Undiagnosed COVID-19 in households with a child with mitochondrial disease

Eliza M Gordon-Lipkin, Christopher Marcum, Shannon Kruk, Elizabeth Thompson, Sophie E M Kelly, Heather Kalish, Kaitlyn Sadtler, Peter J McGuire, Eliza M Gordon-Lipkin, Christopher Marcum, Shannon Kruk, Elizabeth Thompson, Sophie E M Kelly, Heather Kalish, Kaitlyn Sadtler, Peter J McGuire

Abstract

Background: The impact of the COVID-19 pandemic on medically fragile populations, who are at higher risk of severe illness and sequelae, has not been well characterized. Viral infection is a major cause of morbidity in children with mitochondrial disease (MtD), and the COVID-19 pandemic represents an opportunity to study this vulnerable population.

Methods: A convenience sampling cross-sectional serology study was conducted (October 2020 to June 2021) in households (N = 20) containing a child with MtD (N = 22). Samples (N = 83) were collected in the home using a microsampling apparatus and shipped to investigators. Antibodies against SARS-CoV-2 nucleocapsid (IgG), spike protein (IgG, IgM, IgA), and receptor binding domain (IgG, IgM, IgA) were determined by enzyme linked immunosorbent assay.

Results: While only 4.8% of participants were clinically diagnosed for SARS-CoV-2 infection, 75.9% of study participants were seropositive for SARS-CoV-2 antibodies. Most samples were IgM positive for spike or RBD (70%), indicating that infection was recent. This translated to all 20 families showing evidence of infection in at least one household member. For the children with MtD, 91% had antibodies against SARS-CoV-2 and had not experienced any adverse outcomes at the time of assessment. For children with recent infections (IgM + only), serologic data suggest household members as a source.

Conclusions: COVID-19 was highly prevalent and undiagnosed in households with a child with MtD through the 2020-2021 winter wave of the pandemic. In this first major wave, children with MtD tolerated SARS-CoV-2 infection well, potentially due to household adherence to CDC recommendations for risk mitigation.

Funding: This study was funded by the Intramural Research Program of the National Institutes of Health (HG200381-03).

Clinical trial number: NCT04419870.

Conflict of interest statement

COMPETING INTERESTS

The authors have no conflicts of interest to report.

Figures

Figure 1:. SARS-CoV-2 antibody profile in MtD…
Figure 1:. SARS-CoV-2 antibody profile in MtD patients versus family members.
(a) Heatmap showing antibody prevalence in the blood of participants, Nuc = Nucleocapsid, S = Full Spike ectodomain, RBD = Spike Receptor Binding Domain. (b) Anti-spike IgG (c) Anti-spike IgM (d) Anti-spike IgA. (e) Spearman correlation matrix, two-tailed (f) P-values for spearman correlation. Y-axis labels are in Figure 1e. (g) Antibody analytes mean absorbance (OD) between MtD (red) and family (blue), significance = Two-way ANOVA with Tukey post-hoc correction for multiple comparisons *** = p

Figure 2:. SARS-CoV-2 serology for families with…

Figure 2:. SARS-CoV-2 serology for families with a child with MtD.

To highlight the relationship…

Figure 2:. SARS-CoV-2 serology for families with a child with MtD.
To highlight the relationship between individuals in the household and the child(ren) with mitochondrial disease are represented as a spoke diagram. The child(ren) with MtD is located at the center and is connected to household members by spokes. Viral nucleocapsid, spike protein, and receptor binding domain (RBD) serologies were performed as outlined in the methods. Samples were collected for each participant at a single timepoint surrounding the 2020–2021 winter wave of the COVID-19 pandemic. Families are numbered 1 through 20, and SARS-CoV-2 serology status is indicated by the color key. M+ = IgM antibodies, G+ = IgG antibodies, A+ = IgA antibodies, Spike = SARS-CoV-2 spike protein, RBD = receptor binding domain of the SARS-CoV-2 spike protein, Nuc = viral nucleocapsid.
Figure 2:. SARS-CoV-2 serology for families with…
Figure 2:. SARS-CoV-2 serology for families with a child with MtD.
To highlight the relationship between individuals in the household and the child(ren) with mitochondrial disease are represented as a spoke diagram. The child(ren) with MtD is located at the center and is connected to household members by spokes. Viral nucleocapsid, spike protein, and receptor binding domain (RBD) serologies were performed as outlined in the methods. Samples were collected for each participant at a single timepoint surrounding the 2020–2021 winter wave of the COVID-19 pandemic. Families are numbered 1 through 20, and SARS-CoV-2 serology status is indicated by the color key. M+ = IgM antibodies, G+ = IgG antibodies, A+ = IgA antibodies, Spike = SARS-CoV-2 spike protein, RBD = receptor binding domain of the SARS-CoV-2 spike protein, Nuc = viral nucleocapsid.

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