Non-fatal outcomes of COVID-19 disease in children with solid organ transplants associates with down-regulation of senescent pathways

Objective: To study the immune landscape during acute infection (AI) & COVID-19 recovery in children with solid organ transplants (SOTs). Method: Blood collected between Nov 2020 – June 2022 from pediatric SOT recipients 1–14-days after a positive PCR for SARS-CoV-2 (AI), & 15–60-days after a positive PCR (convalescence), for Ficoll of PBMC. Cryopreserved PBMC taken from pediatric SOT recipients before 2019 used as non-infected controls (ctrls). PBMCs stimulated with 15-mer peptides from spike protein & co-stimulation with anti-CD49d & anti-CD28. Immunophenotyping by mass cytometry. Data analyzed using the Astrolabe Cytometry Platform, which follows a standardized pipeline for population identification & statistics & visualized using the t-SNE dimensionality reduction method. Disease severity stratified using WHO criteria. Subjects unvaccinated against COVID-19. Results: 38 children included: median age & time from transplant (TX) at infection: 5.5 (2.1–15.1) & 3.3 (0.2–14.7)-years for AI (n=10); 2.4 (0.6–15.6) & 0.5 (0.2–11.2)-years for ctrls (n=20); 6.7 (1.0–12.9) & 4.3 (0.2–9.7)-years for convalescence (n=8). NK & CD4 +T cell (EM, Th 2) frequency increased during AI {p<0.05}. CD57 expression low in T cells with EM phenotype, NKT, & gdT cells in AI vs. ctrls (p<0.05) & in NK cells in severe disease (p<0.05). CD161 expression high in CD4 +T cell (CM, Th1) in convalescence vs. ctrls{ p=0.04}. Conclusion: contraction in NK cells is not a feature of COVID-19 disease in pediatric SOT & global characteristics of NK, NKT & T cell compartments not compatible with senescence. Upregulation of cytolytic effectors in AI. Above a plausible mechanism for low mortality from COVID-19 disease in this patient population.