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.

中文翻译：

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SARS-CoV-2 特异性 T 细胞和 B 细胞反应与 SARS-CoV-2 奥密克戎感染免疫功能低下个体的早期病毒清除有关。


背景 推动免疫功能低下个体中新致病病毒株开发的延迟病毒清除和宿主内病毒进化的免疫决定因素尚不清楚。因此，我们纵向研究了严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 特异性免疫反应与免疫功能低下个体的病毒清除和进化有关。方法 在 Omicron 感染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、中和滴度和单克隆抗体 （mAb） 耐药相关突变。入组后 28 天的鼻咽标本定义为早期（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 在纳入的 30 例患者 （中位年龄，61.9 [四分位距，47.4-72.3] 岁;50% 为女性）中，20 例 （66.7%） 接受了 mAb 治疗。13 例 （43.3%） 表现出早期病毒清除，17 例 （56.7%） 表现出晚期病毒清除。早期病毒清除患者和无耐药相关突变的患者基线干扰素γ释放显著更高，病毒早期清除患者基线时 SARS-CoV-2 特异性 B 细胞的频率更高。在非 mAb 治疗患者中，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。结论 早期稳健的适应性免疫反应对于有效的病毒清除至关重要，并且与 Omicron 感染免疫功能低下患者 mAb 耐药相关突变的出现较少相关。 这强调了早期 SARS-CoV-2 特异性 T 细胞和 B 细胞反应的重要性，从而为开发新的治疗方法提供了理论依据。