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Background Children can present with overlapping symptoms of acute respiratory illness (ARI) and acute gastroenteritis (AGE). In these cases, it is unclear if the etiologic agent is a respiratory pathogen, gastrointestinal pathogen, or both. Methods We analyzed data collected in Nashville, TN (12/01/2016–2/28/2020) as part of the New Vaccine Surveillance Network, a prospective ARI/AGE surveillance study. Children (< 18 years old) who presented to the emergency department or were admitted with fever and/or respiratory symptoms for < 14 days were enrolled as ARI subjects and had mid-turbinate nasal ± throat swabs collected, while children with ≥1 episode of vomiting and/or ≥3 episodes of diarrhea in 24 hours were enrolled as AGE subjects and had stool collected. Children who met both sets of criteria were dually enrolled. Respiratory specimens were tested for common respiratory viruses by molecular testing and stool specimens were tested for common gastrointestinal (GI) pathogens by Luminex GI Pathogen Panel. We compared detection groups using Pearson’s χ2 test. C. difficile detection in children < 2 years old was considered asymptomatic carriage (n=32). Results We identified 501 dual enrollees, among whom 279 (55.7%) had both a respiratory and stool specimen tested. Overall, 127 (45.5%) had only a respiratory virus detected, 33 (11.8%) had only a GI pathogen detected, 39 (14.0%) had both, and 77 (27.6%) had no detection (Table 1). Vomiting and diarrhea were frequently reported ( >50%) in all dual enrollees whether or not a pathogen was detected (Figure 1). Cough was detected in high frequency in all groups with pathogen detection. Children with respiratory-only or dual detection had a higher frequency of wheezing and shortness of breath than those with GI-only or no detection. The distribution of pathogens did not significantly differ between single and co-detected cases (Figure 2). Table 1Demographic characteristics of N=279* children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status.Figure 1Distribution of signs and symptoms in N=279 children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status. p values represent omnibus comparisons of all four groups.Figure 2Distribution of pathogens detected in N=279 children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status. Conclusion Children presenting with overlapping symptoms of ARI and AGE were more likely to have an ARI-associated virus. Lower respiratory symptoms (namely, wheezing and shortness of breath) were more specific for ARI-associated viral detection compared with other signs and symptoms. Disclosures Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation. more...