Immunocompatibility Group, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK; Centre of Excellence for Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Centre of Excellence for Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Adv Drug Deliv Rev. 2021 Nov;178:113848. doi: 10.1016/j.addr.2021.113848. Epub 2021 Jun 25.
The emergence of SARS-CoV-2, and the ensuing global pandemic, has resulted in an unprecedented response to identify therapies that can limit uncontrolled inflammation observed in patients with moderate to severe COVID-19. The immune pathology behind COVID-19 is complex and involves the activation and interaction of multiple systems including, but not limited to, complement, inflammasomes, endothelial as well as innate and adaptive immune cells to bring about a convoluted profile of inflammation, coagulation and tissue damage. To date, therapeutic approaches have focussed on inhibition of coagulation, untargeted immune suppression and/or cytokine-directed blocking agents. Regardless of recently achieved improvements in individual patient outcomes and survival rates, improved and focussed approaches targeting individual systems involved is needed to further improve prognosis and wellbeing. This review summarizes the current understanding of molecular and cellular systems involved in the pathophysiology of COVID-19, and their contribution to pathogen clearance and damage to then discuss possible therapeutic options involving immunomodulatory drug delivery systems as well as summarising the complex interplay between them.
SARS-CoV-2 的出现以及随之而来的全球大流行，促使人们前所未有地努力寻找能够限制中度至重度 COVID-19 患者中观察到的失控炎症的疗法。COVID-19 的免疫病理学非常复杂，涉及多个系统的激活和相互作用，包括但不限于补体、炎性体、内皮以及先天和适应性免疫细胞，从而导致炎症、凝血和组织损伤的复杂特征。迄今为止，治疗方法主要集中在抑制凝血、非靶向性免疫抑制和/或细胞因子靶向阻断剂上。尽管最近在改善个体患者的预后和生存率方面取得了进展，但仍需要针对涉及的单个系统的改进和集中的方法，以进一步改善预后和幸福感。这篇综述总结了 COVID-19 病理生理学中涉及的分子和细胞系统的当前认识，以及它们对病原体清除和随后损伤的贡献，然后讨论了涉及免疫调节药物递送系统的可能治疗选择，并总结了它们之间的复杂相互作用。
