Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-Spike (S) IgG levels, length of hospitalization and clinical parameters associated with worse clinical progression. While high anti-S IgG levels correlated with worse disease severity, such correlation was time-dependent. Deceased patients did not have higher overall humoral response than live discharged patients. However, they mounted a robust, yet delayed response, measured by anti-S, anti-RBD IgG, and neutralizing antibody (NAb) levels, compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, while sera from 89% of patients displayed some neutralization capacity during their disease course, NAb generation prior to 14 days of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se, but rather with the delayed kinetics of NAb production.

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抗体反应动力学决定 COVID-19 结果

最近的研究提供了对 2019 年冠状病毒病 (COVID-19) 中先天性和适应性免疫动力学的见解。然而，控制 COVID-19 疾病结果的抗体反应的确切特征仍不清楚。在这里，我们分析了 209 名无症状、轻度、中度和重度 COVID-19 患者随时间推移的体液免疫反应，以探讨抗体反应在疾病严重程度和死亡率方面的性质。我们观察到抗 Spike (S) IgG 水平、住院时间和临床参数之间存在相关性，这些参数与更严重的临床进展相关。虽然高抗 S IgG 水平与更严重的疾病严重程度相关，但这种相关性是时间依赖性的。已故患者的总体体液反应并不比活着的出院患者高。然而，通过抗 S、抗 RBD IgG、和中和抗体 (NAb) 水平，与幸存者相比。延迟的血清转化动力学与已故患者的病毒控制受损有关。最后，虽然 89% 患者的血清在其病程中显示出一定的中和能力，但在疾病发作前 14 天产生 NAb 成为恢复的关键因素。这些数据表明，COVID-19 死亡率与横断面抗病毒抗体水平本身无关，而是与 NAb 产生的延迟动力学相关。在疾病发作 14 天之前产生 NAb 成为恢复的关键因素。这些数据表明，COVID-19 死亡率与横断面抗病毒抗体水平本身无关，而是与 NAb 产生的延迟动力学相关。在疾病发作 14 天之前产生 NAb 成为恢复的关键因素。这些数据表明，COVID-19 死亡率与横断面抗病毒抗体水平本身无关，而是与 NAb 产生的延迟动力学相关。