As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress and die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to immunological mechanisms of protection. Here, we profiled SARS-CoV-2-specific humoral responses in a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. Although no differences in SARS-CoV-2-specific IgG levels were observed, spike-specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. Furthermore, this enriched immunodominant spike-specific antibody profile in convalescents was confirmed in a larger validation cohort. These results demonstrate that early antigen-specific and qualitative features of SARS-CoV-2-specific antibodies point to differences in disease trajectory, highlighting the potential importance of functional antigen-specific humoral immunity to guide patient care and vaccine development.

随着SARS-CoV-2感染和死亡人数的持续增加，目前尚不清楚为什么有些人从感染中恢复过来，而另一些人迅速发展并死亡。尽管仍然存在不同临床轨迹基础的免疫机制，但病原体特异性抗体通常指向保护性免疫机制。在这里，我们分析了22位住院患者的SARS-CoV-2特异性体液反应。尽管个体之间存在异质性，但不同的抗体特征仍可以分辨具有不同结果的个体。尽管未观察到SARS-CoV-2特异性IgG水平的差异，但是恢复期个体中的穗特异性体液反应丰富，而死者中对核衣壳的功能抗体反应升高。此外，在较大的验证队列中证实了这种在恢复期中丰富的免疫优势突波特异性抗体谱。这些结果表明SARS-CoV-2特异性抗体的早期抗原特异性和定性特征指出了疾病轨迹的差异，突出了功能性抗原特异性体液免疫对指导患者护理和疫苗开发的潜在重要性。