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COVID-19: Issues related to gastrointestinal disease in adults

COVID-19: Issues related to gastrointestinal disease in adults
Author:
Sunanda V Kane, MD, MSPH
Section Editor:
Lawrence S Friedman, MD
Deputy Editors:
Kristen M Robson, MD, MBA, FACG
Shilpa Grover, MD, MPH, AGAF
Literature review current through: Dec 2022. | This topic last updated: Jul 20, 2022.

INTRODUCTION — At the end of 2019, SARS-CoV-2, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. Coronavirus disease 2019 (COVID-19) primarily manifests as a lung infection with symptoms ranging from those of a mild upper respiratory infection to severe pneumonia, acute respiratory distress syndrome, and death. COVID-19 disproportionately affects patients with pre-existing comorbidities and/or older adults. All medical professionals, including gastroenterology and hepatology clinicians, are tasked with rapidly adjusting their practice to curtail the spread of COVID-19, while providing care to their patients.

This topic will discuss COVID-19-related issues for patients with gastrointestinal (GI) disease. As understanding of COVID-19 illness continues to evolve, the approach to diagnosis and management may require modification as well.

Other important aspects of COVID-19 infection are discussed in detail separately:

(See "COVID-19: Epidemiology, virology, and prevention".)

(See "COVID-19: Clinical features" and "COVID-19: Diagnosis".)

(See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

(See "COVID-19: Management in hospitalized adults".)

(See "COVID-19: Evaluation of adults with acute illness in the outpatient setting" and "COVID-19: Management of adults with acute illness in the outpatient setting".)

(See "COVID-19: Issues related to liver disease in adults".)

POSSIBLE RISK FACTORS FOR COVID-19 — Some patients with chronic gastrointestinal (GI) disease may be at increased risk for more severe illness due to COVID-19. Potential risk factors in these patients include their chronic inflammatory disease, comorbidities (eg, diabetes mellitus), and the use of glucocorticoids [1].

It is unclear if the use of proton pump inhibitors (PPIs) is associated with an increased risk of COVID-19. In a cross-sectional survey of 86,602 individuals, 53,130 reported prior abdominal pain, acid reflux, heartburn, and regurgitation and provided data on H2 receptor antagonist (H2RA) and PPI use [2]. Of these, 3386 individuals (6.4 percent) self-reported a positive COVID-19 test result. In analyses adjusted for socioeconomic, lifestyle, and clinical comorbidities, patients who reported PPI use were significantly more likely to report a positive COVID-19 test result with a dose-dependent increase in the odds of a positive test result (PPI once daily odds ratio [OR] 2.15, 95% CI 1.9-2.4; PPI twice daily OR 3.7, 95% CI 2.9-4.6). H2RA use was not associated with an increase in risk. It is possible that this association is due to residual confounding; further studies are required to validate these results. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'COVID-19'.)

For patients with inflammatory bowel disease (IBD), preliminary data have suggested that the prevalence of COVID-19 is not higher than that of the general population [3-6]. However, the use of glucocorticoids, but not anti-TNF therapy, may increase the risk of severe COVID-19 in patients with IBD [5,7,8]. (See 'Patients with COVID-19' below.)

The GI tract may be susceptible to SARS-CoV-2 infection because of widely expressed angiotensin-converting enzyme 2 (ACE2) receptors in the intestine [9]. ACE2 is a receptor for SARS-CoV-2 virus, and digestive symptoms associated with SARS-CoV-2 infection may be caused by direct viral attack as well as tissue and organ damage due to the immune response [10,11]. Staining of tissue specimens from patients with COVID-19 demonstrated that the positive areas were mainly distributed in the cytoplasm of gastric and intestinal epithelial cells and the cilia of glandular epithelial cells [10]. In addition, viral nucleocapsid protein was detected in the cytoplasm of gastric, duodenal, and rectal glandular epithelial cells. However, understanding of the pathogenesis of digestive disease associated with SARS-CoV-2 virus is evolving, and its effects on existing chronic GI disorders remains uncertain [12].

CLINICAL MANIFESTATIONS AND DIAGNOSTIC TESTING

Symptoms of disease flare that can mimic COVID-19 — The clinical presentation of several gastrointestinal (GI) diseases (eg, Crohn disease, ulcerative colitis) can mimic COVID-19 infection [13]. Examples include diseases that manifest with diarrhea, nausea, vomiting and/or anorexia [14,15]. Thus, for patients with an existing diagnosis of chronic GI disease, the clinician will need to assess whether symptoms are related to a disease flare or COVID-19. The approach to testing for COVID-19 is discussed separately. (See "COVID-19: Diagnosis", section on 'Diagnostic approach'.)

Digestive symptoms — Patients with COVID-19 typically present with fever and respiratory symptoms; however, GI symptoms have been commonly reported in patients diagnosed with COVID-19 [9,14,16-19]. For example, in a study including 318 adult patients who were hospitalized with COVID-19, 195 patients (61 percent) reported at least one digestive symptom, and the most frequently reported symptoms were anorexia in 110 patients (35 percent), diarrhea in 107 patients (34 percent), and nausea in 84 patients (26 percent) [16]. Similarly, in another study of 204 patients with COVID-19, 103 patients (51 percent) reported at least one digestive symptom, and the most commonly reported symptoms were anorexia and diarrhea [14].

Some patients with COVID-19 have presented with isolated GI symptoms that may precede the development of respiratory symptoms [20,21]. As an example, in a study of 1141 patients with COVID-19, 183 patients (16 percent) presented with GI symptoms (eg, diarrhea, nausea, vomiting) in the absence of respiratory complaints [20].

Limited data have suggested that diarrheal symptoms in patients with COVID-19 have been associated with a more favorable prognosis and with detection of virus RNA in stool [17,22-24]. In a cohort study including 190 hospitalized patients with COVID-19, diarrheal symptoms were associated with lower risk of in-hospital mortality compared with the absence of diarrhea (OR 0.38, 95% CI 0.17-0.86) [24]. One possible explanation is that the SARS-CoV-2 virus preferentially targets the intestinal mucosa in some patients who present with GI symptoms, and such patients experience a milder disease course than patients with respiratory symptoms. In a study of 84 patients with SARS-CoV-2 pneumonia, stool samples from patients with diarrhea had higher rates for detecting SARS-CoV-2 virus RNA by real time polymerase chain reaction compared with patients without diarrhea (69 versus 17 percent) [22].

Hepatic manifestations — The clinical presentation of COVID-19 may include hepatic manifestations such as acute hepatitis and abnormal liver biochemical tests [25]. (See "COVID-19: Issues related to liver disease in adults".)

When to test for COVID-19 in patients with GI symptoms — The diagnosis of COVID-19 is suspected primarily in patients with the new onset of fever and/or respiratory tract symptoms (eg, cough, dyspnea), while other consistent symptoms include myalgias, diarrhea, and aberrancy in sense of smell or taste.

For patients with GI symptoms, we favor testing for COVID-19 in the following cases [26]:

Hospitalized patients with the new onset of GI symptoms

Outpatients with the new onset of GI symptoms for over 48 hours

Patients with established GI disease (eg, Crohn disease) with symptoms suggestive of a disease flare (eg, diarrhea, vomiting)

In a minority of patients, GI symptoms such as diarrhea may be the presenting symptom or may precede the development of respiratory symptoms [20,21,26]. While the diagnosis of COVID-19 may be suspected based on presenting symptoms, additional factors that inform the decision to perform testing include the patient's geographic location, risk of exposure, rate of community transmission, and the availability of testing. The epidemiology and diagnosis of COVID-19 are discussed in more detail separately. (See "COVID-19: Diagnosis", section on 'Diagnostic approach'.)

Additionally, stool testing to exclude Clostridioides (C., formerly Clostridium) difficile infection is obtained for patients with diarrhea who are at risk for Clostridioides (C., formerly Clostridium) difficile infection (eg, recent antibiotic use) or who may require therapy (eg, antidiarrheal agents) to control symptoms. (See 'Managing symptoms related to viral infection' below.)

Gastrointestinal complications — Several gastrointestinal complications have been reported in critically ill patients with COVID-19 [27,28]. In an observational study including 184 patients with acute respiratory distress syndrome (ARDS), patients with COVID-19 related ARDS had higher rates of gastrointestinal complications compared with non-COVID-19 matched ARDS (74 versus 37 percent; incidence rate ratio 2.33, 95% CI 1.52-3.63) [27]. Specifically, COVID-19 was associated with higher rates of ileus (48 versus 22 percent), bowel ischemia (4 versus 0 percent), and elevated aminotransferase levels (55 versus 27 percent). While patients in this single center study were propensity matched by age, comorbidity, and Sequential Organ Failure Assessment score on intensive care unit (ICU) admission, they were not matched by inflammatory markers which are known to be associated with worse COVID-19 outcomes. It is also unclear if ileus and bowel ischemia are associated with higher opioid requirements and COVID-19-related coagulopathy. Further studies are needed to validate these findings and elucidate the pathophysiologic mechanisms behind these complications. (See "COVID-19: Gastrointestinal symptoms and complications".)

MANAGEMENT PRINCIPLES

General strategies to reduce risk of infection — If community transmission of SARS-CoV-2 virus is present, preventive measures to reduce exposure to the virus include (see "COVID-19: Epidemiology, virology, and prevention", section on 'Prevention'):

General preventive measures such as hand hygiene and social distancing.

Use of telemedicine visits for ongoing disease management.

Decreased frequency of routine laboratory and imaging surveillance when the associated risk is deemed to be low.

Use of lower-volume laboratories off-site from larger healthcare facilities.

For patients with stable disease and without known or suspected COVID-19, continuing the established medication regimen to avoid a disease flare.

For patients on glucocorticoids for treating inflammatory bowel disease, therapy should not be abruptly discontinued, but should be used at the lowest dose possible to control the underlying disease, regardless of COVID-19 exposure or infection status.

Managing symptoms related to viral infection — For symptomatic therapy for infectious diarrhea, the antidiarrheal agent loperamide can be used in an initial dose of 4 mg and with a maximum daily dose of 16 mg in patients without fever, bloody stools, or risk factors for Clostridioides (C., formerly Clostridium) difficile infection. Use of loperamide for patients with acute diarrhea is discussed separately. (See "Approach to the adult with acute diarrhea in resource-rich settings", section on 'Management'.)

For patients with symptoms of gastroenteritis (eg, nausea, vomiting), antiemetic drugs can often help relieve symptoms, in addition to supportive measures including oral or intravenous hydration. Management of patients with gastroenteritis and use of antiemetics are discussed separately. (See "Acute viral gastroenteritis in adults", section on 'Treatment' and "Characteristics of antiemetic drugs".)

Symptomatic therapy for digestive symptoms may reduce the risk of complications such as electrolyte disturbances (eg, hypokalemia) or colonic ischemia related to volume depletion. (See "Colonic ischemia".)

Specific management for COVID-19 is discussed in more detail separately. (See "COVID-19: Management in hospitalized adults" and "COVID-19: Management of adults with acute illness in the outpatient setting".)

Inflammatory bowel disease

Diagnostic considerations during pandemic — For patients with symptoms of active inflammatory bowel disease (IBD; eg, diarrhea) who are also at risk for COVID-19 (eg, recent exposure, high rate of community transmission), evaluation includes COVID-19 testing, stool studies to exclude enteric infections (eg, C. difficile infection), noninvasive inflammatory markers (eg, C-reactive protein, fecal calprotectin), and serum drug trough levels (for patients on biologic therapy). (See "Treatment of Crohn disease in adults: Dosing and monitoring of tumor necrosis factor-alpha inhibitors", section on 'Monitoring' and "Overview of dosing and monitoring of biologic agents and small molecules for treating ulcerative colitis in adults".)

However, in patients with SARS-CoV-2 virus, nonspecific markers of inflammation (eg, C-reactive protein) may be elevated due to COVID-19 rather than IBD. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults" and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)

If fecal markers (eg, fecal calprotectin, lactoferrin) are not elevated, endoscopic evaluation is not necessary, as negative test results indicate the absence of active bowel inflammation. For most patients with an established diagnosis of IBD, elevated fecal inflammatory marker levels along with typical symptoms of active disease (eg, diarrhea) in the absence of infection are sufficient to initiate IBD treatment. (See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis", section on 'Pretreatment evaluation'.)

Urgent endoscopic evaluation is reserved for patients in whom the results will change management [6]. For example, patients with suspected severe acute ulcerative colitis are typically started on glucocorticoids intravenously but still require at least a limited lower endoscopy with biopsies to confirm the diagnosis and exclude other conditions (eg, viral infection). (See "Management of the hospitalized adult patient with severe ulcerative colitis", section on 'Pretreatment evaluation'.)

Patients without COVID-19

Patients with IBD in remission — Available data have suggested that patients with IBD in remission are not at higher risk for SARS-CoV-2 virus infection and that such patients should continue maintenance therapy to sustain remission [3,4,6]. Discontinuing maintenance therapy has been associated with disease relapse that may require hospitalization and/or glucocorticoid therapy and may increase the risk for severe COVID-19 [3,29].

Therapies for maintaining remission in patients with Crohn disease are discussed separately. (See "Overview of the medical management of mild (low risk) Crohn disease in adults", section on 'Maintenance of remission' and "Overview of medical management of high-risk, adult patients with moderate to severe Crohn disease", section on 'Maintenance therapy'.)

Therapies for maintaining remission in patients with ulcerative colitis are discussed separately. (See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis", section on 'Maintenance of remission' and "Management of moderate to severe ulcerative colitis in adults", section on 'Maintenance of remission'.)

Patients with active IBD — For patients with a flare of Crohn disease or ulcerative colitis in the absence of COVID-19, adding or escalating anti-inflammatory or biologic therapy may be required for symptomatic improvement and inducing remission. (See 'Diagnostic considerations during pandemic' above.) For example, therapeutic options for mild IBD include oral budesonide, aminosalicylates, and topical (rectal) therapy, while options for moderately to severely active IBD include biologic therapies (eg, anti-tumor necrosis factor [TNF] agents, anti-integrin agents, anti-interleukin agents, or small molecules) [6]. The approach to using these therapies has not changed during the pandemic.

However, if systemic glucocorticoids are deemed necessary for patients with active IBD during the pandemic, the lowest dose of glucocorticoid that will result in clinical response is used for a short duration before transitioning to another therapy that is glucocorticoid-sparing [6]. For example, management of a patient who is hospitalized with severe ulcerative colitis in the absence of COVID-19 may include treatment with a glucocorticoid (eg, methylprednisolone 16 to 20 mg intravenously every eight hours) for three days, and if there is no clinical response, medical therapy is escalated to infliximab [6,30,31]. Surgery is an alternative option for patients who do not improve with medical therapy. Additionally, in the COVID-19 era, the initial use of infliximab at a dose of 5 mg/kg rather than glucocorticoid therapy is a reasonable approach. Management of hospitalized patients with ulcerative colitis including escalating medical therapy is discussed in more detail separately. (See "Management of the hospitalized adult patient with severe ulcerative colitis".)

Diagnosis, pretreatment assessment, and medical management of Crohn disease are discussed separately:

(See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)

(See "Overview of the medical management of mild (low risk) Crohn disease in adults".)

(See "Overview of medical management of high-risk, adult patients with moderate to severe Crohn disease".)

Diagnosis, pretreatment assessment, and medical management of ulcerative colitis are discussed separately:

(See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)

(See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis".)

(See "Management of moderate to severe ulcerative colitis in adults".)

(See "Management of the hospitalized adult patient with severe ulcerative colitis".)

Patients with COVID-19

Adjusting IBD medications — Adjustments to medication regimens in patients with IBD with suspected or known COVID-19 should be individualized based on the severity of infection, patient comorbidities, and the existing medication regimen, while balancing the risk of disease flare [32]. Expanding indications for SARS-CoV-2 testing (eg, screening prior to endoscopy) may result in increased identification of asymptomatic patients who are infected [6]. The goal of medication adjustment is to reduce immunosuppression during active viral infection to lower the risk of COVID-19-related complications (eg, pneumonia) [33]. Our overall approach for patients with IBD in remission includes [34-36] (see "COVID-19: Management in hospitalized adults"):

Therapies that can be continued without interruption:

Budesonide

Aminosalicylates, including sulfasalazine

Topical rectal therapy (eg, topical glucocorticoid)

Antibiotics

Therapies that may require temporary adjustment:

Systemic glucocorticoids – The approach to adjusting glucocorticoids depends on the severity of COVID-19:

-For patients with nonsevere COVID-19 (eg, outpatient status) – Reduce dose of systemic glucocorticoid (eg, prednisone dose to <20 mg daily) or transition to oral budesonide. (See "Overview of budesonide therapy for adults with inflammatory bowel disease".)

Although systemic glucocorticoids convey an increased risk of infection and are a potential risk factor for developing severe COVID-19 (table 1), abrupt discontinuation is not possible, and patients should receive the lowest required dose for the shortest period of time necessary to minimize adverse reactions [7]. (See "Major side effects of systemic glucocorticoids".)

-For patients who present with or progress to severe COVID-19 (ie, oxygen requirement) – Continue systemic glucocorticoids without tapering in the setting of COVID-19. The decision to continue systemic glucocorticoids has been informed by data suggesting that low-dose dexamethasone has a role in the management of severe COVID-19. The use of glucocorticoids for treating severe COVID-19 is discussed separately. (See "COVID-19: Management in hospitalized adults", section on 'Dexamethasone and other glucocorticoids'.)

Immunomodulators – Hold thiopurines (ie, azathioprine, 6-mercaptopurine) and methotrexate for patients with active symptoms of COVID-19 until symptoms resolve.

Tofacitinib – Consider holding or reducing dose of tofacitinib (eg, 5 mg twice daily) for patients with active symptoms of COVID-19 until symptoms resolve. Tofacitinib, a small molecule Janus kinase inhibitor, has been associated with an increased risk of other viral infections (ie, herpes zoster infection), and its mechanism of action is to suppress T-cell function. (See "Management of moderate to severe ulcerative colitis in adults", section on 'Janus kinase (JAK) inhibitors'.)

Biologic agents – Consider delaying biologic therapy (anti-TNF agents, ustekinumab, or vedolizumab) for patients with active symptoms of COVID-19 until symptoms resolve.

Preliminary data have identified risk factors for severe illness from COVID-19 among patients with IBD. In a registry-based observational study of 525 patients with IBD and COVID-19, severe infection (defined as intensive care unit [ICU] admission, ventilator use, or death) was reported in 37 patients (7 percent) [7]. In adjusted analyses, risk factors for severe disease included increasing age (odds ratio [OR] 1.04, 95% CI 1.01-1.02), ≥2 comorbidities (OR 2.9, 95% CI 1.1-7.8), systemic glucocorticoid use (OR 6.9, 95% 2.3-20.5), and mesalamine/sulfasalazine use (OR 3.1, 95% 1.3-7.7). Anti-TNF therapy was not associated with severe disease. This study supports the approach of reducing the use of systemic glucocorticoids for patients with IBD and nonsevere COVID-19 [37,38].

Observational data have suggested that thiopurines were associated with increased risk of severe COVID-19. In a cohort study including 1439 patients with IBD and COVID-19, 112 patients (8 percent) experienced severe COVID-19 [39]. In adjusted analyses, combination therapy (ie, anti-TNF agent plus thiopurine) and thiopurine monotherapy were associated with higher risk of severe COVID-19 compared with anti-TNF monotherapy (OR 4.01, 95% CI 1.65-9.78 and OR 4.08, 95% CI 1.73-9.61, respectively). Any mesalamine/sulfasalazine use was also associated with increased risk of severe COVID-19 compared with no mesalamine/sulfasalazine (OR 1.70, 95% CI 1.26-2.29) or with anti-TNF monotherapy (OR 3.52, 95% CI 1.93-6.45). However, it was unclear whether this association was related to unmeasured confounding factors. The risk of severe COVID-19 in patients treated with anti-interleukin 12/23 and anti-integrin therapies was not significantly different compared with anti-TNF monotherapy. This study supports the approach of holding thiopurines for patients with IBD and COVID-19, while further studies are needed to evaluate the safety of mesalamine/sulfasalazine in the setting of active infection. (See 'Prognosis' below.)

Resumption of therapy — The optimal time to resume immunosuppressive medications after SARS-CoV-2 infection is uncertain, while expert consensus has stated that medications (eg, biologic therapies) that were held during symptomatic infection can be resumed after resolution of symptoms [40].

Preliminary data suggested that induction therapy for active ulcerative colitis in the setting of recent mild COVID-19 was not associated with an increased risk for progressing to severe infection. In a case report of a 54-year-old female patient with mild COVID-19 and active ulcerative colitis, treatment with infliximab at weeks 6 and 7 following the diagnosis was associated with achieving clinical remission and recovery from COVID-19 [41].

Prognosis — There are accumulating data pertaining to outcomes in patients with IBD and SARS-CoV-2 infection [5,7,41-43]. In a registry study including 88 fully vaccinated patients with IBD who had COVID-19, five patients (6 percent) were hospitalized, three patients (3 percent) had severe disease, and one patient (1 percent) died [43]. Patients who required hospitalization tended to be older (mean age, 59 versus 39 years), on immunosuppressive therapy, and with comorbid conditions.

Case series including patients with SARS-CoV-2 infection and chronic inflammatory diseases (rheumatoid arthritis, IBD) have also provided outcome data [5,41]. As an example, in a study of 86 patients with COVID-19 in the setting of immune-mediated inflammatory disease (including 37 patients with IBD), 14 patients (16 percent) required hospitalization, and the mortality rate was 7 percent [5].

COVID-19 vaccination — Most patients with IBD on immune-modifying therapy can receive the COVID-19 vaccine [44,45]. SARS-CoV-2 vaccines including mRNA vaccines, replication-incompetent vector vaccines, inactivated vaccines, and recombinant vaccines are safe to administer to patients with IBD (table 2). Data on the immunogenicity of the vaccines in this patient population demonstrate high rates of initial antibody response [46-51]. In a meta-analysis of 31 studies including 9447 patients with IBD who completed the COVID-19 vaccination series, the pooled seroconversion rate was 96 percent (95% CI 94-97 percent) [50]. Seroconversion rates were not significantly different by drug therapy (ie, biologics, small molecules, immunomodulators, and/or glucocorticoids). In most studies that reported durability of serologic response, antibody titers began declining four weeks after vaccination, with a faster rate of decline with anti-TNF agent and/or immunomodulator use [52-54]. These data provide some reassurance for patients on immunosuppressive medications but also lend support for additional vaccine doses in such patients (figure 1).

Guidance regarding administration of COVID-19 vaccines in immunocompromised patients is provided separately. (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

Data have also suggested that full vaccination is effective for reducing risk of COVID-19 in patients with IBD [46,55]. In a Veterans Health Administration study of nearly 15,000 patients with IBD, patients with full vaccination status (ie, >7 days after second dose of mRNA vaccine) but not partial vaccination status had lower risk of SARS-CoV-2 infection compared with unvaccinated patients (0.11 versus 1.34 percent, adjusted hazard ratio [HR] 0.31, 95% CI 0.17-0.56) [55]. IBD medication exposures in this cohort included patients on mesalamine, biologic agents, thiopurines, methotrexate, or glucocorticoids. SARS-CoV-2 vaccine effectiveness did not differ significantly by the medication being used to treat IBD.

DISEASE REGISTRIES — Data on patients with chronic gastrointestinal (GI) disease who have been infected with SARS-CoV-2 virus are accumulating, and disease-specific patient registries include:

SECURE-IBD registry – The SECURE-IBD registry is an international database that collects data on disease severity and outcomes for patients with inflammatory bowel disease (IBD) who have been infected with SARS-CoV-2 virus [56]. The available data have suggested that hospitalization rates have been highest among patients with moderately to severely active IBD, which emphasizes the importance of treating active inflammation. (See 'Patients with COVID-19' above.)

SECURE-EoE/EGID – Eosinophilic Gastrointestinal Diseases is a database of patients previously diagnosed with eosinophilic esophagitis (EoE) and eosinophilic gastrointestinal diseases (EGID) who are under high suspicion or have a confirmed diagnosis of COVID-19.

SECURE-Celiac Disease registry – SECURE-Celiac is an international, pediatric and adult database to monitor and report on outcomes of COVID-19 occurring in patients with celiac disease.

IMPLICATIONS FOR ENDOSCOPY — During the COVID-19 pandemic, nonurgent endoscopic procedures were deferred with goals of reducing transmission of SARS-CoV-2 virus infection, conserving personal protective equipment, and reserving clinical resources for managing patients with COVID-19. The decision to perform endoscopic procedures and the necessary protocols have been informed by local and institutional rules in addition to guidance from professional societies [57,58]. (See 'Society guideline links' below.)

Indications for urgent or emergent procedures that should not be delayed can be found on the American Society for Gastrointestinal Endoscopy website.

Performing elective endoscopy while managing risk of COVID-19 has been informed by several factors including local prevalence of COVID-19 and vaccination rates [59-61] (see "COVID-19: Vaccines"):

Elective endoscopy – In geographic areas where there has been a sustained reduction in the rate of new COVID-19 cases, elective procedures may be performed [61]. General strategies for reducing the risk of transmitting infection during gastrointestinal (GI) endoscopy that have been endorsed by professional societies, including the use of personal protective equipment, can be accessed here.

Preprocedure screening – In geographic areas with low prevalence of COVID-19 and with widespread use of COVID-19 vaccines for health care workers and the general population, routine preprocedure protocols include symptom screening for all patients. However, preprocedure testing for COVID-19 has not been endorsed for patients in these locations [59]. Use of a SARS-CoV-2 testing protocol that is based upon local prevalence of SARS-CoV-2 infection can be accessed here [60].

Infection control strategies for use during aerosol-generating procedures (eg, upper GI endoscopy, endoscopic retrograde cholangiopancreatography [ERCP], endoscopic ultrasound) are discussed separately. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'Infection prevention in the health care setting'.)

Issues related to managing patients with COVID-19 and acute GI or hepatobiliary disease include [62]:

Patients with GI bleeding – Reports suggest that anticoagulant use is common among hospitalized patients with COVID-19 and GI bleeding [63-65]. In a study including 4871 hospitalized patients with COVID-19 who did not require intensive care unit (ICU) level of care, 23 patients (0.5 percent, median age 75 years) had upper GI bleeding [64]. Eighteen of the 23 patients with bleeding (78 percent) were on anticoagulant therapy or thromboprophylaxis. Eighteen patients underwent upper endoscopy, and peptic ulcer disease was the most common finding.

Some patients with COVID-19 and nonvariceal upper GI bleeding have been successfully managed with medical therapy only (ie, continuous intravenous proton pump inhibitor and optimizing coagulation status) [64,66]. For example, in a series of six patients with acute upper GI bleeding and COVID-19 pneumonia, management included intravenous proton pump inhibitor and clinical observation, and no patients required urgent endoscopy during their hospitalization [63]. Rationale for this conservative approach also includes data that have suggested that delaying endoscopy for 24 hours was not associated with increased mortality in patients with acute upper GI bleeding [67].

For most patients with lower GI bleeding in the setting of COVID-19, endoscopic evaluation can be initially delayed and then performed on an outpatient basis after resolution of the acute illness [66]. Timing of endoscopy for patients with GI bleeding is discussed separately. (See "Approach to acute upper gastrointestinal bleeding in adults" and "Approach to acute lower gastrointestinal bleeding in adults".)

Data have suggested that for patients who were hospitalized for GI bleeding during the COVID-19 pandemic, bleeding may have been more severe but was associated with fewer endoscopic procedures [68]. In a study of 211 hospitalized patients with GI bleeding, onset of bleeding during the COVID-19 outbreak was associated with lower rates of endoscopic evaluation compared with patients who presented prior to COVID-19 (28 versus 50 percent; adjusted odds ratio [OR] 0.32, 95% CI 0.15-0.72) [68]. However, patients who were treated for GI bleeding during the COVID-19 outbreak were more likely to require blood transfusion (adjusted OR 2.86, 95% CI 1.25-6.55) and to have a longer length of stay (adjusted OR 2.62, 95% 1.17-5.84). Additional studies are needed to examine the impact of COVID-19 on outcomes for patients with GI bleeding who presented during the pandemic.

Patients with acute cholangitis or biliary obstruction – Strategies for managing patients who have acute cholangitis and/or obstructive jaundice are informed by available resources (eg, endoscopy space, nursing, and anesthesia services), the patient's hemodynamic status and location (eg, intensive care unit) and the availability of alternatives to ERCP (eg, percutaneous transhepatic cholangiography, initial medical management) [66,69]. Management of acute cholangitis is discussed in more detail separately. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: COVID-19 overview (The Basics)" and "COVID-19: Vaccines")

SUMMARY AND RECOMMENDATIONS

Digestive symptoms – Patients with COVID-19 typically present with fever and respiratory symptoms; however, gastrointestinal (GI) symptoms (eg, anorexia, diarrhea, nausea) have been reported in patients diagnosed with COVID-19. (See 'Digestive symptoms' above.)

COVID-19 testing – We favor testing for COVID-19 in the following patients, even in the absence of respiratory symptoms (see 'When to test for COVID-19 in patients with GI symptoms' above):

Hospitalized patients with new onset of GI symptoms

Outpatients with new onset of GI symptoms for over 48 hours

Patients with established GI disease (eg, Crohn disease) with symptoms suggestive of a disease flare (eg, diarrhea, vomiting)

While the diagnosis of COVID-19 may be suspected based on presenting symptoms, additional factors that inform the decision to perform testing include the patient's geographic location, risk of exposure, rate of community transmission, and the availability of testing.

Diagnostic considerations – For patients with symptoms of active inflammatory bowel disease ([IBD]; eg, diarrhea) who are also at risk for COVID-19, evaluation includes COVID-19 testing, stool studies to exclude enteric infections, noninvasive inflammatory markers (eg, fecal calprotectin), and serum drug trough levels (for patients on biologic therapy). (See 'Diagnostic considerations during pandemic' above.)

Patients with IBD – Patients with IBD in remission should continue maintenance therapy to sustain remission. Discontinuing maintenance therapy is associated with disease relapse that may require hospitalization and/or glucocorticoid therapy and may increase the risk for severe COVID-19. (See 'Patients with IBD in remission' above.)

Preventive strategies – Strategies for reducing the risk of transmitting SARS-CoV-2 virus during GI endoscopy that have been endorsed by professional societies can be accessed here. (See 'Implications for endoscopy' above and 'Society guideline links' above.)

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