Yang Otto O
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
J Immunol. 2025 Apr 3. doi: 10.1093/jimmun/vkaf033.
This review provides a broad overview of lessons learned in the five years since COVID-19 was identified. It is a bimodal disease, starting with an initially virus-driven phase, followed by resolution or ensuing inappropriate immune activation causing severe inflammation that is no longer strictly virus dependent. Humoral immunity is beneficial for preventing or attenuating the early stage, without benefit once the later stage begins. Neutralizing antibodies elicited by natural infection or vaccination are short-lived and highly vulnerable to viral sequence variation. By contrast, cellular immunity, particularly the CD8+ T cell arm, has a role in preventing or attenuating severe disease, is far less susceptible to viral variation, and is longer-lived than antibodies. Finally, an ill-defined phenomenon of prolonged symptoms after acute infection, termed "long COVID," is poorly understood but may involve various immunologic defects that are hyperactivating or immunosuppressive. Remaining issues include needing to better understand the immune dysregulation of severe disease to allow more tailored therapeutic interventions, developing antibody strategies that cope with the viral spike sequence variability, prolonging vaccine efficacy, and unraveling the mechanisms of long COVID to design therapeutic approaches.
本综述全面概述了自新冠病毒被发现以来五年间所吸取的经验教训。这是一种双峰疾病，始于最初由病毒驱动的阶段，随后是病情缓解或随之而来的不适当免疫激活，导致严重炎症，而这种炎症不再严格依赖病毒。体液免疫有助于预防或减轻疾病早期阶段，但在后期开始后则无益处。自然感染或疫苗接种所引发的中和抗体寿命短暂，且极易受到病毒序列变异的影响。相比之下，细胞免疫，尤其是CD8 + T细胞分支，在预防或减轻重症方面发挥作用，对病毒变异的敏感性远低于抗体，且比抗体寿命更长。最后，急性感染后出现的症状迁延不愈这一现象，即“长新冠”，目前了解甚少，但可能涉及各种免疫缺陷，这些缺陷可能是免疫亢进或免疫抑制性的。尚存的问题包括需要更好地了解重症疾病的免疫失调情况，以便进行更具针对性的治疗干预；开发应对病毒刺突序列变异性的抗体策略；延长疫苗效力；以及阐明“长新冠”的机制以设计治疗方法。
