Behar-Lagares Raquel, Virseda-Berdices Ana, Martínez-González Óscar, Blancas Rafael, Brochado-Kith Óscar, Manteiga Eva, Muñoz-García Paula, Mallol Poyato María Jose, Molina Del Pozo Jorge, Homez-Guzmán Marcela, Alonso Fernández María A, Resino Salvador, Jiménez-Sousa María Á, Fernández-Rodríguez Amanda
Unit of Viral Infection and Immunity, National Center for Microbiology (CNM), Health Institute Carlos III (ISCIII), Ctra. de Pozuelo, 28, 28222 Majadahonda, Madrid, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Health Institute Carlos III (ISCIII), 28029 Madrid, Spain.
Int J Mol Sci. 2025 Jul 17;26(14):6854. doi: 10.3390/ijms26146854.
Post-acute sequelae of COVID-19 have been associated with an elevated risk of thromboembolism and adverse cardiovascular events (CVEs). We aim to evaluate whether alterations in poorly studied hemostatic and endothelial proteins are associated with CVEs in patients previously admitted to the ICU and evaluated one year post-discharge. We carried out a cross-sectional study involving 63 COVID-19 patients previously admitted to the ICU one year post-discharge. Plasma levels of factor IX (coagulation factor), protein C, protein S (natural anticoagulant), and von Willebrand factor (VWF, an endothelial marker) were measured using a Luminex 200™ analyzer. Generalized linear models (GLMs) were used to assess the association of these coagulation proteins with CVEs and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We found that lower levels of factor IX ( = 0.011), protein C ( = 0.028), and protein S ( = 0.008) were associated with CVEs one year after ICU discharge. Additionally, at the one-year follow-up, we found lower levels of factor IX ( = 0.002) and higher levels of VWF ( = 0.006) associated with higher levels of NT-proBNP, underscoring the involvement of both hemostatic imbalance and persistent endothelial dysfunction. Our findings revealed a gender-specific pattern of associations with NT-proBNP levels. These findings highlight the significant role of persistent hemostatic imbalance and endothelial dysfunction in the development of cardiovascular abnormalities among COVID-19 survivors discharged from the ICU.
新冠病毒病的急性后遗症与血栓栓塞和不良心血管事件（CVE）风险升高有关。我们旨在评估此前入住重症监护病房（ICU）并在出院一年后接受评估的患者中，研究较少的止血和内皮蛋白改变是否与CVE相关。我们进行了一项横断面研究，纳入了63名出院一年前曾入住ICU的新冠病毒病患者。使用Luminex 200™分析仪测量了凝血因子IX、蛋白C、蛋白S（天然抗凝剂）和血管性血友病因子（VWF，一种内皮标志物）的血浆水平。采用广义线性模型（GLM）评估这些凝血蛋白与CVE和N端前脑钠肽（NT-proBNP）的关联。我们发现，ICU出院一年后，凝血因子IX水平降低（P = 0.011）、蛋白C水平降低（P = 0.028）和蛋白S水平降低（P = 0.008）与CVE相关。此外，在一年随访时，我们发现凝血因子IX水平降低（P = 0.002）和VWF水平升高（P = 0.006）与NT-proBNP水平升高相关，这突出了止血失衡和持续性内皮功能障碍的共同作用。我们的研究结果揭示了与NT-proBNP水平相关的性别特异性模式。这些发现凸显了持续性止血失衡和内皮功能障碍在从ICU出院的新冠病毒病幸存者心血管异常发生中的重要作用。
