Evaluating Mucosal and Systemic Immunity in an Observational Cohort of South African Children Hospitalised with Acute Respiratory Tract Infections
International Journal of Infectious Diseases, 2026
van Weelden G., Rabie H., Redfern A., Barday M., Dewandel I., Trutter C., van Niekerk M., Mentor M., Mfazwe A., de Jongh C., Dunbar R., Bosch C., Buddingh E., Lugthart G., Fröberg J., Diavatopoulos D., van Emst L., van Zyl G., Claassen M., Chegou N., de Jonge M., van der Zalm M., Verhagen L.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Respiratory Diseases Infectious Diseases | Pathophysiology Patient Stratification | Serum Saliva |  Olink Target 96 |
Abstract
Objectives: Acute respiratory infections, including SARS-CoV-2, remain a leading cause of childhood morbidity and mortality in low- and middle-income countries (LMICs), yet the underlying immune determinants of disease severity are poorly understood. The increased susceptibility to SARS-CoV-2 could be related to a decreased antibody or altered inflammatory response.
Methods: We conducted a cohort study of South African children hospitalised with acute respiratory infections, and collected mucosal and serum samples over time. Nasopharyngeal aspirates (NPAs) or swabs were tested for viral pathogens by multiplex PCR. Antibody levels, neutralising capacity, and inflammatory proteome profiles were assessed.
Results: In the cohort (median age 7.31 months, IQR 2.9-31.7), 67 children (54%) were SARS-CoV-2 positive at enrolment. Substantial baseline anti-spike IgG was detected in both SARS-CoV-2-positive (68% serum, 58% saliva) and negative (40% serum, 36% saliva) patients, irrespective of disease severity. Lower expression of salivary inflammatory proteins was associated with severe disease (p < 0.05), independent of SARS-CoV-2 status.Conclusion: Disease severity was associated with differences in mucosal inflammatory protein expression rather than antibody levels, irrespective of SARS-CoV-2 status. These findings highlight the potential value of salivary biomarkers for understanding mucosal immune regulation and identifying children at risk of severe respiratory infection outcomes in LMICs.