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Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation

BACKGROUND: Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment...

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Autores principales: Kuchler, Timon, Günthner, Roman, Ribeiro, Andrea, Hausinger, Renate, Streese, Lukas, Wöhnl, Anna, Kesseler, Veronika, Negele, Johanna, Assali, Tarek, Carbajo-Lozoya, Javier, Lech, Maciej, Schneider, Heike, Adorjan, Kristina, Stubbe, Hans Christian, Hanssen, Henner, Kotilar, Konstantin, Haller, Bernhard, Heemann, Uwe, Schmaderer, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542303/
https://www.ncbi.nlm.nih.gov/pubmed/37507580
http://dx.doi.org/10.1007/s10456-023-09885-6
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author Kuchler, Timon
Günthner, Roman
Ribeiro, Andrea
Hausinger, Renate
Streese, Lukas
Wöhnl, Anna
Kesseler, Veronika
Negele, Johanna
Assali, Tarek
Carbajo-Lozoya, Javier
Lech, Maciej
Schneider, Heike
Adorjan, Kristina
Stubbe, Hans Christian
Hanssen, Henner
Kotilar, Konstantin
Haller, Bernhard
Heemann, Uwe
Schmaderer, Christoph
author_facet Kuchler, Timon
Günthner, Roman
Ribeiro, Andrea
Hausinger, Renate
Streese, Lukas
Wöhnl, Anna
Kesseler, Veronika
Negele, Johanna
Assali, Tarek
Carbajo-Lozoya, Javier
Lech, Maciej
Schneider, Heike
Adorjan, Kristina
Stubbe, Hans Christian
Hanssen, Henner
Kotilar, Konstantin
Haller, Bernhard
Heemann, Uwe
Schmaderer, Christoph
author_sort Kuchler, Timon
collection PubMed
description BACKGROUND: Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. METHODS: In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). MEASUREMENTS AND MAIN RESULTS: PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. CONCLUSION: Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management. TRIAL REGISTRATION: This study was previously registered at ClinicalTrials (“All Eyes on PCS—Analysis of the Retinal Microvasculature in Patients with Post-COVID-19 Syndrome”. NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552). GRAPHICAL ABSTRACT: Persistent endothelial dysfunction in post-COVID-19 syndrome. Acute SARS-CoV-2 infection indirectly or directly causes endotheliitis in patients. N = 41 PCS patients were recruited and retinal vessel analysis was performed to assess microvascular endothelial function. Images of SVA and DVA are illustrative for RVA data analysis. For each PCS patient and healthy cohort, venular vessel diameter of the three measurement cycles was calculated and plotted on a diameter-time curve. Patients exhibited reduced flicker-induced dilation in veins (vFID) measured by dynamic vessel analysis (DVA) and lower central retinal arteriolar equivalent (CRAE) and arteriolar-venular ratio (AVR) and a tendency towards higher central retinal venular equivalent (CRVE) when compared to SARS-CoV-2 infection naïve participants. Created with BioRender.com [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10456-023-09885-6.
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spelling pubmed-105423032023-10-03 Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation Kuchler, Timon Günthner, Roman Ribeiro, Andrea Hausinger, Renate Streese, Lukas Wöhnl, Anna Kesseler, Veronika Negele, Johanna Assali, Tarek Carbajo-Lozoya, Javier Lech, Maciej Schneider, Heike Adorjan, Kristina Stubbe, Hans Christian Hanssen, Henner Kotilar, Konstantin Haller, Bernhard Heemann, Uwe Schmaderer, Christoph Angiogenesis Original Paper BACKGROUND: Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. METHODS: In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). MEASUREMENTS AND MAIN RESULTS: PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. CONCLUSION: Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management. TRIAL REGISTRATION: This study was previously registered at ClinicalTrials (“All Eyes on PCS—Analysis of the Retinal Microvasculature in Patients with Post-COVID-19 Syndrome”. NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552). GRAPHICAL ABSTRACT: Persistent endothelial dysfunction in post-COVID-19 syndrome. Acute SARS-CoV-2 infection indirectly or directly causes endotheliitis in patients. N = 41 PCS patients were recruited and retinal vessel analysis was performed to assess microvascular endothelial function. Images of SVA and DVA are illustrative for RVA data analysis. For each PCS patient and healthy cohort, venular vessel diameter of the three measurement cycles was calculated and plotted on a diameter-time curve. Patients exhibited reduced flicker-induced dilation in veins (vFID) measured by dynamic vessel analysis (DVA) and lower central retinal arteriolar equivalent (CRAE) and arteriolar-venular ratio (AVR) and a tendency towards higher central retinal venular equivalent (CRVE) when compared to SARS-CoV-2 infection naïve participants. Created with BioRender.com [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10456-023-09885-6. Springer Netherlands 2023-07-28 2023 /pmc/articles/PMC10542303/ /pubmed/37507580 http://dx.doi.org/10.1007/s10456-023-09885-6 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Paper
Kuchler, Timon
Günthner, Roman
Ribeiro, Andrea
Hausinger, Renate
Streese, Lukas
Wöhnl, Anna
Kesseler, Veronika
Negele, Johanna
Assali, Tarek
Carbajo-Lozoya, Javier
Lech, Maciej
Schneider, Heike
Adorjan, Kristina
Stubbe, Hans Christian
Hanssen, Henner
Kotilar, Konstantin
Haller, Bernhard
Heemann, Uwe
Schmaderer, Christoph
Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
title Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
title_full Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
title_fullStr Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
title_full_unstemmed Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
title_short Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
title_sort persistent endothelial dysfunction in post-covid-19 syndrome and its associations with symptom severity and chronic inflammation
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542303/
https://www.ncbi.nlm.nih.gov/pubmed/37507580
http://dx.doi.org/10.1007/s10456-023-09885-6
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