Blood serum biomarkers in the dynamics of treatment for cerebrovascular pathology in post-COVID-19 patients
![](https://article.accscience.com/imageFile/by.png)
Neurological manifestations after COVID-19 infections can be attributed to chronic immune and inflammatory reactions induced by SARS-CoV-2, as well as endothelial dysfunction and other vascular issues. This study included 24 patients with cerebrovascular disease (CVD) who had contracted COVID-19 1 – 1.5 years before the examination (experimental group) and 20 patients with CVD who had not previously been infected with the coronavirus (comparison group). Both groups were representative in terms of age and gender. Blood serum biomarkers, including interleukin (IL)-6, endothelin-1 (ET-1), and vascular endothelial growth factor A (VEGF-A), were tested before and after a 14-day standard complex therapy in the hospital at our institute using appropriate enzyme-linked immunosorbent assay reagent kits. Increases in the levels of IL-6 (by 20%), ET-1 (by 200%), and VEGF-A (by 100%) were observed in patients with CVD who had contracted COVID-19 1 – 1.5 years earlier compared to the comparison group. The effectiveness of a 2-week therapeutic intervention in patients with a history of COVID-19 was found only for VEGF-A: its serum level decreased twofold, leading to the normalization of this indicator. The concentrations of IL-6 and ET-1 were not affected by the treatment. In addition, the serum levels of ET-1 and VEGF-A in unvaccinated individuals exceeded those in vaccinated patients.
- Siegler JE, Dasgupta S, Abdalkader M, et al. Cerebrovascular disease in COVID-19. Viruses. 2023;15(7):1598. doi: 10.3390/v15071598
- Kempuraj D, Aenlle KK, Cohen J, et al. COVID-19 and long COVID: Disruption of the neurovascular unit, blood-brain barrier, and tight junctions. Neuroscientist. 2023:10738584231194927. doi: 10.1177/10738584231194927
- Crunfli F, Carregari VC, Veras FP, et al. Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. Proc Natl Acad Sci U S A. 2022;119(35):e2200960119. doi: 10.1073/pnas.2200960119
- Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683-690. doi: 10.1001/jamaneurol.2020.1127
- Lindsberg PJ, Grau AJ. Inflammation and infections as risk factors for ischemic stroke. Stroke. 2003;34:2518-2532. doi: 10.1161/01.STR.0000089015.51603.CC
- Merkler AE, Parikh NS, Mir S, et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol. 2020;77(11):1-7. doi: 10.1001/jamaneurol.2020.2730
- Zhang S, Liu Y, Wang X, et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J Hematol Oncol. 2020;13:120. doi: 10.1186/s13045-020-00954-7
- Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417-1418. doi: 10.1016/S0140-6736(20)30937-5
- Page EM, Ariëns RAS. Mechanisms of thrombosis and cardiovascular complications in COVID-19. Thromb Res. 2021;200:1-8. doi: 10.1016/j.thromres.2021.01.005
- Resolution of the telebridge Medical rehabilitation of patients with Long COVID, Kyiv, Ukraine; 2021.
- Giannitrapani L, Mirarchi L, Amodeo S, et al. Can baseline IL-6 levels predict Long COVID in subjects hospitalized for SARS-CoV-2 disease? Int J Mol Sci. 2023;24(2):1731. doi: 10.3390/ijms24021731
- Ruenjaiman V, Sodsai P, Kueanjinda P, et al. Impact of SARS-CoV-2 infection on the profiles and responses of innate immune cells after recovery. J Microbiol Immunol Infect. 2022;55:993-1004. doi: 10.1016/j.jmii.2022.09.001
- Willems LH, Nagy M, Ten Cate H, et al. Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19. Thromb Res. 2022;209:106-114. doi: 10.1016/j.thromres.2021.11.027
- Turgunova L, Mekhantseva I, Laryushina Y, et al. The association of Endothelin-1 with early and long-term mortality in COVID-19. Pers Med. 2023;13(11):1558. doi: 10.3390/jpm13111558
- Morichi S, Morishita N, Takeshita M, et al. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) levels in the cerebrospinal fluid of children with influenza-associated encephalopathy. J Infect Chemother. 2017;23(2):80-84. doi: 10.1016/j.jiac.2016.10.007
- Alkharsah KR. VEGF upregulation in viral infections and its possible therapeutic implications. Int J Mol Sci. 2018;19(6):1642. doi: 10.3390/ijms19061642
- Jin JM, Bai P, He W, et al. Gender differences in patients with COVID-19: Focus on severity and mortality. Front Public Health. 2020;8:152. doi: 10.3389/fpubh.2020.00152
- Li X, Liu L, Yang Y, et al. Gender-associated difference following COVID-19 virus infection: Implications for thymosin alpha-1 therapy. Int Immunopharmacol. 2021;90:107022. doi: 10.1016/j.intimp.2020.107022
- Stein DF, Foley C, Byott M, et al. Biological sex is associated with heterogeneous responses to IL-6 receptor inhibitor treatment in COVID-19-A retrospective cohort study. Sci Rep. 2023;13(1):13504. doi: 10.1038/s41598-023-40744-y
- Froldi G, Dorigo P. Endothelial dysfunction in Coronavirus disease 2019 (COVID-19): Gender and age influences. Med Hypotheses. 2020;144:110015. doi: 10.1016/j.mehy.2020.110015
- Kitselman KA, Bédard-Matteau J, Rousseau S, et al. Sex differences in vascular endothelial function related to acute and long COVID-19. Vasc Pharmacol. 2024;154:107250. doi: 10.1016/j.vph.2023.107250
- Birnhuber A, Fliesser E, Gorkiewicz G, et al. Between inflammation and thrombosis: Endothelial cells in COVID-19. Eur Respir J. 2021;58:2100377. doi: 10.1183/13993003.00377-2021
- Ong SW, Fong SW, Young BE, et al. Persistent symptoms and association with inflammatory cytokine signatures in recovered coronavirus disease 2019 patients. Open Forum Infect Dis. 2021;8:ofab156. doi: 10.1093/ofid/ofab156
- Abraham GR, Kuc RE, Althage M, et al. Endothelin-1 is increased in the plasma of patients hospitalized with Covid-19. J Mol Cell Cardiol. 2022;167:92-96. doi: 10.1016/j.yjmcc.2022.03.007
- Haffke M, Freitag H, Rudolf G, et al. Endothelial dysfunction and altered endothelial biomarkers in patients with post- COVID-19 syndrome and chronic fatigue syndrome (ME/CFS). J Transl Med. 2022;20:138. doi: 10.1186/s12967-022-03346-2
- Vassiliou AG, Vrettou CS, Keskinidou C, et al. Endotheliopathy in acute COVID-19 and long COVID. Int J Mol Sci. 2023;24(9):8237. doi: 10.3390/ijms24098237
- Notarte KI, Catahay JA, Velasco JV, et al. Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review. EClinicalMedicine. 2022;53:101624. doi: 10.1016/j.eclinm.2022.101624
- Zhu X, Gebo KA, Abraham AG, et al. Dynamics of inflammatory responses after SARS- CoV-2 infection by vaccination status in the USA: A prospective cohort study. Lancet. 2023;4(9):e692-e703. doi: 10.1016/S2666-5247(23)00171-4
- Talotta R. Impaired VEGF-A-mediated neurovascular crosstalk induced by SARS-CoV-2 spike protein: A potential hypothesis explaining long COVID-19 symptoms and COVID-19 vaccine side effects? Microorganisms. 2022;10(12):2452. doi: 10.3390/microorganisms10122452