Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) outbreaks that resulted in a catastrophic threat to global health, with more than 500 million cases detected and 5.5 million deaths worldwide. Patients with a COVID-19 infection presented with clinical manifestations ranging from asymptomatic to severe symptoms, resulting in acute lung injury, acute respiratory distress syndrome, and even death. Immune dysregulation through delayed innate immune response or impairment of the adaptive immune response is the key contributor to the pathophysiology of COVID-19 and SARS-CoV-2-induced cytokine storm. Symptomatic and supportive therapy is the fundamental strategy in treating COVID-19 infection, including antivirals, steroid-based therapies, and cell-based immunotherapies. Various studies reported substantial effects of immune-based therapies for patients with COVID-19 to modulate the over-activated immune system while simultaneously refining the body’s ability to destroy the virus. However, challenges may arise from the complexity of the disease through the genetic variance of the virus itself and patient heterogeneity, causing increased transmissibility and heightened immune system evasion that rapidly change the intervention and prevention measures for SARS-CoV-2. Cell-based therapy, utilizing stem cells, dendritic cells, natural killer cells, and T cells, among others, are being extensively explored as other potential immunological approaches for preventing and treating SARS-CoV-2-affected patients the similar process was effectively proven in SARS-CoV-1 and MERS-CoV infections. This review provides detailed insights into the innate and adaptive immune response-mediated cell-based immunotherapies in COVID-19 patients. The immune response linking towards engineered autologous or allogenic immune cells for either treatment or preventive therapies is subsequently highlighted in an individual study or in combination with several existing treatments. Up-to-date data on completed and ongoing clinical trials of cell-based agents for preventing or treating COVID-19 are also outlined to provide a guide that can help in treatment decisions and future trials.

摘要

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是导致 2019 年冠状病毒病 (COVID-19) 爆发的病原体，该疾病对全球健康造成灾难性威胁，全球已发现超过 5 亿例病例，550 万人死亡。COVID-19感染患者的临床表现从无症状到严重症状不等，导致急性肺损伤、急性呼吸窘迫综合征，甚至死亡。先天免疫反应延迟或适应性免疫反应受损导致的免疫失调是导致 COVID-19 和 SARS-CoV-2 诱导的细胞因子风暴病理生理学的关键因素。对症和支持治疗是治疗 COVID-19 感染的基本策略，包括抗病毒药物、类固醇治疗和细胞免疫治疗。各种研究报告了基于免疫的疗法对 COVID-19 患者的显着效果，可以调节过度激活的免疫系统，同时提高身体消灭病毒的能力。然而，由于病毒本身的遗传变异和患者异质性，疾病的复杂性可能会带来挑战，导致传播性增加和免疫系统逃避加剧，从而迅速改变 SARS-CoV-2 的干预和预防措施。正在广泛探索利用干细胞、树突状细胞、自然杀伤细胞和 T 细胞等的细胞疗法，作为预防和治疗 SARS-CoV-2 感染患者的其他潜在免疫学方法，类似的过程已得到有效证明SARS-CoV-1 和 MERS-CoV 感染。这篇综述提供了对 COVID-19 患者先天性和适应性免疫反应介导的基于细胞的免疫疗法的详细见解。随后在一项单独的研究或与几种现有治疗相结合的研究中强调了与用于治疗或预防性治疗的工程化自体或同种异体免疫细胞相关的免疫反应。还概述了用于预防或治疗 COVID-19 的细胞药物已完成和正在进行的临床试验的最新数据，以提供有助于治疗决策和未来试验的指南。