Witowski Andrea, Palmowski Lars, Rahmel Tim, Nowak Hartmuth, Ehrentraut Stefan F, Putensen Christian, von Groote Thilo, Zarbock Alexander, Babel Nina, Anft Moritz, Sitek Barbara, Bracht Thilo, Bayer Malte, Weber Maike, Weisheit Christina, Pfänder Stephanie, Eisenacher Martin, Adamzik Michael, Katharina Rump, Koos Björn, Ziehe Dominik
Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, 44892, Bochum, Germany.
Zentrum für Künstliche Intelligenz, Medizininformatik und Datenwissenschaften, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany.
Infection. 2025 Feb;53(1):107-115. doi: 10.1007/s15010-024-02325-7. Epub 2024 Jun 19.
There is evidence that lower activity of the RAF/MEK/ERK network is associated with positive outcomes in mild and moderate courses of COVID-19. The effect of this cascade in COVID-19 sepsis is still undetermined. Therefore, we tested the hypothesis that activity of the RAF/MEK/ERK network in COVID-19-induced sepsis is associated with an impact on 30-day survival.
We used biomaterial from 81 prospectively recruited patients from the multicentric CovidDataNet.NRW-study cohort (German clinical trial registry: DRKS00026184) with their collected medical history, vital signs, laboratory parameters, microbiological findings and patient outcome. ERK activity was measured by evaluating ERK phosphorylation using a Proximity Ligation Assay.
An increased ERK activity at 4 days after diagnosis of COVID-19-induced sepsis was associated with a more than threefold increased chance of survival in an adjusted Cox regression model. ERK activity was independent of other confounders such as Charlson Comorbidity Index or SOFA score (HR 0.28, 95% CI 0.10-0.84, p = 0.02).
High activity of the RAF/MEK/ERK network during the course of COVID-19 sepsis is a protective factor and may indicate recovery of the immune system. Further studies are needed to confirm these results.
有证据表明，RAF/MEK/ERK网络活性降低与COVID-19轻症和中症病程的良好预后相关。该信号级联反应在COVID-19脓毒症中的作用仍未明确。因此，我们检验了以下假设：COVID-19所致脓毒症中RAF/MEK/ERK网络的活性与对30天生存率的影响相关。
我们使用了来自多中心CovidDataNet.NRW研究队列（德国临床试验注册编号：DRKS00026184）的81例前瞻性招募患者的生物材料，以及收集到的他们的病史、生命体征、实验室参数、微生物学检查结果和患者预后情况。通过使用邻近连接分析法评估ERK磷酸化来测量ERK活性。
在调整后的Cox回归模型中，COVID-19所致脓毒症诊断后4天时ERK活性增加与生存率提高三倍以上相关。ERK活性独立于其他混杂因素，如Charlson合并症指数或序贯器官衰竭评估（SOFA）评分（风险比0.28，95%置信区间0.10 - 0.84，p = 0.02）。
COVID-19脓毒症病程中RAF/MEK/ERK网络的高活性是一个保护因素，可能表明免疫系统正在恢复。需要进一步研究来证实这些结果。
