Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; Department of Otolaryngology, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN, UK.
Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; Haematology Department, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN, UK.
Semin Immunol. 2021 Jun;55:101545. doi: 10.1016/j.smim.2021.101545. Epub 2021 Nov 27.
The global COVID-19 pandemic has caused substantial morbidity and mortality to humanity. Remarkable progress has been made in understanding both the innate and adaptive mechanisms involved in the host response to the causative SARS-CoV-2 virus, but much remains to be discovered. Robust upper airway defenses are critical in restricting SARS-CoV-2 replication and propagation. Further, the nasal abundance of viral uptake receptor, ACE2, and the host epithelial transcriptional landscape, are associated with differential disease outcomes across different patient cohorts. The adaptive host response to systemic COVID-19 is heterogeneous and complex. Blunted responses to interferon and robust cytokine generation are hallmarks of the disease, particularly at the advanced stages. Excessive immune cell influx into tissues can lead to substantial collateral damage to the host akin to sepsis. This review offers a contemporary summary of these mechanisms of disease and highlights potential avenues for diagnostic and therapeutic development. These include improved disease stratification, targeting effectors of immune-mediated tissue damage, and blunting of immune cell-mediated tissue damage.
全球 COVID-19 大流行给人类带来了巨大的发病率和死亡率。在理解宿主对致病 SARS-CoV-2 病毒的固有和适应性反应机制方面已经取得了显著进展，但仍有许多有待发现。强大的上呼吸道防御对于限制 SARS-CoV-2 的复制和传播至关重要。此外，鼻内病毒摄取受体 ACE2 的丰度和宿主上皮细胞转录景观与不同患者群体的不同疾病结局相关。宿主对全身 COVID-19 的适应性反应是异质和复杂的。干扰素反应迟钝和细胞因子生成旺盛是该疾病的特征，特别是在晚期阶段。免疫细胞大量涌入组织会导致宿主的大量附带损伤，类似于败血症。本文综述了这些疾病发生机制，并强调了潜在的诊断和治疗发展途径。这些途径包括改善疾病分层、针对免疫介导的组织损伤效应物以及抑制免疫细胞介导的组织损伤。
