Diverse Humoral Immune Responses in Younger and Older Adult COVID-19 Patients.
Diverse Humoral Immune Responses in Younger and Older Adult COVID-19 Patients.
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DOI：
10.1128/mbio.01229-21
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发表时间：
2021-06-29
期刊：
影响因子：
6.4
通讯作者：
Camerini D
中科院分区：
文献类型：
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作者：
Sasson JM;Campo JJ;Carpenter RM;Young MK;Randall AZ;Trappl-Kimmons K;Oberai A;Hung C;Edgar J;Teng AA;Pablo JV;Liang X;Yee A;Petri WA Jr;Camerini D
我们试图发现对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的抗体反应与患者的临床变量、细胞因子谱和地方性冠状病毒抗体之间的联系。收集了30名年龄较小(26~39 )和年龄较大(69~83 )的患者的血清样本，这些患者的临床严重度从门诊到机械通气不等，并用于探索一种新型的多冠状病毒蛋白芯片。该芯片包含SARS-CoV-2刺突蛋白(S)、包膜蛋白(E)、膜蛋白(M)、核衣壳蛋白(N)和开放阅读框架蛋白(ORF)的可变长度重叠片段。该阵列还包括SARS冠状病毒、中东呼吸综合征冠状病毒(MERS-CoV)、人类冠状病毒OC43(HCoV-OC43)和HCoV-NL63蛋白。在跨越氨基酸(AA)500到650的S1蛋白区域和跨越AA 201到300的N蛋白质区域内的特定表位的免疫球蛋白抗体反应在老年患者中显著升高，在那些接受机械通气的老年患者中进一步显著升高。此外，在当前临床后果的部分新出现的SARS-CoV-2变种中，抗原区和已知突变位置之间存在明显的重叠(B.1.1.7、B1.351、P.1、CAL20.C和B.1.526)。此外，与青年组相比，老年组的抗体反应性与全身细胞因子和趋化因子反应的相关性更一致。然而，一小部分患者对SARS-CoV-2抗原几乎没有反应，临床结果严重得不成比例。对这些慢-低反应个体进行细胞因子分析的进一步特征显示，与队列中血清阳性患者相比，白介素10(IL-10)、IL-15和干扰素诱导蛋白10(IP-10)水平显著升高，而表皮生长因子(EGF)和可溶性CD40配体(SCD40L)水平显著降低。
We sought to discover links between antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patient clinical variables, cytokine profiles, and antibodies to endemic coronaviruses. Serum samples from 30 patients of younger (26 to 39 years) and older (69 to 83 years) age groups and with varying clinical severities ranging from outpatient to mechanically ventilated were collected and used to probe a novel multi-coronavirus protein microarray. This microarray contained variable-length overlapping fragments of SARS-CoV-2 spike (S), envelope (E), membrane (M), nucleocapsid (N), and open reading frame (ORF) proteins created through in vitro transcription and translation (IVTT). The array also contained SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus OC43 (HCoV-OC43), and HCoV-NL63 proteins. IgG antibody responses to specific epitopes within the S1 protein region spanning amino acids (aa) 500 to 650 and within the N protein region spanning aa 201 to 300 were found to be significantly higher in older patients and further significantly elevated in those older patients who were ventilated. Additionally, there was a noticeable overlap between antigenic regions and known mutation locations in selected emerging SARS-CoV-2 variants of current clinical consequence (B.1.1.7, B1.351, P.1, CAL20.C, and B.1.526). Moreover, the older age group displayed more consistent correlations of antibody reactivity with systemic cytokine and chemokine responses than the younger adult group. A subset of patients, however, had little or no response to SARS-CoV-2 antigens and disproportionately severe clinical outcomes. Further characterization of these slow-low-responding individuals with cytokine analysis revealed significantly higher interleukin-10 (IL-10), IL-15, and interferon gamma-induced protein 10 (IP-10) levels and lower epidermal growth factor (EGF) and soluble CD40 ligand (sCD40L) levels than those of seroreactive patients in the cohort.