Section of Rheumatology and Clinical Immunology Department of Internal Medicine Yale University School of Medicine New Haven Connecticut USA.
J Extracell Vesicles. 2020 Oct;10(1):e12004. doi: 10.1002/jev2.12004. Epub 2020 Nov 14.
Exosome extracellular vesicles as biologic therapy for COVID-19 are discussed for two areas. The first involves the growing use of mesenchymal stromal cells (MSCs) for the profound clinical cytokine storm and severe pneumonia in COVID-19 patients. Instead, it is recommended to treat alternatively with their MSC-released exosomes. This is because many reports in the literature and our data have shown that the release of exosomes from the in vivo administered MSC is actually responsible for their beneficial effects. Further, the exosomes are superior, simpler and clinically more convenient compared to their parental MSC. Additionally, in the context of COVID-19, the known tendency of MSC to intravascularly aggregate causing lung dysfunction might synergize with the pneumonia aspects, and the tendency of MSC peripheral vascular micro aggregates might synergize with the vascular clots of the COVID-19 disease process, causing significant central or peripheral vascular insufficiency. The second exosome therapeutic area for severe COVID-19 involves use of convalescent plasma for its content of acquired immune antibodies that must consider the role in this therapy of contained nearly trillions of exosomes. Many of these derive from activated immune modulating cells and likely can function to transfer miRNAs that acting epigenetically to also influence the convalescent plasma recipient response to the virus. There is sufficient evidence, like recovery of patients with antibody deficiencies, to postulate that the antibodies actually have little effect and that immune resistance is principally due to T cell mechanisms. Further, COVID-19 convalescent plasma has remarkably weak beneficial effects if compared to what was expected from many prior studies. This may be due to the dysfunctional immune response to the infection and resulting weak Ab that may be impaired further by antagonistic exosomes in the convalescent plasma. At the least, pre selection of plasma for the best antibodies and relevant exosomes would produce the most optimum therapy for very severely affected COVID-19 patients.
外泌体作为治疗 COVID-19 的生物疗法，在两个方面进行了讨论。第一个方面涉及间充质基质细胞（MSCs）在 COVID-19 患者中严重细胞因子风暴和严重肺炎的广泛应用。相反，建议用它们释放的 MSC 外泌体替代治疗。这是因为文献中的许多报道和我们的数据表明，从体内给予的 MSC 释放的外泌体实际上负责其有益效果。此外，与它们的亲本 MSC 相比，外泌体具有优越性、简单性和临床便利性。此外，在 COVID-19 背景下，MSC 向血管内聚集导致肺功能障碍的已知趋势可能与肺炎方面协同作用，而 MSC 周围血管微聚集的趋势可能与 COVID-19 疾病过程中的血管血栓协同作用，导致明显的中央或外周血管功能不全。第二个用于治疗严重 COVID-19 的外泌体治疗领域涉及使用恢复期血浆，因为其包含的获得性免疫抗体，必须考虑在这种治疗中包含的近万亿个外泌体的作用。其中许多源自激活的免疫调节细胞，可能能够传递 miRNA，通过表观遗传作用也影响恢复期血浆受者对病毒的反应。有充分的证据表明，如抗体缺乏症患者的恢复，可以假设抗体实际上作用不大，免疫抵抗主要是由于 T 细胞机制。此外，如果与许多先前的研究相比，COVID-19 恢复期血浆的有益作用非常弱。这可能是由于对感染的免疫反应功能障碍和由此产生的弱 Ab 进一步受损，可能进一步受到恢复期血浆中拮抗外泌体的影响。至少，对外周血中最佳抗体和相关外泌体的预先选择，将为非常严重的 COVID-19 患者产生最优化的治疗。
