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

IF 9.2 1区医学 Q1 PERIPHERAL VASCULAR DISEASE

Angiogenesis Pub Date : 2023-07-28 DOI:10.1007/s10456-023-09885-6

Timon Kuchler, Roman Günthner, Andrea Ribeiro, Renate Hausinger, Lukas Streese, Anna Wöhnl, Veronika Kesseler, Johanna Negele, Tarek Assali, Javier Carbajo-Lozoya, Maciej Lech, Heike Schneider, Kristina Adorjan, Hans Christian Stubbe, Henner Hanssen, Konstantin Kotilar, Bernhard Haller, Uwe Heemann, Christoph Schmaderer

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引用次数: 0

Abstract

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

Abstract Image

查看原文本刊更多论文

COVID-19后综合征的持续性内皮功能障碍及其与症状严重程度和慢性炎症的关系。

背景：COVID-19后综合征（PCS）是一种持续存在的疾病，其症状包括疲劳和认知障碍，对患者的日常生活产生很大影响。了解PCS的病理生理学是公共卫生的优先事项，因为它仍然对医生的诊断和治疗构成挑战。方法：在这项前瞻性观察性队列研究中，我们使用视网膜血管分析（RVA）分析了一组PCS患者的视网膜微循环，并将其与年龄和性别匹配的健康队列（n = 41，匹配n个 = 204）。测量和主要结果：PCS患者表现出持续的内皮功能障碍（ED），表现为小静脉闪烁诱导的扩张显著降低（vFID；3.42% ± 1.77%对4.64% ± 2.59%；p = 0.02），较窄的视网膜中央动脉当量（CRAE；178.1[167.5-190.2]对189.1[179.4-197.2]，p = 0.01）和较低的小动脉-小静脉比率（AVR；（0.84[0.8-0.9]对0.88[0.8-09]，p = 0.007）。当结合AVR和vFID时，预测得分达到了良好的区分群体的能力（曲线下面积：0.75）。PCS严重程度得分越高，AVR越低（R = -0.37便士 = 0.017）。在表现出较高炎症参数水平的PCS患者中，微血管变化与PCS严重程度的相关性被放大。结论：我们的研究结果表明，内皮功能障碍延长是PCS的标志，微循环障碍似乎可以解释患者持续的症状。随着PCS潜在疗法的出现，RVA参数可能成为诊断和治疗管理的临床生物标志物。试验注册：本研究之前已在临床试验中注册（“所有人的眼睛都在PCS-AnalysisofRetinal Microvasculation in Patients with Post-COVID-19 Syndrome”，NCT05635552）。https://clinicaltrials.gov/ct2/show/NCT05635552）。COVID-19后综合征的持续性内皮功能障碍。急性严重急性呼吸系统综合征冠状病毒2型感染间接或直接导致患者内皮炎。N = 招募了41名PCS患者，并进行视网膜血管分析以评估微血管内皮功能。SVA和DVA的图像用于RVA数据分析。对于每个PCS患者和健康队列，计算三个测量周期的小静脉血管直径，并绘制在直径-时间曲线上。通过动态血管分析（DVA）测量，患者表现出闪烁诱导的静脉扩张（vFID）减少，视网膜中央小动脉当量（CRAE）和小动脉-小静脉比率（AVR）降低，与严重急性呼吸系统综合征冠状病毒2型感染的幼稚参与者相比，患者有更高的视网膜中央小静脉当量（CRVE）的趋势。使用BioRender.com创建。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Angiogenesis PERIPHERAL VASCULAR DISEASE-

CiteScore

21.90

自引率

8.20%

发文量

审稿时长

6-12 weeks

期刊介绍： Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.