Since the beginning of the COVID-19 pandemic, there have been over 775 million reported cases worldwide. A significant proportion of these patients suffer from long-COVID, experiencing symptoms such as severe fatigue, myalgias, and gastrointestinal (GI) dysfunction. Both chronic post-infectious disorders and GI conditions are linked to persistent sympathetic nervous system activation (PSA), however the specific interactions between long-COVID and GI disorders requires additional investigation. We hypothesized that individuals with pre-existing GI disorders would have higher rates of long-COVID. We also postulated that long-COVID increases the risk for GI disorder diagnosis.

We utilized de-identified electronic health record data from TriNetX, a global health research network with over 124 million patients. We constructed queries to identify subjects with upper functional (UF), lower functional (LF), upper structural (US), or lower structural (LS) GI disorder diagnoses. Afterwards, we analyzed the prevalence of long-COVID (defined as new malaise and fatigue symptoms lasting ≥1 month post-infection and not present in the previous 4 years) in patients with and without GI conditions. Additionally, we compared the rates of GI symptom development in patients with and without long-COVID diagnosis. Changes in GI disorder incidence in the 4 years before and after the pandemic onset (January 1, 2020) were also examined. Data were evaluated with chi-squared analysis.

Subjects with long-COVID had higher pre-COVID GI disorder prevalence compared to subjects without long-COVID UF (1.12%), LF (2.33%), US (13.13%), and LS (0.80%). There was also a 0.65%, 0.83%, 4.93% increase in UF, LF, and LS post-COVID diagnoses prevalence, respectively, and a 5.77% decrease in US diagnoses (p<0.001) between patients with long-COVID and without long-COVID. In the general population, post-pandemic, the prevalence of LF and US diagnoses increased by 0.14% and 0.38% (p<0.001), while UF and LS diagnoses decreased by 0.015% and 0.17% (p<0.001).

These results suggest that GI disorders, especially upper structural and functional GI disorders, pose a higher risk for long-COVID symptoms. However, the nuanced prevalences of GI conditions following long-COVID reflect a need for further research on the long-term impacts and mechanisms of PSA-mediated GI tract dysfunction following SARS-CoV-2 infection.