Profiling complement proteins in pediatric tuberculosis children with or without serological evidence of prior...

Coinfection with Mycobacterium tuberculosis (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.

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.

CoV2⁺ children 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 CoV2^- children. However C2 and C5 diminished in CoV2⁺ children 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 CoV2⁺ and CoV2^- groups over time.

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.