The body apparently releases the immune-suppressing messenger Transforming Growth Factor β (TGFβ) too early in some Covid 19 patients. This can have fatal consequences, as a new study shows. However, possible therapeutic approaches can also be derived from this finding.
TGFβ has various functions in the body. Among other things, the messenger substance is responsible for shutting down an immune response after a pathogen has been attacked. In the case of an infection with SARS-CoV-2, however, the body releases this signal molecule too early in some cases, namely at the very beginning of the infection. This then slows down the fight against the virus by the innate immune system and can lead to a severe covid-19 course, according to a paper published in Nature by a team led by Dr. Mario Witkowski of Charité in Berlin. “We did not observe this in other pneumonias and it surprised us a lot,” Witkowski said in a Charité press release.
The incorrect timing of the attenuating TGFβ release affects innate defenses. This is nonspecific in nature, but immediately ready for action. If a virus such as SARS-CoV-2 attacks the body, natural killer cells (NK cells) in particular become active in the course of the innate defense. They are specialized in recognizing virus-infected cells of the body by their altered surface and eliminating them with the help of cytotoxins. However, too early TGFβ release hinders the fight against SARS-CoV-2-.
For their work, the scientists isolated NK cells from the blood of patients with varying degrees of covid-19 and examined their functionality in the laboratory. For comparison, they used cells from healthy individuals or patients with severe colds. This confirmed what had been suspected: NK cells can recognize and kill SARS-CoV-2-infected lung cells. However, according to Witkowski, cells from severely affected Covid-19 patients were much less effective against the virus in the laboratory than cells from people with only mild symptoms.
The researchers found the reason for this in the release of TGFβ too early. For this purpose, they analyzed which genes were active in more than 80,000 NK cells from 68 samples of different stages and severities of Covid 19 disease. They found that NK cells in patients with severe covid-19 were also activated early, but then immediately blocked again by TGFβ. High levels of TGFβ were already detectable in the first days of infection, whereas people with mild symptoms did not produce the messenger until more than three weeks later. In patients with other severe lung infections, the NK cells showed no signs of exposure to TGFβ.