Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT; United Kingdom.
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT; United Kingdom; Pathology Department, VUmc, Amsterdam UMC, Amsterdam, The Netherlands.
Mult Scler Relat Disord. 2020 Aug;43:102174. doi: 10.1016/j.msard.2020.102174. Epub 2020 May 12.
SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS.
To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis.
Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS.
In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.
SARS-CoV-2 病毒感染会导致 COVID-19，进而引发严重急性呼吸窘迫综合征（ARDS），这可能导致高死亡率，因此人们担心多发性硬化症和其他疾病的免疫抑制治疗会对感染和 ARDS 产生重大风险。
研究潜在的 SARS-CoV-2 病毒免疫生物学以及与 COVID-19 相关的免疫诱导病理学，并确定这如何影响多发性硬化症中当前疾病修正治疗的使用。
尽管有关免疫机制的信息很少，但似乎单核细胞/巨噬细胞，然后是 CD8 T 细胞在消除 SARS-CoV-2 病毒方面很重要。这可能是通过抗病毒抗体反应来促进的，这些反应可能防止再次感染。然而，病毒逃逸和白细胞感染会导致淋巴细胞减少、明显的 CD8 T 细胞耗竭，以及细胞因子风暴和血管病理学，这些似乎都促成了 ARDS 的损伤。
与消融性造血干细胞治疗相反，大多数多发性硬化症相关的疾病修正治疗并非特别针对固有免疫系统，而且很少对 CD8 T 细胞产生任何重大的长期影响，以限制对 COVID-19 的保护。此外，很少有药物能阻止在淋巴组织中形成不成熟的 B 细胞，这些 B 细胞将提供针对（再）感染的抗体介导保护。然而，调整剂量方案可能有助于进一步降低感染的风险，并减轻 COVID-19 大流行期间接受治疗的多发性硬化症患者的担忧。
