Activation of the MAPK network provides a survival advantage during the course of COVID-19-induced sepsis: a real-world evidence analysis of a multicenter COVID-19 Sepsis Cohort

MAPK 网络的激活在 COVID-19 诱发的脓毒症过程中提供了生存优势:多中心 COVID-19 脓毒症队列的真实世界证据分析

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作者:Andrea Witowski #, Lars Palmowski #, Tim Rahmel, Hartmuth Nowak, Stefan F Ehrentraut, Christian Putensen, Thilo von Groote, Alexander Zarbock, Nina Babel, Moritz Anft, Barbara Sitek, Thilo Bracht, Malte Bayer, Maike Weber, Christina Weisheit, Stephanie Pfänder, Martin Eisenacher, Michael Adamzik, Ru

Conclusion

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.

Methods

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.

Purpose

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.

Results

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).

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