As millions suffer from fatigue and other symptoms of long COVID, researchers have presented new evidence of triggers for fatigue following the SARS-CoV-2 infection.

The team from University of Vienna and the Medical University of Vienna, led by chemist Christopher Gerner, showed that an exaggerated anti-inflammatory response is likely to be responsible for long COVID syndrome.

Although auto-immunity was previously suspected as the main cause of long COVID, there is no evidence of accompanying inflammatory processes in the long COVID syndrome patients.

According to a new study published in iScience, not the excessive inflammatory reaction but anti-inflammatory substances as the triggers for the long COVID syndrome.

Contrary to previous expectations, the researchers were able to find several anti-inflammatory proteins, lipids and metabolites in long COVID patients, which on the one hand could contribute to the most important long COVID syndrome symptoms, and, on the other hand, point to the formation of alternatively polarised macrophages as the cause.

In the course of a viral infection, there is normally a very strong activation of the immune system. But in virtually all of the long COVID patients studied, corresponding markers such as cytokines, acute phase proteins and eicosanoids, which indicate inflammation, were in fact hardly detectable.

"All important potential markers for acute inflammatory processes were below the levels of healthy donors or not detectable at all in LCS patients," said Gerner.

Surprisingly, the differences were more pronounced in long COVID patients compared to asymptomatic patients recovering from COVID disease than to healthy controls.

"This finding shows that there was indeed some residual inflammatory response detectable in asymptomatic recovered patients, whereas long COVID patients had the opposite finding," Gerner added.

The researchers are confident that in the near future, they will be able to offer significantly improved diagnostic options for long COVID syndrome and, above all, monitoring methods to evaluate the effects of therapy.