Non-fatal outcomes of COVID-19 disease in pediatric organ transplantation associates with down-regulation of senescence pathways

Abstract

AbstractThis is a cross-sectional study examining kinetics and durability of immune response in children with solid organ transplants (SOTs) who had COVID-19 disease between November 2020 through June 2022, who were followed for 60-days at a single transplant center. Blood was collected between 1–14 (acute infection), and 15–60 days of a positive PCR (convalescence). SOT children with peripheral blood mononuclear cells (PBMC) cryopreserved before 2019 were non-infected controls (ctrls). PBMCs stimulated with 15-mer peptides from spike protein and anti-CD49d/anti-CD28. Testing done included mass cytometry, mi-RNA sequencing with confirmatory qPCR. 38 children formed the study cohort, 10 in the acute phase and 8 in the convalescence phase. 20 subjects were non-infected controls. Two subjects had severe disease. Subjects in the acute and convalescent phases were different subjects. The median age and tacrolimus level at blood draw was not significantly different. There was no death, and no subject was lost to follow-up. During acute infection CD57 expression was low in NKT, Th17 effector memory, memory Treg, CD4−CD8−, and γδT cells (p = 0.01, p = 0.04, p = 0.03, p = 0.03, p = 0.004 respectively). The frequencies of NK and Th2 effector memory cells increased (p = 0.01, p = 0.02) during acute infection. Non-switched memory B and CD8 central memory cell frequencies were decreased during acute infection (p = 0.02; p = 0.02), but the decrease in CD8 central memory cells did not persist. CD4−CD8− and CD14 monocyte frequencies increased during recovery (p = 0.03; p = 0.007). Our observations suggest down regulation of CD57 with absence of NK cell contraction protect against death from COVID-19 disease in children with SOTs.