Profiling complement proteins in pediatric tuberculosis children with or without serological evidence of prior SARS-CoV-2 exposure
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Introduction Coinfection with(TB) and SARS-CoV-2 poses unique challenges in pediatric population due to overlapping immune pathways and potential immune dysregulation. The complement system, a key arm of innate immunity, plays a dual role in pathogen clearance and inflammation. Methods This study aimed to investigate complement activation in TB in children with or without serological evidence of prior SARS-CoV-2 exposure. Children aged 2–17 years with pulmonary or extrapulmonary TB were recruited from two tertiary hospitals in South India. Participants were grouped based on SARS-CoV-2 IgG serostatus: CoV2⁺ (n = 30) and CoV2⁻ (n = 30). Blood samples were collected at baseline, and at months 3, and 6 for complement profiling. Levels of classical, lectin, and alternative pathway proteins, as well as regulatory factors, were quantified using multiplex bead-based assays. Canonical discriminant analysis (CDA) and Spearman correlation were used to analyse temporal and relational patterns in complement activation. Results CoV2children had significantly elevated levels of classical pathway proteins (C1q, C3, C4, C5a) and regulatory factors (Factor B, H, and I) at baseline, month 3 and month 6 in comparison to CoV2children. However C2 and C5 diminished in CoV2children in comparison to CoV2-CDA revealed distinct, time-resolved complement activity in CoV2⁻ children, whereas CoV2⁺ profiles showed overlap, suggesting prolonged immune alteration. Correlation analysis identified significant
Abstract
Introduction Coinfection with(TB) and SARS-CoV-2 poses unique challenges in pediatric population due to overlapping immune pathways and potential immune dysregulation. The complement system, a key arm of innate immunity, plays a dual role in pathogen clearance and inflammation. Methods This study aimed to investigate complement activation in TB in children with or without serological evidence of prior SARS-CoV-2 exposure. Children aged 2–17 years with pulmonary or extrapulmonary TB were recruited from two tertiary hospitals in South India. Participants were grouped based on SARS-CoV-2 IgG serostatus: CoV2⁺ (n = 30) and CoV2⁻ (n = 30). Blood samples were collected at baseline, and at months 3, and 6 for complement profiling. Levels of classical, lectin, and alternative pathway proteins, as well as regulatory factors, were quantified using multiplex bead-based assays. Canonical discriminant analysis (CDA) and Spearman correlation were used to analyse temporal and relational patterns in complement activation. Results CoV2children had significantly elevated levels of classical pathway proteins (C1q, C3, C4, C5a) and regulatory factors (Factor B, H, and I) at baseline, month 3 and month 6 in comparison to CoV2children. However C2 and C5 diminished in CoV2children in comparison to CoV2-CDA revealed distinct, time-resolved complement activity in CoV2⁻ children, whereas CoV2⁺ profiles showed overlap, suggesting prolonged immune alteration. Correlation analysis identified significant associations between SARS-CoV-2 IgG and complement proteins, with differing patterns in CoV2and CoV2groups over time. Discussion SARS-CoV-2 seropositivity may contribute to changes in the complement activation trajectory in TB-diseased children, potentially contributing to persistent inflammation. Complement profiling may inform therapeutic strategies and serve as a biomarker of immune recovery in TB– SARS-CoV-2 co-infection.