Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, USA.
Quest Diagnostics at Adventist Healthcare, Rockville, MD, USA.
Nat Commun. 2021 Feb 22;12(1):1221. doi: 10.1038/s41467-021-21463-2.
Hospitalized COVID-19 patients often present with a large spectrum of clinical symptoms. There is a critical need to better understand the immune responses to SARS-CoV-2 that lead to either resolution or exacerbation of the clinical disease. Here, we examine longitudinal plasma samples from hospitalized COVID-19 patients with differential clinical outcome. We perform immune-repertoire analysis including cytokine, hACE2-receptor inhibition, neutralization titers, antibody epitope repertoire, antibody kinetics, antibody isotype and antibody affinity maturation against the SARS-CoV-2 prefusion spike protein. Fatal cases demonstrate high plasma levels of IL-6, IL-8, TNFα, and MCP-1, and sustained high percentage of IgA-binding antibodies to prefusion spike compared with non-ICU survivors. Disease resolution in non-ICU and ICU patients associates with antibody binding to the receptor binding motif and fusion peptide, and antibody affinity maturation to SARS-CoV-2 prefusion spike protein. Here, we provide insight into the immune parameters associated with clinical disease severity and disease-resolution outcome in hospitalized patients that could inform development of vaccine/therapeutics against COVID-19.
住院的 COVID-19 患者常表现出广泛的临床症状。因此，迫切需要更好地了解导致临床疾病缓解或恶化的针对 SARS-CoV-2 的免疫反应。在这里，我们检测了具有不同临床结局的住院 COVID-19 患者的纵向血浆样本。我们进行了免疫受体分析，包括细胞因子、hACE2 受体抑制、中和效价、抗体表位谱、抗体动力学、抗体同种型和针对 SARS-CoV-2 预融合刺突蛋白的抗体亲和力成熟。死亡病例表现出高水平的 IL-6、IL-8、TNFα 和 MCP-1，以及与非 ICU 幸存者相比，持续高比例的 IgA 结合针对预融合刺突的抗体。非 ICU 和 ICU 患者的疾病缓解与抗体结合受体结合基序和融合肽以及针对 SARS-CoV-2 预融合刺突蛋白的抗体亲和力成熟相关。在这里，我们提供了与住院患者临床疾病严重程度和疾病缓解结局相关的免疫参数的见解，这些参数可能为针对 COVID-19 的疫苗/疗法的开发提供信息。
