[Copy of the Apr. 26 section “Maybe stop taking ibuprofen/advil?”, deleted from the main text Jun. 2. A still earlier version just said that some sources were warning about NSAIDs and to therefore avoid them out of an abundance of caution.]
Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARSCoV-2) bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels.[4] The expression of ACE2 is substantially increased in patients with type 1 or type 2 diabetes, who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs).[4] Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2.[5] ACE2 can also be increased by thiazolidinediones and ibuprofen. These data suggest that ACE2 expression is increased in diabetes and treatment with ACE inhibitors and ARBs increases ACE2 expression. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19. We therefore hypothesise that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19.
Qiao et al. conclude that ibuprofen enhances ACE2 in diabetic rats. Qiao et al. is the only study I’ve seen on ‘ibuprofen increases ACE2’, and this claim is uncited in Fang et al. The ibuprofen-ACE2-COVID link doesn’t seem to be widely known / accepted / cared about, based on the discussion on Science Translational Medicine (which argues increased ACE2 might reduce COVID-19 severity; see also the comment section) and Snopes. I also don’t know whether I should expect other NSAIDs to interact with ACE2 in the same way as ibuprofen.
On Mar. 14, Samira Jeimy wrote: “In Germany and France, ICU physicians have noticed that the common thread amongst young patients needing #COVIDー19 related ICU admission is that they had been using NSAIDS (Advil, Motrin, Aleve, Aspirin).” She cites the Lancet paper and Day:
Scientists and senior doctors have backed claims by France’s health minister that people showing symptoms of covid-19 should use paracetamol (acetaminophen) rather than ibuprofen, a drug they said might exacerbate the condition.
The minister, Oliver Veran, tweeted on Saturday 14 March that people with suspected covid-19 should avoid anti-inflammatory drugs. “Taking anti-inflammatory drugs (ibuprofen, cortisone . . .) could be an aggravating factor for the infection. If you have a fever, take paracetamol,” he said.
His comments seem to have stemmed in part from remarks attributed to an infectious diseases doctor in south west France. She was reported to have cited four cases of young patients with covid-19 and no underlying health problems who went on to develop serious symptoms after using non-steroidal anti-inflammatory drugs (NSAIDs) in the early stage of their symptoms. The hospital posted a comment saying that public discussion of individual cases was inappropriate.
But Jean-Louis Montastruc, a professor of medical and clinical pharmacology at the Central University Hospital in Toulouse, said that such deleterious effects from NSAIDS would not be a surprise given that since 2019, on the advice of the National Agency for the Safety of Medicines and Health Products, French health workers have been told not to treat fever or infections with ibuprofen.
Experts in the UK backed this sentiment. Paul Little, a professor of primary care research at the University of Southampton, said that there was 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 added, “The finding in two randomised trials that advice to use ibuprofen results in more severe illness or complications helps confirm that the association seen in observational studies is indeed likely to be causal. Advice to use paracetamol is also less likely to result in complications.”
Ian Jones, a professor of virology at the University of Reading, said that ibuprofen’s anti-inflammatory properties could “dampen down” the immune system, which could slow the recovery process. He added that 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.
Charlotte Warren-Gash, associate professor of epidemiology at the London School of Hygiene and Tropical Medicine, said: “For covid-19, research is needed into the effects of specific NSAIDs among people with different underlying health conditions. In the meantime, for treating symptoms such as fever and sore throat, it seems sensible to stick to paracetamol as first choice.” [...]
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. 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.
So most sources seem to agree that acetaminophen is at least a bit better than ibuprofen for treating fever-causing illnesses in general; but there’s confusion and disagreement about whether ibuprofen is unusually good or bad for COVID-19 in particular, and I don’t get the sense using ibuprofen is widely seen as a terrible idea. Elizabeth van Nostrand writes, “France is recommending against NSAIDs and against ibuprofen in particular. I will be very surprised if that ends up being born out (and WHO agrees with me)”.
Overall, the evidence is such that I’m avoiding ibuprofen right now, but I wouldn’t recommend going to huge lengths to avoid ibuprofen.
See 3E below on whether and when it’s a good idea to manually reduce fevers at all.
[Copy of the Apr. 26 section “Maybe stop taking ibuprofen/advil?”, deleted from the main text Jun. 2. A still earlier version just said that some sources were warning about NSAIDs and to therefore avoid them out of an abundance of caution.]
Fang et al. write in The Lancet:
Qiao et al. conclude that ibuprofen enhances ACE2 in diabetic rats. Qiao et al. is the only study I’ve seen on ‘ibuprofen increases ACE2’, and this claim is uncited in Fang et al. The ibuprofen-ACE2-COVID link doesn’t seem to be widely known / accepted / cared about, based on the discussion on Science Translational Medicine (which argues increased ACE2 might reduce COVID-19 severity; see also the comment section) and Snopes. I also don’t know whether I should expect other NSAIDs to interact with ACE2 in the same way as ibuprofen.
On Mar. 14, Samira Jeimy wrote: “In Germany and France, ICU physicians have noticed that the common thread amongst young patients needing #COVIDー19 related ICU admission is that they had been using NSAIDS (Advil, Motrin, Aleve, Aspirin).” She cites the Lancet paper and Day:
The Snopes page above cites Tom Wingfield saying:
So most sources seem to agree that acetaminophen is at least a bit better than ibuprofen for treating fever-causing illnesses in general; but there’s confusion and disagreement about whether ibuprofen is unusually good or bad for COVID-19 in particular, and I don’t get the sense using ibuprofen is widely seen as a terrible idea. Elizabeth van Nostrand writes, “France is recommending against NSAIDs and against ibuprofen in particular. I will be very surprised if that ends up being born out (and WHO agrees with me)”.
Overall, the evidence is such that I’m avoiding ibuprofen right now, but I wouldn’t recommend going to huge lengths to avoid ibuprofen.
See 3E below on whether and when it’s a good idea to manually reduce fevers at all.