The Quantity and Quality of B-cell Immunity against SARS-CoV-2 in Children with Cancer and Hematological Diseases

Eva Tiselius¹Emil Sundberg²Amanda Ramilo Amor¹Hanna Andersson¹Renata Varnaite³Linda Kolstad⁴Dario Akaberi⁴Jiaxin Ling⁴Arja Harila²Shanie Saghafian-Hedengren¹Tove Hoffman⁴Anna B Nilsson^1*

• ¹Division of pediatric oncology, Dept of Women and Childrens Health, Karolinska Institutet (KI), Solna, Sweden
• ²Department of Women's and Children's Health, Faculty of Medicine, Uppsala University, Uppsala, Uppsala, Sweden
• ³Mabtech (Sweden), Nacka Strand, Stockholm, Sweden
• ⁴Department of Medical Biochemistry and Microbiology, Faculty of Medicine and Pharmacy, Uppsala University, Uppsala, Uppsala, Sweden

Background: Our understanding of protective immunity after natural viral infections in children with cancer and haematological diseases is restricted. Current cancer treatments cause significant immunosuppression, affecting both innate and adaptive immunity which leads to reduced B-cell and antibody responses. The aim of this study was to characterize SARS-CoV-2 immune response in children with cancer or hematological disease. Methods: A single-center study was conducted from June 2020 to June 2023, including 135 patients and 14 healthy siblings. Blood samples were obtained for serological analysis and cellbased assays. SARS-CoV-2 IgG and IgA responses were quantified using suspension immunoassay (SIA), enzyme-linked immunosorbent assay (IgG ELISA) and neutralizing antibody (nAb) responses were assessed by plaque reduction neutralization tests (PRNT). The memory B-cell (MBC) population was evaluated through flow cytometry and MBC responses through FluoroSpot, respectively. Results: In total, 78 patients seroconverted in response to SARS-Co-V-2 but neither immunosuppression nor cancer diagnosis significantly affected seroconversion. SARS-CoV-2 IgG and IgA levels correlated positively with increasing age, and IgA seroconversion was significantly associated with the presence of nAbs. Antigen-specific MBC responses against both spike and receptor-binding domain (RBD) were elevated in older children, while children on immunosuppression had significantly lower RBD IgG-secreting cells. Conclusion: Our results show that most pediatric oncological and hematological patients can mount a broad antibody response upon SARS-CoV-2 natural infection or vaccination, although there is a variability in their responses influenced by increasing age. MBC responses in children with immunosuppression were blunted with fewer RBD IgG-secreting cells. Essentially, our findings underscore that young children with severe treatment-related immunosuppression are at risk for less effective B-cell responses upon viral infection.