Adiposity shapes the immune architecture independent of antibody responses in mild SARS-CoV-2 infection.

INTRODUCTION

Adiposity is linked to immune dysregulation, yet the extent to which body composition shapes the immune architecture and antibody responses after mild SARS-CoV-2 infection remains unclear. We examined how body composition relates to immune organization in a large, low-comorbidity cohort.

METHODS

In a subgroup of the DORM trial, segmental bioelectrical impedance was used to derive fat- and muscle-dominant components. Immune phenotypes were quantified by multiparametric flow cytometry, and neutralizing activity by a spike ACE2-RBD surrogate neutralization assay. Associations were tested using multivariable generalized linear models with effect modification by infection status; immune organizational endotypes were identified by k-means clustering.

RESULTS

We included 1005 predominantly healthy men (mean age 32.5 years; 591 seropositive and 414 seronegative), largely from India and Bangladesh. Fat mass, but not muscle mass, was the principal determinant of immune variation. Higher fat mass was associated with increased naïve B cells, elevated class-switch ratios, higher CD4+ T-cell proportions, and reduced CD8+ T-cell frequencies. These associations were independent of major metabolic covariates and were modified by infection status for T-cell subsets. In contrast, fat mass showed only weak and nonsignificant associations with neutralizing antibody activity. Clustering analyses identified adiposity-aligned immune endotypes characterized by coordinated shifts in B- and T-cell composition but minimal differences in neutralizing responses.

CONCLUSIONS

Adiposity is associated with distinct alterations in immune architecture, particularly affecting B-cell and T-cell composition, even in the absence of overt impairment in antibody neutralization.

GOV NUMBER: NCT04446104.