Supplementary Material
Supplement Figure 1 PRISMA 2009 Flow Diagram
Supplementary Figure 2 The matrix used in the selection of the Chinese studies. The X-axis represents the studies. The Y axis represent the hospitals included in the study. The size of the bubble reflects the number of patients in the study. Two studies by Guan et al101,102 were not included in the plot as they included patients from more than 500 hospitals from 30 or more provinces without providing the names of the hospitals.
Supplementary Figure 3 Forest plot of the prevalence of diarrhea in all admitted patients regardless of the timing of diarrhea.
Supplementary Figure 4 Forest plot of the prevalence of diarrhea as one of the initial symptoms in all patients regardless of hospitalization status.
Supplementary Figure 5 Forest plot of the prevalence of diarrhea as one of the initial symptoms in all admitted patients.
Supplementary Figure 6 Forest plot of the prevalence of diarrhea in outpatients regardless of the timing of diarrhea.
Supplementary Figure 7 Forest plot of the prevalence of nausea/vomiting as one of the initial symptoms in all patients regardless of hospitalization status.
Supplementary Figure 8 Forest plot of the prevalence of abdominal pain as one of the initial symptoms in all patients regardless of hospitalization status.
Supplementary Figure 9 Forest plot of the prevalence of elevated AST.
Supplementary Figure 10 Forest plot of the prevalence of elevated ALT.
Supplementary Figure 11 Forest plot of the prevalence of elevated total bilirubin.
Supplementary Table 1 Summary of Included Studies
Study characteristics Patient characteristics Gastrointestinal manifestations Liver Manifestationsa
Hubei Province, China
 Luo, 202050Zhongnan Hospital (Wuhan)Dates: 01/01/2020-02/20/2020Last follow-up: NR n = 1141Survival: 3.8% (7/183) death, 96.2% recoveredInclusion: Inpatients with COVID-19 (throat swab RT-PCR). All patients received chest CT. Details only provided for the 183 patients with GI symptoms.Age: m 53.8 y (183 patients)Sex: 44.3% (81/183) femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 6.0% (n = 68)Present on admissionAbdominal pain: 3.9% (n = 45)Present on admissionNausea: 11.7% (n = 134)Present on admissionVomiting: 10.4% (119)Present on admissionNausea and vomiting: 3.2% (n = 37)Present on admission183 patients presented with GI symptoms only (diarrhea, abdominal pain, nausea, vomiting, and/or loss of appetite). 96% of them had lung lesions on chest CT AST (183 patients) m 65.8 ± 12.7ALT (183 patients) m 66.4 ± 13.2
 Zhou, 202020Jinyintan Hospital (Wuhan)Dates: 12/29/2019-01/31/2020Last follow-up: 01/31/2020 n = 191Survival: 28.3% death, 71.8% dischargedInclusion: Inpatients with COVID-19 (confirmed with RT-PCR) who died or were discharged. Patients without key information excluded (9).Age: M 56 y (IQR, 46–67 y)Sex: 37.7% femalesGI/liver comorbidities: NRDisease severity: General 28%, severe: 35%, critical 28% Diarrhea: 4.7% (9/191)Present on admission2 died and 7 dischargedNausea/vomiting: 3.7% (7/191)Present on admission3 died and 4 dischargedAbdominal pain: NR AST: NRALT >40: 31.2% (59/189)26 died and 33 dischargedTotal bilirubin: NR
 Zhang, 202023Wuhan No. 7 Hospital (Wuhan)Dates: 1/16/2020-02/03/2020Last follow-up: NR n = 140Survival: NRInclusion: Inpatient with COVID-19 (pharyngeal swab PCR) based on symptoms and chest x-ray.Age: 57 y (range, 25–87 y)Sex: 49.3% femalesGI/liver comorbidities: 5.7% fatty liver and abnormal liver function, 5.0% chronic gastritis and gastric ulcer, 4.3% cholelithiasis, 6.4% cholecystectomy 5.0% appendectomy, 0.7% hemorrhoidectomy, 4.3% tumor surgeryDisease severity: severe 41.4% and nonsevere 58.6% Diarrhea: 12.9% (18/139)Present on admission9/82 nonsevere cases and 9/57 severe casesNausea: 17.3% (24/139)Present on admission19/82 nonsevere cases and 5/57 severe casesVomiting: 5.0% (7/139)Present on admission5/82 nonsevere cases and 2/57 severe casesBelching 5.0% (7/139)Present on admission4/82 nonsevere cases and 3/57 severe casesAbdominal pain: 5.8% (8/139)Present on admission2/82 nonsevere cases and 6/57 severe casesOther pathogens were detected including Mycoplasma pneumoniae in 5, respiratory syncytial virus in 1, Epstein-Barr virus in 1. AST, ALT, and bilirubin: NR
 Chen, 202072Tongji Hospital (Wuhan)Dates: 01/13/2020-02/12/2020Last follow-up: 02/28/2020 n = 274Survival: 52.2% death, 47.8% recoveredInclusion: Moderate severity, severe or critically ill COVID-19 patients (throat swab or bronchoalveolar lavage RT-PCR) who were deceased or discharged.Age: M 62.0 y (IQR, 44–70 y) sex: 37.6% femaleGI/liver comorbidities: 4% hepatitis B surface antigen positivity, 1% GI diseasesDisease severity: moderate severity, severe or critically ill. Diarrhea: 28.1% (n = 77)Present on admission27/113 deceased and 50/161 dischargedNausea: 8.8% (n = 24)Present on admission8/113 deceased and 16/161 dischargedVomiting: 5.8% (n = 16)Present on admission6/113 deceased and 10/161 dischargedAbdominal pain: 6.9% (n = 19)Present on admission6/113 deceased and 13/161 discharged AST >40: 30.7% (84)59/113 deceased and 25/161 dischargedM 30 (IQR, 22–46). Deceased M 45 (IQR, 31–67) and discharged M 25 (IQR, 20–33)ALT >41: 21.9% (60)30/113 deceased and 30/161 dischargedM 23 (IQR, 15–38). Deceased M 28 (IQR, 18–47) and discharged M 20 (IQR, 15–32)BilirubinM 0.6 (IQR, 0.4–0.8). Deceased M 0.7 (IQR, 0.6–1.0) and discharged M 0.5 (IQR, 0.3–0.7)
 Xu, 202031Tongji Hospital (Wuhan)Dates: 1/15/2020-2/19/2020Last follow-up: NR n = 1324Survival: NRInclusion: Outpatient COVID-19 patients presenting to fever clinic, based on PCR.Age: m 48 ± 15.3 ySex: 50.8% femalesGI/liver comorbidities: NRDisease severity: 95.9% light condition, 3.8% severe, 0.3% critical Diarrhea: 2.1% (28)Present on admissionLoss of appetite: 4.2%Present on admissionNausea, vomiting, and abdominal pain: NR NR
 Shi, 202042Renmin Hospital (Wuhan)Dates: 1/1/2020-2/10/2020Last follow-up: 2/15/2020 n = 645Survival: 7.3% death, 5.1% discharged (416 patients)Inclusion: Inpatient laboratory-confirmed COVID-19, consecutive. Detailed results reported for 416 patients with complete results.Age: M 45–64 y (range, 21–95 y)Sex: 52.9% femaleGI/liver comorbidities: 1% hepatitis B infection (of 416 patients)Severity: NR Diarrhea: 4.5% (29)Present on admissionAbdominal pain, nausea, vomiting: NR AST (416 patients)M 30 (IQR, 22–43).ALT (416 patients)M 28 (IQR, 18–46).Bilirubin: NR
 Han, 202062Wuhan No.1 HospitalDates: 1/4/2020-2/3/2020Last follow-up: NR n = 108Survival: NR death, NR recoveredInclusion: Inpatients COVID-19 (confirmed by RT-PCR) with mild pneumonia, no history of other lung infection, initial CT performed.Exclusion: CT scans performed as follow-up for COVID-19 pneumonia, or chest CT image quality insufficient for image analysisAge: mean 45 y (range, 21–90 y)Sex: 64.8% femalesGI/liver comorbidities: Not specifiedDisease severity: NR Diarrhea: 14% (15/108)Abdominal pain, nausea, vomiting: NR No laboratory data reported
 Xu, 202030Union Hospital (Wuhan)Dates: 1/25/2020-2/20/2020Last follow-up: 2/20/2020 n = 355Survival: NRInclusion: Inpatients with COVID-19, confirmed based on RT-PCR.Age: 45.1% aged <50 y, 41.7% aged 50–69 y, 13.2% aged ≥70 ySex: 45.6% femalesGI/liver comorbidities: NRDisease severity: 63.1% mild, 16.9% severe, 20% critical Diarrhea: 36.6% (130/355)Abdominal pain, nausea, vomiting NR AST: 28.7% (102/355) m 40.8 (range, 10–475)ALT: 25.6% (91/355) m 35.0 (range, 1–414)Total bilirubin: 18.6% (66/355) m 0.83 (range, 0.1–29.9)
 Ma, 202049Wuhan Leishenshan Hospital (Wuhan)Dates: 3/5/2020-3/18/2020Last follow-up: NR n = 81Survival: NRInclusion: Inpatients with COVID-19 (RT-PCR on nasal and pharyngeal swabs)Age: M 38 y (IQR, 34.5–42.5 y)Sex: 0% femaleGI/liver comorbidities: NRDisease severity: 2.5% mild, 86.4% moderate, 8.6% severe, 2.5% critical. Diarrhea: 7.41% (6/81)Nausea/vomiting: NRAbdominal pain: NR AST/ALT - composite report 31/81 abnormal but no thresholdAST M 23 (IQR, 12–453)ALT M 43 (IQR, 13–799)Bilirubin: NR
 Liu, 202054General Hospital of Central Theater Command of PLA (Wuhan)Dates: 2/6/2020 - 2/14/2020Last follow-up: NR n = 153 (85 tested negative but had symptoms, we did not include those patients)Survival: NRInclusion: Inpatients with COVID-19 (RT-PCR on pharyngeal swabs)Age: M 55 y (IQR, 38.3–65 y)Sex:39.2% femaleGI/liver comorbidities: NRDisease severity: NR Diarrhea: 9.2% (14/153)Present on admissionNausea: 1.3% (2/153)Present on admissionVomiting: 2% (3/153)Present on admissionAbdominal pain: 0.4% (1/153)Present on admission AST, ALT, and bilirubin: NR
 Huang, 202061The Fifth Hospital of Wuhan (Wuhan)Dates: 1/21/2020-2/10/2020Last follow-up: 2/14/2020 n = 36Survival: 100% deathInclusion: Inpatients with COVID-19 (RT-PCR)Age: mean 69.22 y (SD 9.64 y; range, 50–90 y)Sex:30.56% femaleGI/liver comorbidities: NRDisease severity: NR Diarrhea: 8.33% (3/36)Present on admissionNausea: NRVomiting: NRAbdominal pain: NR AST: >40 58.1% (18/31)M 43 (IQR, 30–51)ALT: >50 13.3% (4/30)M 26 (IQR, 18–38)Bilirubin: >25 12.9% (4/31)M 11.2 (IQR, 7.5–19.2)
 Mao, 202048Union Hospital (Wuhan)Dates: 1/16/2020-2/19/2020Last follow-up: NR n = 214Survival: 1 died but not fully reported.Inclusion: Inpatients with COVID-19 (RT-PCR from throat)Age: m 52.7 ± 15.5 ySex: 59.3% femaleGI/liver comorbidities: NRDisease severity: 58.9% nonsevere, 41.1% severe Diarrhea: 19.2% (41/214)Present on admissionSevere disease 14.8% (13/88), nonsevere disease 22.2% (28/126)Abdominal pain: 4.7% (10/214), not included in the analysisPresent on admissionSevere disease 6.8% (6/88), nonsevere disease 3.2% (4/126)Nausea and vomiting: NR AST 26 (8–8191)Severe 34 (8–8191), non-severe 23 (9–244)ALT 26 (5–1933)Severe 32.5 (5–1933), non-severe 23 (6–261)
 Ai, 202076Xiangyang No.1 People’s HospitalDates: Cross-sectional study 2/9/2020 n = 102Survival: 2.9% died, 6.9% survived, 90.2% still hospitalizedInclusion: Inpatients with laboratory-confirmed COVID-19Age: m 50.4 ± 16.9 ySex: 49.1% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 14.3% (15)Present on admissionDiarrhea was the first symptom in 2 patientsNausea: 8.8% (9)Present on admissionVomiting: 2.0% (2)Present on admissionAbdominal pain: 2.9% (3)Present on admission AST >40: 25.5% (26/102)Mean 30.59 (SD 15.03)ALT >50: 19.6% (20/102)Mean 27.77 (SD 21.13)Total bilirubin NR
 Liu, 202052Central Hospital of Wuhan (Wuhan)Dates: 1/2/2020-2/1/2020Last follow-up: NR n = 109Survival: 28.4% died, NR otherwiseInclusion: Inpatient with COVID-19 confirmed based on RT-PCR on throat swabAge: M 62.5 y (IQR, 47.25–65 y)Sex: 33.3% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 11% (12)Present on admission6/12 with ARDS and 6/12 with no ARDSNausea, vomiting and abdominal pain: NR AST:M 30 (IQR, 21–40)No ARDS 29 (19–38); ARDS 31 (25–44)ALT:M 23 (IQR, 15–36)No ARDS 23 (14–41); ARDS 24 (16–31)Total bilirubin: NR
 Shu, 202041Cabin Hospital of Wuhan Stadium (Wuhan)Dates: 2/13/2020-2/29/2020Last follow-up: NR n = 545Survival: 85.9% discharged, 14.1% still hospitalized, 0% diedInclusion: Inpatient with COVID-19 confirmed based on RT-PCR. Severe cases requiring transfer were excluded.Age: M 50 y (IQR, 38–58 y)Sex: 51.2% femalesGI/liver comorbidities: 0 chronic liver diseaseDisease severity: 2.9% mild, 97.1% moderate, 0 severe (excluded). Diarrhea: 8.9% (49)Present on admissionNausea or vomiting: 0% (0)Present on admission AST >45: 6.4% (35)M 32.1 (IQR, 24.5–36.4)ALT >50: 7.5% (41)M 34.6 (IQR, 26.2–42.3)Bilirubin >1.2: 34.7% (189)M 1.1 (IQR, 0.8–1.3)
 Wei, 202034Wuhan Integrated Chinese and Western Medicine Hospital (Wuhan)Dates: 2/1/2020-2/28/2020Last follow-up: NR n = 100Survival: 3% died, 1% discharged, 96% still hospitalized.Inclusion: Inpatients with COVID-19 confirmed based on RT-PCR. Only mild cases.Age: m 49.1 ± 17.2 ySex: 60% femalesGI/liver comorbidities: 9% digestive system diseases, 6% chronic gastritisDisease severity: 100% mild. Diarrhea: 2% (2)Present on admissionVomiting: 2% (2)Present on admission AST elevated: 5 (5%)ALT elevated: 17 (17%)Total bilirubin abnormal: 0 (0%)
Other Chinese Provinces
 Chen, 202073The First Affiliated Hospital of Wanan Medical College (Wuhu)AnhuiDates: NA (Case series) n = 9Survival: 100% dischargedInclusion: Inpatients with COVID-19 confirmed on RT-PCR via swabAge: range, 25–56 ySex: 44.4% femalesGI/liver comorbidities: NRDisease severity: 55.6% moderately ill and 44.4% severely ill Diarrhea: 22.2% (2)Nausea/vomiting: 0% (0)Abdominal pain: 0% (0) AST, ALT, and bilirubin: NR
 Zhao, 202021First Affiliated Hospital of University of Science and Technology of China (Hefei)AnhuiDates: 1/21/2020-2/16/2020Last follow-up: NR n = 75Survival: NRInclusion: Inpatients with COVID-19 based on RT-PCR.Age: M 47 y (IQR, 34–55 y)Sex: 44% femalesGI/liver comorbidities: chronic liver disease 5.3%Disease severity: NR Diarrhea: 9.3% (7)Present on admissionAbdominal pain: 1.3% (1)Present on admissionNausea/vomiting: NR AST > 40: 18.7% (14)M 27 (IQR, 21–37)ALT >40: 20% (15)M 23 (IQR, 14–43)Bilirubin >1.2: 16% (12)M 0.85 (IQR, 0.65–1.06)ALT, ALT, and total bilirubin were not associated with elevated interleukin-6 (a study outcome)
 Zhao, 202022Beijing YouAn HospitalBeijingDates: 1/21/2020-2/8/2020Last follow-up: 2/29/2020 n = 77Survival: 6.5% died, 83.1% discharged, 10.4% still hospitalizedInclusion: Inpatients with COVID-19 based on RT-PCR.Age: m 52 ± 2 ySex: 55.8% femalesGI/liver comorbidities: 10.4% digestive diseasesDisease severity: 74% non-severe, 26% severe Diarrhea: 1.3% (1)Present on admission1/57 nonsevere and 0/20 severeNausea or vomiting: 7.8% (6)Present on admission3/57 nonsevere and 3/20 severeAbdominal pain: NR AST > 40: 26.0% (20)11/57 non-severe and 9/20 severeM 19 (IQR, 21–42)ALT >40: 33.8% (26)17/57 non-severe and 9/20 severeM 28 (IQR, 20–46)BilirubinNR
 Yang, 202026Chinese PLA General HospitalBeijingDates: 12/272019-2/18/2020Last follow-up: 2/18/2020 n = 55Survival: 3.6% diedInclusion: Inpatients with COVID-19, confirmed with RT-PCR.Age: M 44 y (IQR, 34–54 y, range, 3–85 y)Sex: 40% femalesGI/liver comorbidities: 1.8% chronic liver diseaseDisease severity: 38.2% mild, 36.4% common, 23.6% severe, and 1.8% extremely severe. Diarrhea: 3.6% (2)Present on admission0/21 of the patients without pneumonia on admission and 2/34 of the patients with pneumoniaNausea, vomiting, and abdominal pain: NR AST, ALT, and bilirubin: NR
 Li, 202056The Second Affiliated Hospital of Chongqing Medical University, ChongqingDates: 1/2020-2/2020Last follow-up: n = 83Survival: NRInclusion: Inpatients with COVID-19 and at least one abnormal CT scan. Patients with normal CT were excluded (8).Age: m 45 ± 12.3 ySex: 47% femalesGI/liver comorbidities: NRDisease severity: 69.9% ordinary, and 30.1% severe/critical Diarrhea and abdominal pain: 8.4% (7)Present on admissionNausea or vomiting: NR AST, ALT, and bilirubin: NR
 Qi, 202045Chongqing Public Health Medical Center, Chongqing Three Georges Central Hospital, and Qianjiang Central Hospital of ChongqingChongqingDates: 1/19/2020-2/16/2020Last follow-up: 2/16/2020 n = 267Survival: 1.5% died, 38.6% discharged, 59.9% still hospitalized.Inclusion: Inpatients with COVID-19 based on RT-PCR. Excluded patients with missing data (42).Age: M 48 y (IQR, 25–65 y)Sex: 44.2% femalesGI/liver comorbidities: GI diseases 4.5%Disease severity: 81.3% non-severe and 18.7% severe Diarrhea: 3.7% (10)Present on admission7/217 nonsevere and 3/50 severeNausea or vomiting: 2.2% (6)Present on admission5/217 nonsevere and 1/50 severeAnorexia: 17.2% (46)Present on admission33/217 nonsevere and 13/50 severeAbdominal pain: NR AST >35: 7.2% (19)9/217 non-severe and 10/50 severeALT >40: 7.5% (20)10/217 non-severe and 10/50 severeBilirubin >1.5: 2.2% (6)3/217 non-severe and 3/50 severe
 Xu, 202029Guangzhou Eighth People’s Hospital (Guangzhou)GuangdongDates: 1/23/2020-2/4/2020Last follow-up: NR n = 90Survival: NRInclusion: Inpatients with COVID-19 based on RT-PCR who had baseline chest CT.Age: M 50 y (range, 18–86 y)Sex: 56.7% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 5.6% (5)Vomiting: 5.6% (5)Nausea: 2.2% (2) NR
 Lin, 202055The Fifth Affiliated Hospital of Sun Yat-sen University (Zhuhai)GuangdongDates: 1/17/2020-2/15/2020Last follow-up: 2/15/2020 n = 95Survival: 0% died, 38.9% discharged, 61.1% still hospitalizedInclusion: Inpatients with confirmed COVID-19.Age: 45.3 ± 18.3 ySex: 52.6% femalesGI/liver comorbidities: NRDisease severity: 78.9% non-severe, 21.1% severe Diarrhea: 24.2% (23)5.2% (5) present on admission.Loose or watery stool, 2-10 bowel movements daily.Vomiting: 4.2% (4)0% (0) present on admission.Nausea: 17.9% (17)3.2% (3) present on admission.Abdominal pain: 2.1% (2)0% (0) present on admission.Epigastric discomfort.11 patients with GI symptoms did not have pneumonia.Viral RNA detected in 31/65 patients including 22/42 who had GI symptoms and 9/23 who did not have GI symptoms. AST >35 for females and >40 for males: 4.2% (4)ALT >40 for females and >50 for males: 5.3% (5)Bilirubin >1.5: 23.2% (22)
 Wen, 202033All Shenzhen CityGuangdongDates: 1/1/2020-2/28/2020Last follow-up: 2/28/2020 n = 417Survival: 0.7% died, 71.7% discharged, 27.6% still hospitalized.Inclusion: Inpatients with COVID-19 based on RT-PCR.Age: m 45.4 ySex: 52.8% femalesGI/liver comorbidities: NRDisease severity: 8.9% mild, 82.5% moderate, 8.6% severe/critical Diarrhea: 7.0% (29)Present on admission.23/381 of mild/moderates and 6/36 of severe/criticalNausea, vomiting, and abdominal pain: NR ALT, AST, and bilirubin: NR
 Xu, 202028First Affiliated Hospital of Guangzhou Medical University (Guangzhou), Dongguan People's Hospital (Dongguan), Foshan First People's Hospital (Foshan), Huizhou Municipal Central Hospital (Huizhou), First Affiliated Hospital of Shantou University Medical College (Shantou), Affiliated Hospital of Guangdong Medical University (Zhanijiang), Zhongshan City People's Hospital (Zhongshan)GuangdongDates: ?-2/28/2020Last follow-up: 2/28/2020 n = 45Survival: death 0.2%, 24.4% discharged, 73.3% still hospitalized.Inclusion: Critically ill patients with COVID-19 pneumonia.Age: m 56.7 ± 15.4 ySex: 35.6% femalesGI/liver comorbidities: NRDisease severity: 100% critical Diarrhea: 0% (0)Present on admission AST or ALT >40: 37.8% (17)AST (n = 44)M 27 (IQR, 22.0–39.5)ALT (n = 44)M 29 (IQR, 20.1–50.0)Bilirubin (n = 44)M 0.91 (IQR, 0.61–1.3)
 Yan, 202027All Hainan ProvinceHainanDates: 1/22/2020-3/13/2020Last follow-up: 3/13/2020 n = 168Survival: 3.6%, 1.2% still hospitalized, 95.2% discharged.Inclusion: Inpatient with COVID-19 based on RT-PCR.Age: M 51 y (IQR, 36–62 y)Sex: 51.8% femalesGI/liver comorbidities: 3.6% chronic liver diseaseSeverity: 78.6% nonsevere, 21.4% severe Diarrhea: 7.1% (12)Present on admission8/132 nonsevere, 4/36 severeVomiting: 4.2% (7)Present on admission5/132 nonsevere, 2/36 severeNausea: 5.4% (9)Present on admission6/132 nonsevere, 3/36 severeAbdominal pain: 4.2% (7)Present on admission5/132 nonsevere, 2/36 severe AST >40: 17.3% (18/104)7/75 non-severe, 11/29 severeALT >40: 8.0% (9/112)5/81 non-severe, 4/31 severeBilirubin >1.5: 0M 0.51 (IQR, 0.37–0.78)
 Wang, 202035First Affiliated Hospital of Zhengzhou University (Zhengzhou)HenanDates: 1/21/2020-2/7/2020Last follow-up: 2/7/2020 n = 18Survival: 0 died, 33.3% discharged, 66.7% still hospitalizedInclusion: Inpatients with COVID-19Age: M 39 y (IQR, 29–55 y)Sex: 50% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 16.7% (3)Present on admissionVomiting, nausea, abdominal pain: NR AST or ALT elevated: 25% (4)Bilirubin: NR
 Chen, 202071First Hospital of Changsha (Changsha) and Loudi Central Hospital (Loudi)HunanDates: 1/23/2020-2/14/2020Last follow-up: 2/202/2020 n = 291Survival: 0.7% died, 54.6% discharged, 44.7% still hospitalizedInclusion: Inpatients with COVID-19 based on RT-PCRAge: M 46 y (IQR, 34–59 y, range, 1–84 y)Sex: 50.2% femalesGI/liver comorbidities: 5.2% chronic liver diseaseDisease severity: 10% mild, 72.8% moderate, 17.2% severe/critical Diarrhea: 8.6% (25)Present on admission3/29 mild, 17/212 moderate, 5/50 severe/criticalNausea or vomiting: 5.8% (17)Present on admission6/29 mild, 9/212 moderate, 2/50 severe/criticalAbdominal pain: 0.3% (1)Present on admission0/29 mild, 0/212 moderate, 1/50 severe/critical AST >37: 15.1% (44)5/29 mild, 23/212 moderate, 16/50 severe/criticalM 24.7 (IQR, 19.9–31.4)ALT >42: 10.3% (30)4/29 mild, 16/212 moderate, 10/50 severe/criticalM 20.7 (IQR, 14.9-28.9)Bilirubin >1.2: 9.3% (27)4/29 mild, 17/212 moderate, 6/50 severe/criticalM 0.6 (IQR, 0.5–0.9)
 Liu, 202053All Jiangsu ProvinceJiangsuDates: 1/10/2020-2/18/2020Last follow-up: 2/18/2020 n = 620Survival: 0 died, 3.2% in ICU, 56.1% still hospitalized, 40.6% dischargedInclusion: Inpatient with COVID-10 based on RT-PCR. Patients without records excluded.Age: m 44.5 ± 17.2 ySex: 47.4% femalesGI/liver comorbidities: NRDisease severity: 15.6% asymptomatic/mild, 75.8% moderate, 8.5% severe/critical Diarrhea: 8.5% (53)Present on admission4/97 asymptomatic/mild, 43/469 moderate, 6/53 severe/critically illNausea, vomiting, and abdominal pain: NR AST (387) m 23.3 ± 18.5m 27.3 ± 14.9 in mild/asymptomatic, 32.3 ± 17.5 in moderate, 42.9 ± 28.6 in severe/critically illALT (420) m 31.0 ± 22.4m 26.8 ± 21.6 in asymptomatic/mild, m 31.2 ± 21.1 in moderate, m 39.3 ± 32.5 in severe/critically illBilirubin (460) m 0.6 ± 0.4m 0.7 ± 0.5 mild/asymptomatic, m 0.6 ± 0.4 moderate, m 0.7 ± 0.4 severe/critically
 Fan, 202067Shenyang Chest Hospital (Shenyang)LiaoningDates: 1/20/2020-3/15/2020Last follow-up: NR n = 55Survival: 100% recoveredInclusion: Recovered hospitalized COVID-19 patients, based on RT-PCR.Age: m 46.8 ySex: 45.5% femalesGI/liver comorbidities: NRDisease severity: 85.4% mild, 14.5% severe Diarrhea: 10.9% (6)4/47 mild/moderate, 2/8 severe/criticalVomiting: 7.3% (4)2/47 mild/moderate, 2/8 severe/criticalAbdominal pain: NR ALT m 40.6m 27.8 in mild/moderate and m 57.1 in severe/criticalBilirubin m 19.5m 19.0 in mild/moderate and m 22.4 in severe/criticalAST: NR
 Yao, 202025Tangdu Hospital (Xi’an)ShaanxiDates: 1/21/2020-2/21/2020Last follow-up: NR n = 40Survival:Inclusion: Inpatients with COVID-19. No baseline LFT abnormality.Age: m 53.9 ± 15.8 y (range, 22–83 y)Sex: 37.5% femalesGI/liver comorbidities: 0% liver disease or damage.Disease severity: 45% non-severe, and 55% severe Diarrhea: 7.5% (3)8 patients developed diarrhea due to lopinavir/ritonavir.Nausea: 7.5% (3)Vomiting and abdominal pain: NR AST >46: 40% (16)Occurred as early as the 4th day up to the 26th day.ALT >66: 52.5% (21)Occurred as early as the 4th day up to the 26th day.Bilirubin >1.2: 25% (10)Occurred as early as the 4th day up to the 16th day. Mostly sligh increase.Liver injury occured in 17/22 critical cases 5/18 noncritical cases.
 Tian, 202036Liaocheng Infectious Diseases Hospital (Liaocheng) and Liaocheng People’s Hospital (Liaocheng)ShandongDates: NRLast follow-up: NR n = 37Survival: 100% dischargedInclusion: Inpatients with COVID-19.Age: m 44.3 ± 1.67 ySex: 54% femalesGI/liver comorbidities: 2.7% cirrhosis/liver cancerDisease severity: 13.5% mild, 81.1% moderate, 2.7% severe, 2.7% critical Diarrhea or vomiting: 25.8% (8/31)Present on admissionVomiting or abdominal pain: NR AST >40: 10.8% (4)ALT >40: 5.4% (2)Bilirbuin >1: 35.1% (13)
 Lu, 202051Shanghai Public Health Clinical CenterShanghaiDates: ?-2/9/2020Last follow-up: 2/9/2020 n = 265Survival: 0.4% died, 17.7% discharged.Inclusion: Inpatients with COVID-19 based on RT-PCRAge: NRSex: NRGI/liver comorbidities: 0.4%Disease severity: 91.7% mild/moderate, 8.3% severe/critically ill Diarrhea: 6.4% (17)Present on admission17/243 mild/moderate and 0/22 severe/criticalNausea or vomiting: 2.3% (6)Present on admission6/243 mild/moderate and 0/22 severe/criticalAbdominal pain: NR ASTM 24 (IQR, 19–33)M 24 (IQR, 19–31) in mild/moderate and M 39.5 (IQR, 29.7–53.5) in severe/criticalALTM 23 (IQR, 15–33)M 21 (IQR, 15–33) in mild/moderate and M 30 (24.5–34.5) in severe/criticalBilirubinM 0.5 (0.4–0.6)
 Fu, 202065Chengdu Public Health Clinical Medical Center (Chengdu)SichuanDates: 1/1/2020-2/20/2020Last follow-up: 2/29/2020 n = 52Survival: 100% (excluded patients who were not discharged)Inclusion: Inpatients with COVID-19 confirmed by RT-PCR. Excluded patients who died or were not discharged.Age: M 44.5 y (IQR, 33.0–56.5 y)Sex: 46% femalesGI/liver comorbidities: NRDisease severity: common coronavirus pneumonia type 73.1%, severe 19.2%, critically severe 7.7% Diarrhea: 13.5% (7/52)Present on admissionNausea: 1.9 % (1/52)Present on admissionVomiting and abdominal pain: NR AST M 27 (IQR, 21.2–34.0)ALT M 24 (IQR, 15.3–49)Bilirubin 85 patients M 67.3 (IQR, 63.5–71.4)Patients with laboratory results on admission and discharge n = 23ASTOn presentation M 27 (IQR, 23–35)After discharge M 25 (IQR, 19–39)ALTOn presentation M 25 (IQR, 14–41)After discharge M 31 (IQR, 15–41)BilirubinOn presentation M 66 (IQR, 60–72)After discharge M 65 (IQR, 60–69
 Fu, 202066Third People’s Hospital of Kunming (Kunming)YunnanDates: 1/26/2020-2/15/2020Last follow-up: NR n = 36Survival: 17% discharged, 6% ICU, 78% still hospitalized.Inclusion: Inpatients with COVID-19 based RT-PCR.Age: 45 ySex: 55.6% femalesGI/liver comorbidities: NRDisease severity: mild 11% (4), common 83% (30), severe, critical 6% (2) Diarrhea: % (3)Present on admissionVomiting, nausea, and abdominal pain: NR AST 11.1% (4)ALT 11.1% (4)Bilirubin 30.56% (11)
 Jin, 202060First Affiliated Hospital of College of Medicine, Zhejiang University (Hangzhou)ZhejiangDates: 1/17/2020-02/08/2020Last follow-up: 02/08/2020 n = 651Survival: 0.2% death, NR for the othersInclusion: Inpatients with COVID-19.Age: m 45 ± 14.4 ySex: 49.2% femalesGI/liver comorbidities: NRDisease severity: Severe/critical 9.8% Diarrhea: 8.6% (56)Present on admission and prior to treatment.Defined as loose stool >3 times daily. Stool cultures were performed with negative results for all patients. Clostridium difficile not detected in stool and no recent antibiotic use.Median duration was 4 d (IQR, 3–6 d, range, 1–9 d). Most was self-limiting.Nausea/vomiting: 4.3% (28)Present on admission.11 only vomiting; 10 only nausea; 3 nausea, vomiting and diarrhea; 4 nausea and vomiting.Any GI Symptom: 11.4 (74)Nausea, vomiting or diarrhea.21 patients lacked respiratory symptoms of coughing and sputum production, and presented only with GI symptomsSevere/critical: 17/74 with GI symptoms vs 47/577 without GI symptom. In those with GI symptoms, risk factors for severe/critical disease were sputum production, increased lactate dehydrogenase and increased glucose on multivariate analysis.ARDS: 5/74 with GI symptoms vs 12/577 without GI symptomShock: 1/74 with GI symptoms vs 1/577 without GI symptomLiver injury: 13/74 with GI symptoms vs 51/577 without GI symptomMechanical ventilation: 5/74 with GI symptoms vs 12/577 without GI symptom ICU admission: 5/74 with GI symptoms vs 12/577 without GI symptom AST >40: NRGI symptoms M 29.4 (IQR, 29.9–38.6) vs no GI symptoms M 24.4 (IQR, 19.0–32.0)ALT >50: NRGI symptoms M 25.0 (IQR, 15.8–38.5) vs no GI symptoms M 21.5 (IQR, 15.0–32.8)Total bilirubinGI symptoms M 0.6 (IQR, 0.4–0.8) vs no GI symptoms M 0.6 (IQR, 0.4–0.8)
 Qian, 202044Xiaoshan District People's Hospital (Hangzhou), Ningbo City First Hospital (Ningbo City), Ninghai County First Hospital (Ningbo City), Xiangshan County People's First Hospital (Ningbo City), Affiliated Hospital of Shaoxing University (Shaoxing)ZhejiangDates: 1/20/2020-2/11/2020Last follow-up: 2/16/2020 n = 91Survival: 0% died, 34.1% discharged, 65.9% still hospitalized.Inclusion: Inpatients with COVID-19 (88 based on RT-PCR and 3 based on clinical diagnosis)Age: M 50 y (IQR, 36.5–57 y)Sex: 59% femalesGI/liver comorbidities: NRDisease severity: 90.1% mild and 9.9% severe Diarrhea: 23.1% (21)Present on admissionVomiting, nausea, and abdominal pain: not extracted Not extracted
 Chen, 202074Wenzhou Central Hospital (Wenzhou) and Sixth People’s Hospital of Wenzhou (Wenzhou)ZhejiangDates: 1/11/2020-2/15/2020Last follow-up: NR n = 175Survival: 29.7% discharge, not reported otherwiseInclusion: Inpatients with COVID-19 based on RT-PCR.Age: M 46 y (IQR, 34–54 y)Sex: 52.6% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 19.4% (34)Present on admissionAverage of 6 episodes per day, and often ended within 1-4 daysVomiting, nausea, and abdominal pain: not extracted Not extracted
 Kuang, 202058All Zhejiang ProvinceZhejiangDates: 1/1/2020-2/10/2020Last follow-up: NR n = 944Survival: NRInclusion: All reported COVID-19 cases. Both inpatients and outpatients.Age: m 47.4 ± 22.9 ySex: 49.6% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 2.7% (21)Vomiting, nausea and abdominal pain: NR NR
US studies
 Arentz, 202075Evergreen Hospital (Kirkland)WashingtonDates: 2/20/2020-3/5/2020Last follow-up: 3/17/2020 n = 21Survival: 52.4% died, 9.5% out of IC, 38.1% still in ICU.Inclusion: Critically ill COVID-19 patients.Age: m 70 y (range, 43–92 y)Sex: 48% femalesGI/liver comorbidities: 4.8% cirrhosis, 9.5% solid organ transplantDisease severity: 100% critically ill Diarrhea, nausea, vomiting, and abdominal pain: NR AST m 273 (range, 14-4432)ALT m 108 (range, 11-1414)Bilirubin m 0.6 (range, 0.2-1.1)
 Cholankeril, 202070Stanford University HospitalsCaliforniaDates: 3/4/2020-3/24/2020Last follow-up: 3/24/2020 n = 116Survival: 0.9% died, 86.2% discharged, 4.3% still hospitalized.Inclusion: COVID-19 confirmed based on RT-PCR.Age: M 50 y (IQR, 35–67 y)Sex: 46.6% femalesGI/liver comorbidities: 2.6% chronic liver diseaseDisease severity: 71.6% evaluated in ED/clinic only, 20.7% admitted to the medical floor, and 7.8% admitted to ICU. Diarrhea: 10.3% (12)Present on admissionNausea and/or vomiting: 10.3% (12)Present on admissionAbdominal pain: 8.8% (10)Present on admissionNone of the patients had isolated GI symptoms or as the initial symptoms.31.9% reported GI symptoms. Median duration of GI symptoms was 1 day (IQR, 0–4). AST (n = 65)M 35 (IQR, 22–58)In those with any abnormal LFT, M 64 (IQR, 24–76)ALT (n = 65)M 32 (IQR, 22–48)In those with any abnormal LFT, M 59 (IQR, 22–76)Total bilirubin (n = 65)M 0.4 (IQR, 0.3–0.7)In those with any abnormal LFT, M 0.5 (IQR, 0.3–0.7)26 patients developed liver enzyme elevation. 22 of them had normal baseline liver enzymes.
 Nobel, 202047New York–Presbyterian Hospital/Columbia University Irving Medical CenterNew YorkDates: 3/10/2020-3/21/2020Last follow-up: 18 days after testing n = 278Survival: 3.2% died,Inclusion: Patients tested for COVID-19 at clinic or emergency department for respiratory symptoms with intent to hospitalize or the same symptoms in essential personnel. Excluded patients with insufficient data (42). Charts randomly selected.Age: 11% aged 18–30 y, 25% aged 31–50 y, 37% aged 51–70 y, and 27% aged >70 ySex: 48% femalesGI/liver comorbidities: NRDisease severity: 74.5% admitted to hospital, 15.8% admitted to ICU, 3.2% died. Diarrhea: 20.1% (56)Present on admission42/207 admitted to hospital, 11/44 admitted to ICU, 0/9 died.Vomiting/vomiting: 22.7% (63)Present on admission51/207 admitted to hospital, 8/44 admitted to ICU, 0/9 died.Abdominal pain: NR35% had GI symptoms. Patients with GI symptoms were more likely to have illness duration of ≥1 week (33%) compared to patients without symptoms (22%).Presence of GI symptoms (diarrhea or nausea/vomiting) was associated with a 70% increased risk of testing positive (adjusted odds ratio 1.7; 95% CI, 1.1–2.5) AST: NRALT: NRBilirubin: NR
 Hajifathalian, 202063NewYork-Presbytarian Hospital/Weill Cornell Medical CenterNew YorkDates: 3/4/2020 to 4/9/2020Last follow-up: 4/16/2020 n = 1059 (768 inpatients and 291 outpatients)Survival: 9.1% diedInclusion: Adults with COVID-19, inpatients and outpatients.Age: m 61 ± 18 ySex: 42.3% femalesGI/liver comorbidities: 1.6% IBD, 3.0% chronic liver disease, 2.4% solid organ transplant.Disease severity: NR Diarrhea: 22.1% (234)Present on admissionInpatients 24.3% (187/768) and outpatients 16.1% (47/291).Vomiting: 8.3% (91)Present on admissionInpatients 8.7% (67/768) and outpatients 8.2% (24/291).Nausea: 15.3% (168)Present on admissionInpatients 16.0% (123/768) and outpatients 15.5% (45/291).Abdominal pain: 6.6% (72)Present on admissionInpatients 7.3% (56/768) and outpatients 5.5% (16/291). AST ≥40: 56% (n = 844) m 60 ± 79ALT ≥40: 39% (n = 844) m 50 ± 65Bilirubin >1.2: 11% (n = 844) m 0.7 ± 0.6Presence of liver injury at presentation was associated with higher risk of admission on multivariate analysis.
 Kujawski, 202057Center of Disease ControlCalifornia, Illinois, Arizona, Massachusetts, Washington, WisconsinDates: 1/20/2020-2/5/2020Last follow-up: 2/22/2020 n = 12Survival: 0% died, 8.3% hospitalized, 41.7% home isolation, 50% recovered.Inclusion: Patients under investigation who tested positive for COVID-19.Age: M 53 y (range, 21–68 y)Sex: 33.3% femalesGI/liver comorbidities: 8.3% HBV and 8.3% fatty liver disease.Disease severity: 5 outpatients and 7 inpatients. Diarrhea: 33.3% (4)8.3% (1) present on admission3 while on remdesivir (1 of tham had Giardia and C difficile). 1 patient had symptoms for 1 day then developed fever and cough.Nausea: 25% (3)8.3% (1) present on admissionAbdominal pain: 16.7% (2)Stool PCR positive in 70% (7/10) patients AST: 58.3% (7)M 129 (IQR, 46–190)ALT 58.3% (7)M 136 (IQR, 66–389)BilirubinNR
 Rubin, 202043Stanford University School of MedicineCaliforniaDates: ?-3/11/2020Last follow-up: NR n = 54Survival: NR.Inclusion: COVID-19 patients, not clear otherwise.Age: M 53.5 y (IQR, 32–75 y, range, 20–91 y)Sex: 46.3% femalesGI/liver comorbidities: 1.8% HBVDisease severity: 33.3% inpatients and 66.7% outpatients Diarrhea, nausea, vomiting, and abdominal pain: NR ASTFemales m 73.4 ± 61.8 (9) and males m 45.1 ± 19.5 (14)ALTFemales m 69.6 ± 65.2 (9) and males m 43.9 ± 25.8 (13)BilirubinNR
Other countries
 COVID-19 National Emergency Response Center, 202069South KoreaDates: 1/10/2020-2/14/2020Last follow-up: NR n = 28Survival: NRInclusion: Inpatients or outpatient with COVID-19Age: m 42.6 y (range, 20–73 y)Sex: 46.1% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 7%% (2)Present on admission1 started 2 d after fevers and chills and 1 started 2 d after muscle achesAbdominal pain: 4% (1)Present on admissionStomachache 2 d after muscle acheVomiting and nausea: NR NR
 Young, 202024SingaporeDates: 1/23/2020-2/3/2020Last follow-up: 2/25/2020 n = 18Survival: NRInclusion: Inpatients COVID-19 based on RT-PCRAge: M 47 y (range, 31–73 y)Sex: 50% femalesGI/liver comorbidities: NRDisease severity: NR (12 patients uncomplicated (67%) 6 required oxygen (33%) Diarrhea: 17% (3)Present on admissionNone of these patients required supplemental oxygenVomiting, nausea, and abdominal pain: NRVirus detected by PCR in stool in 4/8 (50%) and in whole blood 1/12 (8%)4 of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results NR
 Sun, 202039The National Centre for Infectious DiseasesSingaporeDates: 1/26/2020-2/16/2020Last follow-up: NR n = 54Survival: NRInclusion: Patients referred for testing for COVID-19.Age: M 42 y (IQR, 34–54 y)Sex: 46% femalesGI/liver comorbidities: 0 liver diseaseDisease severity: NR GI symptoms: 37% (20/54)General GI symptoms per different models were associated with positive COVID adjusted odds ratio. 3.73 (95% CI, 1.23–12.45) AST, ALT, and bilirubin NR
 Pung, 202046SingaporeDates: ?-2/15/2020Last follow-up: NR n = 17Survival: 0% diedInclusion: Inpatients COVID-19 based on PCRAge: M 40 y (36–51 y)Sex:59 % femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 23.5% (4)Nausea/Vomiting: 5.9%% (1)Abdominal pain: NR AST, ALT, and bilirubin: NR
 Tabata, 202038Diamond Princess CruiseJapanDates: 2/11/2020-2/25/2020Last follow-up: NR n = 104Survival: 0% died, NR othewiseInclusion: Laboratory confirmed patients with COVID-19 on Diamond Princess Cruise shipAge: M 68 y (IQR, 46.8–75 y; range, 25–93 y)Sex: 54.8% femalesGI/liver comorbidities: NRDisease severity: 31.7% asymptomatic, 41.3% mild, 26.9% severe. Diarrhea: 9.6% (8)Present on admission.2 additional patients develop diarrhea during the hospitalizationVomiting, nausea and abdominal pain: NR AST >38: 17.3% (18)9/76 (11.8%) nonsevere and 9/28 (32.1%) severeALT >45: 16.3% (17)10/76 (13.2%) nonsevere and 7/28 (25%) severeBilirubin: NR
 Kluytmans, 202059Breda and Tiburg, The NetherlandsDates: 3/7/2020-3/12/2020Last follow-up: NR n = 86Survival: 0 deaths, 2 required short hospitalization.Inclusion: Health care workers with fever or mild respiratory symptoms more than 10 d with subsequent positive tests. Outpatients.Age: M 49 y (range, 22–66 y)Sex: 4.6% femalesGI/liver comorbidities: NRDisease severity: 2 hospitalized, 19 recovered Diarrhea: 18.6% (16)Interviewed within 7 d of onset of symptoms: 5/31,Interviewed after 7 d of onset of symptoms: 11/55Decreased appetite or nausea: 17.4% (15)Interviewed within 7 d of onset of symptoms: 1/31,Interviewed after 7 d of onset of symptoms: 14/55Abdominal pain: 5.8% (5)Interviewed within 7 d of onset of symptoms: 1/31Interviewed after 7 d of onset of symptoms: 3/55 AST, ALT, and bilirubin: NR
 Wolfel, 202032Munich, GermanyDates: 1/23/2020-?Last follow-up: NR n = 9Survival: NRInclusion: lab confirmed SARS-Co-V-2 in upper respiratory specimensAge: NRSex: NRGI/liver comorbidities: NRDisease severity: NR Diarrhea: 22% (2)Present on admissionDiarrhea was never the only symptomPCR was positive for up to 11 d;Authors were not able to isolate infectious virus, despite high stool RNA viral loads.Vomiting, nausea and abdominal pain: NR AST, ALT, and bilirubin: NR
 Dreher, 202068Aachen, GermanyDates:2/1/2020-3/1/2020Last follow-up:NR n = 50Survival: 14% died, 16% discharged, 70% still hospitalizedInclusion: Inpatients with laboratory confirmed COVID-19Age: median 65 y (IQR, 58–76 y)Sex: 34% femalesGI/liver comorbidities: chronic liver failure 8%, chronic hepatitis 10%Disease severity: 48% ARDS,52% non-ARDS Diarrhea: 16% (8/50)Present on admission6/24 ARDS, 2/26 non-ARDSNausea: 1/50Present on admission0/24 ARDS, 1/26 nonARDSVomiting: 2/50Present on admission1/24 ARDS, 1/26 non-ARDSStool PCR done in 15 patients and found positive in 2 patients with ARDS AST, ALT, and bilirubin: NR
 Gritti, 202064Papa Giovanni XXIII HospitalBergamo, ItalyDates:3/11/2020-3/24/2020Last follow-up: NR n = 21Survival: 4.7% died, NR for the othersInclusion: Inpatients with confirmed COVID-19 who receivedAge: m 64 y (range, 48–75 y)Sex: 14% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 23.8% (5)Present on admissionNausea or vomiting, or abdominal pain: NR AST, ALT, and bilirubin: NR
 Spiteri, 202040Germany, Finland, Italy, Russia, Spain, France, Sweden, and BelgiumDates:1/24/2020-2/21/2020Last follow-up:2/21/2020 n = 38Survival: 2.6% died, 11.4% still hospitalizedInclusion: Inpatients (n = 35) and outpatients (N=2) with COVID-19 confirmed based on RT-PCRAge: M 42 (range, 2–81 y)Sex: 34.2% femalesGI/liver comorbidities: NRDisease severity: NR Diarrhea: 3.2% (1/31)Present on diagnosisNausea: 3.2% (1/31)Present on diagnosisAbdominal pain: NR AST, ALT, and bilirubin: NR
 COVID-19 National Incident Room Surveillance Team, 202037AustraliaDates: National data until 3/14/2020Last follow-up: 3/14/2020 n = 295Survival: 1.0% diedInclusion: All individuals with COVID-19 (both outpatients and inpatients)Age: M 47 y (range, 0–94 y)Sex: (approximately) 50% femaleComorbidities: NRDisease severity: NR Diarrhea: 16.3% (48)Nausea/vomiting: 11.5% (34)Abdominal pain: 2.0% (6) No laboratory data reported
ARDS, acute respiratory distress syndrome; CT, computed tomography; HBV, hepatitis B virus; ICU, intensive care unit; IQR, interquartile range; M, median; m, mean; ±, standard deviation; NR, not reported.
a AST and ALT are reported as units per liter while bilirubin is reported as milligrams per deciliter.
Supplementary Table 2 Direct Evidence of Proposed COVID-19 Therapies
Medication class Medication Sourcea Study Design GI adverse effects
Nausea/vomiting Abdominal pain Diarrhea Jaundice Hepatotoxicity
Antiviral Favipiravir Cai, 2020109 Open-label control study (favipiravir and lopinavir/ ritonavir) for COVID-19 NR NR 2/35 (5.7%) had diarrhea 1/35 (2.9%)
Chen, 202092 Open-label RCT for favipiravir vs arbidol (n = 120) in COVID-19 “Digestive tract reactions” 16/116 (13.79%) NR 9/116 (7.76%)
Lopinavir/ritonavir Cao,89 2020 RCT in severe COVID-19 (n = 199) 10/95 with nausea + 6/96 vomiting (reported separately) vs 0/99 with nausea and 0/99 with vomiting in control 4/95 in treatment group vs 2/99 in control group 4/95 in treatment group vs 0/99 in control group 6/95 in treatment group vs. 5/99 in control group Elevated AST: 4/95 in treatment vs. 9/99 in control group; Elevated ALT: 2/95 in treatment vs 5/99 in control group
Remdesivir Holshue,103 2020 Case report (first COVID in United States): remdesvir given day 7; no adverse events reported
Antimalarial Chloroquine Cortegiani,104 2020 Systematic review on efficacy and safety in COVID-19 Not reported in systematic review or primary studies
Hydroxychloroquine
NR, not reported.
a Sources include existing systematic reviews where possible. If not available, primary sources are listed.
Supplementary Table 3 Indirect Evidence of Proposed COVID-19 Therapies
Medication class Medication Sourcea Indirect GI adverse events Other
Nausea/vomiting Abdominal pain Diarrhea Jaundice Hepatotoxicity
Antiviral Lopinavir/ritonavir FDA/ manufacturer's label110 HIV Nausea (5%–16%); vomiting (children 21%; adults 2%–7%) Reported 1%–11% 7%–28%; greater with once-daily dosing — Increased serum ALT: 1%–11%; hepatitis including AST/ALT/GGT elevations: 4%; hyperbilirubinemia (children 3%; adults 1%) Dysgeusia (children 22%; adults <2%); hyperamylasemia (3%–8%), dyspepsia (<6%), increased lipase (3%–5%), flatulence (1-4%), gastroenteritis (3%)
NIH Liver Tox111 HIV Range from mild to ALF. Recovery takes 1–2 mo. Do not re-challenge with medication. Monitor for exacerbation of HBV/HCV
Momattin,105 2019 MERS Prevalence of GI AEs not reported in this SR
Yao,106 2020 SARS/MERS AEs not reported in this SR (can check primary studies) SARS: 2 retrospective cohort studies (combined with steroids); MERS: 1 RCT combined with IFN, 1 retrospective cohort combined with IFN/ribavirin, and 2 case reports also combined with IFN/ribavirin
Remdesivir Al-Tawfiq,107 2020 MERS
Sheahan,108 2020 MERS
Antimalarial Chloroquine FDA/ manufacturer's label/NIH Liver Tox111,112 Malaria Reported; frequency not defined Abdominal cramps reported; frequency not defined Reported; frequency not defined Rarely linked to aminotransferase elevations or clinically apparent liver injury. In patients with AIP or PCT, it can trigger an attack with fever and serum aminotransferase elevations, sometimes resulting in jaundice Minor metabolism by liver (∼30%); mostly excreted in urine Likelihood score: D (possible rare cause of clinically apparent liver injury)
Hydroxychloroquine113 FDA / Manufacturer's label Malaria / SLE Reported; frequency not defined Reported; frequency not defined Reported; frequency not defined Same as chloroquine above; can be exchanged with chloroquine as most reactions are hypersensitivity and no known cross reactivity to hepatic injury Likelihood score: D (possible rare cause of clinically apparent liver injury)
AE, adverse event; AIP, acute intermittent porphyria; ALF, acute liver failure; GGT, gamma-glutamyl transferase; HBV, hepatitis B virus; HCV, hepatitis C virus; IFN, interferon; NIH, National Institutes of Health; PCT, porphyria cutanea tarda; SLE, systemic lupus erythematosus; SR, systematic review.
a Sources include existing systematic reviews where possible. If not available, primary sources are listed. Conflicts of interest All members were required to complete the disclosure statement. These statements are maintained at the AGA headquarters in Bethesda, Maryland, and pertinent disclosures are published with this report. None of the panel members had any conflict relevant to this guideline.
Funding This document represents the official recommendations of the American Gastroenterological Association (AGA) and was developed by members of the AGA Clinical Guideline Committee and Clinical Practice Update Committee and approved by the AGA Governing Board. No internal or external funding was provided for the development of this guideline. Expiration date: 3 months.
Note: To access the supplementary material accompanying this article, visit the online version of Gastroenterology at www.gastrojournal.org, and at https://doi.org/10.1053/j.gastro.2020.05.001.