Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration; Silver Spring, Maryland, United States of America.
Office of Biostatistics, Office of Translational Science, Center for Drug Evaluation and Research, Food and Drug Administration; Silver Spring, Maryland, United States of America.
PLoS Pathog. 2021 Jul 19;17(7):e1009766. doi: 10.1371/journal.ppat.1009766. eCollection 2021 Jul.
Neutralizing antibodies to the SARS CoV-2 spike proteins have been issued Emergency Use Authorizations and are a likely mechanism of vaccines to prevent COVID-19. However, benefit of treatment with monoclonal antibodies has only been observed in clinical trials in outpatients with mild to moderate COVID-19 but not in patients who are hospitalized and/or have advanced disease. To address this observation, we evaluated the timing of anti SARS-CoV-2 antibody production in hospitalized patients with the use of a highly sensitive multiplexed bead-based immunoassay allowing for early detection of antibodies to SARS-CoV-2. We found significantly lower levels of antibodies to the SARS-CoV-2 spike protein in the first week after symptom onset in patients who expired as compared to patients who were discharged. We also developed a model to characterize the relationship between each patient's individual antibody level trajectory and eventual COVID 19 outcome which can be adapted into a prediction model with more data.
针对严重急性呼吸系统综合征冠状病毒 2 刺突蛋白的中和抗体已获得紧急使用授权，并且可能是预防 COVID-19 的疫苗的作用机制。然而，仅在患有轻度至中度 COVID-19 的门诊患者的临床试验中观察到了使用单克隆抗体进行治疗的益处，而在住院和/或患有晚期疾病的患者中则未观察到。为了解决这一观察结果，我们使用高度敏感的基于珠的多重免疫分析评估了住院患者中针对 SARS-CoV-2 的抗体产生的时间，该分析可早期检测到针对 SARS-CoV-2 的抗体。我们发现，与出院的患者相比，症状发作后第一周的 SARS-CoV-2 刺突蛋白抗体水平明显较低。我们还开发了一种模型，以描述每个患者的个体抗体水平轨迹与最终 COVID-19 结局之间的关系，该模型可以随着更多数据而适应到预测模型中。
