Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases.
Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases.
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DOI：
10.3389/fimmu.2021.748291
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发表时间：
2021
影响因子：
7.3
通讯作者：
Heeney JL
中科院分区：
文献类型：
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作者：
Castillo-Olivares J;Wells DA;Ferrari M;Chan ACY;Smith P;Nadesalingam A;Paloniemi M;Carnell GW;Ohlendorf L;Cantoni D;Mayora-Neto M;Palmer P;Tonks P;Temperton NJ;Peterhoff D;Neckermann P;Wagner R;Doffinger R;Kempster S;Otter AD;Semper A;Brooks T;Albecka A;James LC;Page M;Schwaeble W;Baxendale H;Heeney JL
在COVID-19大流行期间，在大规模疫苗推广和严重急性呼吸综合征相关冠状病毒-2 （SARS-CoV-2）关注变体（VOC）流行率上升期间，精确监测抗体反应变得越来越重要。同样重要的是确定SARS-CoV-2感染和COVID-19疾病的保护相关物（CoP）。来自流行病学研究和疫苗试验的数据确定病毒中和抗体（Nab）和SARS-CoV-2抗原特异性（特别是RBD和S）结合抗体是候选CoP。在这项研究中，我们使用世界卫生组织（WHO）国际标准来基准中和抗体反应和大量结合抗体测定来比较从以下患者获得的恢复期血清：a) COVID-19患者；b) SARS-CoV-2血清阳性的卫生保健工作者（HCW）和c)血清阴性的HCW。这项研究的最终目的是鉴定体液免疫的生物标志物，这些生物标志物可用于区分严重、轻度或无症状的SARS-CoV-2感染。在使用疫苗接种突破和/或再感染病例样本的进一步血清学研究中，其中一些生物标志物可用于定义CoP。在合适的情况下，研究样本的抗体水平以国际单位（IU）表示，用于病毒中和试验，或以结合抗体单位（BAU）表示，用于ELISA试验。在这项工作中，我们使用了商业和非商业抗体结合测定；检测sars - cov -2特异性IgG/IgM的侧流试验；SARS-CoV-2刺突(S)、核衣壳(N)和受体结合域（RBD）蛋白的高通量多路复用颗粒流式细胞术检测；多重抗原半自动免疫印迹法测定IgM、IgA和IgG；假型微中和试验（pMN）和电穿孔依赖性中和试验（EDNA）。我们的研究结果表明，总体而言，重症COVID-19患者的sars - cov -2特异性中和抗体水平（平均1029 IU/ml）高于轻度或无症状感染的血清阳性HCW患者（379 IU/ml），并且基于世卫组织指南的临床严重程度评分与中和和RBD/S抗体密切相关。此外，严重程度、n抗体测定和细胞内病毒中和之间存在正相关。
Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID-19 disease. Data from epidemiological studies and vaccine trials identified virus neutralising antibodies (Nab) and SARS-CoV-2 antigen-specific (notably RBD and S) binding antibodies as candidate CoP. In this study, we used the World Health Organisation (WHO) international standard to benchmark neutralising antibody responses and a large panel of binding antibody assays to compare convalescent sera obtained from: a) COVID-19 patients; b) SARS-CoV-2 seropositive healthcare workers (HCW) and c) seronegative HCW. The ultimate aim of this study is to identify biomarkers of humoral immunity that could be used to differentiate severe from mild or asymptomatic SARS-CoV-2 infections. Some of these biomarkers could be used to define CoP in further serological studies using samples from vaccination breakthrough and/or re-infection cases. Whenever suitable, the antibody levels of the samples studied were expressed in International Units (IU) for virus neutralisation assays or in Binding Antibody Units (BAU) for ELISA tests. In this work we used commercial and non-commercial antibody binding assays; a lateral flow test for detection of SARS-CoV-2-specific IgG/IgM; a high throughput multiplexed particle flow cytometry assay for SARS-CoV-2 Spike (S), Nucleocapsid (N) and Receptor Binding Domain (RBD) proteins); a multiplex antigen semi-automated immuno-blotting assay measuring IgM, IgA and IgG; a pseudotyped microneutralisation test (pMN) and an electroporation-dependent neutralisation assay (EDNA). Our results indicate that overall, severe COVID-19 patients showed statistically significantly higher levels of SARS-CoV-2-specific neutralising antibodies (average 1029 IU/ml) than those observed in seropositive HCW with mild or asymptomatic infections (379 IU/ml) and that clinical severity scoring, based on WHO guidelines was tightly correlated with neutralisation and RBD/S antibodies. In addition, there was a positive correlation between severity, N-antibody assays and intracellular virus neutralisation.