has been shared thousands of times.
 
It claims to be ‘expert advice’, saying there are ‘four young people with non-underlying conditions’ in a serious condition at Cork University Hospital with COVID-19 associated with the use of ibuprofen.
 
The Infectious Diseases Society Ireland has announced this is a ‘fake message’ that people should ignore and delete.
 
Countless similar messages are still circulating at present.
 
The WHO recommendation
In response to these issues, the WHO initially recommended people with COVID-19 symptoms avoid taking ibuprofen. Spokesperson Christian Lindmeier told reporters in Geneva the UN health agency’s experts are ‘looking into this to give further guidance’.
 
‘In the meantime, we recommend using rather paracetamol, and do not use ibuprofen as a self-medication. That’s important,’ he said.
 
Mr Lindmeier added that if ibuprofen had been ‘prescribed by the healthcare professionals, then, of course, that’s up to them’.

However, the WHO has since retracted that initial recommendation.
 
‘Based on currently available information, WHO does not recommend against the use of ibuprofen,’ it stated on its official Twitter account.
 
The WHO went on to state, ‘We are also consulting with physicians treating COVID-19 patients and are not aware of reports of any negative effects of ibuprofen, beyond the usual known side effects that limit its use in certain populations.
 
‘WHO is not aware of published clinical or population-based data on this topic.’
 
What should GPs advise patients about taking long-term ibuprofen at this stage?
Dr Evan Ackermann, immediate past chair of the RACGP Expert Committee – Quality Care (REC–QC), told newsGP he strongly encourages patients on long-term NSAIDs use to continue taking their medication as usual.
 
‘I think from a patient advice point of view, at this point in time, this is an unresolved issue,’ he said.
 
‘If you’re taking [ibuprofen] long term, or any non-steroidal long term, this is not a reason to stop them. Please continue with them.
 
‘Have a talk with your GP if you’ve got any concern at this point in time, but don’t stop taking long-term medication.’
 
Dr Ackermann is keen to note, however, that this issue requires further research.
 
In terms of the hypothesis that taking NSAIDs may increase a person’s chance of contracting COVID-19 due to its effect on ACE-2 receptors, Dr Ackermann said he would not let that notion influence his advice about using NSAIDs.
 
At this stage, he does not think people need to avoid taking NSAIDs because of a potential and theoretical increased risk of developing COVID-19.
 
‘I would wait for really confirmatory research,’ he said.
 
Associate Professor Louis Irving is the director of respiratory and sleep medicine at the Royal Melbourne Hospital. He told newsGP now is a good opportunity for doctors to question whether patients really need to be on long-term NSAIDs.
 
‘This an opportunity for a holiday from the drug, and it’s a good time to find that out,’ he said.
 
‘I certainly wouldn’t recommend wholesale everyone ceasing [ibuprofen]. But there may be people who can withdraw the drug and see what happens.’
 
What should GPs advise patients with confirmed COVID-19 about taking ibuprofen for symptomatic relief?
An article, COVID-19: Ibuprofen should not be used for managing symptoms, say doctors and scientists, published in The BMJ on 17 March explores this question.
 
In the article, Paul Little, a Professor of Primary Care Research at the University of Southampton, said there is good evidence ‘that prolonged illness or the complications of respiratory infections may be more common when NSAIDs are used – both respiratory or septic complications and cardiovascular complications’.
 
He acknowledges the findings are likely to be causal, but wrote that advice to use paracetamol ‘is also less likely to result in complications’.
 
In the article, Ian Jones, a Professor of Virology at the University of Reading, said ibuprofen’s anti-inflammatory properties could ‘dampen down’ the immune system, which could slow the recovery process.
 
He added it was likely, based on similarities between the new virus (SARS-CoV-2) and SARS I, that COVID-19 reduces a key enzyme that part regulates the water and salt concentration in the blood and could contribute to the pneumonia seen in extreme cases.
 
‘Ibuprofen aggravates this, while paracetamol does not,’ he said.
 
But Dr Ackermann does not believe patients diagnosed with COVID-19 need to stop taking NSAIDs altogether, based on what is currently known.
 
‘It has been supported by some very low-level evidence to say use of NSAIDs in some acute respiratory illnesses and some sepsis get little bit worse outcomes, but it’s not strong [evidence],’ he said.
 
‘There’s nothing to say definitively that people with COVID-19 get worse with [ibuprofen].’

Meanwhile, Dr Irving is advocating for a more cautious response regarding usage of NSAIDs for symptomatic relief of COVID-19.
 
‘That is, if you don’t need to take them, use an alternative such as paracetamol,’ he said.
 
Dr Irving said it is possible that NSAIDs may alter the body’s inflammatory response to infection ‘in an adverse way’.
 
‘Therefore, if you need something for the fever and the aches and pains [of COVID-19], the concept of using paracetamol rather than [ibuprofen] to me makes sense,’ he said.

This article has been updated to reflect the fact the WHO retracted its initial recommendation regarding ibuprofen and COVID-19.
 
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