Robineau Olivier, Hüe Sophie, Surenaud Mathieu, Lemogne Cédric, Dorival Céline, Wiernik Emmanuel, Brami Sebastien, Nicol Jerome, de Lamballerie Xavier, Blanché Hélène, Deleuze Jean-François, Ribet Céline, Goldberg Marcel, Severi Gianluca, Touvier Mathilde, Zins Marie, Levy Yves, Lelievre Jean-Daniel, Carrat Fabrice
Sorbonne Université, Inserm, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Paris, France; EA2694, Centre Hospitalier de Tourcoing, Univ Lille, France.
Faculté de Médecine, INSERM U955, Team 16, Vaccine Research Institute, Université Paris-Est Créteil, Créteil, France.
EBioMedicine. 2025 May 30;117:105792. doi: 10.1016/j.ebiom.2025.105792.
BACKGROUND: Several studies reported long-term consequences of severe COVID-19. However, pathophysiological mechanisms of Post-Acute Sequelae following COVID-19 (PASC) in patients with mild acute COVID-19 have been less investigated. Specifically, the link between PASC and immuno-inflammatory abnormalities is inconsistent in the literature. The hypothesis that different pathophysiological mechanisms could explain the persistent symptoms needs to be explored. METHODS: The COPER cohort is a prospective study that included participants with PASC and with a history of COVID-19 without persistent symptoms. None were hospitalised for COVID-19. Participants underwent two home visits six months apart for biological sample collection and completed questionnaires on medical history, infection, vaccination, symptoms, and mental health. The study analysed association between persistent symptoms and 14 blood biomarkers, comparing participants with PASC with recovered participants. FINDINGS: Between June and November 2022, 1000 participants were included in the study, 199 were excluded due to missing data or sample (35), SARS-CoV-2 infection less than 3 months (36) or lack of known SARS-CoV-2 infection and negative serology (128), with two groups analysed: recovered (n = 490), PASC (n = 311). Participants with PASC were more frequently women, had a higher BMI and a median number of 3 persistent symptoms, with common symptoms being asthenia, dyspnoea, cough, and sleep disorders. Biological analysis revealed significant associations between certain PACS symptoms and biomarkers of viral activation (IFNγ, IP-10), COVID-19 severity (CD163) and vascular activation (VCAM-1, ICAM-1), mainly in subjects whose symptoms had lasted less than a year. However, these associations did not persist over time. INTERPRETATION: The results suggest a polymorphic and dynamic pathophysiology according to symptoms and time since infection. Other hypotheses, beyond those related to persistent inflammation, should be explored. FUNDING: French Ministry of Health and Prevention and the French Ministry of Higher Education, Research and Innovation.
背景：多项研究报告了重症新型冠状病毒肺炎（COVID-19）的长期后果。然而，轻度急性COVID-19患者感染新冠后急性后遗症（PASC）的病理生理机制研究较少。具体而言，PASC与免疫炎症异常之间的联系在文献中并不一致。需要探索不同病理生理机制可解释持续症状这一假说。 方法：COPER队列研究是一项前瞻性研究，纳入了患有PASC以及有COVID-19病史但无持续症状的参与者。均未因COVID-19住院。参与者在相隔六个月的时间里接受了两次家访以采集生物样本，并完成了关于病史、感染、疫苗接种、症状和心理健康的问卷调查。该研究分析了持续症状与14种血液生物标志物之间的关联，将患有PASC的参与者与康复参与者进行比较。 研究结果：在2022年6月至11月期间，1000名参与者纳入研究，199名因数据缺失或样本问题（35名）、SARS-CoV-2感染少于3个月（36名）或缺乏已知SARS-CoV-2感染且血清学检测呈阴性（128名）而被排除，最终分析两组：康复组（n = 490），PASC组（n = 311）。患有PASC的参与者女性更为常见，体重指数更高，平均有3种持续症状，常见症状为乏力、呼吸困难、咳嗽和睡眠障碍。生物学分析显示，某些PACS症状与病毒激活生物标志物（IFNγ、IP-10）、COVID-19严重程度（CD163）和血管激活生物标志物（VCAM-1、ICAM-1）之间存在显著关联，主要见于症状持续时间少于一年的受试者。然而，这些关联并未随时间持续存在。 解读：结果表明，根据症状和感染后的时间不同，病理生理过程具有多态性和动态性。除了与持续炎症相关的假说外，还应探索其他假说。 资金来源：法国卫生与预防部以及法国高等教育、研究与创新部。
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