抗严重急性呼吸综合征冠状病毒 2 抗体反应的幅度和动力学及其与疾病严重程度的关系。

Magnitude and Kinetics of Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Responses and Their Relationship to Disease Severity.

机构信息

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.

Scientific Affairs, American Red Cross, Gaithersberg, Maryland, USA.

出版信息

Clin Infect Dis. 2021 Jan 27;72(2):301-308. doi: 10.1093/cid/ciaa979.

DOI:10.1093/cid/ciaa979

PMID:33501951

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7454426/

Abstract

BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets.

METHODS

Sera (n = 533) from patients with real-time polymerase chain reaction-confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity.

RESULTS

Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG.

CONCLUSIONS

High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.

摘要

背景

严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染可以通过测量宿主免疫反应来间接检测。对于某些病毒，抗体浓度与宿主保护和病毒中和相关，但在极少数情况下，抗病毒抗体可能会促进疾病进展。阐明 SARS-CoV-2 抗体反应的动力学和幅度对于了解 2019 年冠状病毒病（COVID-19）的发病机制和确定潜在的治疗靶点至关重要。

方法

使用高通量定量免疫球蛋白 M（IgM）和免疫球蛋白 G（IgG）检测试剂盒（该试剂盒可检测针对刺突蛋白受体结合域和核衣壳蛋白的抗体）检测实时聚合酶链反应确诊的 COVID-19 患者（急性感染患者 94 例，恢复期患者 59 例）的血清（n=533）。检测了个体和系列样本，包括初始诊断时、疾病期间和恢复后。我们评估了抗体动力学以及反应幅度与疾病严重程度之间的相关性。

结果

SARS-CoV-2 抗体产生的模式差异很大。在 52 例有 3 个或更多连续样本的患者中，44 例（84.6%）和 42 例（80.8%）分别在第 8 和第 10 天观察到 IgM 和 IgG 血清转化。与疾病较轻的患者相比，所有时间间隔为 6 至 20 天的 IgM 和所有间隔 5 天后的 IgG 中，入住重症监护病房的患者的峰值测量值均显著更高。