Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
J Investig Med. 2023 Jun;71(5):545-562. doi: 10.1177/10815589231158041. Epub 2023 Mar 6.
In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global coronavirus disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited syndrome comparable to other upper respiratory viral pathogens, a portion of individuals develop severe illness leading to substantial morbidity and mortality. Furthermore, an estimated 10%-20% of SARS-CoV-2 infections are followed by post-acute sequelae of COVID-19 (PASC), or long COVID. Long COVID is associated with a wide variety of clinical manifestations including cardiopulmonary complications, persistent fatigue, and neurocognitive dysfunction. Severe acute COVID-19 is associated with hyperactivation and increased inflammation, which may be an underlying cause of long COVID in a subset of individuals. However, the immunologic mechanisms driving long COVID development are still under investigation. Early in the pandemic, our group and others observed immune dysregulation persisted into convalescence after acute COVID-19. We subsequently observed persistent immune dysregulation in a cohort of individuals experiencing long COVID. We demonstrated increased SARS-CoV-2-specific CD4 and CD8 T-cell responses and antibody affinity in patients experiencing long COVID symptoms. These data suggest a portion of long COVID symptoms may be due to chronic immune activation and the presence of persistent SARS-CoV-2 antigen. This review summarizes the COVID-19 literature to date detailing acute COVID-19 and convalescence and how these observations relate to the development of long COVID. In addition, we discuss recent findings in support of persistent antigen and the evidence that this phenomenon contributes to local and systemic inflammation and the heterogeneous nature of clinical manifestations seen in long COVID.
2019 年末，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引发了全球 2019 年冠状病毒病（COVID-19）大流行。虽然大多数感染引起类似于其他上呼吸道病毒病原体的自限性综合征，但一部分人会发展为严重疾病，导致发病率和死亡率显著增加。此外，据估计，SARS-CoV-2 感染的 10%-20%会继发 COVID-19 的急性后后遗症（PASC）或长新冠。长新冠与广泛的临床表现相关，包括心肺并发症、持续疲劳和神经认知功能障碍。严重急性 COVID-19 与过度激活和炎症增加有关，这可能是一部分人长新冠的潜在原因。然而，驱动长新冠发展的免疫机制仍在研究中。在大流行早期，我们小组和其他小组观察到，急性 COVID-19 后恢复期的免疫失调持续存在。随后，我们在经历长新冠的个体队列中观察到持续的免疫失调。我们发现，经历长新冠症状的患者的 SARS-CoV-2 特异性 CD4 和 CD8 T 细胞反应和抗体亲和力增加。这些数据表明，长新冠症状的一部分可能是由于慢性免疫激活和持续存在 SARS-CoV-2 抗原。本综述总结了迄今为止关于急性 COVID-19 和恢复期的 COVID-19 文献，以及这些观察结果与长新冠发展的关系。此外，我们讨论了支持持续抗原的最新发现，以及这一现象导致局部和全身炎症以及长新冠临床表现异质性的证据。
