Abstract Background Few data exist on the clinical features and outcome of pediatric patients with persistent unwellness following acute COVID. Methods Norton Children’s and the University of Louisville School of Medicine opened a Post-COVID Clinic (PCC) in Oct 2020. The study cohort included all 104 patients referred to the PCC through Dec 2021. Clinical data were collected using a standardized template during routine care. Diagnostic tests and subspecialty referrals were ordered at the discretion of clinic physicians. A telephone interview in 2022 assessed long-term outcomes. Results The median age at first visit was 14 y (IQR=12,16); the age distribution of PCC patients was different from that of Pediatric Infectious Diseases Clinic (PIDC) patients in that there were few patients under 10 y. Males and females were equally represented. The racial distribution was similar to that of PIDC, but patients were more often from mid/upper socioeconomic status (using commercial insurance as a surrogate; p=0.001). The median interval from onset of COVID to the first PCC visit was 2 mo (IQR=1.5,4.4), and an increase in referrals was seen 2 mo after each COVID wave in the community (Figure 1). Most PCC patients reported good health prior to COVID. Fifty-four percent of patients experienced moderate or severe disability according to Modified Functional Disability Inventory scores at the first PCC visit (Figure 2; median score 14, IQR=6,19). Common symptoms were fatigue or lethargy (73%), headache (60%), shortness of breath or difficulty breathing (48%), exercise intolerance (47%), and chest pain (39%). Few abnormalities were found on routine diagnostic tests. Common subspecialty referrals were to Neurology, Cardiology, Pulmonology, Physical Therapy, and Psychiatry; the total number and types of referrals varied widely among patients. Most patients did not receive a specific diagnosis other than post-COVID syndrome. Sixty-three follow-up interviews were completed a median of 6 mo after the initial PCC visit; 79% of patients were improved or back to normal. Figure 1Reported COVID-19 cases in persons <20 years of age in Jefferson County, KY and number of new patients seen in Norton Children’s Infectious Diseases Post-COVID Clinic, by 2-week intervals. Figure 2 Box and whisker plot of Modified Functional Disability Inventory scores at first visit to Post-COVID Clinic. Upper and lower quartiles are marked by the top and bottom of the boxes. The median is marked by a horizontal line inside the box and the mean is shown by the “x.” Top whiskers indicate the largest value ≤ the 3rd quartile plus 1.5 times the interquartile range; bottom whiskers indicate the smallest value ≥ the 1st quartile minus 1.5 times the interquartile range. Open circles extending beyond the whiskers represent outliers. Disability categories are from Kashikar-Zuck S, et al. Pain 2011;152:1600-1607. Conclusion This large experience with a PCC established early in the pandemic demonstrates that symptoms of post-COVID unwellness are non-specific and varied, routine tests are seldom diagnostic, and the natural history is one of gradual recovery. Disclosures Shanna M. Barton, M.D., M.Sc., Sanofi Pasteur: Grant/Research Support Victoria A. Statler, M.D., M.Sc., Astellas: University Research Support|Gilead: University Research Support|Pfizer: Advisor/Consultant|Sanofi: University Research Support|Seqirus: Advisor/Consultant Gary S. Marshall, MD, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Advisor/Consultant|Seqirus: Grant/Research Support|Seqirus: Honoraria.