Post-acute sequelae of COVID-19 (PASC), or Long COVID, is a chronic condition following acute SARS-CoV-2 infection. Symptoms include exertion fatigue, respiratory issues, myalgia, and neurological manifestations such as ‘brain fog,’ posing concern for their debilitating nature and potential role in other neurological disorders. However, the underlying potential pathogenic mechanisms of the neurological complications of PASC is largely unknown. Herein, we investigated differences in antigen-specific T cell responses from the peripheral blood towards SARS-CoV-2, latent viruses, or neuronal antigens in 14 PASC individuals with neurological manifestations (PASC-N) versus 22 individuals fully recovered from COVID-19. We employed Activation Induced Marker (AIM), ICS and FluoroSpot assays to determine the specificity and magnitude of CD4 and CD8 T cell responses towards SARS-CoV-2 (Spike and rest of proteome), latent viruses (CMV, EBV), and several neuronal antigens. Overall, we observed similar antigen-specific T cell frequencies and cytokine effector T cell responses between PASC donors compared to recovered controls for all antigens tested (viral or autoantigen) in both CD4 and CD8 T cell compartments. Our findings suggest that PASC-N does not appear to be associated with changes in antigen-specific T cell responses towards a subset of disease-relevant targets, but more studies in a larger cohort are needed to confirm these unaltered responses.

中文翻译：

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研究与 COVID-19 急性后遗症相关的病毒和自身免疫 T 细胞反应

COVID-19 急性后遗症 (PASC) 或称长 COVID 是急性 SARS-CoV-2 感染后的一种慢性疾病。症状包括劳累性疲劳、呼吸系统问题、肌痛和“脑雾”等神经系统表现，令人担心其使人衰弱的性质以及在其他神经系统疾病中的潜在作用。然而，PASC 神经系统并发症的潜在致病机制在很大程度上尚不清楚。在此，我们研究了 14 名具有神经系统表现的 PASC 个体 (PASC-N) 与 22 名从 COVID-19 中完全康复的个体外周血对 SARS-CoV-2、潜伏病毒或神经元抗原的抗原特异性 T 细胞反应的差异。我们采用激活诱导标记 (AIM)、ICS 和 FluoroSpot 检测来确定 CD4 和 CD8 T 细胞对 SARS-CoV-2（刺突和蛋白质组的其余部分）、潜伏病毒（CMV、EBV）和多种病毒的反应的特异性和程度。神经元抗原。总体而言，我们在 CD4 和 CD8 T 细胞区室中观察到与恢复的对照相比，PASC 供体之间的抗原特异性 T 细胞频率和细胞因子效应 T 细胞反应相似。我们的研究结果表明，PASC-N 似乎与针对疾病相关靶点子集的抗原特异性 T 细胞反应的变化无关，但需要在更大的队列中进行更多研究来证实这些未改变的反应。