在接受白细胞介素 6 阻断治疗后从重症 COVID-19 中康复的患者中对 SARS-CoV-2 具有强大的长期免疫力。
Robust long-term immunity to SARS-CoV-2 in patients recovered from severe COVID-19 after interleukin-6 blockade.
机构信息
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain; Clinical Medicine Department, Universidad Miguel Hernández de Elche, Alicante, Spain.
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
出版信息
EBioMedicine. 2022 Aug;82:104153. doi: 10.1016/j.ebiom.2022.104153. Epub 2022 Jul 8.
BACKGROUND
Whether interleukin-6 (IL-6) blockade in patients with COVID-19 will affect the protective immunity against SARS-CoV-2 has become an important concern for anti-IL-6 therapy. We aimed to investigate the effects of IL-6 blockade on long-term immunity to SARS-CoV-2.
METHODS
Prospective, longitudinal cohort study conducted in patients hospitalized for severe or critical COVID-19 with laboratory confirmed SARS-CoV-2 infection. We assessed humoral (anti-S1 domain of the spike [S], anti-nucleocapsid [N], anti-trimeric spike [TrimericS] IgG, and neutralizing antibodies [Nab]) and T-cell (interferon-γ release assay [IGRA]) responses and evaluated the incidence of reinfections over one year after infection in patients undergoing IL-6 blockade with tocilizumab and compared them with untreated subjects.
FINDINGS
From 150 adults admitted with confirmed SARS-CoV-2 infection, 78 were 1:1 propensity score-matched. Patients receiving anti-IL6 therapy showed a shorter time to S-IgG seropositivity and stronger S-IgG and N-IgG antibody responses. Among unvaccinated subjects one year after infection, median (Q1-Q3) levels of TrimericS-IgG (295 vs 121 BAU/mL; p = 0.011) and Nab (74.7 vs 41.0 %IH; p = 0.012) were higher in those undergoing anti-IL6 therapy, and a greater proportion of them had Nab (80.6% vs 57.7%; p = 0.028). T-cell immunity was also better in those treated with anti-IL6, with higher median (Q1-Q3) interferon-γ responses (1760 [702-3992] vs 542 [35-1716] mIU/mL; p = 0.013) and more patients showing positive T-cell responses in the IGRA one year after infection. Patients treated with anti-IL6 had fewer reinfections during follow-up and responded to vaccination with robust increase in both antibody and T-cell immunity.
INTERPRETATION
IL-6 blockade in patients with severe COVID-19 does not have deleterious effects on long-term immunity to SARS-CoV-2. The magnitude of both antibody and T-cell responses was stronger than the observed in non-anti-cytokine-treated patients with no increase in the risk of reinfections.
FUNDING
Instituto de Salud Carlos-III (Spain).
背景
白细胞介素 6（IL-6）阻断治疗是否会影响 COVID-19 患者对 SARS-CoV-2 的保护性免疫，已成为抗 IL-6 治疗的一个重要关注点。本研究旨在探讨 IL-6 阻断对 SARS-CoV-2 长期免疫的影响。
方法
这是一项前瞻性、纵向队列研究，纳入因 COVID-19 住院且实验室确诊 SARS-CoV-2 感染的患者。我们评估了体液（抗 S 蛋白域 [S]、抗核衣壳 [N]、三聚体 S [TrimericS] IgG 和中和抗体 [Nab]）和 T 细胞（干扰素-γ释放试验 [IGRA]）应答，并评估了感染后一年患者再次感染的发生率，比较了接受托珠单抗 IL-6 阻断治疗的患者和未接受治疗的患者。
发现
在 150 名因 COVID-19 住院且经实验室确诊 SARS-CoV-2 感染的成年人中，有 78 人进行了 1:1 倾向评分匹配。接受抗 IL-6 治疗的患者出现 S-IgG 血清阳性的时间更短，S-IgG 和 N-IgG 抗体应答更强。在感染后一年未接种疫苗的患者中，接受抗 IL-6 治疗的患者的 TrimericS-IgG（295 vs 121 BAU/mL；p = 0.011）和 Nab（74.7 vs 41.0 %IH；p = 0.012）中位（Q1-Q3）水平更高，并且它们的 Nab 阳性比例更高（80.6% vs 57.7%；p = 0.028）。接受抗 IL-6 治疗的患者 T 细胞免疫也更好，IGRA 感染后一年的中位（Q1-Q3）干扰素-γ应答（1760 [702-3992] vs 542 [35-1716] mIU/mL；p = 0.013）更高，并且更多的患者对 IGRA 检测有阳性 T 细胞应答。在随访期间，接受抗 IL-6 治疗的患者再感染较少，并且对疫苗接种有更强的抗体和 T 细胞免疫应答。
解释
COVID-19 重症患者的 IL-6 阻断治疗对 SARS-CoV-2 的长期免疫没有不良影响。抗体和 T 细胞反应的强度均大于未接受细胞因子治疗的患者的观察结果，且再感染风险并未增加。
资助
西班牙卡洛斯三世健康研究所（Instituto de Salud Carlos-III）。
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