S519 Impact of COVID-19 on Motility Practices: New Onset Gastrointestinal and Autonomic Dysfunction After COVID-19 and the Effects of Vaccination in a Nationwide Cohort Study (2022)

Introduction: COVID-19 has been linked to a higher risk of enteric and autonomic dysfunction, but studies have been limited by small sample sizes and follow-up. Methods: We performed a retrospective cohort study using the TriNetX Research Network, including over 80M patients from 57 academic medical centers in the US. Using ICD-10 and CPT codes, patients diagnosed with COVID-19 between Jan 1 to Dec 31, 2020 were propensity score matched for risk factors to negative controls (NC), and patients diagnosed with either Influenza, Lyme’s disease (LD), Infectious Mononucleosis (IM), Herpes Zoster (HZ), Varicella Zoster (VZ) and Cytomegalovirus (CMV). A Kaplan-Meier analysis was used to estimate the hazard ratio (HR) and cumulative incidence of new-onset outcomes within 3 months and 1 year after the diagnosis of the respective health event, including: GI symptoms or diagnoses, symptoms of autonomic (AN) sensory (SN), and motor (MN) neuropathy. We quantified the impact of prior vaccination for COVID-19 on these outcomes. Results: A total of 1,355,657 COVID-19 patients were matched to 1,889,175 NCs, 698,253 Influenza, 61,826 IM, 129,246 LD, 457,984 HZ, 45,811 VZ, and 8,441 CMV patients. Both the risk of GI diagnoses and AN were increased (HR >1, p< 0.05) after COVID-19 compared to every other control population, except for GI diagnoses after CMV (HR 0.89, p:0.26). COVID-19 significantly (p< 0.05) increased the risk of vomiting (HR 1.78), diarrhea (HR 1.53) and irritable bowel syndrome (HR 1.07) compared to NCs, but it did not differ with that observed after Influenza (p >0.05). Although COVID-19 increased the risk of developing functional dyspepsia (HR 1.09), inflammatory bowel disease (HR 1.5) and abdominal pain (HR 1.38) compared to NCs, a diagnosis of Influenza yielded an even higher risk (p< 0.05); for all other GI diagnoses, the risk was consistently increased (p< 0.05) compared to both NCs and Influenza. Prior vaccination did not alter the risk of developing GI outcomes after COVID-19 (HR 0.95, p:0.32), but it did increase the risk of AN (HR 1.13, p:0.02) and MN (HR 1.6, p< 0.05). (Table) Conclusion: This nationwide analysis reveals that COVID-19 increases the risk of new-onset ENS and ANS dysfunction compared to NCs and patients infected by neurotrophic and non-neurotrophic pathogens, but less pronounced compared to CMV. Given the magnitude of COVID-19 infections, a significant increase in patients with dysmotility and ANS dysfunction is expected, for which Gastroenterology as a specialty needs to prepare. Table 1. - Kaplan Meier analysis comparing new-onset outcomes between patients diagnosed with COVID-19 and a matched Influenza and negative control cohort New-onset outcomes COVID-19 vs Negative controls (n=1,889,175) COVID-19 vs Influenza (n=698,253) HR (95% CI) Probability COVID Probability NC P-value HR (95% CI) Probability COVID Probability Influenza P-value Gastrointestinal (GI) symptoms or diagnoses 1.37 (1.35 - 1.39) 11.43% 8.44% < 0.001 1.04 (1.03 - 1.06) 11.41% 10.87% < 0.001 Dysphagia 1.37 (1.33 - 1.41) 1.4% 1.03% < 0.001 1.18 (1.14 - 1.23) 1.23% 1.03% < 0.001 Gastro-esophageal reflux disease 1.30 (1.28 - 1.33) 4.21% 3.23% < 0.001 1.13 (1.11 - 1.16) 3.97% 3.5% < 0.001 Heartburn 1.15 (1.09 - 1.21) 0.42% 0.37% < 0.001 1.20 (1.12 - 1.28) 0.44% 0.36% < 0.001 Nausea 1.54 (1.50 - 1.58) 2.39% 1.56% < 0.001 1.12 (1.09 - 1.15) 2.51% 2.24% < 0.001 Vomiting 1.78 (1.71 - 1.85) 0.87% 0.49% < 0.001 1.04 (0.99 - 1.08) 0.9% 0.87% 0.116 Early satiety 1.31 (1.20 - 1.43) 0.15% 0.12% < 0.001 1.63 (1.44 - 1.85) 0.14% 0.09% < 0.001 Abdominal and pelvic pain 1.38 (1.36 - 1.41) 6.38% 4.63% < 0.001 0.97 (0.96 - 0.99) 6.62% 6.74% 0.01 Bloating 1.28 (1.24 - 1.33) 1.01% 0.78% < 0.001 1.29 (1.24 - 1.35) 0.97% 0.75% < 0.001 Gastroparesis 1.47 (1.35 - 1.60) 0.18% 0.12% < 0.001 1.39 (1.25 - 1.55) 0.17% 0.12% < 0.001 Functional dyspepsia 1.09 (1.02 - 1.17) 0.22% 0.2% 0.016 0.79 (0.73 - 0.86) 0.21% 0.27% < 0.001 Constipation 1.35 (1.32 - 1.38) 2.61% 1.94% < 0.001 1.17 (1.14 - 1.21) 2.4% 2.04% < 0.001 Diarrhea 1.53 (1.49 - 1.57) 2.62% 1.71% < 0.001 1.01 (0.98 - 1.03) 2.63% 2.61% 0.631 Irritable bowel syndrome 1.07 (1.02 - 1.12) 0.5% 0.47% 0.006 1.04 (0.98 - 1.10) 0.52% 0.5% 0.188 Inflammatory bowel disease 1.50 (1.45 - 1.56) 1.06% 0.71% < 0.001 0.75 (0.72 - 0.78) 1.05% 1.4% < 0.001 Autonomic neuropathy 1.32 (1.30 - 1.34) 8.69% 6.64% < 0.001 1.15 (1.13 - 1.17) 8.22% 7.1% < 0.001 Postural symptoms 1.43 (1.41 - 1.46) 5.89% 4.15% < 0.001 1.15 (1.13 - 1.18) 5.64% 4.88% < 0.001 Urinary dysfunction 1.22 (1.19 - 1.25) 2.76% 2.26% < 0.001 1.12 (1.09 - 1.16) 2.53% 2.24% < 0.001 Sexual dysfunction 0.99 (0.95 - 1.03) 0.66% 0.66% 0.751 1.04 (0.98 - 1.10) 0.59% 0.56% 0.168 Exocrine gland dysfunction 1.22 (1.18 - 1.26) 1.24% 1.02% < 0.001 1.26 (1.21 - 1.31) 1.17% 0.93% < 0.001 Sensory neuropathy 1.12 (1.09 - 1.15) 1.71% 1.53% < 0.001 0.89 (0.86 - 0.92) 1.69% 1.89% < 0.001 Motor neuropathy 1.22 (1.19 - 1.25) 1.52% 1.25% < 0.001 0.98 (0.95 - 1.01) 1.47% 1.49% 0.247 Outcomes are presented as a HR, in which the numerator consists of the COVID-19 population. The cumulative incidence of the outcomes between 3 months and 1 year after the index is presented for each cohort. A P-value was calculated using a log-rank test.