Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Sendai Viralytics LLC, Acton, MA, United States.
Front Immunol. 2022 Dec 1;13:1050478. doi: 10.3389/fimmu.2022.1050478. eCollection 2022.
Our review summarizes the evidence that COVID-19 can be complicated by SARS-CoV-2 infection of immune cells. This evidence is widespread and accumulating at an increasing rate. Research teams from around the world, studying primary and established cell cultures, animal models, and analyzing autopsy material from COVID-19 deceased patients, are seeing the same thing, namely that some immune cells are infected or capable of being infected with the virus. Human cells most vulnerable to infection include both professional phagocytes, such as monocytes, macrophages, and dendritic cells, as well as nonprofessional phagocytes, such as B-cells. Convincing evidence has accumulated to suggest that the virus can infect monocytes and macrophages, while data on infection of dendritic cells and B-cells are still scarce. Viral infection of immune cells can occur directly through cell receptors, but it can also be mediated or enhanced by antibodies through the Fc gamma receptors of phagocytic cells. Antibody-dependent enhancement (ADE) most likely occurs during the primary encounter with the pathogen through the first COVID-19 infection rather than during the second encounter, which is characteristic of ADE caused by other viruses. Highly fucosylated antibodies of vaccinees seems to be incapable of causing ADE, whereas afucosylated antibodies of persons with acute primary infection or convalescents are capable. SARS-CoV-2 entry into immune cells can lead to an abortive infection followed by host cell pyroptosis, and a massive inflammatory cascade. This scenario has the most experimental evidence. Other scenarios are also possible, for which the evidence base is not yet as extensive, namely productive infection of immune cells or trans-infection of other non-immune permissive cells. The chance of a latent infection cannot be ruled out either.
我们的综述总结了 COVID-19 可能因 SARS-CoV-2 感染免疫细胞而变得复杂的证据。这些证据广泛存在，并以越来越快的速度积累。来自世界各地的研究团队，在原代和已建立的细胞培养物、动物模型以及分析 COVID-19 死亡患者的尸检材料方面开展研究，都看到了同样的情况，即某些免疫细胞受到了感染，或者能够被病毒感染。最易受感染的人类细胞包括专业吞噬细胞，如单核细胞、巨噬细胞和树突状细胞，以及非专业吞噬细胞，如 B 细胞。大量令人信服的证据表明，病毒可以感染单核细胞和巨噬细胞，而关于树突状细胞和 B 细胞感染的数据仍然很少。病毒对免疫细胞的感染可以通过细胞受体直接发生，但也可以通过吞噬细胞的 Fcγ受体被抗体介导或增强。抗体依赖性增强（ADE）很可能发生在初次接触病原体时，即初次 COVID-19 感染期间，而不是在二次感染期间，这是由其他病毒引起的 ADE 的特征。疫苗接种者的高度岩藻糖基化抗体似乎不能引起 ADE，而急性初次感染或恢复期患者的去岩藻糖基化抗体则可以。SARS-CoV-2 进入免疫细胞可导致宿主细胞发生细胞焦亡的无效感染，随后引发大规模炎症级联反应。这种情况具有最充分的实验证据。其他情况也可能存在，而这些情况的证据基础尚不够广泛，即免疫细胞的有效感染或其他非免疫许可细胞的转染感染。潜伏感染的可能性也不能排除。
