Biomarker der COVID-19 Erkrankung: Zytokinspiegel und deren prognostische Bedeutung

Im Dezember 2019 wurde erstmalig ein neuartiges Coronavirus, SARS-CoV-2 genannt und Auslöser der Erkrankung COVID-19, beschrieben. Die Mehrzahl der COVID-19 Patienten zeigt einen milden Verlauf, während einige COVID-19-Patienten jedoch intensivmedizinisch betreut werden müssen und einen tödlichen Ve...

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Bibliographic Details
Main Author: Greib, Sarah Christina
Contributors: Skevaki, Chrysanthi (PD Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2023
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In December 2019, a novel coronavirus, called SARS-CoV-2 and the trigger of the disease COVID-19, was described for the first time. The majority of COVID-19 patients have a mild course, while some patients, however, require intensive care and suffer a fatal course. In these patients, hyperactivation of the immune system and hyperinflammation can lead to a cytokine storm. This dissertation aims to give a better characterization of cytokine levels for the diagnosis and prognosis of COVID-19 patients. From April to June 2020, cytokine levels of IL-1B, IL-2R, IL-6, IL-8, IL-10, and TNF-a were determined at admission and discharge or before decease. A total of 46 patients with suspected COVID-19 infection were included. In 24 patients, the infection was confirmed by PCR, 22 patients had a negative PCR and thus formed the comparison group. There was no difference in cytokine levels in either group and thus no cytokine that could specifically support the diagnosis of COVID-19 disease. In the COVID-19 group, correlations between IL-6/IL-8, IL-6/TNF, TNF/IL-1, TNF/IL2R, IL-6/IL-2R, IL-8/TNF, and IL-8/IL-2R were detectable. Regarding risk stratification of COVID-19 patients, IL-6 and IL-8 were found to be significantly elevated in patients requiring intensive care at the time of admission, so specific cut-off values were determined. Thus, determination of IL-6 and IL-8 at admission may contribute to risk stratification and identify patients requiring intensive care treatment at an early stage. In addition, the most recently measured cytokine levels for IL-8 were also found to be elevated in patients receiving intensive care, as well as IL-6 and IL-8 in deceased patients. Thus, the progression of IL-8 and IL-6 concentration could also help in the detection of a lethal course. In terms of cytokine dynamics, a decrease between admission and discharge for IL-6, IL-10, IL-2R and TNF was evident considering all COVID-19 patients. Also in the subgroups, a decrease was detectable for IL-2R, IL-6, IL-10 and TNF in patients treated in intensive care units and for IL-6 and IL-10 in patients treated in the normal ward. Furthermore, a reduction of IL-2R, IL-6, IL-8 and IL-10 was found in recovered patients. However, this was not shown for any of the analyzed cytokines in patients who died. Therefore, monitoring these cytokines could also be used to monitor the progression of the COVID-19 disease. More comprehensive cytokine panels at different time points and stages of COVID-19 disease in larger cohorts are research approaches that should be pursued further - also concerning viral variants and influences of vaccination.