Most patients inflamed by the new SARS-CoV-2 coronavirus have mild or no symptoms. However, between 10 and 20% of patients develop COVID-19 disease pneumonia, some of them with life-threatening consequences. “The reasons for these serious adjustments to the disease are still little understood. The maximum degrees of inflammation measured in affected Americans actually involve a strong immune response. Clinical results, however, involve a rather useless immune response. It’s a contradiction.” Joachim Schultze, professor at the University of Bonn and director of a study organization in DZNE. “So we assume that immune cells are produced in giant amounts, but that they serve as defective. Therefore, we analyze the blood of patients with other degrees of severity of COVID-19”, explains Leif Erik Sander, professor of infection immunology and medical director. Charity Medical Service, Division of Infectious Diseases and Respiratory Medicine.
High-precision methods
The study was carried out as part of a national consortium, the German coVID-19 OMICS (DeCOI) initiative, meaning that research and interpretation of knowledge is distributed among other groups and sites. Joachim Schultze very concerned about the coordination of the project. Blood samples were obtained here from a total of 53 men and women with COVID-19 in Berlin and Bonn, whose progression of the disease was classified as mild or severe according to world health organization classification. Blood samples from patients with other viral respiratory tract infections, as well as healthy Americans, served as vital controls.
The studies concerned single-mobile OMIC technologies, a collective term for fashion lab strategies used to determine, for example, gene activity and the amount of proteins in the individual mobile point, therefore at a very high resolution. With this data, scientists characterized the homes of immune mobiles circulating in the blood, so-called white-blooded mobiles. “The application of bioinformatics strategies to this very comprehensive data set on the genetic activities of individual mobile devices allowed us to obtain a review of the mobile activity of white blood cells,” explains Yang Li, professor at the Center for Individualized Infection Medicine (CiiM). and the Helmholtz Centre for Infection Research (HZI) in Hanover. ” The mix of sequencing with the detection of vital proteins on the surface of immune mobiles allowed us to decipher adjustments in the immunological formula of patients with COVID-19′, adds Birgit Sawitzki, professor at the Institute of Medical Immunology at Virchow- Campus in Klinikum.
“Immature” cells
The human immune formula comes with a giant arsenal of cells and other defense mechanisms that interact with each other. In the existing study, they focus on so-called myeloid cells, which come with neutrophils and monocytes. These are immune cells found at the front of the immune reaction chain, i.e. they mobilize very early to protect against infections. They also influence the next formation of antibodies and other cells that contribute to immunity. This gives myeloid cells a key position.
“With so-called neutrophils and monocytes, we found that these immune cells are activated, that is, in a position to protect the patient against COVID-19 in case of progression of benign disease. They are also programmed to activate the rest of the immune system. “This ultimately leads to an effective immune reaction opposed to the virus,” explains Antoine-Emmanuel Saliba, director of a research organization at the Helmholtz Institute for Research on RNA-Based Infections (HIRI) in Wurzburg. .
But the scenario is another in severe cases of COVID-19, Sawitzki explains: “Here, neutrophils and monocytes are only partially activated and do not paint correctly. There are many more immature cells that have a fairly inhibitory effect on the immune reaction. Sander adds: “The phenomenon can also be seen in other serious infections, although the explanation is uncertain. There are many indications that the immune formula receives serious episodes of COVID-19 in its own way. This can eventually lead to a lack of immune reaction opposite the corona virus, with simultaneous severe inflammation of lung tissue. “
Therapy approaches?
Current findings may point to new remedies, says Anna Aschenbrenner of the LIMES Institute at the University of Bonn: “Our knowledge recommends that in severe cases of COVID-19, methods deserve to be considered as beyond the remedy of other viral diseases.” The Bonn scholar says that in the case of viral infections, we don’t really need to suppress the immune formula. “However, if there are too many dysfunctional immune cells, as our test shows, then we would very much like to remove or reprogram those cells.” Jacob Nattermann, professor at medical clinic I at the University Hospital of Bonn and director of a study organization at DZIF, explains extra: “Drugs that act on the immune formula can help. But it’s a sensitive balance. After all, it’s not about completely preventing the immune formula, but only about slowing down cells, so to speak. In this case, these are immature cells. Maybe we can be informed of cancer studies. Target those cells.”
National effort