Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged recently and has created a global pandemic. Symptomatic SARS-CoV-2 infection, termed coronavirus disease 2019 (COVID-19), has been associated with a host of symptoms affecting numerous organ systems, including the lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract, and skin, among others.

Objective

Although several risk factors have been identified as related to complications from and severity of COVID-19, much about the virus remains unknown. The host immune response appears to affect the outcome of disease. It is not surprising that patients with intrinsic or secondary immune compromise might be particularly susceptible to complications from SARS-CoV-2 infection. Pathogenic loss-of-function or gain-of-function heterozygous variants in nuclear factor-κB2 have been reported to be associated with either a combined immunodeficiency or common variable immunodeficiency phenotype.

Methods

We evaluated the functional consequence and immunologic phenotype of a novel NFKB2 loss of function variant in a 17-year-old male patient and describe the clinical management of SARS-CoV-2 infection in this context.

Results

This patient required a 2-week hospitalization for SARS-CoV-2 infection, including 7 days of mechanical ventilation. We used biologic therapies to avert potentially fatal acute respiratory distress syndrome and treat hyperinflammatory responses. The patient had an immunologic phenotype of B-cell dysregulation with decreased switched memory B cells. Despite the underlying immune dysfunction, he recovered from the infection with intense management.

Conclusions

This clinical case exemplifies some of the practical challenges in management of patients with SARS-CoV-2 infection, especially in the context of underlying immune dysregulation.

中文翻译：

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NF-κB2 功能丧失致病变异背景下的严重 SARS-CoV-2 疾病

背景

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是最近出现的一种新型冠状病毒，已引起全球大流行。症状性 SARS-CoV-2 感染，称为2019 年冠状病毒病(COVID-19)，与影响许多器官系统的一系列症状有关，包括肺、心血管系统、肾脏、中枢神经系统、胃肠道和皮肤，其中。

客观的

尽管已确定几个风险因素与 COVID-19 的并发症和严重程度有关，但有关该病毒的许多信息仍然未知。宿主免疫反应似乎会影响疾病的结果。具有内在或继发性免疫受损的患者可能特别容易受到 SARS-CoV-2 感染并发症的影响，这并不奇怪。据报道，核因子-κB2 中的致病性功能丧失或功能获得杂合变体与联合免疫缺陷或常见可变免疫缺陷表型有关。

方法

我们评估了一名 17 岁男性患者新型NFKB2功能丧失变异体的功能后果和免疫表型，并在此背景下描述了 SARS-CoV-2 感染的临床管理。

结果

该患者因 SARS-CoV-2 感染需要住院 2 周，其中包括 7 天的机械通气。我们使用生物疗法来避免可能致命的急性呼吸窘迫综合征并治疗过度炎症反应。该患者具有 B 细胞失调的免疫表型，并伴有转换记忆 B 细胞减少。尽管存在潜在的免疫功能障碍，但他通过严格的管理从感染中恢复过来。

结论

这个临床案例体现了 SARS-CoV-2 感染患者管理中的一些实际挑战，尤其是在潜在免疫失调的情况下。