在 SARS-CoV-2 奥密克戎感染免疫功能低下个体中，强大的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）特异性 T 细胞和 B 细胞反应与早期病毒清除相关。

A Robust Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Specific T- and B-Cell Response Is Associated With Early Viral Clearance in SARS-CoV-2 Omicron-Infected Immunocompromised Individuals.

机构信息

Center for Experimental and Molecular Medicine, Amsterdam University Medical Center, location AMC, University of Amsterdam, Amsterdam, The Netherlans.

Amsterdam institute for Infection and Immunity, Infectious Diseases.

出版信息

J Infect Dis. 2024 Oct 16;230(4):e860-e871. doi: 10.1093/infdis/jiae306.

DOI:10.1093/infdis/jiae306

PMID:38843052

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11481360/

Abstract

BACKGROUND

The immunological determinants of delayed viral clearance and intrahost viral evolution that drive the development of new pathogenic virus strains in immunocompromised individuals are unknown. Therefore, we longitudinally studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in relation to viral clearance and evolution in immunocompromised individuals.

METHODS

Among Omicron-infected immunocompromised individuals, we determined SARS-CoV-2-specific T- and B-cell responses, anti-spike immunoglobulin G (IgG) and IgG3 titers, neutralization titers, and monoclonal antibody (mAb) resistance-associated mutations. The 28-day post-enrollment nasopharyngeal specimen defined early (reverse-transcription polymerase chain reaction [RT-PCR] negative ≤28 days) or late (RT-PCR positive >28 days) viral clearance.

RESULTS

Of 30 patients included (median age, 61.9 [interquartile range, 47.4-72.3] years; 50% females), 20 (66.7%) received mAb therapy. Thirteen (43.3%) demonstrated early and 17 (56.7%) late viral clearance. Patients with early viral clearance and patients without resistance-associated mutations had significantly higher baseline interferon-γ release, and patients with early viral clearance had a higher frequency of SARS-CoV-2-specific B cells at baseline. In non-mAb-treated patients, day 7 IgG and neutralization titers were significantly higher in those with early versus late viral clearance.

CONCLUSIONS

An early robust adaptive immune response is vital for efficient viral clearance and associated with less emergence of mAb resistance-associated mutations in Omicron-infected immunocompromised patients. This emphasizes the importance of early SARS-CoV-2-specific T- and B-cell responses and thereby provides a rationale for development of novel therapeutic approaches.

摘要

背景

免疫决定因素导致免疫功能低下个体中病毒清除延迟和宿主内病毒进化，从而产生新的致病性病毒株。因此，我们纵向研究了严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）特异性免疫反应与免疫功能低下个体中病毒清除和进化的关系。

方法

在感染奥密克戎的免疫功能低下个体中，我们确定了 SARS-CoV-2 特异性 T 细胞和 B 细胞反应、抗刺突免疫球蛋白 G（IgG）和 IgG3 滴度、中和滴度以及单克隆抗体（mAb）耐药相关突变。以 28 天随访时的鼻咽拭子为界，定义早期（逆转录聚合酶链反应[RT-PCR]阴性≤28 天）或晚期（RT-PCR 阳性>28 天）病毒清除。

结果

共纳入 30 例患者（中位年龄 61.9[四分位数间距，47.4-72.3]岁；50%为女性），其中 20 例（66.7%）接受了 mAb 治疗。13 例（43.3%）患者发生早期病毒清除，17 例（56.7%）患者发生晚期病毒清除。早期病毒清除患者和无耐药相关突变患者的基线干扰素-γ释放显著更高，早期病毒清除患者的 SARS-CoV-2 特异性 B 细胞频率也更高。在未接受 mAb 治疗的患者中，早期病毒清除患者的第 7 天 IgG 和中和滴度显著高于晚期病毒清除患者。