Internal medicine

Gastrointestinal bleeding

Disease

Coronavirus Infections

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Pandemic

Gastroenterology

Outbreak

Political science

Intensive care medicine

Virology

Betacoronavirus

MEDLINE

2019-20 coronavirus outbreak

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Medicine

European Journal of Gastroenterology & Hepatology

Dear Editor, Coronavirus disease-2019 (COVID-19) is a global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although it is primarily a respiratory illness, gastrointestinal involvement is increasingly being observed, such as anorexia (26.8%), nausea/vomiting (7.8%), diarrhea (5–10%) and abdominal pain (3.9–6.8%) [1,2]. Despite limited evidence from literature about gastrointestinal bleed (GIB) management in COVID-19, stable patients are often managed conservatively because endoscopies are high-risk aerosol-generating procedures. Herein, we systematically reviewed published literature about the point prevalence of causes of GIB in COVID-19 patients and their outcomes. A systematic search of PubMed, Google Scholar, Embase and Scopus databases was undertaken to extract articles relevant to GIB in COVID-19 on 13 September 2020. The search strategy was implemented using various combinations of the following search terms: "gastrointestinal bleed," "melena," "hematochezia," "upper GI bleed," "lower GI bleed," "rectal bleeding," "hematemesis," "coffee-ground emesis," "black tarry stools," maroon-colored stools," "COVID-19", "SARS-COV-2", "coronavirus." Data about management and clinical outcomes such as rebleeding, mortality and length of hospital stay (LoS) was collected from available case reports, case series and observational studies and summarized using descriptive statistics. From the initial 400 articles retrieved, 21 studies were finally included after eliminating nonrelevant articles, reviews and duplicates. There were 13 case reports, 5 case series, 2 retrospective observational studies and 1 case–control study. The total sample size consisted of 123 patients with a positive SARS-CoV-2 reverse transcriptase-PCR. The mean age was 63.1 ± 16.4 years, with the majority being males (88/123, 71.5%). Endoscopic evaluation was performed only in 40% cases (49/123), esophagogastroduodenoscopy (EGD) in 40, colonoscopy in 5 and sigmoidoscopy in 4 patients (Table 1). The most common finding on EGD was gastroduodenal ulcers (42.5%, 17/40 patients), followed by esophagitis and esophageal ulcers in 15% (6/40) of individuals. Less common findings included esophageal varices and erosive/hemorrhagic gastritis in 10% (4/40) of patients. Most patients (108/123, 87.8%) were managed conservatively with proton pump inhibitors, somatostatin analogs, vasopressin analogs, intravenous fluid resuscitation and local hemostatic agents. Endoscopic interventions were performed in 12.2% of cases (15/123). Only half (62/123) patients received packed red blood cell transfusion, with a mean number of four transfusions. The GIB-related mortality rate was 1.6% (2/123). Rebleeding occurred in 12 patients (10%). The median LoS was 8 days (interquartile range: 7–28 days). Table 1. - Clinical presentation of gastrointestinal bleeding, management and outcomes of included cases Author Country Type ofstudy Clinical presentation Risk factors Management PRBC transfusion Outcomes Lotti et al. [6] Italy Case report 62 years, maleHematochezia – Endoscopy to localize the source NA Resolution Carvalho et al. [5] USA Case report 71 years, femaleBloody diarrhea Lisinopril leading to increased risk of severe COVID? Sigmoidoscopy to localize the source NA Resolution Cho et al. [7] USA Case series Median age 68 years,2 maleHematochezia h/o anticoagulation use and aspirin (low dose) in one patient. PPI, antifungals and antibiotics and colonoscopy to localize the source NA Spontaneous resolution Guotao et al. [8] China Case report 83 years, maleHematochezia – Colonoscopy to reveal the source of bleeding, oral PPI tablet NA Resolution Li et al. [9] USA Case report 39 years, maleHematemesis, melena, and hematochezia Thrombocytopenia Conservative with IV PPI and IVIG for thrombocytopenia NA Resolution Gulen et al. [10] Turkey Case report 53 years, maleMelena h/o aspirin use, CRF PPI infusion 3 units PRBC transfusion Resolution Li et al. [11] China Case report 77 years, maleCoffee ground emesis – Mucosal protective and hemostatic agents, IV PPI, octreotide, gastroscopy to identify the source of bleeding NA Resolution within 48 h Xiao et al. [12] China Case report 78 years, maleCoffee ground gastric contents in the nasogastric tube and fecal occult blood test positive – To identify the source of bleeding, Octreotide, PPI NA Resolution Buckholz et al. [13] USA Case report 35 years, maleMelena Sickle cell trait, post-renal transplantation Conservative 3 units PRBC transfusion Resolution in 4 weeks Malik et al. [14] USA Case report 32 years, maleHematemesis Varices Protonix IV, Endoscopic band ligation 6 units PRBC transfusion andiron sucrose Resolution Chen et al. [15] China Case report 84 years, maleHematochezia Conservative; octreotide, hemocoagulase and esomeprazole 6 units PRBC transfusion Died due to unresolved GI bleed Kassas et al. [16] Egypt Case report 59 years, maleHematemesis HCV-related chronic liver disease Endoscopy to diagnose varices and subsequent band ligation NA resolved Barrett et al. [17] USA Case series Median age-75 years,all- male.Melena in 4, hematochezia in 2 Prior anticoagulation in 2 patients, h/o internal hemorrhoids and diverticulosis in one Conservative management in all, diagnostic endoscopy in one 2 units PRBC transfusions in one patient GI bleed resolved in all the patients. Gadiparthi et al. [18] USA Case series Median age 57 years,1 male and 2 females; Melena in 2, rectal bleed in one h/o RYGB in one, use of fecal management system in the other Conservative with IV PPI 2 units PRBC transfusions each in all 3 patients GI bleed resolved in 2; 1 patient had recurrent severe bleeding requiring ICU admission Cavaliere et al. [19] USA Case series Median age 69 years;3 males and 3 females;4 melena, 2 hematemesis – Conservative with IV PPI 2 units PRBC transfusions in four patients Spontaneous resolution in all Mellazini et al. [20] Italy Case series Median age 77 years, all Males.Upper GI bleeding; melena and hypotension h/o anticoagulation use in all All except one underwent GI endoscopy to identify the source of bleeding; therapeutic endoscopic intervention (adrenaline and clips) in one patient NA Resolved in all except one with rebleeding who was treated arterial embolization Aurelio et al. [21] Italy Retrospective observational study Median age 75 years; 18 male and 15 female;Upper GI bleeding;black tarry stools in 12, hematemesis in 5, coffee ground vomitus in 3, severe progressive anemia and dark stools in 3 patients 7 patients on antiplatelet therapy, 18 patients on anticoagulants Diagnostic EGD in 18 patients, therapeutic in 7,IV PPI therapy given to all except one who was given vasoactive agent because of suspected varices History of blood transfusion in four patients Resolved in all, except 3 patients who rebled Martin et al. [22] USA Case–Control Study Median age 69 years.27 male and 14 female.Hematemesis in 2, melena in 20, maroon-colored stool in 4, hematochezia in 11, bloody nasogastric tube output, and melena + hematochezia in one each Past h/o anticoagulation use in 29 patients, antiplatelet use in 20 Diagnostic endoscopy: EGD-10,colonoscopy-1, sigmoidoscopy-4; Therapeutic endoscopic treatment-4 PRBC transfusion given to 30 patients, mean PRBC 3 units In hospital GIB mortality-1, recurrent bleeding in 5 Shalimar et al. [23] India Retrospective observational study Median age 46 years, 17 male and 7 female;Hematemesis in 12, melena in 4, and combined hematemesis and melena in 7 patients, whereas only one patient had fresh bleeding per rectum (hemorrhoidal bleeding). History of variceal bleed was present in 14/23 (60.9%), history of hepatic encephalopathy was present in 3 (13.0%), the low platelet count in 5, INR (>2) in 3, and creatinine (>1 mg/dl) in 9. Only one patient had Child C and creatinine (>1 mg/dl). Conservative in all patients (23) PRBC transfusions in 14 patients Bleeding resolved in all Lin et al. [24] China Case report 77 years, malehematemesis Diagnostic endoscopy to localize the source of bleeding in the esophagus Papanikolao et al. [25] Greece Case report 40 years, maleHematemesis Alcoholic chronic liver disease Diagnostic endoscopy to identify esophageal varices followed by band ligation NA Died due to worsening hepatic dysfunction Dashes indicate not reported.CRF, chronic renal failure, EGD, esophagogastroduodenoscopy, GI, gastrointestinal; GIB, gastrointestinal bleed; HCV, hepatitis C virus; NA, not applicable; PPI, proton pump inhibitors; PRBC, packed red blood cell; RYGB, Roux-en-Y gastric bypass. Our study results show that less than half of the COVID-19 patients (40%) presenting with GIB underwent endoscopic evaluation. Low rates of endoscopy could be attributed to the fear of potential endoscopic transmission of SARS-CoV-2, a need for conserving personal protective equipment, or multiple GI societies' recommendations to defer nonurgent endoscopy [3,4]. Peptic ulcer disease remains the most common finding, and mortality related to GIB in COVID-19 is low (2%), even with low rates of endoscopies during the pandemic. SARS-CoV-2 has also reported to cause acute hemorrhagic colitis; however, the exact role of the virus in causing GIB is still needed to be defined [5]. Furthermore, any case of GIB needs individualized attention, and clinical judgment should prevail, and the focus should be the patient outcome. Acknowledgements Conception and design: H.G. Statistical analysis: H.G. and S.S. First draft: S.S. All authors critically revised, edited and finally approved the manuscript. Conflicts of interest B.T. serves as a consultant for Medtronic and Boston Scientific. For the remaining authors, there are no conflicts of interest.

Management of gastrointestinal bleeding during COVID-19: less is more!