Systemic defects in the immune response of circulating immune cells to acute infections associated with Long-Covid disease

Status:

completed 03/2025

Aims:

The aim was to investigate possible systemic immunosuppression in connection with Long Covid disease. Since systemic inflammation and dysregulation of immune cell activity play a central role in Covid-19 disease, it can be assumed that this may also be the case with Long Covid symptoms. The first step was therefore to investigate whether the activation of circulating immune cells in patients with Long Covid symptoms is altered in response to various pathogens, thereby disrupting the body's defense against infections caused by bacteria, viruses and fungi. Follow-up projects will also measure inflammation markers in blood sera and correlate the cell culture data with demographic, clinical and blood count/laboratory parameters.

Activities/Methods:

The objective was investigated in a human cell culture model. Peripheral blood mononuclear cells (PBMCs) and blood sera were isolated from the whole blood of patients with Long Covid symptoms and healthy reference subjects. In the laboratory, the cells were then stimulated with relevant microorganisms and toxins for various periods of time in order to simulate the immune system's response to infections. Following stimulation, the distribution and immune response of the various immune cells of patients with Long-Covid symptoms were examined in comparison to reference subjects using immunophenotyping (FACS analysis) and cytokine release (ELISA analysis). The blood sera were initially frozen and will be analyzed for systemic cytokine markers in a follow-up project.

Results:

The cellular composition and phenotyping of the isolated immune cells provided no evidence for a possible pre-activation of the immune cells of patients with Long Covid symptoms. Similarly, there were no significant differences in the populations of immune cells in the course of activation with various pathogens for different periods of time when comparing the two groups healthy versus Long Covid. However, in contrast to FACS-phenotyping, the investigations of the immune response using ELISA revealed statistically significant differences with regard to the release of cytokines. Partially, a reduced immune response of the Long Covid group to various pathogens was observed (e.g. in the case of Il-6, CCL-2, IL-2, IFN-gamma), which supported the original working hypothesis of a possible immunosuppression in connection with Long Covid.

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