Most infections with the SARS-CoV-2 coronavirus are mild or even asymptomatic. However, 10 to 20 per cent of those affected develop pneumonia during the course of Covid-19, sometimes with life-threatening consequences. "Little is still known about the causes of these severe courses. The high inflammation levels measured in those affected actually indicate a strong immune response. However, clinical findings tend to favour an ineffective immune response. There is a contradiction here," says Prof Dr Joachim Schultze from the University of Bonn, who is also a research group leader at the German Centre for Neurodegenerative Diseases (DZNE). "We therefore suspected that although immune cells are produced in large quantities, their function is impaired. We therefore examined the blood of patients with varying degrees of COVID-19 disease severity," reports Prof Dr Leif Erik Sander from Charité's Department of Infectious Diseases and Pulmonology.
Large-scale study with many partners
The study was conducted as part of a nationwide consortium - the "German COVID-19 OMICS Initiative" (DeCOI) - so that the analysis and interpretation of the data was spread across various teams and locations. Experts from Charité - Universitätsmedizin Berlin, the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the Helmholtz Centre for Infection Research (HZI) and the German Center for Infection Research (DZIF) were involved. Prof Schultze was significantly involved in the implementation of the project as coordinator.
High demands on biobanking
The blood samples came from a total of 53 women and men with Covid-19 from Berlin and Bonn, whose disease progression was categorised as mild or severe according to the World Health Organisation's classification. Blood samples from people with other viral respiratory tract infections and from healthy people served as an important benchmark. The Central Biobank Charité/BIH (ZeBanC) was responsible for biobanking the samples from the Berlin cohort. In the partner biobank of the German Biobank Alliance (GBA), biosamples are collected, processed and stored in a standardised manner in accordance with the highest scientific standards and under ISO-certified conditions. Among other things, single-cell OMICs technologies were used for the analyses in the study: a collective term for modern measurement methods that can be used, for example, to determine gene activity and the occurrence of proteins for individual cells - and therefore very precisely. "An important aspect of biobanking for this research project was the preparation of blood samples for so-called CyTOF analyses. To do this, we had to fix and process living blood cells with the utmost precision and adhere exactly to certain reaction times before freezing the cells at -80 degrees Celsius," says Dr Denise Treue, coordinator at ZeBanC.
Immune system "getting in its own way"
The human immune system comprises a broad arsenal of cells and other defence mechanisms that influence 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 mobilised very early on to defend against infections. They also influence the later formation of antibodies and other cells that contribute to immunity. In severe cases of Covid-19, the authors of the CELL publication found that although neutrophils and monocytes are partially activated, their function is also impaired. There were significantly more immature cells, which tended to have an inhibitory effect on the immune response. "There is much to suggest that the immune system gets in its own way to a certain extent in severe Covid-19 cases," says Prof Sander. "This may result in an inadequate immune response against the coronavirus, accompanied by severe inflammation in the lung tissue." Drugs that act on the immune system could help. However, this is a balancing act, as the aim is not to completely shut down the immune system, but only the immature cells.
Strength of the study: cooperation and exchange
In view of the many people involved, Prof. Schultze emphasises the cooperation within the research consortium: "The parallel evaluation of two independent patient cohorts is one of the strengths of our study. We analysed patient groups from two different locations using different methods and were thus able to validate our findings directly. This is only possible if research data is shared openly and there is trustful cooperation. This is particularly important in the current crisis situation."
Source: The original version of this text appeared as a press release on the website of Charité - Universitätsmedizin Berlin.
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