Wednesday, March 18, 2020

Should you take Ibuprofen if you have COVID-19 infection symptoms? What about diabetes and hypertension treatments?


Should you take Ibuprofen if you have COVID-19 infection symptoms? What about diabetes and hypertension treatments?

The global controversy wreaked havoc on March 14th, when French minister, Oliver Veran, tweeted that people with suspected COVID-19 symptoms should avoid anti-inflammatory drugs because “taking anti-inflammatory drugs (ibuprofen, cortisone...) could be an aggravating factor for the infection. If you have a fever, take paracetamol,” he tweeted. Then, some false claims published in social media created a lot of confusion (see below for details).

Apparently, the match that started the fire was a study published on March 11th that analysed other 3 studies on the outcomes of COVID-19 infected patients who also suffered from diabetes or hypertension. They reported that the most frequent comorbidities (this is the presence of one or more additional conditions co-occurring with a primary condition) reported in patients with COVID-19 are often treated with angiotensin-converting enzyme (ACE) inhibitors; however, treatment was not assessed in either study.

COVID-19 particles bind to their target cells through angiotensin-converting enzyme 2 (ACE-2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels. The expression of ACE-2 is substantially increased in patients with diabetes or hypertension, who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs). Also, ACE-2 can be increased by thiazolidinediones and ibuprofen. They hypothesised that the increased expression of ACE-2 would facilitate infection with COVID-19 and therefore diabetes and hypertension treatment with ACE-2-stimulating drugs increases the risk of developing severe and fatal COVID-19.

In response to this study, many doctors and international medical organizations, have strongly advised patients with diabetes or hypertension to continue taking their treatments, as some contradictory hypothesis would indicate that ACE inhibitors might reduce the “free” ACE2 proteins that are available to bind the coronavirus particles. Some animal studies, indeed, show that these treatments give the mouse models better outcomes after the viral infection.

Ibuprofen or Advil (b-Isobutylhydratropic Acid) is a nonsteroidal anti-inflammatory drug (aka NSAID) that reduces the number of proteins that cause inflammation and pain in the body, so it is widely used to relieve pain, swelling and fever. Importantly, you shouldn’t take more than a recommended dose because an overdose can damage your stomach and/or gut. The maximum amount of ibuprofen for adults is 800 milligrams per dose or 3200 mg per day (4 maximum doses). Use only the smallest amount needed.

Also, it is recommended to take ibuprofen with food or milk to lessen stomach upset. On a side note, once I was suffering terrible endometriosis-related pain and I took 1 gram of ibuprofen on an empty stomach, keep in mind I was a petit adult (45 kg), and I got sicker and vomited. Lesson learned. This is just an anecdotal situation; however, it is an example of how good medicine can be misused.

Importantly, there is no official research about the use of ibuprofen and its implication on Covid-19 outcomes! There are some studies that suggest ibuprofen use during a respiratory infection, by other viruses, can result in deterioration of the disease or other complications. Probably, because of the Ibuprofen effect in the immune system. In the case of dengue virus infection, it is recommended to not take ibuprofen or aspirin since they can increase the risk of bleeding. Paracetamol (acetaminophen) can be an option to bring down fever and reduce joint pains.

On the other hand, there are studies showing mechanisms of action of NSAIDs which may assist in designing a convenient strategy for treating viral infections. For example, for Zika virus-infected patients. One study showed that NSAIDs can improve the antiretroviral activity of nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. Although Zika virus and HIV belong to different viral families than COVID-19.

Until we have more information about the effects of NSAIDs, some authorities recommend taking paracetamol to deal with fever and pain. Paracetamol must be taken strictly according to the recommended dose because too much of it can damage the liver. If you are already taking ibuprofen or another non-steroidal anti-inflammatory (NSAID) on the advice of a doctor, do not stop taking it without checking first.
The NHS website advices:
There is currently no strong evidence that ibuprofen can make coronavirus (COVID-19) worse. But until we have more information, take paracetamol to treat the symptoms of coronavirus, unless your doctor has told you paracetamol is not suitable for you.

PSA, please check if the studies that you are reading about were done with humans, rats, mice, ferrets, monkeys, any other animal model and/or tested on cultivated cells! Sometimes results can be extrapolated but it is dangerous to make uneducated assumptions without checking the sources.

These are false claims published in social networks:

• "There are four young people in an intensive care unit in Cork who have no underlying illnesses - all were taking anti-inflammatories and there are concerns this has caused a more severe illness"
• The University of Vienna has sent a memo warning people with coronavirus symptoms not to take ibuprofen, "because it has been discovered that it increases the speed of reproduction of the coronavirus Covid-19 in the body and this is the reason why people in Italy have reached the current bad stage and rapid spread"
• "At the university hospital in Toulouse, France, there are four very critical cases of coronavirus in [young people] who do not have any health problems. Their problem is that when they all appeared to have symptoms, they all took painkillers like ibuprofen"

For more information:

Coronavirus Pandemic Update 37: The ACE-2 Receptor - The Doorway to COVID-19 (ACE Inhibitors & ARBs)
https://www.youtube.com/watch?v=1vZDVbqRhyM


Image from  Heurich et al. Journal of Virology January 2014

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