The SARS-CoV-2 pandemic is impacting the global population. This study was designed to assess the interplay of antibodies with the cytokine response in SARS-CoV-2 patients. We demonstrate that significant levels of anti-SARS-CoV-2 antibody to receptor binding domain (RBD), nucleocapsid, and spike S1 subunit of SARS-CoV-2 develop over the first 10 to 20 days of infection. The majority of patients produced antibodies against all three antigens (219/255 SARS-CoV-2⁺ patient specimens, 86%), suggesting a broad response to viral proteins. Antibody levels to SARS-CoV-2 antigens were different based on patient mortality, sex, blood type, and age. Analyses of these findings may help explain variation in immunity between these populations. To better understand the systemic immune response, we analyzed the levels of 20 cytokines by SARS-CoV-2 patients throughout infection. Cytokine analysis of SARS-CoV-2⁺ patients exhibited increases in proinflammatory markers (interleukin 6 [IL-6], IL-8, IL-18, and gamma interferon [IFN-γ]) and chemotactic markers (IP-10 and eotaxin) relative to healthy individuals. Patients who succumbed to infection produced decreased IL-2, IL-4, IL-12, RANTES, tumor necrosis factor alpha (TNF-α), GRO-α, and MIP-1α relative to patients who survived infection. We also observed that the chemokine CXCL13 was particularly elevated in patients who succumbed to infection. CXCL13 is involved in B cell activation, germinal center development, and antibody maturation, and we observed that CXCL13 levels in blood trended with anti-SARS-CoV-2 antibody levels. Furthermore, patients who succumbed to infection produced high CXCL13 and had a higher ratio of nucleocapsid to RBD antibodies. This study provides insights into SARS-CoV-2 immunity implicating the magnitude and specificity of response in relation to patient outcomes.

中文翻译：

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抗体和细胞因子产生的相互作用揭示 CXCL13 作为致命 SARS-CoV-2 感染的潜在新型生物标志物

SARS-CoV-2 大流行正在影响全球人口。本研究旨在评估 SARS-CoV-2 患者中抗体与细胞因子反应的相互作用。我们证明，在感染的前 10 至 20 天内，针对 SARS-CoV-2 的受体结合域 (RBD)、核衣壳和刺突 S1 亚基的抗 SARS-CoV-2 抗体出现了显着水平。大多数患者产生针对所有三种抗原的抗体（219/255 SARS-CoV-2 ⁺患者标本，86%），表明对病毒蛋白有广泛的反应。SARS-CoV-2 抗原的抗体水平因患者死亡率、性别、血型和年龄而异。对这些发现的分析可能有助于解释这些人群之间免疫力的差异。为了更好地了解全身免疫反应，我们分析了 SARS-CoV-2 患者在整个感染过程中 20 种细胞因子的水平。SARS-CoV-2 ⁺患者的细胞因子分析显示促炎标记物（白细胞介素 6 [IL-6]、IL-8、IL-18 和 γ 干扰素 [IFN-γ]）和趋化标记物（IP-10 和嗜酸细胞趋化因子）增加）相对于健康个体。与感染后幸存的患者相比，感染后的患者产生的 IL-2、IL-4、IL-12、RANTES、肿瘤坏死因子 α (TNF-α)、GRO-α 和 MIP-1α 减少。我们还观察到，趋化因子 CXCL13 在死于感染的患者中尤其升高。CXCL13 参与 B 细胞激活、生发中心发育和抗体成熟，我们观察到血液中 CXCL13 水平与抗 SARS-CoV-2 抗体水平呈趋势。此外，死于感染的患者产生高CXCL13，并且核衣壳与RBD抗体的比例较高。这项研究提供了对 SARS-CoV-2 免疫的见解，涉及与患者结果相关的反应的程度和特异性。