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First it was called fake news, then the WHO issued a warning about ibuprofen, only to retract it two days later. What’s behind the confusion over ibuprofen and SARS-CoV-19?
In the current corona pandemic, people with pre-existing conditions such as high blood pressure, cardiovascular disease and diabetes are particularly at risk. Not only because their health is weakened, but possibly also — it is suspected — because they are taking medicines that can cause a severe course of infection with the new coronavirus SARS-CoV-2.
About a quarter of the world's population has high blood pressure, and in many industrialized countries, such as Germany, up to a third of the population is affected. And many people take antihypertensive drugs such as ACE inhibitors or Sartan, which are believed to promote severe courses of the new coronavirus infection.
Diabetes drugs such as the insulin sensitizer thiazolidinedione (glitazone) and the well-known painkiller ibuprofen are also suspected of upregulating the very ACE2 receptor that enables SARS viruses to enter cells.
While an unconfirmed theory, as of yet not backed by reliable studies, the World Health Organization (WHO) initially advised infected coronavirus patients not to take ibuprofen without first seeking medical advice. Instead, the WHO recommended paracetamol, their spokesperson Christian Lindmeier announced in Geneva on Tuesday.
To make things even more confusing, the WHO retracted this advice two days later after consulting medical experts once more.
What do leading German virologists say?
In view of the lack of hard facts and data, leading German virologists have so far been very cautious about possible negative effects of ibuprofen. The same applies to the acetylsalicylic acid preparations (ASS; aspirin) and diclofenac, which belong to this group of active ingredients.
"We know little about the pathogenesis of the SARS-CoV-2 virus, and there are no clinical data available to date," said virologist Jonas Schmidt-Chanasit of the Bernhard Nocht Institute for Tropical Medicine (BNITM).
Virologist Christian Drosten of the Berlin Charité also said he has doubts. Although the virus is new, other coronaviruses have been studied for some time, and with these "there is no indication that ibuprofen intake would worsen anything. I think that we would know that by now if this were the case," said Drosten.
However, all the experts strongly advise against patients panicking and no longer taking prescribed ACE inhibitors or Sartan therapy and switching to medicines with other active ingredients.
Where does the suspicion come from?
The basis for the current suspicion that ACE inhibitors and also ibuprofen could have a similar negative effect is an article published in Lancet Respiratory Medicine on March 11, 2020.
In it, the three authors L. Fang, G. Karakiulakis and M. Roth explain that ACE inhibitors and Sartan, but also thiazolidinediones and ibuprofen, could exacerbate the COVID-19 process. However, the authors have explicitly formulated this as a hypothesis.
Tests with rats have already shown that ACE inhibitors and angiotensin-1 receptor blockers actually upregulate ACE2 in heart cells, and tests with diabetic rats have shown an influence of ibuprofen on the regulatory system.
However, without strong data and evidence to back it up, it is still impossible to make a reliable assessment based on current findings.
How does the coronavirus penetrate cells
Understanding the way all these things are interconnected is complicated, as it has to do with the body’s highly complex biochemical processes.
The surfaces of cells have ACE receptors that bind ACE enzymes. SARS viruses, including the new SARS-CoV-2, use the transmembrane enzyme ACE2 (angiotensin-converting enzyme 2) to enter their host cells and begin replication. Scientists have known about this process since the SARS epidemic in 2002/2003.
Therapeutically used ACE inhibitors do not bind directly to ACE2, but intercept and block the angiotensin-converting enzyme (ACE). It is assumed that the ACE receptors remain free, which allows the viruses to dock with them and penetrate the cell. There is a chance cells could even increase the number of ACE2 receptors when the ACE enzyme is intercepted and give the dangerous viruses even more points of attack.
In the case of a viral attack, ACE2 downregulation would lead to the loss of the natural protective function and the drugs would additionally promote the severe progression of the new lung disease COVID-19. According to the hypothesis formulated in Lancet, ibuprofen is believed to have a similar effect.
According to the supporters of the still unconfirmed hypothesis, the high coronavirus mortality rate seen in Italy could possibly be explained by this process since Italy has a high rate of ACE inhibitor use. Reliable data for this hypothesis, however, is also not yet available.