Background Texas Children’s Hospital is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exist about SARS-CoV-2 infection (COVID-19) in the pediatric SOT population. We evaluated the impact of different SARS-CoV-2 variants in a cohort of PCR positive SOT recipients. Methods SOT recipients with a positive SARS-CoV-2 PCR test from 3/1/2020 to 2/28/2022 were included in the cohort. The study period was divided into 3 eras based on the predominant circulating variant of SARS-CoV-2: 3/20-6/21 original strain/Alpha, 7/21-11/21 Delta, and 12/21-2/22 Omicron variants. Retrospective medical record review was performed; Chi-squared and Fischer exact test were used to compare groups. Results A total of 269 of 1031 (26%) SOT recipients tested positive for SARS-CoV-2 during the study period. By organ, 87/335 (26%) heart, 57/224 (25%) kidney, 92/405 (23%) liver, and 25/67 (37%) lung recipients had COVID-19 infection. By era, there were 99 (37%) original strain/ Alpha, 65 (24%) Delta, and 105 (39%) Omicron. The patients’ median age was 12.72 years (IQR 6.6, 15.1) with a minority of recipients being female (42%). Common comorbidities included hypertension (50%), obesity (13%), diabetes (10%), and chronic kidney disease (10%); 34% had no comorbidities aside from chronic immunosuppression post-transplant. Overall, 80% of recipients were symptomatic (Figure 1), and 50 (19%) required hospitalization. Hospitalization rates were highest (29%) during Delta, compared with 18% for original/Alpha and 13% for Omicron (p=0.02) eras. Need for respiratory support, ICU admission, and all-cause mortality did not vary by era (Table 1). Three SOT recipients (2 original/Alpha and 1 Delta) were diagnosed with multi-inflammatory syndrome in children (MIS-C). Conclusion Our study suggests that pediatric SOT recipients have a high risk for hospitalization and short-term complications with COVID-19; Omicron appears to cause less severe disease, including MIS-C. Additional studies are needed to understand long-term complications of COVID-19 in SOT recipients. Disclosures Elizabeth A. Moulton, MD, PhD, Pfizer: Grant/Research Support Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB.
Background Despite widespread use of prevention strategies, CMV DNAemia remains common in PLTR. Contemporary data, however, is limited. We sought to determine the frequency of, risk factors for, and long term outcomes of CMV DNAemia in a large, single center cohort of PLTR. Methods A retrospective cohort study of PLTR < 22 yrs of age transplanted from 2011-2018 was completed. Per protocol, CMV prophylaxis with ganciclovir/valganciclovir was universally implemented; high risk (HR)(D+/R-) and intermediate risk (IR)(R+) patients received 6 months while low risk (LR)(D-/R-) patients received 3 months. Primary outcomes included any CMV DNAemia, CMV DNAemia >1000 IU/mL and long term outcomes including rejection, graft failure, hepatic steatosis (HS), and de novo autoimmune hepatitis (AIH). Associations with CMV DNAemia were measured using Fisher exact and multivariate regression. Survival analysis, time to CMV infection, and time to PLTR long term outcomes were assessed using Kaplan-Meier plots. Results Among 270 PLTR, 81 (30%) had quantifiable CMV DNAemia; 36 (13%) had CMV DNAemia >1000 IU/mL. Fifty (19%) developed CMV DNAemia while on prophylaxis. Median time (range) to CMV DNAemia was 162 days (5-2213). HR (OR 4.18; 95% CI 1.84-9.49, p< 0.01) status was associated with CMV DNAemia and time to CMV DNAemia. CMV DNAemia was not associated with age at transplantation or cold ischemic time. Eight PLTR (3%) developed CMV syndrome (4 HR, 3 IR, 1 LR), the median peak (range) DNAemia was 2133 IU/mL (202-58000) for these patients. No PLTR developed CMV tissue invasive disease. CMV DNAemia was not associated with rejection (15% vs. 33%, p=0.62), graft failure (7% vs. 13%, p=0.17), HS (8% vs. 12%, p=0.32), or AIH (10% vs. 8%, p= 0.68). CMV DNAemia was associated with a longer time to rejection (p=0.02). Time to development of graft failure, HS, and AIH were not associated with CMV DNAemia (Figure 1). Finally, there was no difference in survival during the study follow-up period (1 – 9 yrs) for PLTR with vs. without CMV DNAemia (p=0.58). Figure 1 Conclusion This large cohort of PLTR demonstrates high rates of CMV DNAemia but low rates of CMV disease. HR status remains associated with CMV DNAemia. CMV DNAemia did not increase the risk of long term adverse outcomes such as rejection, graft failure, HS, and AIH. Disclosures All Authors: No reported disclosures
Background Despite the widespread use of prevention strategies, CMV remains a common opportunistic infection in SOTR. Contemporary data regarding CMV in pediatric SOTR are limited. We sought to determine the frequency of and risk factors for CMV infection and disease in a large single-center cohort of pediatric SOTR. Methods A retrospective cohort study of patients <22 years of age who received lung, heart, liver, kidney, or multi-organ transplants at TCH between 2010 and 2018 was completed. Universal CMV prophylaxis was used based on risk status (Figure 1). The primary outcome was quantifiable CMV DNAemia. Associations with CMV DNAemia were measured using Fisher exact, Kruskal–Wallis, and multivariate logistic regression. Survival analysis and time to CMV infection were assessed using Kaplan–Meier plots. Results Among 788 SOTR, 132 (17%) had quantifiable CMV DNAemia; this included 20/105 (19%) lung, 69/290 (24%) liver, 28/178 (16%) heart, 2/15 (13%) multi-organ, and 13/200 (7%) kidney recipients. Fifty-one (6%) SOTR had CMV DNAemia while on antiviral prophylaxis. Post-prophylaxis, 69 (9%) SOTR had CMV reactivation and 12 (2%) had primary infection. The median time to quantifiable DNAemia for patients that developed CMV was 290 days post-transplant for lung, 162 for liver, 186 for heart, and 294 for kidney (P < 0.01), reflecting differences in prophylaxis strategies. High-risk CMV status (D+/R– for heart, liver, kidney, and D+ and/or R+ for lung) was associated with CMV DNAemia (P < 0.01). Type of organ transplanted also showed an association with CMV DNAemia (P = 0.02) with liver transplant recipients more being more likely to have a positive CMV PCR. DNAemia was not associated with age at transplantation, type of organ, or the use of induction immunosuppression. There was no difference in survival during the study follow-up period (1–9 yr) for SOTR with vs. without DNAemia (P = 0.48). Overall, 22/788 (3%) SOTR had CMV disease, 3 (3%) lung, 4 (2%) heart, 8 (3%) liver, 1 (6%) multi-organ, and 6 (3%) kidney recipients. Twenty had CMV syndrome and 2 had tissue invasive disease. Median (range) maximum viral loads were 27700 IU/mL (233-3912694) for SOTR with vs. 900 IU/mL (26-112000) for SOTR without CMV disease (P < 0.01). Conclusion This large contemporary cohort of pediatric SOTR on universal prophylaxis demonstrates low overall rates of CMV DNAemia and CMV disease. High-risk CMV status remains associated with CMV DNAemia, suggesting that further interventions targeting this group may be warranted.
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