Pediatric Gastrointestinal Outcomes During the Post-Acute Phase of COVID-19

Background The impact of COVID-19 on gastrointestinal (GI) outcomes in children during the post-acute and chronic phases of the disease is not well understood. Methods We conducted a retrospective cohort study across twenty-nine healthcare institutions from March 2020 to September 2023, including 413,455 pediatric patients with confirmed SARS-CoV-2 infection and 1,163,478 controls without infection. Infection was confirmed via polymerase chain reaction (PCR), serology, antigen tests, or clinical diagnosis of COVID-19 and related conditions. We examined the incidence of predefined GI symptoms and disorders during the post-acute (28 to 179 days post-infection) and chronic (180 to 729 days post-infection) phases. The adjusted risk ratios (aRRs) were calculated using stratified Poisson regression, with stratification based on propensity scores. Results Our cohort comprised 1,576,933 patients, with females representing 48.0% of the sample. The analysis revealed that children with SARS-CoV-2 infection had an increased risk of developing at least one GI symptom or disorder in both the post-acute (8.64% vs. 6.85%; aRR 1.25, 95% CI 1.24-1.27) and chronic phases (12.60% vs. 9.47%; aRR 1.28, 95% CI 1.26-1.30) compared to uninfected peers. Specifically, the risk of abdominal pain was higher in COVID-19 positive patients during the post-acute phase (2.54% vs. 2.06%; aRR 1.14, 95% CI 1.11-1.17) and chronic phase (4.57% vs. 3.40%; aRR 1.24, 95% CI 1.22-1.27). Interpretation Children with a history of SARS-CoV-2 infection are at an increased risk of GI symptoms and disorders during the post-acute and chronic phases of COVID-19. This highlights the need for ongoing monitoring and management of GI outcomes in this population. Evidence before this study We searched PubMed, Scopus, and Google Scholar databases up to September 2023 for studies assessing the incidence and risk of gastrointestinal (GI) symptoms and disorders in children following viral infections, including COVID-19. We included studies published in any language and involving various methodologies (observational studies, cohort studies, and clinical trials). Our search terms included "COVID-19," "SARS-CoV-2," "gastrointestinal symptoms," "children," "post-acute," and "chronic." The evidence prior to this study suggested an increased risk of GI disorders in adults after viral infections but was less definitive for the pediatric population. Added value of this study This study significantly extends the existing literature by specifically examining the risk of GI symptoms and disorders in the pediatric population during the post-acute and chronic phases of COVID-19. Using a large retrospective cohort design encompassing over 1.5 million children and adolescents from 29 healthcare institutions, our analysis provides robust evidence of increased GI symptoms like abdominal pain, diarrhea, and constipation among COVID-19 positive patients compared to non-infected peers. It is one of the largest studies of its kind and the first to provide such comprehensive data for the U.S. pediatric population, with follow-up extending up to two years post-infection. Implications of all the available evidence The findings underscore the importance of monitoring children and adolescents for persistent GI symptoms following COVID-19, suggesting that these symptoms may be more common and prolonged than previously recognized. These insights are crucial for pediatric healthcare providers and could influence guidelines for the follow-up care of children recovering from COVID-19. The study also highlights the need for future research to explore the underlying mechanisms of post-acute and chronic GI symptoms in children to develop targeted interventions and improve long-term outcomes. Authorship Statement Authorship has been determined according to ICMJE recommendations. ### Competing Interest Statement Dr. Becich reports PCORnet funding as MPI for the PaTH Clinical Research Network. All other authors have no conflicts of interest to report. ### Funding Statement This research was funded in part by the National Institutes of Health (NIH) Agreement OTA OT2HL161847-01 as part of the Researching COVID to Enhance Recovery (RECOVER) Research Initiative. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the University of Pennsylvania institutional review board (No. 851604) with a waiver of informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data can be shared with the request to the RECOVER initiative.