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。