SARS-CoV-2-Specific Immune Responses to Vaccination in Children and Adolescents with Suppressed Immune Systems: A Prospective, Observational Study.

Abstract

To investigate the concern that children and young people (CYP) receiving immune-suppressing treatments mount impaired responses to vaccines, in CYP compared with healthy controls. We prospectively enrolled CYP aged 5-17 years who are receiving we measured humoral and cellular biological response-modifying therapies for rheumatologic inflammatory conditions (RICs), or post solid organ transplant (PSOT), or cancer chemotherapy before and/or after routine vaccinations with BNT162b2 vaccine. Responses to SARS-CoV-2 vaccination were assessed by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics) and T-cell responses (Oxford Immunotec). Response to wild-type and SARS-CoV-2 variants (BA5, XBB1.5) was assessed by microneutralization assay. Control data were from ComCOV3. We enrolled 125 eligible participants (RIC n = 54 [43.2%], PSOT n = 49 [39.2%], cancer n = 22 [17.6%]); 58 (46.4%) female; mean age, 12.9 ± 2.9 years. Seventy-nine participants (63.2%) had prior COVID-19 and 28 (22.4%) were unvaccinated before the study; 97 participants (77.6%) received ≥1 vaccines; 13 (10.4%) reported COVID-19 infection during follow-up. CYP receiving chemotherapy for cancer had lower antibody responses post vaccine: anti-SARS-CoV-2 spike antibodies (median, 26.7 AU/mL; IQR, 2.3-1088.0 AU/mL) compared with RIC (median, 6970.0 AU/mL; IQR, 1417.0-18163.0 AU/mL) and PSOT (medina, 7899.0 AU/mL; IQR, 1711.0-19201.0 AU/mL) (both P < .0001). T-cell responses were also reduced in the cancer group (median, 8.0 SFC/10⁶ PBMCs; IQR, 0.0-48.0 SFC/10⁶ PBMCs) compared with RIC (median, 110.0 SFC/10⁶ PBMCs; IQR, 44.0-260.0 SFC/10⁶ PBMCs; P = .009) and PSOT (median, 74.0 SFC/10⁶ PBMCs; IQR, 32.0-160.0 SFC/10⁶ PBMCs; P = .003). Children receiving immune-suppressing therapies for RIC and PSOT had antibody and T-cell responses after the third vaccine dose that approached levels reported in healthy controls. Children who were receiving cancer chemotherapy, however, showed substantially reduced humoral and T-cell responses. ISRCTN 12821688; https://www.isrctn.com/ISRCTN12821688.