Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used ‘omic” assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4⁺ T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8⁺ T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.

至少 10% 的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染后会出现长新冠病毒 (LC)，但其病因仍知之甚少。我们使用“组学”检测和血清学来深入表征感染后 8 个月具有明确 LC 和非 LC 临床轨迹的个体血液中的整体免疫和 SARS-CoV-2 特异性免疫。我们发现 LC 个体表现出全身炎症和免疫失调。 T 细胞亚群分布的整体差异（意味着持续的免疫反应）以及溶细胞亚群的性别特异性扰动证明了这一点。 LC 个体表现出准备迁移至发炎组织的 CD4 ⁺ T 细胞频率增加，并且 SARS-CoV-2 特异性 CD8 ⁺ T 细胞耗尽，SARS-CoV-2 抗体水平较高，并且 SARS-CoV-2 之间的协调失调。 2 特异性 T 和 B 细胞反应。我们的分析表明，LC 中细胞和体液适应性免疫之间存在不适当的串扰，这可能导致免疫失调、炎症和与这种衰弱病症相关的临床症状。