Management of GI Disorders in a

Primary Care Setting: Partnering

with our Gastroenterology
Colleagues

Topic: COVID-19

Linda Geng, MD, PhD (Primary Care and Population Health)

J ohn Gubatan, MD (Division of Gastroenterology and Hepatology)
Stanford University School of Medicine
J anuary 22, 2022
 Disclosures
• No conflicts of interests to disclose related to the material in
this presentation
 Outline
• Clinical Vignette Part I (Acute GI Complication of COVID-19)
• SARS-COV-2 and GI Tract
• GI Manifestations of COVID-19
• GI Symptoms and COVID-19 Clinical Outcomes
• GI Complications of COVID-19
• Clinical Vignette Part II (GI Sequelae of COVID-19)
• GI Symptoms/FGID After COVID-19
• SARS-COV-2 Vaccinations and GI Symptoms
• Dietary Supplements/Probiotics and COVID-19
• Take Home Points
• CME Questions/Interactive Session with Audience
 Clinical Vignette Part I

50 year-old man with history of GERD presents to PCP with

several days of epigastric abdominal pain, nausea, and
vomiting. Patient has no respiratory symptoms.

• Differential Diagnosis?

• Primary Care Workup and Triage?

Clinical Vignette Part I: Patient with COVID-19 and GI Symptoms

50 year-old man with history of GERD presents to PCP with

several days of epigastric abdominal pain, nausea, and
vomiting. Patient has no respiratory symptoms.

• Differential Diagnosis?

• Primary Care Workup and Triage?

He is found to have positive SARS-COV-2 RNA.

 SARS-CoV-2 and the Gastrointestinal Tract

• ACE2 mRNA and

protein are highly
expressed in the
small intestine and
colon, specifically
at the enterocyte
level
• ACE2 is also
expressed in
gallbladder
epithelial cells and
pancreatic ductal,
acinar, and islet
cells
D’Amico et al 2020, Clinical Gastroenterology and hepatology
 SARS-CoV-2 and the Gastrointestinal Tract

• SARS-CoV-2 RNA has been detected in multiple GI sites by RT-

PCR
• In a study of 65 hospitalized patients with COVID-19🡪🡪 SARS-
CoV-2 RNA was detected in the fecal samples from more than 50%
patients with GI symptoms (40% in patients without GI symptoms)
• In a meta-analysis of 12 studies and 138 patients, the pooled
prevalence of stool samples that were positive for the SARS-CoV-2
RNA was 48.1 percent

Lin et al 2020, Gut, 69(6), pp.997-1001.

Cheung et al 2020, Gastroenterology, 159(1), pp.81-95.
Gastrointestinal Manifestations in Patients with Active COVID-19

• Cross-sectional Study: 2,552

COVID-19 patients were
included.
• The prevalence of GI
symptoms was 21.0%
(537/2,552).
• Diarrhea (8.9%, 226/2,552)
was the most common GI
symptom.
Chen et al 2021. Frontiers in Medicine
 Incidence of Adverse Outcomes in COVID-19 Patients with
and without GI symptoms

• Patients with GI symptoms had

a significantly longer hospital
length of stay (18.16 ± 10.62 vs.
13.97 ± 8.07; P < 0.001) than
those without

• Patients with GI symptoms had

Chen et al 2021. Frontiers in Medicine
significantly higher proportions
of transferring to ICU (6.0 vs.
2.5%; P < 0.001), requiring
mechanical ventilation (4.8 vs.
2.3%; P = 0.001), death (3.5 vs.
1.7%; P = 0.008
 Acute Gastrointestinal Complications of COVID-19
• Patients with severe COVID-19 are at a particularly high risk for
developing GI complications
• DDx of Acute GI Complications of COVID-19 (not to miss diagnoses):
• Acute liver injury and elevated transaminases: Nearly two-thirds of patients with
severe COVID-19 develop elevated liver transaminases 🡪🡪 with mean AST and ALT
above 400 units per liter of serum)
• Acute cholecystitis: Most commonly acalculous cholecystitis. Managed with
antibiotics and percutaneous cholecystostomy rather than surgery
• Acute pancreatitis: Acute pancreatitis in COVID patients is managed in the same way
as that in non-COVID patients.
• Ileus and feeding intolerance: critically ill patients🡪🡪 occur in 46 to 56%
• Acute colonic pseudo-obstruction: severe gaseous distention with no obvious distal
obstruction,🡪🡪 Ogilvie's syndrome
• Mesenteric ischemia: Most serious GI complication in COVID-19🡪🡪 surgical
management
• Colitis/New onset IBD: Case reports, workup and management like non-COVID-19
IBD patients
Up-to-Date (March 2021): COVID-19: Gastrointestinal symptoms and complications
 Clinical Vignette Course

• Labs: WBC 15, Hgb 16, Tbili 1.7, AST 60, ALT 78, AP 250,
Lipase 3X ULN (750s), normal Ca, triglycerides
• Only takes Omeprazole 20 mg PO QDaily for GERD
• CT Abdomen and Pelvis shows no cholecystitis, no cholelithiasis,
choledocholithiasis, edema and stranding around pancreas, mild
thickening of rectosigmoid colon
• Admitted to hospital for management of idiopathic pancreatitis🡪🡪
aggressive IV LR fluids, pain medications, bowel rest
• Patient improves, diet advanced, patient discharged home
 Clinical Vignette: Patient with history of COVID-19 and ongoing
GI symptoms

• Patient from first vignette presents to PCP for follow-up 6

months after COVID-19 and pancreatitis
• After hospitalization, patient received 2 standard doses of
Pfizer COVID-19 vaccine
• Patient now reports intermittent abdominal pain and diarrhea
• Pain is different from pancreatitis episode. Patient is localized
to lower abdomen. No nausea or vomiting.
• No weight loss, melena, or hematochezia
• Pain is improved with bowel movements.
Clinical Vignette Part II: Patient with history of COVID-19 and ongoing
GI symptoms

• CBC, Chem panel, LFTs, lipase, CRP, TSH are all normal
• CT Abdomen and Pelvis unremarkable
• C. diff, GI PCR negative
• Repeat SARS-COV-2 nasopharyngeal RNA swab is
NEGATIVE
• Differential Diagnosis?
 Gastrointestinal Sequelae of COVID-19
• At a median of 106 days after
discharge following
hospitalization for COVID-19
(N=150 patients), 16% of
unselected patients reported
new GI symptoms at follow-
up.
• Among 285 respondents to an
online survey for self-identified
COVID-19 survivors without
pre-existing GI symptoms, 113
(40%) reported new GI
symptoms after COVID-19
(95% CI 33.9 to 45.6%).

Blackett et al 2021. Prevalence and risk factors for gastrointestinal symptoms after recovery
from COVID‐19. Neurogastroenterology & Motility, p.e14251.
 Risk of Post-COVID-19 Functional GI Disorders
• Prospective case-control (280 patients
SARS-COV-2+, GI Sx During with COVID-19 and 264 historical
Symptomatic COVID-19
healthy controls)🡪🡪 were followed up
at 6-month for FGID (Rome IV criteria
🡪🡪 irritable bowel syndrome (IBS),
SARS-COV-2+,
No GI Sx During
uninvestigated dyspepsia).
Asymptomatic
COVID-19
• At 6-month follow-up, symptomatic
patients with who were SARS-COV-
2+ 🡪🡪 more often developed FGIDs
(14.6% vs 1.17%, P= 0.0003) vs
Ghoshal et al J Gastroenterol Hepatol. 2021
asymptomatic SARS-COV-2+ patients.

• At 6-month follow-up, patients with COVID-19 who had GI symptoms on

presentation 🡪🡪 more often developed FGIDs (14.8% vs 6.8%, P= 0.032) than
COVID-19 patient who did not have GI symptoms are presentation.
 Outpatient Management of Post-COVID-19 GI Symptoms and FGID
• Retest for SARS-COV-2, confirm patient does not have active COVID-19
• Rule out other causes (CBC, Chem panel, LFTs, abdominal ultrasound, KUB)
• If alarm features (weight loss, melena, hematochezia)🡪🡪 refer to Gastroenterology
• If unrevealing workup and no alarm features, empiric treatment of post-infectious
(COVID-19) functional GI disorder
• Irritable bowel syndrome: fiber, anti-spasmodics (e.g. dicyclomine), if diarrhea (anti-
motility agents), if constipation🡪🡪 bowel regimen (Miralax, etc)
• Heartburn/Acid Reflux: Trial of proton pump inhibitor
• Dyspepsia🡪🡪 trial of FDGard (OTC peppermint oil) for functional dyspepsia

• If refractory GI symptoms above despite conservative management above🡪🡪 refer to GI

for further test and management
• Motility testing: gastric emptying, anorectal manometry
• Glucose/Lactulose breath testing for small intestinal bacterial overgrowth (SIBO)
• Neuromodulators (TCAs), promotility (e.g. Linaclotide) agents
 COVID-19 Vaccination and Gastrointestinal Symptoms

• GI symptoms reported to
occur after SARS-CoV-2
vaccination (prospective
observational study of >
600K vaccinated patients)
• Nausea was reported in 2-
5.7% of patients after
SARS-CoV-2 vaccination
Menni et al 2021, The Lancet Infectious Diseases.
• Diarrhea was reported in
• Rare (case reports) post-vaccine GI 1.5-2% of patients after
adverse effects: transaminitis, acute SARS-CoV-2 vaccination
pancreatitis, colitis
 Dietary Supplements/Probiotics and Risk of COVID-19
• App-based community survey: In 372 720
UK participants (175 652 supplement users
and 197 068 non-users)
• Some supplements and probiotics were
associated with lower risk of SARS-COV-2
infection after adjusting for potential
confounders:
• Probiotics🡪🡪 14% (95% CI (8% to
19%)
• Omega-3 fatty acids🡪🡪 12% (95% CI
(8% to 16%)
• Multivitamins🡪🡪 13% (95% CI (10% to
16%))
• Vitamin D🡪🡪 9% (95% CI (6% to 12%)

• Use of supplements/probiotics for active

COVID-19 area of active investigation
Louca et al 2021. BMJ nutrition, prevention & health. (ongoing clinical trials)
 Take Home Points
• GI symptoms among patients with active COVID-19 are not
uncommon
• GI symptoms in patients with COVID-19 are associated with more
severe disease course
• Acute GI complications may occur in patients with COVID-19;
important to keep broad differential and initial lab/imaging workup
• Post-infectious (COVID-19) functional GI disorders may occur (e.g.
IBS, dyspepsia, gastroparesis)
• GI adverse effects after SARS-COV-2 vaccination are uncommon,
minor in severity, and often self-limited
• Probiotics and some supplements (omega-3 fatty acids, multivitamin,
vitamin D) have been associated with lower risk of SARS-COV-2
infection in observational studies
 CME Question 1:
• Q1: Among patients with active COVID-19, what is the
prevalence of gastrointestinal symptoms?

• A. 10%
• B. 20%
• C. 30%
• D. 50%
• E. 75%
 CME Question 1:
• Q1: Among patients with active COVID-19, what is the
prevalence of gastrointestinal symptoms?

• A. 10%
• B. 20% (Estimates around 20% of patients with COVID-
19 develop at least one GI symptom)
• C. 30%
• D. 50%
• E. 75%
 CME Question 2:
• Q2: What is the most common GI manifestation of active
COVID-19?

• A. Nausea/Vomiting
• B. Abdominal Pain
• C. GI Bleeding
• D. Diarrhea
• E. Ileus
 CME Question 2:
• Q2: What is the most common GI manifestation of active
COVID-19?

• A. Nausea/Vomiting (5.9%)
• B. Abdominal Pain (4.2%)
• C. GI Bleeding (1.6%)
• D. Diarrhea (~9%)
• E. Ileus (rare-case reports/series)
 CME Question 3:
• Q3: What percentage of patients develop post-infectious functional GI
disorders (IBS, etc) after recovering from symptomatic active COVID-
19?

• A. 15%
• B. 30%
• C. 45%
• D. 60%
• E. Greater than 75%
 CME Question 3:

• Q3: What percentage of patients develop post-infectious functional GI

disorders (IBS, etc) after recovering from symptomatic active COVID-
19?

• A. 15% (IBS and dyspepsia)

• B. 30%
• C. 45%
• D. 60%
• E. Greater than 75%
 CME Question 4:

• Q4: What is the most common gastrointestinal symptom

reported after SARS-CoV-2 vaccination

• A. Diarrhea
• B. Weight Loss
• C. GI Bleeding
• D. Odynophagia
• E. Nausea
 CME Question 4:
• Q4: What is the most common gastrointestinal symptom
reported after SARS-CoV-2 vaccination

• A. Diarrhea (1.5-2%)
• B. Weight Loss (No reports)
• C. GI Bleeding (No reports)
• D. Odynophagia (No reports)
• E. Nausea (~5.7%)
 References

• Chen, H., Tong, Z., Ma, Z., Luo, L., Tang, Y., Teng, Y., Yu, H., Meng, H., Peng, C., Zhang, Q.
and Zhu, T., 2021. Gastrointestinal Bleeding, but Not Other Gastrointestinal Symptoms, Is
Associated With Worse Outcomes in COVID-19 Patients. Frontiers in Medicine, 8.
• D’Amico, F., Baumgart, D.C., Danese, S. and Peyrin-Biroulet, L., 2020. Diarrhea during COVID-
19 infection: pathogenesis, epidemiology, prevention, and management. Clinical Gastroenterology
and hepatology, 18(8), pp.1663-1672.
• Blackett, J.W., Li, J., Jodorkovsky, D. and Freedberg, D.E., 2021. Prevalence and risk factors for
gastrointestinal symptoms after recovery from COVID‐19. Neurogastroenterology & Motility,
p.e14251.
• Ghoshal UC, Ghoshal U, Rahman MM, Mathur A, Rai S, Akhter M, Mostafa T, Islam MS, Haque
SA, Pandey A, Kibria MG, Ahmed F. Post-infection functional gastrointestinal disorders following
coronavirus disease-19: A case-control study. J Gastroenterol Hepatol. 2021 Oct
20:10.1111/jgh.15717. doi: 10.1111/jgh.15717. Epub ahead of print. PMID: 34672022; PMCID:
PMC8657345.
• Louca, P., Murray, B., Klaser, K., Graham, M.S., Mazidi, M., Leeming, E.R., Thompson, E.,
Bowyer, R., Drew, D.A., Nguyen, L.H. and Merino, J., 2021. Modest effects of dietary
supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19
Symptom Study app. BMJ nutrition, prevention & health.
• Menni, C., Klaser, K., May, A., Polidori, L., Capdevila, J., Louca, P., Sudre, C.H., Nguyen, L.H.,
Drew, D.A., Merino, J. and Hu, C., 2021. Vaccine side-effects and SARS-CoV-2 infection after
vaccination in users of the COVID Symptom Study app in the UK: a prospective observational
study. The Lancet Infectious Diseases.
Questions?