Anti-nucleocapsid antibody levels reflect post-acute sequelae of COVID-19 symptom burden in children

Abstract

Background: Post-acute sequelae of COVID-19 (PASC) presents significant challenges in pediatric care due to the lack of standardized diagnostic criteria. Understanding the lingering effects of the virus in pediatric patients is paramount. This study aims to explore the clinical and immunological dimensions of pediatric PASC, with a focus on anti-nucleocapsid (anti-N) IgG.

Methods: The Diagnosis and Support for COVID-19 Children to Enhance Recovery (DISCOVER) cohort, initiated in July 2022, enrolled 92 children in central Taiwan. A specialized PASC condition scale was developed to assess multisystem symptoms. Blood biomarkers, immune cytokine and immune checkpoint protein levels, IgG against SARS-CoV-2 antigens, and virus nucleocapsid gene were measured.

Results: Higher PASC scores correlated positively with monocytes (R² = 0.284) and neutrophils (R² = 0.207), and negatively with eosinophils (R² = -0.275). Virus persistence was minimal within this study cohort. Although anti-N IgG, macrophage inflammatory protein-1 alpha (MIP-1α), interleukin (IL)-2, and IL-21 were significantly elevated in children with PASC, levels of these immune cytokines did not correlate with the PASC severity. Only anti-N IgG levels positively correlated with monocyte counts (R² = 0.230). ROC analysis further identified anti-N IgG as a predictor for PASC severity, with an optimal cutoff value of 11. Unsupervised clustering revealed that patients with higher anti-N IgG exhibited greater symptom severity.

Conclusions: These findings suggest that elevated anti-N IgG may serve as a potential biomarker for stratifying disease severity in pediatric PASC.

Keywords: SARS-CoV-2 infection; anti-nucleocapsid antibody; biomarker; coronavirus disease; pediatric; post-acute sequelae of COVID-19 (PASC).