A lot has happened in science since the World Health Organization (WHO) declared COVID-19 a global pandemic on March 11, 2020: There are vaccines and drug therapies, so that the acute illness has lost much of its former horror.

While most people recover fully from recovering from COVID-19, others continue to suffer. Chronic weakness, headaches, memory problems, but also things like hair loss and loss of libido are on the long list of symptoms that are lumped together under the vague term “Long COVID”.

In a review article in the journal Nature microbiology, the authors estimate that at least 65 million people worldwide suffer from Long COVID. “I still think that number is too low,” says Akiku Iwasaki, an immunologist at Yale University in the United States.

Iwasaki, together with three other scientists, will give an overview of the state of research on Long COVID in a virtual panel at the Leopoldina, the National Academy of Sciences in Germany. The experts agree: there are still many more questions than answers.

But as the data on Long COVID is accumulating, Iwasaki and other researchers have been able to identify four main causes that lead to numerous biological changes in the body and that explain the wide variety of Long COVID symptoms.

The first cause of Long COVID symptoms could be chronic inflammation – triggered by reservoirs of SARS-CoV-2, the coronavirus that triggers COVID-19, always residing somewhere in the body. These virus clusters multiply again and again and keep the immune system constantly on its toes.

“More and more studies are coming out showing that both viral antigens and viral RNA can still be circulating in the body months after acute infection,” Iwasaki said.

An acute infection could provoke immune reactions that no longer only turn against the virus that is to be fought, but also attacks and destroys the body’s own cells. This connection between infectious diseases and autoimmunity is well known, according to Iwasaki. “Therefore, it’s possible that autoimmunity could be another cause of Long COVID.”

An example of this could be Myalgic Encephalomyelitis, better known as Chronic Fatigue Syndrome (ME/CFS). What sounds like a bit more fatigue is actually a serious neurological condition that has been known for decades.

But as a result of the pandemic, the cases increased. “We set up an observational study in the summer of 2020 to find out if ME/CFS could be a consequence of COVID-19. The answer is yes,” says immunologist Carmen Scheibenbogen, who researches chronic fatigue syndrome at the Berlin Charité.

“There is evidence that autoantibodies play a role in the development of ME/CFS,” says Scheibenbogen. However, the next cause could also be involved in the development of ME/CFS.

“The third hypothesis we are investigating is the reactivation of latent viruses, such as the Epstein-Barr virus (EBV) or other herpes viruses,” says Iwasaki.

After an infection with herpes viruses, these remain in the body and do not cause any problems as long as the immune system is on alert. However, a COVID-19 infection binds the immune system sufficiently to reawaken the herpes virus.

“We were able to observe this reactivation in a proportion of patients,” says Iwasaki. Perhaps this reactivation is another reason why people get ME/CFS, adds Scheibenbogen.

The more severe the acute illness with COVID-19, the greater the likelihood of permanent damage that long COVID symptoms can cause, says Iwasaki about the fourth hypothesis that the researchers are investigating.

“These four biological processes can occur individually, one after the other or together,” says the immunologist. However, it is important to differentiate them using certain biomarkers in order to be able to treat those affected correctly.

And that is the question that worries the researchers in particular: How can long-COVID-affected people be helped?

“Long COVID is another reason to get vaccinated,” says epidemiologist Michael Gem of Bar-Ilan University in Ramat Gan, Israel. Vaccination very reliably prevents severe courses and thus reduces the likelihood of permanent damage. “Meta-analysis shows that the risk of developing long COVID [in vaccinated people] decreases by about 25 to 30 percent,” says Juwel.

But the ultimate solution to the Long COVID problem isn’t vaccination either, Gemstone admits. The scientists would like more effort and money to be put into research into Long COVID in order to be able to clarify the many unanswered questions.

What influence does the time of vaccination and the number of doses have? What medications that may already be on the market could be used to treat Long COVID patients? And why do some people develop symptoms similar to long-COVID sufferers after the vaccinations? To get closer to the answer to the last question, Iwasaki and her team are currently setting up a study.

Despite many question marks, according to the experts, one finding is certain: Long COVID symptoms have no psychological cause. Since Long COVID can put a heavy strain on the everyday life of those affected, psychosomatic phenomena could of course be a consequence, a comorbidity, so to speak. But nothing more.

“The described immunological characteristics can predict Long COVID with an accuracy of 96 percent,” says Iwasaki of the results of an as yet unpeered study she helped to create. “There is no reason to cite psychosomatic illnesses as the cause.”

The researchers even consider this to be harmful, after all it would only mislead doctors and those affected when looking for help and appropriate therapy.

Author: Julia Vergin

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The original of this article “Researchers identify four main causes of Long COVID” comes from Deutsche Welle.