The urgent need for an effective SARS-CoV-2 vaccine has forced development to progress in the absence of well-defined correlates of immunity. While neutralization has been linked to protection against other pathogens, whether neutralization alone will be sufficient to drive protection against SARS-CoV-2 in the broader population remains unclear. Therefore, to fully define protective humoral immunity, we dissected the early evolution of the humoral response in 193 hospitalized individuals ranging from moderate to severe. Although robust IgM and IgA responses evolved in both survivors and non-survivors with severe disease, non-survivors showed attenuated IgG responses, accompanied by compromised Fcɣ receptor binding and Fc effector activity, pointing to deficient humoral development rather than disease-enhancing humoral immunity. In contrast, individuals with moderate disease exhibited delayed responses that ultimately matured. These data highlight distinct humoral trajectories associated with resolution of SARS-CoV-2 infection and the need for early functional humoral immunity.

对有效 SARS-CoV-2 疫苗的迫切需求迫使研发在缺乏明确的免疫相关性的情况下取得进展。虽然中和作用与针对其他病原体的保护有关，但仅中和作用是否足以在更广泛的人群中推动针对 SARS-CoV-2 的保护仍不清楚。因此，为了充分定义保护性体液免疫，我们剖析了 193 名中度至重度住院患者体液反应的早期演变。尽管患有严重疾病的幸存者和非幸存者都出现了强烈的 IgM 和 IgA 反应，但非幸存者表现出 IgG 反应减弱，并伴有 Fcɣ 受体结合和 Fc 效应子活性受损，这表明体液发育不足，而不是疾病增强的体液免疫。相比之下，患有中度疾病的个体表现出最终成熟的延迟反应。这些数据强调了与 SARS-CoV-2 感染消退相关的独特体液轨迹以及早期功能性体液免疫的需要。