COVID-19: Innate immune system is profoundly reprogrammed

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Long-lasting and profound reprogramming of immune cells.

The immune system’s response to infection with SARS-CoV-2 has significant implications for the course of COVID-19, and an exaggerated immune response has been blamed for several impending complications. The far-reaching changes that the virus triggers in the innate immune system are made clear by a new study.

The research team led by first author Dr. Sebastian Theobald of the University Hospital of Cologne examined the effect of the spike protein, a typical feature of the coronavirus, on the innate immune system. This showed that SARS-CoV-2 infection causes a “profound and long-lasting reprogramming of macrophages,” the researchers write. The study results were published in the journal EMBO Molecular Medicine.

Critical release of cytokines

Why some infected individuals react with an exaggerated immune response to SARS-CoV-2 remains not well understood, according to the researchers. What is clear is that SARS-CoV-2 infection can lead to massive release of pro-inflammatory signaling substances called cytokines, which cause severe organ damage in some infected individuals and attract additional activated immune cells to the tissues in a chain reaction. How the virus triggers the release of cytokines, however, is not clearly understood.

Response to the spike protein investigated

For the first time, the researchers have now been able to demonstrate the effect of the spike protein on the innate immune system and they found that human defense cells (macrophages, also known as phagocytes) are massively stimulated by the viral spike protein to produce the pro-inflammatory signal substance interleukin 1.

However, this was only the case when macrophages from COVID-19 infected individuals were examined in the experiments. Macrophages from people who had not yet had contact with SARS-CoV-2 did not respond by releasing interleukin 1, the researchers report.

Very unusual immune response

“This selective immune response of a classical signaling pathway of the innate immune system is very unusual and has not yet been described in this way,” emphasizes Dr. Jan Rybniker, head of the research laboratory of infectious diseases at the University Hospital of Cologne. The expert also sees “many starting points here to understand why some people react with an exaggerated immune system response.”

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