Paniskaki Krystallenia, Konik Margarethe J, Anft Moritz, Heidecke Harald, Meister Toni L, Pfaender Stephanie, Krawczyk Adalbert, Zettler Markus, Jäger Jasmin, Gaeckler Anja, Dolff Sebastian, Westhoff Timm H, Rohn Hana, Stervbo Ulrik, Scheibenbogen Carmen, Witzke Oliver, Babel Nina
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Bochum, Germany.
Front Microbiol. 2023 Jun 2;14:1196721. doi: 10.3389/fmicb.2023.1196721. eCollection 2023.
The role of adaptive SARS-CoV-2 specific immunity in post-acute sequelae of COVID-19 (PASC) is not well explored, although a growing population of convalescent COVID-19 patients with manifestation of PASC is observed. We analyzed the SARS-CoV-2-specific immune response, via pseudovirus neutralizing assay and multiparametric flow cytometry in 40 post-acute sequelae of COVID-19 patients with non-specific PASC manifestation and 15 COVID-19 convalescent healthy donors. Although frequencies of SARS-CoV-2-reactive CD4+ T cells were similar between the studied cohorts, a stronger SARS-CoV-2 reactive CD8+ T cell response, characterized by IFN production and predominant T phenotype but low functional TCR avidity was detected in PASC patients compared to controls. Of interest, high avidity SARS-CoV-2-reactive CD4+ and CD8+ T cells were comparable between the groups demonstrating sufficient cellular antiviral response in PASC. In line with the cellular immunity, neutralizing capacity in PASC patients was not inferior compared to controls. In conclusion, our data suggest that PASC may be driven by an inflammatory response triggered by an expanded population of low avidity SARS-CoV-2 reactive pro-inflammatory CD8+ T cells. These pro-inflammatory T cells with TEMRA phenotype are known to be activated by a low or even without TCR stimulation and lead to a tissue damage. Further studies including animal models are required for a better understanding of underlying immunopathogensis. Summary: A CD8+ driven persistent inflammatory response triggered by SARS-CoV-2 may be responsible for the observed sequelae in PASC patients.
尽管观察到越来越多的新冠康复患者出现新冠后急性后遗症（PASC），但适应性SARS-CoV-2特异性免疫在PASC中的作用尚未得到充分研究。我们通过假病毒中和试验和多参数流式细胞术分析了40例有非特异性PASC表现的新冠后急性后遗症患者和15例新冠康复健康供体的SARS-CoV-2特异性免疫反应。尽管在研究队列中，SARS-CoV-2反应性CD4+T细胞的频率相似，但与对照组相比，在PASC患者中检测到更强的SARS-CoV-2反应性CD8+T细胞反应，其特征是产生IFN和占主导地位的T表型，但功能性TCR亲和力较低。有趣的是，高亲和力的SARS-CoV-2反应性CD4+和CD8+T细胞在两组之间相当，表明PASC中有足够的细胞抗病毒反应。与细胞免疫一致，PASC患者的中和能力与对照组相比并不逊色。总之，我们的数据表明，PASC可能由低亲和力SARS-CoV-2反应性促炎CD8+T细胞数量增加引发的炎症反应驱动。已知具有TEMRA表型的这些促炎T细胞可被低水平或甚至无TCR刺激激活，并导致组织损伤。需要进一步的研究，包括动物模型，以更好地理解潜在的免疫发病机制。总结：SARS-CoV-2引发的由CD8+驱动的持续性炎症反应可能是PASC患者中观察到的后遗症的原因。
