Long-term gastrointestinal outcomes of COVID-19

Abstract

A comprehensive evaluation of the risks and 1-year burdens of gastrointestinal disorders in the post-acute phase of COVID-19 is needed but is not yet available. Here we use the US Department of Veterans Affairs national health care databases to build a cohort of 154,068 people with COVID-19, 5,638,795 contemporary controls, and 5,859,621 historical controls to estimate the risks and 1-year burdens of a set of pre-specified incident gastrointestinal outcomes. We show that beyond the first 30 days of infection, people with COVID-19 exhibited increased risks and 1-year burdens of incident gastrointestinal disorders spanning several disease categories including motility disorders, acid related disorders (dyspepsia, gastroesophageal reflux disease, peptic ulcer disease), functional intestinal disorders, acute pancreatitis, hepatic and biliary disease. The risks were evident in people who were not hospitalized during the acute phase of COVID-19 and increased in a graded fashion across the severity spectrum of the acute phase of COVID-19 (non-hospitalized, hospitalized, and admitted to intensive care). The risks were consistent in comparisons including the COVID-19 vs the contemporary control group and COVID-19 vs the historical control group as the referent category. Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19. Post-covid care should involve attention to gastrointestinal health and disease.

Conflict of interest statement

The authors declare no competing interests.

© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Figures

Fig. 1. Risks and 1-year burdens of incident post-acute COVID-19 gastrointestinal outcomes compared with the contemporary control cohort.

Outcomes were ascertained 30 d after the COVID-19-positive test until the end of follow-up. COVID-19 cohort (n  =  154,068) and contemporary control cohort (n  =  5,638,795). Panel A describes the risks and burdens of incident diagnoses (light green) and panel B describes the risks and burdens of incident laboratory abnormalities (orange). Adjusted HRs (dots) and 95% (error bars) CIs are presented, as are estimated excess burdens (bars) and 95% CIs (error bars). Burdens are presented per 1000 persons at 12 months of follow up. The dashed line marks a HR of 1.00; lower limits of 95% CIs with values greater than 1.00 indicate significantly increased risk. GERD, gastroesophageal reflux disorder; IBS irritable bowel syndrome, PT prothrombin time, PTT partial thromboplastin time, INR international normalized ratio, ALT alanine transaminase, AST aspartate transaminase, LDH lactate dehydrogenase, CRP c-reactive peptide, ALP alkaline phosphatase, GGT γ-glutamyl transferase.

Fig. 2. Risks and 1-year burdens of incident post-acute COVID-19 composite gastrointestinal outcomes compared with the contemporary control cohort.

Composite outcomes consisted of incident diagnoses (GERD, PUD, acute pancreatitis, functional dyspepsia, acute gastritis, IBS, and cholangitis), signs and symptoms (constipation, abdominal pain, diarrhea, vomiting, and bloating), coagulation studies (PT, PTT, INR), liver and biliary tree function tests (albumin, ALT, total protein, AST, LDH, CRP, ALP, total bilirubin, GGT, direct bilirubin, lipase, and amylase) and any gastrointestinal outcome (incident occurrence of any gastrointestinal outcome studied). Outcomes were ascertained 30d after the COVID-19-positive test until the end of follow-up. COVID-19 cohort (n  =  154,068) and contemporary control cohort (n  =  5,638,795). Adjusted HRs (dots) and 95% (error bars) CIs are presented, as are estimated excess burdens (bars) and 95% CIs (error bars). Burdens are presented per 1000 persons at 12 months of follow up. The dashed line marks a HR of 1.00; lower limits of 95% CIs with values greater than 1.00 indicate significantly increased risk. GERD gastroesophageal reflux disorder, IBS irritable bowel syndrome, PT prothrombin time, PTT partial thromboplastin time, INR international normalized ratio, ALT alanine transaminase, AST aspartate transaminase, LDH lactate dehydrogenase, CRP c-reactive peptide, ALP alkaline phosphatase, GGT γ-glutamyl transferase.

Fig. 3. Subgroup analyses of the risks of incident post-acute COVID-19 composite gastrointestinal outcomes compared with the contemporary control cohort.

Composite outcomes consisted of incident diagnoses (GERD, PUD, acute pancreatitis, functional dyspepsia, acute gastritis, IBS, and cholangitis), signs and symptoms (constipation, abdominal pain, diarrhea, vomiting, and bloating), coagulation studies (PT, PTT, INR), liver and biliary tree function tests (albumin, ALT, total protein, AST, LDH, CRP, ALP, total bilirubin, GGT, direct bilirubin, lipase, and amylase) and any gastrointestinal outcome (incident occurrence of any gastrointestinal outcome studied). Outcomes were ascertained 30d after the COVID-19-positive test until the end of follow-up. COVID-19 cohort (n  =  154,068) and contemporary control cohort (n  =  5,638,795). Adjusted HRs (dots) and 95% (error bars) CIs are presented. The dashed line marks a HR of 1.00; lower limits of 95% CIs with values greater than 1.00 indicate significantly increased risk. GERD gastroesophageal reflux disorder, IBS irritable bowel syndrome, PT prothrombin time, PTT partial thromboplastin time, INR international normalized ratio, ALT alanine transaminase, AST aspartate transaminase, LDH lactate dehydrogenase, CRP c-reactive peptide, ALP alkaline phosphatase, GGT γ-glutamyl transferase.

Fig. 4. Risks and 1-years burdens of incident post-acute COVID-19 gastrointestinal outcomes compared with the contemporary control cohort by care setting of the acute infection.

Risks and burdens were assessed at 1-year in mutually exclusive groups comprising non-hospitalized individuals with COVID-19 (green), individuals hospitalized for COVID-19 (orange) and individuals admitted to intensive care for COVID-19 during the acute phase (first 30 d) of COVID-19 (blue). Outcomes were ascertained 30 d after the COVID-19-positive test until the end of follow-up. The contemporary control cohort served as the referent category. Within the COVID-19 cohort, non-hospitalized (n  =  131,915), hospitalized (n  =  16,764), admitted to intensive care (n  =  5389) and contemporary control cohort (n  =  5,606,761). Panel A describes the risks and burdens of incident diagnoses and panel B describes the risks and burdens of incident laboratory abnormalities. Adjusted HRs (dots) and 95% (error bars) CIs are presented, as are estimated excess burdens (bars) and 95% CIs (error bars). Burdens are presented per 1000 persons at 12 months of follow up. The dashed line marks a HR of 1.00; lower limits of 95% CIs with values greater than 1.00 indicate significantly increased risk. GERD gastroesophageal reflux disorder, IBS irritable bowel syndrome, PT prothrombin time, PTT partial thromboplastin time, INR international normalized ratio, ALT alanine transaminase, AST aspartate transaminase, LDH lactate dehydrogenase, CRP c-reactive peptide, ALP alkaline phosphatase, GGT γ-glutamyl transferase.

Fig. 5. Risks and 1-year burdens of incident post-acute COVID-19 composite gastrointestinal outcomes compared with the contemporary control cohort by care setting of the acute infection.

Risks and burdens were assessed at 1-year in mutually exclusive groups comprising non-hospitalized individuals with COVID-19 (green), individuals hospitalized for COVID-19 (orange) and individuals admitted to intensive care for COVID-19 during the acute phase (first 30 d) of COVID-19 (blue). Composite outcomes consisted of incident diagnoses (GERD, PUD, acute pancreatitis, functional dyspepsia, acute gastritis, IBS, and cholangitis), signs and symptoms (constipation, abdominal pain, diarrhea, vomiting, and bloating), coagulation studies (PT, PTT, INR), liver and biliary tree function tests (albumin, ALT, total protein, AST, LDH, CRP, ALP, total bilirubin, GGT, direct bilirubin, lipase, and amylase) and any gastrointestinal outcome (incident occurrence of any gastrointestinal outcome studied). Outcomes were ascertained 30 d after the COVID-19-positive test until the end of follow-up. The contemporary control cohort served as the referent category. Within the COVID-19 cohort, non-hospitalized (n  =  131,915), hospitalized (n  =  16,764), admitted to intensive care (n  =  5389) and contemporary control cohort (n  =  5,606,761). Adjusted HRs (dots) and 95% (error bars) CIs are presented, as are estimated excess burdens (bars) and 95% CIs (error bars). Burdens are presented per 1000 persons at 12 months of follow up. The dashed line marks a HR of 1.00; lower limits of 95% CIs with values greater than 1.00 indicate significantly increased risk. GERD gastroesophageal reflux disorder, IBS, irritable bowel syndrome, PT prothrombin time, PTT partial thromboplastin time, INR international normalized ratio, ALT alanine transaminase, AST aspartate transaminase, LDH lactate dehydrogenase, CRP c-reactive peptide, ALP alkaline phosphatase, GGT γ-glutamyl transferase.