Many patients with COVID-19 present with “typical” symptoms such as fever, cough, shortness of breath, or sore throat. However, in addition to these, there are increasing data to support that many patients can also develop a myriad of gastrointestinal (GI) symptoms, which include mild diarrhea, nausea, vomiting and abdominal pain 1,2.   A recent meta-analysis conducted by Cheung et al found that among 60 studies comprising of 4243 patients, the pooled prevalence of all GI symptoms was 17.6% (95% CI, 12.3%-24.5%)2.  As these data have continued to accumulate, there have also been several reports of more “atypical” GI presentations that may be important to note when evaluating patients during the COVID-19 pandemic. Case reports on these presentations have described instances of severe diarrhea, GI bleeding, hemorrhagic colitis and acute hepatitis.

The type of diarrhea experienced by most patients with COVID-19 has been described as mild, semi-formed (not voluminous), and occurring up to 3 times daily without blood1.  Cappell reported a case of a woman aged 41 years who presented with typical COVID-19 symptoms after exposure to a sick contact. However, she experienced voluminous diarrhea with up to 10 watery, blood-tinged bowel movements per day3.  It is important to note that the patient was taking medications prior to symptoms developing. These included rivaroxaban, for history of a prior transverse sinus thrombosis, and metformin for diabetes. Upon physical examination, the patient appeared dehydrated and had guaiac positive stool. Laboratory findings indicated electrolyte abnormalities, acute kidney injury and mildly elevated serum aminotransferases with AST 53 U/L (0-34) and ALT 64 U/L (8-37). Stool infectious workup was negative. The patient continued to decompensate and have significant diarrhea, but there was no overt GI bleeding or worsening serum aminotransferases.  She eventually passed away from progressive respiratory and renal failure. 

Xiao et al described a case of a man aged 78 years who presented with COVID-19 and rapidly decompensated, requiring intubation and mechanical ventilation on day 4 of admission4.  On day 10, the patient developed coffee-ground contents in his orogastric tube and had fecal occult positive stool. The patient underwent upper endoscopy and colonoscopy with “mucosal damage” noted in the esophagus.  The authors did not describe any other endoscopic findings. Multiple biopsies were performed during both procedures. These showed positive staining for ACE2 and SARS-CoV-2 predominantly in the gastric, duodenal and rectal glandular epithelial cells but rarely in the esophageal epithelium. The authors report that similar findings were found in other patients who had stool testing positive for SARS-CoV-2; however, additional information regarding these patients was not provided.

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Bleeding stopped within 1 day of treatment with esomeprazole and octreotide. Although it is unclear if COVID-19 directly led to GI bleeding, it is important to note that both ACE2 and SARS-CoV-2 were noted in biopsies of the GI tract. In addition, the authors did not include detailed information regarding the endoscopic appearance of patients undergoing these procedures or pertinent laboratory findings such as hemoglobin and platelet counts, INR, and polypharmacy. Therefore, it cannot be ascertained that COVID-19 directly caused GI bleeding from this case report alone.


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Carvalho described a case of a woman aged 71 years with recent travel to Egypt who presented with abdominal pain, nausea, vomiting, and non-bloody diarrhea that eventually became bloody5. Laboratory findings showed normal hemoglobin and mild acute kidney injury. Contrast enhanced imaging of her abdomen and pelvis showed pan-colitis. The patient was placed on antibiotics, and had stool studies that were negative for infection. The patient eventually developed respiratory symptoms and tested positive for SARS-CoV-2 (both via nasopharyngeal and stool swab).  Interestingly, the patient also tested positive for rhinovirus and herpes simplex virus 1 via the nasopharyngeal swab test. Investigators determined C-reactive protein (CRP) level was elevated at 11.6 mg/dL. Abdominal pain and bloody diarrhea persisted in the patient, therefore, clinicians performed a flexible sigmoidoscopy, which showed evidence of patchy areas of focal erythema without ulceration in the descending colon, sigmoid and rectum.  Biopsies were relatively non-specific and inconsistent with ischemia and other infections or inflammatory etiologies. The patient eventually decompensated and was treated with hydroxychloroquine for respiratory symptoms.  Bloody diarrhea and abdominal pain improved within 48 hours and repeat imaging of her abdomen showed resolution of the previously noted colonic inflammation.

COVID-19 has been reported to cause mild elevations in serum aminotransferases1,6.  Wander et al published a case report woman aged 59 years with HIV who initially presented with dark urine and elevated AST 1230 IU/L (normal < 50), ALT 697 IU/L (normal < 50), alkaline phosphatase 141 IU/L (normal < 125) and normal bilirubin and INR7.  The patient reportedly had initially showed normal serum aminotransferases and was being treated with elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide.  Abdominal ultrasound and viral serologies were negative. The patient eventually developed fever and increasing oxygen requirements, after which she tested positive for SARS-CoV-2.  Clinicians treated her with hydroxychloroquine. Her condition improved with down-trending AST and ALT. The authors stated that this was the first report of acute non-icteric hepatitis in a patient with COVID-19 who developed these presentations prior to fever and respiratory symptoms. 

Finally, there have been limited reports of how COVID-19 may impact pancreatic enzymes.  Wang et al reported 9/52 (17%) of patients reviewed with COVID-19 pneumonia had “pancreatic injury,” which was defined as any abnormality in amylase or lipase8.  Although this is a relatively non-specific finding, it is another additional parameter to consider reviewing in patients with COVID-19. Those patients with abnormal pancreatic enzymes had increased incidence of diarrhea, anorexia and severity of illness.

It is important to note that the patients discussed above represent case reports of what can be considered atypical GI presentations of COVID-19.  All newly published research on GI manifestations of COVID-19 should be reviewed. Based on limited data, it appears that biopsies of the GI tract in patients with COVID-19 appear to be somewhat non-specific, without any distinct findings.  Although the number of procedures performed by gastroenterologists has been significantly reduced during the COVID-19 pandemic, it is unclear if all facilities would have access to the specific type of staining needed to confirm ACE2 and SARS-CoV-2 if biopsies were performed. When evaluating a patient in person, who is set to undergo aGI procedure, it is important to review all local, state, national, and societal guidelines with respect to wearing appropriate personal protective equipment (PPE).

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References

1.     Pan L, Mu M, Yang P, et al. Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study. Am J Gastroenterol. 2020;115(5):766‐773. doi:10.14309/ajg.0000000000000620

2.     Cheung KS, Hung IF, Chan PP, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis [published online ahead of print, April 3, 2020]. Gastroenterology. 2020;S0016-5085(20)30448-0. doi:10.1053/j.gastro.2020.03.065

3.     Cappell MS. Severe diarrhea and impaired renal function in COVID-19 disease. Am J Gastroenterol. Available at:  https://journals.lww.com/ajg/Documents/Cappell%20COVID%20Case%20Report%20FINAL.pdf. Accessed April 14, 2020.

4.     Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2 [published online March 3, 2020]. Gastroenterology. doi:10.1053/j.gastro.2020.02.055

5.     Carvalho A et al. SARS-CoV-2 gastrointestinal infection causing hemorrhagic colitis:  implications for detection and transmission of COVID-19 disease. Am J Gastroenterol. Available at:  https://journals.lww.com/ajg/Documents/COVID19_Bernstein_et_al_AJG_Preproof.pdf. Accessed April 15, 2020.

6.     Guan W-J, Ni Z-Y, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China [published online February 28, 2020]. N Engl J Med. doi:10.1056/NEJMoa2002032

7.     Wander P et al. COVID-19 presenting as acute hepatitis. Am J Gastroenterol.  Available at:  https://journals.lww.com/ajg/Documents/COVID19_Bernstein_et_al_AJG_Preproof.pdf. Accessed April 15, 2020.

8.     Wang F, Wang H, Fan J, Zhang Y, Wang H, Zhao Q. Pancreatic injury patterns in patients with COVID-19 pneumonia [published online ahead of print, 2020 Apr 1]. Gastroenterology. doi:10.1053/j.gastro.2020.03.055 

This article originally appeared on Gastroenterology Advisor