Related Experiment Video
Updated: Jun 23, 2026
Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
Evaluating mucosal and systemic immunity in an observational cohort of South African children hospitalized with acute
Geert van Weelden1, Helena Rabie2, Andrew Redfern3
1Laboratory of Medical Immunology and Radboudumc Community for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Insights
Severe respiratory infections in children in low- and middle-income countries are linked to lower salivary inflammatory proteins, not antibody levels. Salivary biomarkers may help identify children at risk for severe outcomes.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Global Health
Background:
- Acute respiratory infections (ARIs), including SARS-CoV-2, cause significant childhood morbidity and mortality in low- and middle-income countries (LMICs).
- The immune factors determining ARI severity, particularly in children, are not well understood.
- Previous hypotheses suggested altered antibody or inflammatory responses might increase susceptibility to severe SARS-CoV-2.
Purpose of the Study:
- To investigate the immune determinants of acute respiratory infection severity in hospitalized South African children.
- To compare the roles of antibody levels and mucosal inflammatory profiles in disease severity.
- To explore the potential of salivary biomarkers for assessing mucosal immune responses.
Main Methods:
- A cohort study was conducted with South African children hospitalized with ARIs.
- Mucosal (saliva) and serum samples were collected longitudinally.
- Multiplex PCR identified viral pathogens, while antibody levels and inflammatory proteome profiles were assessed.
Main Results:
- Of 67 children (54%) positive for SARS-CoV-2 at enrollment, substantial anti-spike IgG was found in both SARS-CoV-2-positive and negative patients.
- Antibody levels did not correlate with disease severity.
- Lower expression of salivary inflammatory proteins was significantly associated with severe disease, independent of SARS-CoV-2 status.
Conclusions:
- Mucosal inflammatory protein expression, not antibody levels, is associated with respiratory infection severity in children.
- Salivary biomarkers show promise for understanding mucosal immune regulation.
- Identifying children at risk for severe respiratory infections in LMICs may be facilitated by salivary biomarker analysis.
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 an altered inflammatory response.
Methods:
We conducted a cohort study of South African children hospitalized 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 this cohort (median age 7.31 months, IQR 2.94-31.7), 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 higher odds of 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.
