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 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), along with colleagues from a nationwide research network, present these findings in the scientific journal "Cell".
Most patients infected with the novel 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 Joachim Schultze, professor at the University of Bonn and member of the Cluster of Excellence ImmunoSensation.
"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 Leif Erik Sander, Professor of Infection Immunology and Senior Physician at Charité's Medical Department, Division of Infectious Deseases and Respiratory Medicine. The investigations involved 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.
Using this data, the scientists characterized the properties of immune cells in the blood - so-called white blood cells. The researchers found out that neutrophils and monocytes were activated during a case of mild disease courses and could thereby initiate and effective immune response. In contrast, the situation is different in severe cases of COVID-19, where neutrophils and monocytes are only partially activated and they do not function properly. There are more immature cells that have 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.
"If the case of excessive dysfunctional immune cells, as our study shows, one would however very much wish to suppress or reprogram such cells.", says Anna Aschenbrenner LIMES Institute at the University of Bonn.
Jacob Nattermann, Professor at the Medical Clinic I of the University Hospital Bonn and head of a research group at the DZIF, further explains: "Drugs that act on the immune system might be helpful. 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. We can possibly learn from cancer research. There is experience with therapies that target these cells."
Publication
Severe COVID-19 is marked by a dysregulated myeloid cell compartment, Schulte-Schrepping et al., CELL (2020), DOI: 10.1016/j.cell.2020.08.001
