Ichor Biologics LLC, New York, NY 10027, USA; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt 5480000, Chile.
Department of Microbiology, Faculty of Biological Science, Universidad de Concepción, Concepción 4070386, Chile.
Cell Rep. 2022 May 31;39(9):110904. doi: 10.1016/j.celrep.2022.110904. Epub 2022 May 16.
Despite SARS-CoV-2 being a "novel" virus, early detection of anti-spike IgG in severe COVID-19 patients may be caused by the amplification of humoral memory responses against seasonal coronaviruses. Here, we examine this phenomenon by characterizing anti-spike IgG responses in non-hospitalized convalescent individuals across a spectrum of COVID-19 severity. We observe that disease severity positively correlates with anti-spike IgG levels, IgG cross-reactivity against other betacoronaviruses (β-CoVs), and FcγR activation. Analysis of IgG targeting β-CoV-conserved and non-conserved immunodominant epitopes within the SARS-CoV-2 spike protein revealed epitope-specific relationships: IgG targeting the conserved heptad repeat (HR) 2 region significantly correlates with milder disease, while targeting the conserved S2'FP region correlates with more severe disease. Furthermore, a lower HR2-to-S2'FP IgG-binding ratio correlates with greater disease severity, with ICU-hospitalized COVID-19 patients showing the lowest HR2/S2'FP ratios. These findings suggest that HR2/S2'FP IgG profiles may predict disease severity and offer insight into protective versus deleterious humoral recall responses.
尽管 SARS-CoV-2 是一种“新型”病毒，但在重症 COVID-19 患者中早期检测到针对刺突蛋白的 IgG 可能是由于针对季节性冠状病毒的体液记忆反应的扩增所致。在这里，我们通过对 COVID-19 严重程度不同的非住院康复个体的抗刺突 IgG 反应进行表征来研究这一现象。我们观察到疾病严重程度与抗刺突 IgG 水平、针对其他β冠状病毒（β-CoVs）的 IgG 交叉反应性以及 FcγR 激活呈正相关。对针对 SARS-CoV-2 刺突蛋白中β-CoV 保守和非保守免疫显性表位的 IgG 进行分析，揭示了表位特异性关系：针对保守的七肽重复（HR）2 区的 IgG 与较轻的疾病显著相关，而针对保守的 S2'FP 区的 IgG 与更严重的疾病相关。此外，较低的 HR2/S2'FP IgG 结合比与更高的疾病严重程度相关，重症监护病房（ICU）住院的 COVID-19 患者显示出最低的 HR2/S2'FP 比值。这些发现表明 HR2/S2'FP IgG 谱可能预测疾病严重程度，并深入了解保护性和有害性体液记忆反应。
