IgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (~6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses, but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high levels of afucosylated IgG antibodies against SARS-CoV-2, amplifying pro-inflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.

中文翻译：

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无岩藻糖基化 IgG 表征包膜病毒反应并与 COVID-19 严重程度相关

IgG 抗体对于抵御入侵的病原体至关重要。IgG-Fc 尾部中高度保守的 N-连接聚糖对 IgG 功能至关重要，在人类中显示出不同的组成。无岩藻糖基化 IgG 变体已用于抗癌治疗抗体，因为它们通过 Fc 受体 (FcγRIIIa) 提高了活性。在这里，我们报告了无岩藻糖基化 IgG（人类总 IgG 的约 6%）是专门针对包膜病毒形成的，但通常不针对其他抗原。这介导了更强的 FcγRIIIa 反应，但也会放大酝酿中的细胞因子风暴和免疫介导的病理。重症 COVID-19 患者（但不是那些症状较轻的患者）具有高水平的抗 SARS-CoV-2 无岩藻糖基化 IgG 抗体，从而放大促炎细胞因子的释放和急性期反应。因此，