Copyright
©The Author(s) 2020.
World J Meta-Anal. Oct 28, 2020; 8(5): 348-374
Published online Oct 28, 2020. doi: 10.13105/wjma.v8.i5.348
Published online Oct 28, 2020. doi: 10.13105/wjma.v8.i5.348
Table 1 Prevalence of common gastrointestinal symptoms reported by coronavirus disease 2019 patients in studies from Wuhan, China, n (%)
| Ref. | Number of patients | Diarrhea | Nausea | Vomiting | Anorexia | Abdominal pain |
| Huang et al[42] | 41 | 1 (3) | NA | NA | NA | NA |
| Yang et al[58] | 52 | NA | NA | 2 (4) | NA | NA |
| Chen et al[1] | 99 | 2 (2) | 1(1) | NA | NA | |
| Ping et al[83] | 9 | 1 (11.1) | 1(11.1) | 1(11.1) | 6 (66.7) | NA |
| Wang et al[13] | 138 | 14 (10.1) | 14 (10.1) | 55 (40) | 3 (2.2) | |
| Luo et al[75] | 1141 | 68 (6) | 134 (11.7) | 119 (10.4) | NA | 45 (3.9) |
| Zhou et al[84] | 191 | 9 (4.7) | 7 (3.7) | NA | NA | |
| Zhang et al[85] | 140 | 18 (12.9) | 24 (17.3) | 7 (5) | NA | 8 (5.8) |
| Chen et al[86] | 274 | 77 (28.1) | 24 (8.8) | 16 (5.8) | NA | 19 (6.9) |
| Xu et al[87] | 1324 | 28 (2.1) | NA | NA | 56 (4.2) | NA |
| Shi et al[88] | 645 | 29 (4.5) | NA | NA | NA | NA |
| Han et al[89] | 108 | 15 (14) | NA | NA | NA | NA |
| Fang et al[90] | 305 | 146 (49.5) | 59 (29.4) | 3 (2) | 101 (50.2) | 12 (6) |
| Xu et al[91] | 355 | 130 (36.6) | NA | NA | NA | NA |
| Ma et al[92] | 81 | 6 (7.41) | NA | NA | NA | NA |
| Liu et al[93] | 238 | 14 (9.2) | 2 (1.3) | 3 (2) | 14 (9.2) | 1 (0.7) |
| Huang et al[94] | 36 | 3 (8.3) | NA | NA | NA | NA |
| Mao et al[95] | 214 | 41 (19.2) | NA | NA | NA | 10 (4.7) |
| Liu et al[96] | 109 | 12 (11) | NA | NA | NA | NA |
| Shu et al[97] | 545 | 49 (8.9) | 0 (0) | NA | NA | |
Table 2 Prevalence of common gastrointestinal symptoms reported by coronavirus disease 2019 patients in Chinese studies outside Wuhan, n (%)
| Ref. | Number of patients | Diarrhea | Nausea | Vomiting | Anorexia | Abdominal pain |
| Ai et al[98] | 102 | 15 (14.3) | 9 (8.8) | 2 (2) | NA | 3 (2.9) |
| Chen et al[99] | 9 | 2 (22) | 0 (0) | NA | 0 (0) | |
| Zhao et al[100] | 77 | 1 (1.3) | 6 (7.8) | NA | NA | NA |
| Chang et al[101] | 13 | 1 (7.7) | NA | NA | NA | NA |
| Zhao et al[102] | 75 | 7 (9.3) | NA | NA | NA | 1 (1.3) |
| Yang et al[103] | 55 | 2 (3.6) | NA | NA | NA | NA |
| Li et al[104] | 83 | 7 (8.4) | NA | NA | NA | 7 (8.4) |
| Qi et al[105] | 267 | 10 (3.7) | 6 (2.2) | 46 (17.2) | NA | |
| Xu et al[106] | 90 | 5(5.6) | 2 (2.2) | 5 (5.6) | NA | NA |
| Xiao et al[67] | 73 | 26 (35.6) | NA | NA | NA | NA |
| Lin et al[107] | 95 | 23 (24.2) | 17 (17.9) | 4 (4.2) | 17 (17.8) | 2 (2.1) |
| Wen et al[108] | 417 | 29 (7) | NA | NA | NA | NA |
| Xu et al[109] | 45 | 0 (0) | NA | NA | NA | NA |
| Yan et al[110] | 168 | 12 (7.1) | 9 (5.4) | 7 (4.2) | 14 (8.3) | 7 (4.2) |
| Wang et al[111] | 18 | 3 (16.7) | 1 (5.6) | NA | NA | |
| Chen et al[112] | 291 | 25 (8.6) | 17 (5.8) | NA | 1 (0.3) | |
| Liu et al[113] | 620 | 53 (8.5) | NA | NA | NA | NA |
| Fan et al[114] | 55 | 6 (10.9) | NA | 4 (7.3) | NA | NA |
| Yao et al[115] | 40 | 3 (7.5) | 3 (7.5) | NA | NA | NA |
| Tian et al[116] | 37 | 8 (25.8) | NA | NA | NA | NA |
| Song et al[117] | 51 | 5 (10) | 3 (6) | 9 (18) | NA | NA |
| Lu et al[118] | 265 | 17 (6.4) | 6 (2.3) | NA | NA | |
| Fu et al[119] | 52 | 7 (13.5) | 1 (1.9) | NA | NA | NA |
| Fu et al[120] | 36 | 3 (8.3) | NA | NA | NA | NA |
| Xu et al[121] | 62 | 3 (4.8) | NA | NA | NA | NA |
| Jin et al[76] | 651 | 56 (8.6) | 28 (4.3) | NA | NA | |
| Qian et al[122] | 91 | 21 (23.1) | 11 (12.1) | 6 (6.6) | 23 (25.3) | NA |
| Chen et al[123] | 175 | 35 (20) | NA | 7 (4) | NA | 5 (3) |
| Kuang et al[124] | 944 | 21 (2.7) | NA | NA | NA | NA |
| Hu et al[125] | 24 | 2 (8.3) | NA | NA | NA | NA |
| Guan et al[48] | 1099 | 42 (3.8) | 55 (5) | NA | NA | |
Table 3 Prevalence of common gastrointestinal symptoms reported by coronavirus disease 2019 patients in studies from United States, n (%)
| Ref. | Number of patients | Diarrhea | Nausea | Vomiting | Anorexia | Abdominal pain |
| Cholankeril et al[126] | 207 | 22 (10.8) | 22 (10.8) | NA | 14 (7.1) | |
| Hajifathalian et al[78] | 1059 | 234 (22.1) | 168 (15.3) | 91 (8.6) | 240 (22.7) | 72 (6.8) |
| Kujawski et al[127] | 12 | 4 (33.3) | 3 (25) | NA | NA | 2 (16.7) |
| Ferm et al[77] | 892 | 177 (19.8) | 148 (16.6) | 91 (10.2) | 105 (11.8) | 70 (7.8) |
| Redd et al[79] | 318 | 107 (33.7) | 84 (26.4) | 49 (15.4) | 110 (34.8) | 46 (14.5) |
Table 4 Prevalence of common gastrointestinal symptoms reported by coronavirus disease 2019 patients in studies from across the world
| Ref. | Location | Number of patients | Diarrhea | Nausea | Vomiting | Anorexia | Abdominal pain |
| COVID-19 National Emergency response Center[128] | South Korea | 28 | 2 (7) | NA | NA | NA | 1 (4) |
| Young et al[129] | Singapore | 18 | 3 (17) | NA | NA | NA | NA |
| Pung et al[130] | Singapore | 17 | 4 (23.5) | 1 (5.9) | NA | NA | |
| Tabata et al[131] | Diamond Princess Cruise Ship | 104 | 8 (9.6) | NA | NA | NA | NA |
| Kluytmans et al[132] | Netherlands | 86 | 16 (18.6) | NA | NA | NA | 5 (5.8) |
| Wölfel et al[133] | Germany | 9 | 2 (22) | NA | NA | NA | NA |
| Dreher et al[134] | Germany | 50 | 8 (16) | 1 (2) | 2 (4) | NA | NA |
| Gritti et al[135] | Italy | 21 | 5 (23.8) | NA | NA | NA | NA |
| Spiteri et al[136] | Europe | 38 | 1 (3.2) | NA | NA | NA | NA |
| COVID-19 National Incident Room Surveillance Team[137] | Australia | 295 | 48 (16.3) | 34 (11.5) | NA | 6 (1) | |
| Sierpiński et al[80] | Poland | 1942 | 470 (24.2) | NA | NA | NA | NA |
Table 5 Prevalence of hepatic abnormalities reported in different studies, n (%)
| Ref. | Location | Number of patients | AST elevation | ALT elevation | T. Bili elevation |
| Huang et al[42] | Wuhan, China | 41 | 15 (37) | NA | NA |
| Chen et al[1] | Wuhan, China | 99 | 35 (35) | 28 (28) | 18 (18) |
| Zhou et al[84] | Wuhan, China | 191 | NA | 59 (31) | NA |
| Chen et al[86] | Wuhan, China | 274 | 84 (31) | 60 (27) | NA |
| Xu et al[91] | Wuhan, China | 355 | 102 (28.7) | 91 (25.6) | 66 (18.6) |
| Huang et al[94] | Wuhan, China | 36 | 18 (58) | 4 (13.3) | 4 (12.9) |
| Shu et al[97] | Wuhan, China | 545 | 35 (10.1) | 41 (7.5) | 189 (34.7) |
| Cai et al[146] | Shenzhen City, Guangdong, China | 298 | 25 (8.4) | 39 (13.1) | 24 (8.1) |
| Ai et al[98] | Xiangyang, China | 102 | 26 (25.5) | 20 (19.6) | NA |
| Zhao et al[102] | Hefei, Anhui, China | 75 | 14 (18.7) | 15 (20) | 12 (16) |
| Zhao et al[100] | Beijing, China | 77 | 20 (26) | 26 (33.8) | NA |
| Qi et al[105] | Chongqing, China | 267 | 19 (7.1) | 20 (7.5) | 6 (2.2) |
| Lin et al[107] | Zhuhai, Guangdong, China | 95 | 4 (4.2) | 5 (5.3) | 22 (23.2) |
| Xu et al[109] | Multiple locations in China (All outside Hubei province) | 45 | NA | NA | NA |
| Yan et al[110] | Hainan Province, China | 168 | 18 (17.3) | 9 (8) | 7 (6.4) |
| Wang et al[111] | Zhengzhou, Henan, China | 18 | Abnormal LFTs 4 (25) | NA | |
| Chen et al[112] | Changsha and Loudi, Hunan, China | 291 | 44 (15.1) | 30 (10.3) | 27(9.3) |
| Yao et al[115] | Xi’an, Shaanxi, China | 40 | 16 (40) | 21 (52.5) | 10 (25) |
| Tian et al[116] | Liaocheng, Shandong, China | 37 | 4 (10.8) | 2 (5.4) | 13 (35.1) |
| Fu et al[120] | Kunming, Yunnan, China | 36 | 4 (11.1) | 4 (11.1) | 11 (30.56) |
| Xu et al[121] | Zhejiang, China | 62 | 10 (16.1) | NA | NA |
| Qian et al[122] | Multiple sites, Zhejiang, China | 91 | 9 (9.9) | 7 (7.7) | NA |
| Chen et al[123] | Multiple sites, Wenzhou, Zhejiang, China | 175 | 19 (11) | 23 (13) | NA |
| Guan et al[48] | Multiple sites across China | 1099 | 168 (22.2) | 158 (21.3) | 76 (10.5) |
| Ferm et al[77] | New York, United States | 892 | Borderline elevation (1-2 × ULN) 40% | Borderline elevation (1-2 × ULN) 26.5% | 4.3% |
| mild elevation (2-5 × ULN) 13.8% | mild elevation (2-5 × ULN) 11.5% | ||||
| moderate to severe elevation (> 5 × ULN) 2.8% | moderate to severe (> 5 × ULN) 1.9% | ||||
| Tabata et al[131] | Diamond Princess Cruise, Japan | 104 | 18 (17.3) | 17 (16.3) | NA |
Table 6 Commonly administered pharmacotherapy for coronavirus disease 2019 and their gastrointestinal adverse effects[162]
| Drug | Proposed mechanism in COVID-19 | GI side effects | Hepatic side effects | Pancreatic side effects |
| Remdesivir | Inhibitor of viral RNA-dependent RNA polymerase. | Nausea, Vomiting, gastroparesis, GI bleeding | Increased LFTs | NA |
| Chloroquine and Hydroxychloroquine | Disruption of endosome-mediated viral entry and transport. | Nausea, vomiting, abdominal cramping | NA | NA |
| Lopinavir/Ritonavir | Protease inhibitor. Disrupts viral replication. | Diarrhea, nausea, vomiting | LFT elevation, hepatitis, worsening of underlying CLD | Pancreatitis |
| Ribavirin | Nucleoside analog inhibitor of viral RNA synthesis. | Nausea | NA | NA |
| Nitazoxanide | Increase production of type I IFNs enhancing antiviral activity. | Abdominal pain, nausea, diarrhea, acid reflux | NA | NA |
| Nelfinavir | HIV-1 protease inhibitor. Action against SARS-CoV-2 unclear. | Diarrhea, nausea, increased flatulence | LFT elevation | NA |
| INF-α | Enhances cell mediated immune response against the virus. | NA | Auto-immune hepatitis | NA |
| Barcitinib | JAK inhibitor. Downregulation of hyper-inflammatory state seen in severe disease. | Nausea | LFT elevation | NA |
| Tocilizumab | IL-6 inhibitor. Downregulation of hyper-inflammatory state seen in severe disease. | Gastrointestinal perforation in patients on high dose steroids or history of diverticulitis | LFT elevation | NA |
Table 7 Selected American Association for the Study of Liver Diseases, Asian Pacific Association for the Study of the Liver, and European Association for the Study of the Liver recommendations for liver disease management during the coronavirus disease 2019 pandemic[164]
| Selected recommendations | |
| To limit nosocomial spread | (1) Limit in-person visits by effective triaging; (2) Use of virtual platforms such as telehealth to provide alternatives for in-person visits; (3) Symptom and exposure screening prior to entering the healthcare facility to identify at-risk individuals; (4) Minimize staffing to essential staff only; (5) Decrease frequency of laboratory and imaging monitoring; (6) Ensure adherence to recommended PPE by HCW and patients; (7) Ensure adequate social distancing at the healthcare facility (Remodel if necessary); (8) Postpone and delay nonurgent or elective procedures (refer to Table 12); and (9) Minimize research activities including clinical trials wherever possible. |
| Management of CLD patients with COVID-19 | (1) Early hospital admission is recommended for these patients; (2) Prioritization of COVID-19 testing for cirrhotics, CLD patients on immunosuppressive therapy and those with acute decompensation; (3) Frequent LFT monitoring is recommended; (4) Consider early enrollment in clinical trial when possible; (5) Include non-COVID-19 etiologies in differentials for liver dysfunction; (6) Pay special attention to COVID-19 patients with NAFLD, which is often associated with severe COVID-19; (7) Consider hepatitis B surface antigen screening; (8) Monitor for drug induced liver injury; (9) 2-3 g/d of acetaminophen is generally safe and can be used in these patients. NSAIDs can also be used as needed but limit their use whenever possible; (10) Consider HBV prophylaxis prior to initiating immunosuppressive medications, especially IL-6; and (11) Hold Remdesivir in patients with decompensated liver disease and ALT > 5 × ULN. |
| Management of chronic viral hepatitis (HCV and HBV) | (1) Continuing treatment for chronic HCV and HBV despite COVID-19 status is recommended; (2) Can hold initiating treatment for HBV in the absence of flare; and (3) Treatment for HCV and HBV in the uninfected should continue according to established guidelines. |
| Management of HCC | (1) Based on the risk and benefit, a delay in surveillance of up to 2 mo is acceptable for high risk individuals; (2) Continuation of HCC treatment per guidelines is recommended, however can be postponed if necessary; (3) For COVID-19 patients, can consider postponing elective transplant and resection surgery and withholding immunotherapy; and (4) Early inpatient admission is advised for HCC patients. |
| Management of pre- and post- transplant recipients | (1) Screening of both, the donor and recipient for COVID-19 is recommended; (2) Donors testing positive for COVID-19 should be deferred; (3) CMS has classified transplant surgeries as Tier 3b. As such, these procedures should not be postponed or delayed; (4) Patients with poor short-term prognosis should be prioritized; (5) Low threshold for admitting transplant listed COVID-19 patients to the hospital is recommended; (6) For post-transplant patients, immunosuppressive dose reductions can be considered in moderate COVID-19 cases. For mild COVID-19 cases no immunosuppressive dose reduction is advised; and (7) Vaccination against pneumonia and influenza is recommended in post-transplant recipients. |
Table 8 Expert guidance for management of autoimmune liver disease during coronavirus disease 2019 pandemic[168]
| Selected recommendations from EASL, AASLD for management of auto-immune hepatitis | |
| (1) In-person visits should be minimized as much as possible. Switch to virtual platforms whenever possible; and (2) COVID-19 testing is recommended in cases of acute decompensation and liver failure. | |
| Low risk of complications (stable patient on chronic immunosuppressive treatment) | (1) Frequent patient-provider communications for close monitoring; (2) Use of virtual platforms should be preferred whenever possible; and (3) Ensure adequate drug supply and refills to reduce running out of medications. |
| Moderate risk of complications (symptomatic disease in the absence of cirrhosis, compensated cirrhosis) | (1) Can empirically treat via virtual healthcare platform whenever possible; and (2) Avoiding liver biopsy whenever possible is also recommended. |
| High risk of complications (acute flare, decompensated cirrhosis) | (1) Minimize invasive procedures wherever possible; (2) In COVID-19 patients, dose reduction of antimetabolites is recommended if lymphopenia develops; and (3) In case of infection corticosteroids should be tapered as quickly as possible. |
Table 9 Expert guidance on immunosuppression for liver disease in the setting of coronavirus disease 2019[168]
| Selected recommendations from AASLD and EASL on use of immunosuppressive therapies in CLD patients | |
| (1) Initiating corticosteroids and immunosuppressive therapy should be preceded; and (2) by careful risk vs benefit assessment. | |
| Patients uninfected by COVID-19 on immunosuppressive therapy | Dosage reductions or adjustment is not advised. |
| Patients infected with COVID-19 on immunosuppressive therapy | (1) Corticosteroid dose reductions after specialist consultation (consider tapering to avoid adrenal insufficiency); and (2) Dose reductions in azathioprine, cyclosporine, mycophenolate is recommended in severe COVID-19 (especially with accompanying lymphopenia). |
| Patients requiring initiation of immunosuppressive therapy | Initiating treatment is recommended in these patients regardless of COVID-19 status. |
Table 10 Recommendations on use of immunosuppressive therapies in inflammatory bowel diseases[169]
| Asymptomatic infection | Mild to moderate infection | Severe or Critical infection | |
| Corticosteroids | (1) Dose reduction of Prednisone to < 20 mg/d; and (2) Consider switching to budesonide. | (1) Discontinue; and (2) Taper in chronic users. | |
| Immunomodulators (thiopurines, methotrexate) | (1) Consider risks vs benefits; and (2) Can resume after 14 d in asymptomatic patients or when test negative. | ||
| Biologicals | (1) Consider risks vs benefits; (2) Can resume after 14 d in asymptomatic patients or when test negative; (3) Can decrease infusion frequencies for infliximab and vedolizumab; and (4) Tofacitinib and JAK inhibitors should be discontinued. | ||
Table 11 Interim infection prevention and control guidelines by Centers for Disease Control and Prevention[172]
| Interim Infection Prevention and Control guidelines by CDC |
| Encourage and promote Telehealth visits over in-person visits whenever possible. |
| COVID-19 symptom screening for everyone entering a healthcare facility. |
| Limiting entry points to a healthcare facility, ensuring effective screening for all. |
| Encourage hand hygiene and source control measures for everyone, especially HCWs. |
| Encourage physical distancing and limiting the number of visitors and personnel at any given time. |
| Implementing use of PPEs (e.g. N95/PAPR) for HCWs in areas with moderate to substantial community spread. |
| To mitigate spread from asymptomatic carriers; depending on the availability, a targeted SARS-CoV-2 testing for all patients can be considered. |
| To reduce exposures for HCWs the use of Engineering controls should be optimized. |
Table 12 Procedures that can be delayed during the ongoing pandemic
| Procedures that can be delayed | Procedures that cannot be delayed |
| Diagnostic procedures for mild/stable dysphagia[177]. | Endoscopies for upper GI bleeding (Blatchford score > 1)[166,171,177]. |
| Diagnostic procedures for suspected GI malignancy can be delayed for up to a few months[171]. | Upper endoscopies for foreign body with severe/progressive dysphagia[177]. |
| Routine surveillance and screening colonoscopies are non-urgent and can be postponed[171]. | Lower endoscopies for acute obstruction requiring decompression[177]. |
| Procedures for asymptomatic (with normal LFTs) gallstones and biliary strictures can be postponed[177]. | ERCP for acute cholangitis or symptomatic common bile duct stone[166,177]. |
| Follow up Colonoscopies for positive FIT test can be delayed for up to 7 to 9 mo without any adverse impact on outcomes[178]. | Follow up band ligation for recent variceal bleeding[166,177]. |
| Placement of percutaneous endoscopic gastrostomy or jejunostomy tubes[177]. | |
| Procedures that can significantly impact medical decisions should be performed. These can include endoscopies for evaluation of high likelihood GI malignancies, resection of high-grade dysplasia or histologically proven neoplasia and investigation for IBD flares[171,177]. | |
| Colonoscopies for lower GI bleeding can be delayed up to 72 h without any change in outcome[178]. | |
| Liver biopsies to diagnose autoimmune hepatitis and transplant rejection in liver transplant patients[166]. | |
| Transplant surgeries are categorized Tier 3b by CMS and should be performed[175]. | |
| Endoscopic drainage of infected pancreatic fluid collections and necrosectomies[177]. |
Table 13 Recommended personal protective equipment during gastrointestinal procedures[171]
| Recommendations for PPEs during GI procedures | |
| Masks | Regardless of patient’s COVID-19 status, NIOSH approved N95/PAPR should be used by staff for any GI procedure. |
| Gloves | Regardless of patient’s COVID-19 status, gloves should be worn by providers during any GI procedure. Double gloves are preferred over single. |
| Negative Pressure Rooms | GI procedures for confirmed COVID-19 patients should be performed in negative pressure rooms when available. |
| Disinfection | Standard endoscope disinfectants can reduce microorganisms by 99.99% and should be sufficient for SARS-CoV-2. |
- Citation: Pasha SB, Swi A, Hammoud GM. Gastrointestinal and hepatic manifestations of COVID-19 infection: Lessons for practitioners. World J Meta-Anal 2020; 8(5): 348-374
- URL: https://www.wjgnet.com/2308-3840/full/v8/i5/348.htm
- DOI: https://dx.doi.org/10.13105/wjma.v8.i5.348