Abstract 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.