SARS-CoV-2-Specific Immune Responses to Vaccination in Children and Adolescents with Suppressed Immune Systems: A Prospective, Observational Study.
Brugha R., Kirkham A., Bate J., Burke GAA., Hughes A., Magwaro S., Pope AM., Beesley R., Lax S., Kelly E., Greenland M., Minassian AM., Liu X., Billingham L., McInnes I., Goodyear CS., Kearns P., Wedderburn LR., OCTAVE-Minor Collaborative Group .
OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: ISRCTN 12821688; https://www.isrctn.com/ISRCTN12821688.