Background The clinical course of COVID‐19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi‐center, multi‐organ cohort analysis of COVID‐19 positive transplant recipients ≤ 18 years at time of transplant. Methods Data were collected via institutions’ respective electronic medical record systems. Local review boards approved this cross‐institutional study. Results Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. 6 were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n=12 (46%)), fever (n=9 (35%)), dry/sore throat (n=3 (12%)), rhinorrhea (n=3 (12%)), anosmia (n=2 (8%)), chest pain (n=2 (8%)), diarrhea (n=2 (8%)), dyspnea (n=1 (4%)), and headache (n=1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post‐transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Conclusions Our multi‐institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID‐19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.

In X-linked hypophosphatemia (XLH) and in its murine homologue, the Hyp mouse, increased circulating concentrations of fibroblast growth factor 23 (FGF-23) are critical to the pathogenesis of disordered metabolism of phosphate (Pi) and 1,25-dihydroxyvitamin D [1,25(OH)2D]. In this study, we hypothesized that in Hyp mice, FGF-23-mediated suppression of renal 1,25(OH)2D production and Pi reabsorption depends on activation of mitogen-activated protein kinase (MAPK) signaling. Wild-type and Hyp mice were administered either vehicle or the MEK inhibitor PD0325901 (12.5 mg/kg) orally daily for 4 days. At baseline, the renal abundance of early growth response 1 (egr1) mRNA was approximately 2-fold greater in Hyp mice than in wild-type mice. Treatment with PD0325901 greatly suppressed egr1 mRNA abundance in both wild-type and Hyp mice. In Hyp mice, PD0325901 induced an 8-fold increase in renal 1α-hydroxylase mRNA expression and a 4-fold increase in serum 1,25(OH)2D concentrations compared with vehicle-treated Hyp mice. Serum Pi levels in Hyp mice increased significantly after treatment with PD0325901, and the increase was associated with increased renal Npt2a mRNA abundance and brush-border membrane Npt2a protein expression. These findings provide evidence that in Hyp mice, MAPK signaling is constitutively activated in the kidney and support the hypothesis that the FGF-23-mediated suppression of renal 1,25(OH)2D production and Pi reabsorption depends on activation of MAPK signaling via MEK/ERK1/2. These findings demonstrate the physiologic importance of MAPK signaling in the actions of FGF-23 in regulating renal 1,25(OH)2D and Pi metabolism.

The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)₂D] production, and rachitic bone disease. Increased serum fibroblast growth factor-23 concentration is responsible for the disordered metabolism of Pi and 1,25(OH)₂D. In the present study, we tested the hypothesis that chronic inhibition of fibroblast growth factor-23-induced activation of MAPK signaling in Hyp mice can reverse their metabolic derangements and rachitic bone disease. Hyp mice were administered the MAPK inhibitor, PD0325901 orally for 4 wk. PD0325901 induced a 15-fold and 2-fold increase in renal 1α-hydroxylase mRNA and protein abundance, respectively, and thereby higher serum 1,25(OH)₂D concentrations (115 ± 13 vs. 70 ± 16 pg/ml, P < 0.05), compared with values in vehicle-treated Hyp mice. With PD0325901, serum Pi levels were higher (5.1 ± 0.5 vs. 3 ± 0.2 mg/dl, P < 0.05), and the protein abundance of sodium-dependent phosphate cotransporter Npt2a, was greater than in vehicle-treated mice. The rachitic bone disease in Hyp mice is characterized by abundant unmineralized osteoid bone volume, widened epiphyses, and disorganized growth plates. In PD0325901-treated Hyp mice, mineralization of cortical and trabecular bone increased significantly, accompanied by a decrease in unmineralized osteoid volume and thickness, as determined by histomorphometric analysis. The improvement in mineralization in PD0325901-treated Hyp mice was confirmed by microcomputed tomography analysis, which showed an increase in cortical bone volume and thickness. These findings provide evidence that in Hyp mice, chronic MAPK inhibition improves disordered Pi and 1,25(OH)₂D metabolism and bone mineralization.

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