The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [ 18 F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [ 18 F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein–encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein–encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations.

中文翻译：

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SARS-CoV-2 感染后，基于组织的 T 细胞激活和病毒 RNA 可持续长达 2 年


SARS-CoV-2 感染 [Long Covid (LC)] 后急性后医疗状况和不明原因症状的机制尚不完全清楚。越来越多的证据表明，病毒持续存在、免疫失调和 T 细胞功能障碍可能起着重要作用。我们使用放射性药物在急性 SARS-CoV-2 感染后 27 至 910 天的时间点对 24 名参与者进行了全身正电子发射断层扫描成像。 18 F]F-AraG，一种选择性示踪剂，可对活化的 T 淋巴细胞进行解剖定量。急性后 COVID-19 组（包括有或没有持续症状的患者）在许多区域（包括脑干、脊髓、骨髓、鼻咽和肺门淋巴组织、心肺组织和脑组织）的示踪剂摄取量高于大流行前对照。肠壁。脊髓和肠壁中 T 细胞的激活与 LC 症状的存在相关。此外，在那些有持续肺部症状的人中，肺组织中的示踪剂摄取量更高。在许多没有 LC 的个体中也观察到这些组织中 T 细胞活化增加。鉴于高[ 18在肠道中检测到 F]F-AraG 摄取后，我们获得了结直肠组织，对 5 名患有 LC 症状的参与者进行了原位杂交 SARS-CoV-2 RNA 和免疫组织化学研究。 我们在所有五名参与者的直肠乙状结肠固有层组织中鉴定出细胞内 SARS-CoV-2 单链刺突蛋白编码 RNA，并在三名参与者中鉴定出双链刺突蛋白编码 RNA，直至初始 COVID-19 后 676 天，这表明组织病毒的持续存在可能与长期的免疫扰动有关。