Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition. Experts present these findings in the scientific journal Cell.
Most patients infected with the coronavirus SARS-CoV-2 show mild or even no symptoms. However, 10 to 20 percent of those affected develop pneumonia during the course of COVID-19 disease, some of them with life-threatening effects. "There is still not very much known about the causes of these severe courses of the disease. The high inflammation levels measured in those affected actually indicate a strong immune response. Clinical findings, however, rather tend to indicate an ineffective immune response. This is a contradiction," says the research group leader. "We therefore assume that although immune cells are produced in large quantities, their function is defective. That is why we examined the blood of patients with varying degrees of COVID-19 severity," explains another author.
The study was carried out within the framework of a nationwide consortium - the "German COVID-19 OMICS Initiative" (DeCOI) - resulting in the analysis and interpretation of the data being spread across various teams and sites. The blood samples came from a total of 53 men and women with COVID-19 from Berlin and Bonn, whose course of disease was classified as mild or severe according to the World Health Organization classification. Blood samples from patients with other viral respiratory tract infections as well as from healthy individuals served as important controls.
The investigations involved the use of single-cell OMICs technologies, a collective term for modern laboratory methods that can be used to determine, for example, the gene activity and the amount of proteins on the level of single, individual cells - thus with very high resolution. Using this data, the scientists characterized the properties of immune cells circulating in the blood - so-called white blood cells. "By applying bioinformatics methods on this extremely comprehensive data collection of the gene activity of each individual cell, we could gain a comprehensive insight of the ongoing processes in the white blood cells," explains another author. "In combination with the observation of important proteins on the surface of immune cells, we were able to decipher the changes in the immune system of patients with COVID-19," adds another author.
The human immune system comprises a broad arsenal of cells and other defense mechanisms that interact with each other. In the current study, the focus was on so-called myeloid cells, which include neutrophils and monocytes. These are immune cells that are at the very front of the immune response chain, i.e. they are mobilized at a very early stage to defend against infections. They also influence the later formation of antibodies and other cells that contribute to immunity. This gives the myeloid cells a key position.
"With the so-called neutrophils and the monocytes we have found that these immune cells are activated, i.e. ready to defend the patient against COVID-19 in the case of mild disease courses. They are also programmed to activate the rest of the immune system. This ultimately leads to an effective immune response against the virus," explains the author.
But the situation is different in severe cases of COVID-19, explains the author: "Here, neutrophils and monocytes are only partially activated and they do not function properly. We find considerably more immature cells that have a rather inhibitory effect on the immune response." The author adds: "The phenomenon can also be observed in other severe infections, although the reason for this is unclear. Many indications suggest that the immune system stands in its own way during severe courses of COVID-19. This could possibly lead to an insufficient immune response against the corona virus, with a simultaneous severe inflammation in the lung tissue."
The current findings could point to new therapeutic options, says the author: "Our data suggest that in severe cases of COVID-19, strategies should be considered that go beyond the treatment of other viral diseases." The Bonn researcher says that in the case of viral infections one does not actually want to suppress the immune system. "If, however, there are too many dysfunctional immune cells, as our study shows, then one would very much like to suppress or reprogram such cells." Another author further explains: "Drugs that act on the immune system might be able to help. But this is a delicate balancing act. After all, it's not a matter of shutting down the immune system completely, but only those cells that slow down themselves, so to speak. In this case these are the immature cells. Possibly we can learn from cancer research. There is experience with therapies that target these cells."
Immature and Dysfunctional Immune Cells in COVID-19
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