School of Medicine, Klinikum Rechts Der Isar, Department of Nephrology, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
Medizinische Klinik Und Poliklinik IV, LMU University Hospital Munich, Ziemssenstraße 5, 80336, Munich, Germany.
Angiogenesis. 2023 Nov;26(4):547-563. doi: 10.1007/s10456-023-09885-6. Epub 2023 Jul 28.
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.
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).
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.
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.
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 ). 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.
新冠后综合征（PCS）是一种持续存在症状的疾病，如疲劳和认知障碍，对患者的日常生活有很大影响。了解 PCS 的病理生理学是公共卫生的重点，因为它仍然对医生的诊断和治疗构成挑战。
在这项前瞻性观察队列研究中，我们使用视网膜血管分析（RVA）分析了 PCS 患者的视网膜微循环，并将其与年龄和性别匹配的健康对照组（n=41，从 n=204 中匹配）进行了比较。
PCS 患者表现出持续的内皮功能障碍（ED），这表明静脉闪烁诱导扩张（vFID）明显降低（3.42%±1.77%比 4.64%±2.59%；p=0.02），中央视网膜动脉当量（CRAE）更窄（178.1[167.5-190.2]比 189.1[179.4-197.2]，p=0.01），动静脉比（AVR）更低（0.84[0.8-0.9]比 0.88[0.8-0.9]，p=0.007）。当结合 AVR 和 vFID 时，预测评分达到了良好的分组区分能力（曲线下面积：0.75）。较高的 PCS 严重程度评分与较低的 AVR 相关（R=-0.37，p=0.017）。在表现出更高炎症参数水平的 PCS 患者中，微血管变化与 PCS 严重程度的关联得到了放大。
我们的结果表明，持续的内皮功能障碍是 PCS 的标志，而微循环的损伤似乎可以解释患者持续存在的症状。随着针对 PCS 的潜在疗法的出现，RVA 参数可能成为诊断和治疗管理的临床生物标志物。
该研究先前在 ClinicalTrials 注册（“All Eyes on PCS-Analysis of the Retinal Microvasculature in Patients with Post-COVID-19 Syndrome”。NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552）。急性 SARS-CoV-2 感染间接或直接引起患者的血管内皮炎。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 的图像是 RVA 数据分析的说明性示例。对于每个 PCS 患者和健康对照组，计算了三个测量周期的静脉血管直径，并绘制在直径-时间曲线上。与 SARS-CoV-2 感染未感染者相比，患者的静脉闪烁诱导扩张（vFID）（通过动态血管分析（DVA）测量）和中央视网膜小动脉当量（CRAE）和动静脉比（AVR）降低，且中央视网膜小静脉当量（CRVE）有升高趋势。使用 BioRender.com 创建。
