Most patients infected with the coronavirus SARS-CoV-2 show mild or even no symptoms. However, 10 to 20 percent of patients develop pneumonia during the course of Covid-19 disease, some of them with life-threatening consequences. “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 indicate an ineffective immune response. This is a contradiction,” says Prof. Dr. Joachim Schultze of the University of Bonn and the DZNE. “We therefore assumed that immune cells are produced in large quantities, but that their function is defective. Therefore, we analyzed the blood of patients with varying degrees of Covid-19 severity,” explains Prof. Dr. Leif Erik Sander of Charité’s Medical Department, Division of Infectious Diseases and Respiratory Medicine.
Large-scale study with many partners
The study was carried out within the framework of a nationwide consortium - the “German COVID-19 OMICS Initiative” (DeCOI) - meaning that the analysis and interpretation of the data was spread across various teams and sites. 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 centrally involved in coordinating the project.
High demands on biobanking
The blood samples were derived 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 Central Biobank Charité/BIH (ZeBanC) was responsible for the biobanking of the samples from the Berlin cohort. The partner biobank of the German Biobank Alliance (GBA) collects, processes and stores biospecimens uniformly according to the highest scientific standards under ISO-certified conditions. The investigations involved the use of single-cell OMICs technologies, a collective term for modern laboratory methods used to determine, for example, the gene activity and the amount of proteins on the level of individual cells – thus with very high resolution. “An important aspect of biobanking for this research project was the preparation of blood samples for so-called CyTOF analyses. We had to fix and process living blood cells with highest accuracy, precisely adhering to specific reaction times before freezing the cells at -80 degrees Celsius,” says Dr. Denise Treue, coordinator at ZeBanC.
Immune system “standing in its own way”
The human immune system comprises a broad arsenal of cells and other defense mechanisms that closely interact with each other. The current study focused on so-called myeloid cells, which include neutrophils and monocytes. These are immune cells that are mobilized at a very early stage to defend against infections. These cells also impact subsequent responses including formation of antibodies and other cells that contribute to immunity.
In severe cases of covid-19, the authors of the CELL publication stated, neutrophils and monocytes are partially activated, but do not function properly. They found significantly more immature cells, which had a rather inhibitory effect on the immune response. “The findings indicate that the immune system stands in its own way during severe courses of COVID-19,” says Prof. Sander. “This possibly leads to an insufficient immune response against the coronavirus, while severe inflammation in the lung tissue proceeds.” Drugs that act on the immune system could help further. However, it would a balancing act, as the goal would not be to shut down the immune system entirely, but only the immature cells.
Strength of the study: cooperation and exchange
In view of the many people involved, Prof. Schultze emphasizes the cooperation within the research consortium: “The parallel analysis of two independent patient cohorts is one of the strengths of our study. We analyzed patient cohorts from two different sites using different methods and were thus able to validate our findings directly. This is only possible if research data is shared openly, and cooperation is based on trust. This is extremely important, especially in the current crisis.”
Source: The original version of this text appeared as a press release on the website of Charité - Universitätsmedizin Berlin.
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