Comprehensive profiling of the human viral exposome in households containing an at-risk child with mitochondrial disease during the 2020-2021 COVID-19 pandemic

Eliza M Gordon-Lipkin; Christopher S Marcum; Shannon Kruk; Elizabeth Thompson; Sophie E M Kelly; Heather Kalish; Lorenza Bellusci; Surender Khurana; Kaitlyn Sadtler; Peter J McGuire

doi:10.1002/ctm2.1100

Comprehensive profiling of the human viral exposome in households containing an at-risk child with mitochondrial disease during the 2020-2021 COVID-19 pandemic

Clin Transl Med. 2022 Nov;12(11):e1100. doi: 10.1002/ctm2.1100.

Affiliations

¹ Metabolism, Infection and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
² Data Science Policy, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
³ Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
⁴ Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
⁵ Section on Immunoengineering, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: COVID-19; VirScan; infection; mitochondrial disease; viral exposome.

Publication types

Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural

MeSH terms

COVID-19* / epidemiology
Child
Exposome*
Humans
Mitochondrial Diseases*
Pandemics
SARS-CoV-2
United States
Virus Diseases*