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784 CLINICAL COURSE OF PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS WITH POSITIVE COVID-19 ANTIBODY TESTING AT A SINGLE, TERTIARY CARE CENTER

Background: The impact of SARS-CoV-2 infection on patients with IBD is still not fullyunderstood. We aimed to evaluate the clinical course of pediatric IBD patients with positiveCOVID-19 antibody titers. Methods: This is a single-center, retrospective study of pediatric(<18y) IBD patients with positive COVID-19 Antibody Testing, using a serological enzymelinkedimmunosorbent assay developed at Mount Sinai, Icahn School of Medicine. A COVID-19 Antibody Titer was sent routinely at time of biologic infusion or clinic visit betweenApril and November 2020 to better understand IBD patients’ seroconversion and long-termresponse to COVID-19. Data on demographics, disease behavior, location and activity (HarveyBradshaw index or partial Mayo score) and treatment were gathered at time of antibodytesting. Data were collected on antibody titer level (Amanat, F et al. Nat Med (2020) 26,1033–1036) and, if available, on presence of symptomatic COVID-19 illness, worsening ofIBD following SARS-CoV-2 infection, and changes to medications due to illness. Associationsof COVID-19 symptom severity with biologic use and COVID-19 antibody titer were assessedwith chi-square and Pearson product-moment correlation respectively. Results: Twenty-sixchildren had a positive COVID-19 antibody test between May 6, 2020 and November 5,2020;demographic, phenotype, and medication data are in Table 1. A majority (86%) ofCD patients were in clinical remission, compared to only 1 (20%) UC patient. Median [IQR]antibody titer was 960 [320-1440]. Nineteen children (73%) had documentation regarding their COVID-19 course;68% with symptoms consistent with COVID-19 and 32% asymptomatic.All but two patients (89%) identified a known exposure from a family member or aclose contact. One recently diagnosed CD male had a complicated course of COVID-19with Multisystem Inflammatory Syndrome in children (MIS-C);all other cases were outpatientand uncomplicated. Four (15%) children were diagnosed with IBD with IBD symptomsstarting shortly (Mean: 4.75 [Range: 2-8] weeks) following their SARS-CoV-2 infection. Afurther 4 with established IBD had a subjective worsening of IBD symptoms during orimmediately following infection and none had IBD medications held due to COVID-19.There was no association between biologic use and symptomatic infection with SARS-CoV-2 (P=0.88). There was a moderate negative correlation of titer level with symptomaticinfection with SARS-CoV-2 (r = -0.56, P= 0.02). Conclusions: Despite biologic exposuremany antibody positive pediatric IBD patients did not have any active COVID -19 symptomsand their treatment continued without interruption. There were a significant number ofpatients diagnosed with IBD following their course of COVID-19, warranting further studyinto the downstream effects of SARS-CoV-2 infection. (Table Presented)

. Gastrointestinal symptoms in the five domains of the Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) according to SARS-CoV-2 infection Table 2. Frequency of patients with IBS and loose stools and scores of Symptom Check List (SCL)-12 for somatization and of Hospital Anxiety and Depression Scale (HADS) according to previous SARS-CoV-2 infection. Background Colorectal cancer (CRC) screening programs worldwide have been disrupted during the COVID-19 pandemic. CRC screening has been well-established to reduce longterm CRC incidence and mortality. Any disruption to screening would reduce these health benefits. This study aimed to estimate the impact of hypothetical disruptions to organized CRC screening programs on short-and long-term CRC incidence and mortality in three countries using microsimulation modelling. Methods Using well-calibrated and validated CRC microsimulation models for Australia (Policy1-Bowel), Canada (OncoSim) and the Netherlands (ASCCA and MISCAN-Colon) participating in the COVID-19 and Cancer Global Modelling Consortium (CCGMC), we simulated a range of hypothetical scenarios to assess the potential impact of disruptions to screening on CRC incidence and mortality. All models simulate the adenoma-carcinoma pathway, and ASCCA and Policy1-Bowel additionally simulate the serrated pathway. Modelled scenarios varied by disruption duration (3-, 6-and 12-months), post-disruption participation reduction (3-months -50% and 3-months -25%, and 6-months -50%), and catchup screening strategies (no catch-up, immediate, and 6-months delayed catch-up). Results Without catch-up screening, CRC incidence would increase by 0.1-0.3%, 0.2-0.6%, and 0.4-1.2% over 2020-2050 among individuals aged 50 years and older in the three S-158 AGA Abstracts modelled countries after 3-, 6-, and 12-month disruptions, respectively ( Figure 1). CRC mortality would increase by 0.2-0.5%, 0.4-1.0%, and 0.8-2.0% over 2020-2050 among individuals aged 50 years and older in the three modelled countries after 3-, 6-, and 12month disruptions, respectively, compared to undisrupted screening ( Figure 2). A 6-month disruption without catch-up would result in an estimated 3,552, 2,844 and 803-1,803 additional CRC diagnoses and an estimated 1,964, 1,319, and 676-856 additional CRCrelated deaths in Australia, Canada and the Netherlands, respectively, compared to undisrupted screening. A post-disruption reduction in participation could increase CRC diagnoses by 0.2-0.9% and CRC-related deaths by 0.5-1.6% compared to undisrupted screening depending on the size of the reduction in participation. Providing catch-up could minimize the impact of the disruption to an increase of 0.0-0.2% in CRC diagnoses and CRCrelated deaths. Conclusion Although the relative impact of the modelled CRC screening disruptions (when considered over the long-term, 30 years) due to the COVID-19 pandemic appears modest, given a high burden of CRC, there is a substantial impact on CRC diagnoses and deaths across all countries considered. It is crucial that, if disrupted, screening programs ensure participation rates return to previously observed rates and provide catch-up screening wherever possible, as the impact of any disruption could be considerably larger otherwise.

IMPACT OF COVID-19 RELATED DISRUPTIONS TO COLORECTAL CANCER SCREENING PROGRAMS IN THREE COUNTRIES: A COMPARATIVE MODELLING STUDY
Change in CRC incidence relative to the comparator scenario (no disruption) by MISCAN-Colon, ASCCA, Policy1-Bowel and OncoSim Abbreviations: CRC, Colorectal Cancer. Note: the base case scenario is the scenario in which a 6-month disruption period from April to September 2020 was assumed, with no catch-up or changes to participation in the recovery period.
Change in CRC mortality relative to the comparator scenario by MISCAN-Colon, ASCCA, Policy1-Bowel and OncoSim Abbreviations: CRC, Colorectal Cancer. Note: the base case scenario is the scenario in which a 6-month disruption period from April to September 2020 was assumed, with no catch-up or changes to participation in the recovery period.

CLINICAL COURSE OF PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS WITH POSITIVE COVID-19 ANTIBODY TESTING AT A SINGLE, TERTIARY CARE CENTER Elizabeth A. Spencer, Eyal Klang, Michael T. Dolinger, Marla Dubinsky
Background: The impact of SARS-CoV-2 infection on patients with IBD is still not fully understood. We aimed to evaluate the clinical course of pediatric IBD patients with positive COVID-19 antibody titers. Methods: This is a single-center, retrospective study of pediatric (<18y) IBD patients with positive COVID-19 Antibody Testing, using a serological enzymelinked immunosorbent assay developed at Mount Sinai, Icahn School of Medicine. A COVID-19 Antibody Titer was sent routinely at time of biologic infusion or clinic visit between April and November 2020 to better understand IBD patients' seroconversion and long-term response to COVID-19. Data on demographics, disease behavior, location and activity (Harvey Bradshaw index or partial Mayo score) and treatment were gathered at time of antibody testing. Data were collected on antibody titer level (Amanat, F et al. Nat Med (2020) 26, 1033-1036 and, if available, on presence of symptomatic COVID-19 illness, worsening of IBD following SARS-CoV-2 infection, and changes to medications due to illness. Associations of COVID-19 symptom severity with biologic use and COVID-19 antibody titer were assessed with chi-square and Pearson product-moment correlation respectively. Results: Twenty-six children had a positive COVID-19 antibody test between May 6, 2020 and November 5, 2020; demographic, phenotype, and medication data are in Table 1. A majority (86%) of CD patients were in clinical remission, compared to only 1 (20%) UC patient. Median [IQR] antibody titer was 960 [320-1440]. Nineteen children (73%) had documentation regarding their COVID-19 course; 68% with symptoms consistent with COVID-19 and 32% asymptomatic. All but two patients (89%) identified a known exposure from a family member or a close contact. One recently diagnosed CD male had a complicated course of COVID-19 with Multisystem Inflammatory Syndrome in children (MIS-C); all other cases were outpatient and uncomplicated. Four (15%) children were diagnosed with IBD with IBD symptoms starting shortly (Mean: 4.75 [Range: 2-8] weeks) following their SARS-CoV-2 infection. A further 4 with established IBD had a subjective worsening of IBD symptoms during or immediately following infection and none had IBD medications held due to COVID-19. There was no association between biologic use and symptomatic infection with SARS-CoV-2 (P=0.88). There was a moderate negative correlation of titer level with symptomatic infection with SARS-CoV-2 (r = -0.56, P= 0.02). Conclusions: Despite biologic exposure many antibody positive pediatric IBD patients did not have any active COVID -19 symptoms and their treatment continued without interruption. There were a significant number of patients diagnosed with IBD following their course of COVID-19, warranting further study into the downstream effects of SARS-CoV-2 infection.

SARS-COV-2 INFECTS ENTEROCYTES IN VIVO AND CAN PERSIST UP TO 7 MONTHS FOLLOWING RESOLUTION OF SYMPTOMS
Minami Tokuyama, Mark S. Ladinsky, Divya Jha, Francesca Cossarini, Alexandra E. Livanos, Jason Reidy, Michael Tankelevich, Gustavo Martinez-Delgado, Pamela J. Bjorkman, Saurabh Mehandru Background: Host proteins ACE-2 and TMPRSS2 facilitate SARS-CoV-2 infection and are highly expressed in the gastrointestinal (GI) tract, particularly in the small bowel, as well as the lungs. GI symptoms represent the most common extrapulmonary manifestation of COVID-19 and viral RNA has been isolated from fecal samples from COVID-19 patients, where it can persist longer than detection in nasopharyngeal swabs. While SARS-CoV-2 infection of enterocytes has been demonstrated in vitro, in vivo studies are lacking. Here we examined human intestinal tissue at various stages following SARS-CoV-2 infection. Methods: Small intestinal biopsies from patients who underwent clinically indicated endoscopic procedures after a positive SARS-CoV-2 nasopharyngeal swab (n=27) or were found to have positive serology (n=2) were analyzed by immunofluorescence (IF) (n=25) and electron microscopy (EM) (n=14) for the presence of virus. Clinical details were also collected (Table 1). Results: Patients were between 15 days and 7 months of symptom onset. Sixteen of 29 patients had detectable SARS-CoV-2 antigen by either IF or EM (Figure 1). Virus was restricted to the epithelium and patchy in distribution. It was detected as soon as 15 days after symptom onset and persisted up to 7 months after symptom resolution. Despite the presence of virus, only half of these patients had any signs of inflammation on histology, and when present, this was mild. Seven patients were nasopharyngeal swab positive within 3 days of the procedure and, of these, 6 had detectable antigen in intestinal tissue. In two patients where virus was present at 3 months and 4 months after mild COVID-19, additional biopsies were obtained at 7 months and 6 months, respectively. Viral antigen was persistently detected in both patients and both patients were nasopharyngeal swab negative for all procedures. Interestingly, only 37.5% (6 of 16) of patients with virus detected in the small bowel had GI symptoms (diarrhea, nausea or vomiting) during their acute COVID-19 illness as compared to 46.1% (6/13) of patients where no virus could be detected in the intestines. Conclusions: SARS-CoV-2 infects enterocytes in humans in vivo and can persist in the intestines up to 7 months following symptom resolution. This persistence is not associated with an overt inflammatory infiltrate and does not appear to correlate with presence of GI symptoms in the acute COVID-19 setting. The COVID pandemic has delayed colorectal (CRC) screening. We estimate the impact of the pandemic on CRC incidence and deaths in the United States. Methods We compared screening strategies and alternative resource allocation in a validated Markov model. We focused on individuals who had not been previously screened for CRC at ages 45 and 50 (common ages of initiation of CRC screening) and 65 (the age at which individuals become eligible for Medicare and colorectal cancer screening if not previously available). We compared the impact of colonoscopy and FIT screening at ages 45, 50, and 65 to the age-dependent natural history of colorectal cancer development as well as modeled a one year delay in CRC screening, which could be anticipated by pandemic-related delays. Results were expressed as CRC per 100,000 individuals in the population and CRC deaths per 100,000 individuals in the population. Results: (Table 1) FIT screening, when compared to age-dependent natural history, reduced CRC incidence by 61% when initiated at age 45, 57% when initiated either at age 50, and 43% at age 65. Colonoscopy screening, when compared to natural history, reduced CRC incidence by 75% when initiated at age 45, 70% when initiated either at age 50, and 66% when initiated age 65. One-year delays in screening resulted in losses in effectiveness that were modest at best compared to the impact of screening vs. not screening. Discussion: Anticipated delays in CRC screening due to COVID pandemic will impact CRC prevention, but if the delays are short (e.g. 1 year), the overall impact is small compared to screening versus not screening. During the period of disruption, resources should be allocated to providing care for patients with established CRC diagnosis, or colonoscopy follow-up after abnormal FIT, with less concern about screening.