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Background <p>Chronic cough is a frequent symptom of pediatric Long COVID, hypothetically driven by viral neurotropism and sensory nerve sensitization. We investigated the neuro-immune axis in pediatric asthma to determine if the magnitude of post-SARS-CoV-2 humoral immunity correlates with objective airway afferent nerve hypersensitivity.</p> Methods <p>This prospective observational study included 61 pre-pubertal children (aged 8 to &lt; 12&#xa0;years) with well-controlled, predominantly inhaled corticosteroid (ICS)-treated (93.4%) bronchial asthma and confirmed past SARS-CoV-2 infection. Systemic humoral memory was quantified via anti-Spike IgG and IgA titers. Objective cough reflex sensitivity was measured using a capsaicin challenge test, establishing C2 and C5 values. Subjective symptom burden was evaluated using parent-proxy questionnaires (PCQ, VAS, PedsQL).</p> Results <p>Stratification by median anti-Spike IgG (125.77 BAU/ml) revealed no significant differences in basal (C2, <i>p</i> = 0.301) or motor response (C5, <i>p</i> = 0.714) capsaicin thresholds between robust and waning humoral memory states. IgA stratification yielded identical results. Spearman’s correlation confirmed a complete lack of association between absolute IgG titers and neurophysiological markers (<i>p</i> &gt; 0.05). Crucially, parent-reported chronic cough severity (PCQ, VAS) and asthma-specific quality of life demonstrated a complete dissociation from objective capsaicin thresholds across all evaluated domains (all <i>p</i> &gt; 0.05). Supplementary subgroup analysis revealed no significant differences in cough thresholds based on acute COVID-19 severity (<i>p</i> &gt; 0.05).</p> Conclusion <p>A robust post-viral humoral immune response to SARS-CoV-2 does not precipitate peripheral airway nerve hypersensitivity in properly controlled, ICS-treated asthmatic children. The complete uncoupling of subjective parent-reported symptoms from objective neurophysiology cautions against diagnosing neurogenic Long COVID based solely on questionnaires, emphasizing the necessity of objective testing and evaluation of alternative atopic etiologies.</p>

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Serological Profiling and Neuro-Immune Resilience: The Dissociation Between Anti-SARS-CoV-2 Antibodies and Post-Viral Airway Hyperresponsiveness in Pediatric Asthma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月24日

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  • Peter Kunc,
  • Jaroslav Fabry,
  • Jana Mazuchova,
  • Martin Pec,
  • Renata Pecova

摘要

Background

Chronic cough is a frequent symptom of pediatric Long COVID, hypothetically driven by viral neurotropism and sensory nerve sensitization. We investigated the neuro-immune axis in pediatric asthma to determine if the magnitude of post-SARS-CoV-2 humoral immunity correlates with objective airway afferent nerve hypersensitivity.

Methods

This prospective observational study included 61 pre-pubertal children (aged 8 to < 12 years) with well-controlled, predominantly inhaled corticosteroid (ICS)-treated (93.4%) bronchial asthma and confirmed past SARS-CoV-2 infection. Systemic humoral memory was quantified via anti-Spike IgG and IgA titers. Objective cough reflex sensitivity was measured using a capsaicin challenge test, establishing C2 and C5 values. Subjective symptom burden was evaluated using parent-proxy questionnaires (PCQ, VAS, PedsQL).

Results

Stratification by median anti-Spike IgG (125.77 BAU/ml) revealed no significant differences in basal (C2, p = 0.301) or motor response (C5, p = 0.714) capsaicin thresholds between robust and waning humoral memory states. IgA stratification yielded identical results. Spearman’s correlation confirmed a complete lack of association between absolute IgG titers and neurophysiological markers (p > 0.05). Crucially, parent-reported chronic cough severity (PCQ, VAS) and asthma-specific quality of life demonstrated a complete dissociation from objective capsaicin thresholds across all evaluated domains (all p > 0.05). Supplementary subgroup analysis revealed no significant differences in cough thresholds based on acute COVID-19 severity (p > 0.05).

Conclusion

A robust post-viral humoral immune response to SARS-CoV-2 does not precipitate peripheral airway nerve hypersensitivity in properly controlled, ICS-treated asthmatic children. The complete uncoupling of subjective parent-reported symptoms from objective neurophysiology cautions against diagnosing neurogenic Long COVID based solely on questionnaires, emphasizing the necessity of objective testing and evaluation of alternative atopic etiologies.