Laboratory Division, Boston Heart Diagnostics/Eurofins Scientific Network, Framingham, Massachusetts, United States of America.
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
PLoS One. 2021 Jun 10;16(6):e0252818. doi: 10.1371/journal.pone.0252818. eCollection 2021.
Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (P<0.0001). Neutralizing antibody levels correlated significantly with IgG (r = 0.875; P<0.0001). Having combined values of IL-6 ≥10 pg/mL and CRP ≥10 mg/L occurred in 97.7% of inpatients versus 1.8% of outpatients (odds ratio 3,861, C statistic 0.976, P = 1.00 x 10-12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if <30 years of age, 4.38 if 30-44 years of age, 7.89 if 45-54 years of age, 9.52 if 55-64 years of age, and 10.64 if ≥65 years of age (P = 2.96 x 10-38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.
大多数严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染导致的死亡发生在老年人中。我们评估了血清炎症标志物白细胞介素 6（IL-6）、C 反应蛋白（CRP）和铁蛋白（罗氏，印第安纳波利斯，IN），以及 SARS-CoV-2 免疫球蛋白 G（IgG）、免疫球蛋白 M（IgM）和中和抗体（Diazyme，Poway，CA）的效用。在对照组、非住院患者和评估 SARS-CoV-2 RNA 的住院患者（n=278）中，阴性患者的 IgG 水平以任意单位（AU）/mL 中位数为 0.05，阳性门诊患者为 14.83，阳性住院患者为 30.61（P<0.0001）。中和抗体水平与 IgG 显著相关（r=0.875；P<0.0001）。住院患者中同时出现 IL-6≥10pg/mL 和 CRP≥10mg/L 的比例为 97.7%，而门诊患者为 1.8%（优势比 3861，C 统计量 0.976，P=1.00 x 10-12）。抗体或铁蛋白水平对预测住院无显著意义。对 SARS-CoV-2 RNA 阳性病例的家庭成员和接触者（n=759）进行抗体检测对病例发现非常有价值。持续存在的 IgM 水平与慢性 COVID-19 症状有关。在 81624 名筛查对象中，IgG 水平阳性（≥1.0 AU/mL）的比例为 5.21%，而 IgM 水平阳性的比例为 2.96%。在阳性患者中，AU/mL 中位数的 IgG 水平为 30 岁以下为 3.14，30-44 岁为 4.38，45-54 岁为 7.89，55-64 岁为 9.52，≥65 岁为 10.64（P=2.96 x 10-38）。我们的数据表明：1）联合 IL-6≥10pg/mL 和 CRP≥10mg/L 可识别需要住院的 SARS-CoV-2 阳性患者；2）IgG 水平与中和抗体水平显著相关，且具有广泛的反应范围；3）IgG 水平对暴露于 SARS-CoV-2 的患者的病例发现具有显著的实用性；4）持续升高的 IgM 水平与慢性症状有关；5）与年轻患者相比，阳性老年患者的 IgG 水平显著更高。
