The SARS-CoV-2 virus inhibits the immune response by inducing the cytokine TGFβ in COVID-19 patients with severe disease

Researchers at the DRFZ and the Charité – University Medicine Berlin have investigated the reasons why some patients suffer from a severe COVID-19 disease course. The result is surprising: the Corona virus induces the expression of the cytokine TGFβ in these patients, which inhibits their immune system. Usually, TGFβ is only produced at the end of an immune reaction in order to terminate it. However, in COVID-19 patients with severe disease, TGFβ is produced from the beginning of the immune response. This inactivates the Natural Killer (NK) cells that would normally recognize and kill virus-infected cells, thereby inhibiting the replication of the virus. This research has now been published in the journal NATURE (Witkowski et al.).  The same researchers have previously shown that the cells producing antibodies are also affected by the cytokine TGFβ, resulting in a chronic immune reaction, that is no longer directed against the virus (Ferreira-Gomez, Nature Communications 2021). TGFβ is also likely to be involved in the formation of thromboses and fibroses. These results open up a new opportunity to detect severe cases of COVID-19 from the outset, through monitoring of early TGFβ production, and then possibly also to mitigate such severe disease, through therapeutic inhibition of this cytokine.

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