Alterations of anti-SARS-CoV-2 immune response in children vary according to the nature of their immunosuppression.
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OBJECTIVES: Effective adaptive immune responses are essential for immune protection against SARS-CoV-2. We investigated the impact of various forms of acquired or iatrogenic immunodeficiency on anti-SARS-CoV-2 humoral and cellular immune responses among children. DESIGN: We analyzed anti-spike (S) immunoglobulin G levels, neutralizing activities, and the magnitude and polyfunctionality of anti-S T-cell responses in immunocompromised children compared with immunocompetent children, prospectively recruited between June and October 2021, before vaccination. RESULTS: We observed marked quantitative and functional alterations in anti-S humoral immune response in children with inflammatory bowel diseases treated with anti-tumor necrosis factor-α. In children living with HIV and children after kidney transplantation, the production of anti-S antibody was conserved but with a decrease of their neutralizing activity against SARS-CoV-2 strains. Regarding anti-S cellular immune response, immunocompetent and immunocompromised children similarly harbored a low anti-S response, predominantly displaying a clusters of differentiations (CD)4+ phenotype, with a preserved CD4+ T-cell polyfunctionality. CONCLUSION: The intensity and the nature of the anti-viral immune alterations depend on the type and the degree of the immune impairment. Evaluating the specific host immune actors responsible for maintaining a protective response appears essential to adapt vaccine strategy in these patients, opening the door to new, more personalized vaccination approaches.