PDF(Pubmed)
Abstract：
BACKGROUND: New onset or worsening of a headache disorder substantially contributes to the disease burden of post-COVID-19. Its management poses a suitable means to enhance patients\' participation in professional, social, and personal activities. Unfortunately, the pathophysiology of post-COVID-19 headaches is poorly understood. This study aims to investigate the role of (neuro-) inflammatory mechanisms in order to guide the development of anti-inflammatory treatment strategies.
METHODS: We included patients from the interdisciplinary post-COVID-19 Rehabilitation Study (PoCoRe, n = 184 patients) run at a tertiary care university hospital, comprising patients with PCR-confirmed SARS-CoV-2 infection ≥ 6 weeks prior to their initial consultation. Patients reporting any headache since their infection were considered for this study (n = 93). These were interviewed and classified according to the International Classification of Headache Disorders, Third Edition (ICHD-3) by headache specialists. Patient sera were additionally analysed for levels of VILIP-1, MCP-1 (CCL2), sTREM-2, BDNF, TGF-ß1, VEGF, IL-6, sTREM-1, ß-NGF, IL-18, TNF-alpha, sRAGE, and CX3CL1 (Fractalkine). Markers of inflammation were compared between four groups of patients (none, unchanged, worsened, or new headache disorder).
RESULTS: Patients reported experiencing more severe headaches (n = 17), new onset headaches (n = 46), unchanged headaches (n = 18), and surprisingly, some patients denied having any headaches (n = 12) despite self-reports. Serum levels of CX3CL1 were increased in the worsened (2145 [811-4866] pg/ml) and new onset (1668 [0-7357] pg/ml) headache group as compared to patients with no (1129 [0-5379] pg/ml) or unchanged (1478 [346-4332] pg/ml) headaches. Other markers also differed between groups, but most significantly between patients with worsened (TGF-ß1: 60 [0-310] pg/ml, VEGF: 328 [86-842] pg/ml, ß-NGF: 6 [3-38] pg/ml) as compared to unchanged headaches (TGF-ß1: 29 [0-77] pg/ml, VEGF: 183 [72-380] pg/ml, ß-NGF: 3 [2-89] pg/ml). The results did not differ between headache phenotypes.
CONCLUSIONS: This study provides evidence that worsened or new headaches following COVID-19 are associated with pro-(neuro-)inflammatory profiles. This supports the use of anti-inflammatory treatment options in this population, especially in the subacute phase.
METHODS: We included patients from the interdisciplinary post-COVID-19 Rehabilitation Study (PoCoRe, n = 184 patients) run at a tertiary care university hospital, comprising patients with PCR-confirmed SARS-CoV-2 infection ≥ 6 weeks prior to their initial consultation. Patients reporting any headache since their infection were considered for this study (n = 93). These were interviewed and classified according to the International Classification of Headache Disorders, Third Edition (ICHD-3) by headache specialists. Patient sera were additionally analysed for levels of VILIP-1, MCP-1 (CCL2), sTREM-2, BDNF, TGF-ß1, VEGF, IL-6, sTREM-1, ß-NGF, IL-18, TNF-alpha, sRAGE, and CX3CL1 (Fractalkine). Markers of inflammation were compared between four groups of patients (none, unchanged, worsened, or new headache disorder).
RESULTS: Patients reported experiencing more severe headaches (n = 17), new onset headaches (n = 46), unchanged headaches (n = 18), and surprisingly, some patients denied having any headaches (n = 12) despite self-reports. Serum levels of CX3CL1 were increased in the worsened (2145 [811-4866] pg/ml) and new onset (1668 [0-7357] pg/ml) headache group as compared to patients with no (1129 [0-5379] pg/ml) or unchanged (1478 [346-4332] pg/ml) headaches. Other markers also differed between groups, but most significantly between patients with worsened (TGF-ß1: 60 [0-310] pg/ml, VEGF: 328 [86-842] pg/ml, ß-NGF: 6 [3-38] pg/ml) as compared to unchanged headaches (TGF-ß1: 29 [0-77] pg/ml, VEGF: 183 [72-380] pg/ml, ß-NGF: 3 [2-89] pg/ml). The results did not differ between headache phenotypes.
CONCLUSIONS: This study provides evidence that worsened or new headaches following COVID-19 are associated with pro-(neuro-)inflammatory profiles. This supports the use of anti-inflammatory treatment options in this population, especially in the subacute phase.
摘要：
背景：头痛障碍的新发作或恶化在很大程度上导致了COVID-19后的疾病负担。它的管理提供了一个合适的手段，以提高患者的专业参与，社会,和个人活动。不幸的是,对COVID-19后头痛的病理生理学知之甚少。本研究旨在探讨（神经）炎症机制的作用，以指导抗炎治疗策略的发展。
方法：我们纳入了COVID-19后跨学科康复研究的患者(PoCoRe，n=184名患者)在三级护理大学医院运行，包括初次咨询前6周经PCR确认SARS-CoV-2感染的患者。本研究考虑自感染以来报告任何头痛的患者（n=93）。这些人接受了采访，并根据国际头痛疾病分类进行了分类，第三版（ICHD-3）由头痛专家。另外分析了患者血清的VILIP-1，MCP-1（CCL2）水平，sTREM-2,BDNF,TGF-β1,VEGF,IL-6，sTREM-1，β-NGF，IL-18,TNF-α,SRAGE,和CX3CL1(Fractalkine)。比较四组患者的炎症标志物(无，不变,恶化，或新的头痛症）。
结果：患者报告经历了更严重的头痛（n=17），新发头痛（n=46），不变的头痛（n=18），令人惊讶的是，一些患者否认有任何头痛（n=12），尽管自我报告。与无（1129[0-5379]pg/ml）或无变化（1478[346-4332]pg/ml）的患者相比，恶化（2145[811-4866]pg/ml）和新发作（1668[0-7357]pg/ml）头痛组的血清CX3CL1水平升高。其他标记也不同的群体之间，但在恶化的患者中最显著(TGF-β1:60[0-310]pg/ml，VEGF:328[86-842]pg/ml,β-NGF：6[3-38]pg/ml）与不变的头痛（TGF-β1：29[0-77]pg/ml，VEGF:183[72-380]pg/ml,β-NGF:3[2-89]pg/ml)。头痛表型之间的结果没有差异。
结论：这项研究提供了证据，表明COVID-19后加重或新出现的头痛与前（神经）炎症谱有关。这支持在该人群中使用抗炎治疗方案，尤其是在亚急性期。
方法：我们纳入了COVID-19后跨学科康复研究的患者(PoCoRe，n=184名患者)在三级护理大学医院运行，包括初次咨询前6周经PCR确认SARS-CoV-2感染的患者。本研究考虑自感染以来报告任何头痛的患者（n=93）。这些人接受了采访，并根据国际头痛疾病分类进行了分类，第三版（ICHD-3）由头痛专家。另外分析了患者血清的VILIP-1，MCP-1（CCL2）水平，sTREM-2,BDNF,TGF-β1,VEGF,IL-6，sTREM-1，β-NGF，IL-18,TNF-α,SRAGE,和CX3CL1(Fractalkine)。比较四组患者的炎症标志物(无，不变,恶化，或新的头痛症）。
结果：患者报告经历了更严重的头痛（n=17），新发头痛（n=46），不变的头痛（n=18），令人惊讶的是，一些患者否认有任何头痛（n=12），尽管自我报告。与无（1129[0-5379]pg/ml）或无变化（1478[346-4332]pg/ml）的患者相比，恶化（2145[811-4866]pg/ml）和新发作（1668[0-7357]pg/ml）头痛组的血清CX3CL1水平升高。其他标记也不同的群体之间，但在恶化的患者中最显著(TGF-β1:60[0-310]pg/ml，VEGF:328[86-842]pg/ml,β-NGF：6[3-38]pg/ml）与不变的头痛（TGF-β1：29[0-77]pg/ml，VEGF:183[72-380]pg/ml,β-NGF:3[2-89]pg/ml)。头痛表型之间的结果没有差异。
结论：这项研究提供了证据，表明COVID-19后加重或新出现的头痛与前（神经）炎症谱有关。这支持在该人群中使用抗炎治疗方案，尤其是在亚急性期。
