Metabolism, Infection and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Data Science Policy, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Clin Transl Med. 2022 Nov;12(11):e1100. doi: 10.1002/ctm2.1100.
Viral infection is a major cause of morbidity in children with mitochondrial disease (MtD). As a result, families with children with MtD are highly adherent to risk mitigation behaviours (RMBs) advised by the Centers for Disease Control and Prevention during the COVID-19 pandemic that can modulate infection risk.
Deep serologic phenotyping of viral infections was performed via home-based sampling by combining SARS-CoV-2 serologic testing and phage display immunoprecipitation and sequencing. Samples were collected approximately 1 year apart (October 2020 to April 2021 and October 2021 to March 2022) on households containing a child with MtD.
In contrast to our first collection in 2020-2021, SARS-CoV-2 antibody profiles for all participants in 2021-2022 were marked by greater isotype diversity and the appearance of neutralizing antibodies. Besides SARS-CoV-2, households (N = 15) were exposed to >38 different respiratory and gastrointestinal viruses during the study, averaging five viral infections per child with MtD. Regarding clinical outcomes, children with MtD (N = 17) experienced 34 episodes of illness resulting in 6 hospitalizations, with some children experiencing multiple episodes. Neurologic events following illness were recorded in five patients. Infections were identified via clinical testing in only seven cases. Viral exposome profiles were consistent with clinical testing and even identified infections not captured by clinical testing.
Despite reported adherence to RMBs during the COVID-19 pandemic by families with a child with MtD, viral infection was pervasive. Not all infections resulted in illness in the child with MtD, suggesting that some were subclinical or asymptomatic. However, selected children with MtD did experience neurologic events. Our studies emphasize that viral infections are inexorable, emphasizing the need for further understanding of host-pathogen interactions through broad serologic surveillance.
病毒感染是儿童患线粒体疾病（MtD）的主要病因。因此，在 COVID-19 大流行期间，患有 MtD 儿童的家庭高度遵守疾病控制与预防中心（CDC）建议的降低风险行为（RBM），以降低感染风险。
通过家庭采样，结合 SARS-CoV-2 血清学检测和噬菌体展示免疫沉淀和测序，对病毒感染进行深度血清表型分析。样本采集相隔约 1 年（2020 年 10 月至 2021 年 4 月和 2021 年 10 月至 2022 年 3 月），采样家庭中包含患有 MtD 的儿童。
与我们 2020-2021 年的第一次采集相比，2021-2022 年所有参与者的 SARS-CoV-2 抗体谱均表现出更高的同型多样性和中和抗体的出现。除了 SARS-CoV-2，家庭（N=15）在研究期间还暴露于 >38 种不同的呼吸道和胃肠道病毒，每个患有 MtD 的儿童平均发生 5 次病毒感染。关于临床结果，患有 MtD 的儿童（N=17）经历了 34 次疾病发作，导致 6 次住院，有些儿童经历了多次发作。5 名患者记录了疾病后的神经事件。只有在 7 例情况下通过临床检测发现了感染。病毒暴露组谱与临床检测一致，甚至确定了临床检测未捕捉到的感染。
尽管患有 MtD 儿童的家庭报告在 COVID-19 大流行期间遵守 RBM，但病毒感染仍很普遍。并非所有感染都导致 MtD 儿童生病，这表明有些是亚临床或无症状的。然而，一些患有 MtD 的儿童确实经历了神经事件。我们的研究强调了病毒感染是不可避免的，这强调了通过广泛的血清监测进一步了解宿主-病原体相互作用的必要性。
