How difficult is the course of Covid-19? And who will need ventilation? Munich researchers have now identified a new marker for the severity of the coronavirus infection. According to this, a molecule on the surface of white blood cells reveals how a patient is doing – and apparently more reliably than conventional markers, as the team reports. The molecule called phosphatidylserine is released when platelets are activated and blood cells are destroyed, and then accumulates on the blood cells along with cell debris.
If a person becomes infected with the Sars-CoV-2 coronavirus, this can have very different consequences: While young people in particular often hardly develop symptoms, others get seriously ill with Covid-19. In addition to the lungs and other organs, the blood and the vascular system are also often affected: Inflammatory reactions lead to changes in the vessel walls and increased activation of blood platelets. This then leads to an increased tendency to blood clots and thrombosis. At the same time, the immune reaction is often deregulated in patients who are seriously ill with Covid-19: excessive amounts of inflammatory messenger substances such as cytokines are released, while the T cells required for the immune system are exhausted. If Covid-19 is severe, it is often not the virus itself that leads to the severe symptoms and, in extreme cases, death, but rather the reactions it triggers in the body.
Marker molecule on white blood cells
In search of an indicator of how severely the infection affects the blood and immune systems, Lisa Rausch from the Biomedical Center of the Ludwig Maximilians University in Munich (LMU) and her colleagues took a closer look at a molecule that occurs in the blood. A molecule called phosphatidylserine is usually found on the inside of cell walls. However, when a cell dies or is infected by a virus, the phosphatidylserine moves from the inside to the outside of the cell membrane. “There it can now interact with extracellular proteins, including coagulation or the complement system of the immune system,” explains the research team. The complement system is a part of the defense system in which proteins attach to pathogens or infected cells, clump with them and mark them for destruction. At the same time, inflammatory messengers are released.
For the study, the research team examined blood samples from 54 patients who were treated with various degrees of severity of Covid-19 between April 2020 and February 2021. For comparison, they added samples from 35 healthy and 12 recovered donors. So-called mononuclear cells of the peripheral blood (PMBC) were isolated from all samples. These are certain white blood cells such as lymphocytes and monocytes. These were examined with the help of a special variant of flow cytometry, in which the cells flow through a thin cannula and are analyzed and photographed for phosphatidylserine. This enabled Rausch and her colleagues to determine how much phosphatidylserine was on the surface of these immune cells in the blood.
Indicator of the severity of the disease
There was a clear connection between the severity of Covid-19 in the patients and the amount of phosphatidylserine on the immune cells of their blood. These not only carried more of the marker molecule on their surface, but were also loaded with fragments of blood platelets. “With this, phosphatidylserine could serve as a signal generator for misdirected inflammatory processes or blood clotting disorders in Covid-19,” says senior author Thomas Brocker from LMU. The decisive factor, however, is that the new molecular marker proved to be a reliable prognostic factor for the course of a patient. “As a marker, phosphatidylserine surpassed established laboratory markers for inflammatory processes in the body, for leukocytes and for coagulation factors that are currently used for the clinical evaluation of Covid-19,” said Brocker. The marker molecule proved to be particularly prognostic for the need for ventilation, but also for subsequent death from Covid-19.
According to the scientists, phosphatidylserine is therefore well suited as a marker for the severity of Covid-19 in a patient – possibly even as a prognostic indicator for the further course of the disease. Because flow cytometry equipment is already in place in many hospital laboratories, it could be a useful new analytical tool.
Source: Lisa Rausch (Ludwig Maximilians University Munich) et al., Journal of Extracellular Vesicles, doi: 10.1002 / jev2.12173