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智利免疫功能低下患者队列中对灭活严重急性呼吸综合征冠状病毒 2 疫苗的免疫反应降低。

Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile.

机构信息

Departamento de Enfermedades Infecciosas del Adulto, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

Departamento de Enfermedades Infecciosas e Inmunologia Pediatrica. Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile.

出版信息

Clin Infect Dis. 2022 Aug 24;75(1):e594-e602. doi: 10.1093/cid/ciac167.

Abstract

BACKGROUND

Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients.

METHODS

This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined.

RESULTS

NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups.

CONCLUSIONS

Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients.

CLINICAL TRIALS REGISTRATION

NCT04888793.

摘要

背景

已在中低收入国家广泛使用灭活严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)疫苗。然而,免疫功能低下患者的免疫原性尚未确定。在此,我们旨在评估 CoronaVac 疫苗在这些患者中的免疫反应。

方法

这是一项前瞻性队列研究,纳入了 193 名患有 5 种不同免疫功能低下疾病的患者和 67 名对照者,他们在入组前 8-12 周接种了 2 剂 CoronaVac。该研究于 2021 年 5 月至 8 月在智利圣地亚哥的 Red de Salud UC-CHRISTUS 进行。测定了中和抗体(NAb)阳性率、总抗 SARS-CoV-2 免疫球蛋白 G 抗体(TAb)浓度和 T 细胞反应。

结果

对照组的 NAb 阳性率和中位数中和活性分别为 83.1%和 51.2%,而实体器官移植组分别为 20.6%和 5.7%(均 P<.001),自身免疫性风湿病组分别为 41.5%和 19.2%(均 P<.0001),癌症伴实体瘤组分别为 43.3%(P<.001)和 21.4%(P<.01 或 P=.001),人类免疫缺陷病毒(HIV)感染组分别为 45.5%和 28.7%(均 P<.001),造血干细胞移植组分别为 64.3%和 56.6%(差异均无统计学意义)。与对照组相比,实体器官移植(20.6%;P<.0001)、风湿性疾病(61%;P<.001)和 HIV 组(70.9%;P=.003)的 TAb 血清阳性率也较低。另一方面,所有免疫功能低下情况下针对 SARS-CoV-2 的干扰素 γ 斑点形成 T 细胞数量均较低,但组间无显著差异。

结论

不同的免疫功能低下情况显著降低了 CoronaVac 疫苗的体液反应。这些发现表明,在这些脆弱的患者中应考虑加强疫苗接种策略。

临床试验注册

NCT04888793。

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