Background
Methods
Search strategy and selection criteria
Data extraction and definitions
Assessment of study quality
Data synthesis and statistical analysis
Results
Search results and study characteristics
No. of study | First author | Study location | No. of patients | Age (year) | Male | Special patient population | NOS score |
---|---|---|---|---|---|---|---|
1 | Alizadehsani R et al. | Iran | 123 | 45 | 62 | None | 8 |
2 | An P et al. | China | 205 | 54 | 122 | None | 8 |
3 | Atalla E et al. | USA | 111 | 87 | 23 | Older patients | 7 |
4 | Caillard S et al. | France | 243 | 62 | 162 | Kidney transplant recipients | 7 |
5 | Chadalavada P et al. | USA | 84 | 60 | 52 | None | 8 |
6 | Chen R et al. | China | 1077 | 59 | 532 | None | 9 |
7 | Chen T et al. | China | 274 | 62 | 171 | Critically ill patients | 7 |
8 | Comoglu Ş et al. | Turkey | 1086 | 48 | 563 | None | 8 |
9 | Crespo M et al. | Spain | 414 | 62 | 265 | Kidney transplant recipients | 7 |
10 | Doganci S et al. | Turkey | 397 | 57 | 200 | None | 8 |
11 | Du H et al. | China | 182 | 6 | 120 | Pediatric patients | 7 |
12 | Elimian K et al. | Nigeria | 3215 | 36 | 2293 | None | 8 |
13 | Ferm S et al. | USA | 877 | 59 | 534 | None | 8 |
14 | Gayam V et al. | USA | 408 | 67 | 231 | African-Americans | 7 |
15 | Ghoshal U et al. | India | 252 | 40 | 204 | None | 8 |
16 | Hajifathalian K et al. | USA | 1059 | 61 | 611 | None | 8 |
17 | Huang H et al. | China | 49 | 37 | 23 | Patients with pre-existing ILD | 7 |
18 | Jiang Y et al. | China | 281 | 70 | 143 | Older severe patients | 7 |
19 | Jin X et al. | China | 651 | 46 | 331 | None | 9 |
20 | Kang M et al. | Korea | 118 | 59 | 52 | None | 8 |
21 | Kim D et al. | USA | 867 | 57 | 473 | Patients with chronic liver disease | 7 |
22 | Lanthier N et al. | Belgium | 50 | 88 | NA | Geriatric patients | 7 |
23 | Laszkowska M et al. | USA | 2804 | 66 | 1565 | None | 8 |
24 | Leal T et al. | Portugal | 201 | 71 | 113 | Symptomatic patients | 7 |
25 | Liang J et al. | China | 109 | 65 | 57 | Patients with cancer | 7 |
26 | Liu J et al. | China | 29,393 | 47 | 15,501 | None | 8 |
27 | Livanos A et al. | USA | 634 | 61 | 369 | None | 8 |
28 | Luo S et al. | China | 1411 | 54 | 895 | None | 8 |
29 | Ma X et al. | China | 467 | 44 | 289 | None | 8 |
30 | Montazeri M et al. | Iran | 611 | 56 | 377 | None | 8 |
31 | Moura D et al. | Brazil | 400 | 56 | 225 | None | 8 |
32 | Nobel Y et al. | USA | 278 | NA | 145 | None | 7 |
33 | Pan L et al. | China | 204 | 53 | 107 | None | 9 |
34 | Peng X et al. | China | 49 | 63 | 17 | Critically ill patients | 7 |
35 | Ramachandran P et al. | USA | 150 | 57 | 83 | None | 8 |
36 | Redd W et al. | USA | 318 | 63 | 174 | None | 9 |
37 | Renelus B et al. | USA | 734 | 68 | 379 | None | 8 |
38 | Russell B et al. | UK | 156 | 65 | 90 | Patients with cancer | 7 |
39 | Schettino M et al. | Italy | 190 | 65 | 127 | None | 8 |
40 | Shang H et al. | China | 564 | 59 | 286 | None | 8 |
41 | Soares R et al. | Brazil | 1152 | NA | 494 | None | 8 |
42 | Sulaiman T et al. | Iraq | 140 | 45 | 100 | None | 8 |
43 | Tsibouris P et al. | Greece | 61 | 70 | 34 | None | 8 |
44 | Vena A et al. | Italy | 275 | 71 | 183 | None | 8 |
45 | Villanego F et al. | Spain | 1011 | 60 | 635 | Kidney transplant recipients | 7 |
46 | Vrillon A et al. | France | 52 | 90 | 34 | Older adults | 7 |
47 | Wan, Y et al. | China | 230 | 48 | 129 | None | 8 |
48 | Wang Z et al. | China | 59 | 67 | 38 | Critically ill patients | 7 |
49 | Yang X et al. | China | 52 | 60 | 35 | Critically ill adults | 7 |
50 | Zhang J et al. | China | 663 | 56 | 321 | None | 7 |
51 | Zhang L et al. | China | 409 | 65 | 234 | Severe COVID-19 patients | 7 |
52 | Zhou F et al. | China | 191 | 56 | 72 | None | 7 |
53 | Zhou Z et al. | China | 254 | 50 | 115 | None | 9 |
No. of study | Author | No. of patients | No. of death | No. of GI symptom | No. of diarrhea | No. of nausea/vomiting | No. of abdominal pain |
---|---|---|---|---|---|---|---|
1 | Alizadehsani R et al. | 123 | 15 (12.2%) | 11 (8.9%) | NA | NA | NA |
2 | An P et al. | 205 | 6 (2.9%) | 79 (38.5%) | NA | NA | NA |
3 | Atalla E et al. | 111 | 48 (43.2%) | 8 (7.2%) | 8 (7.2%) | 2(1.8%) | NA |
4 | Caillard S et al. | 243 | 43 (17.7%) | 96 (39.5%) | 96 (39.5%) | NA | NA |
5 | Chadalavada P et al. | 84 | 11 (13.1%) | 44 (52.4%) | NA | NA | NA |
6 | Chen R et al. | 1077 | 85 (7.9%) | 359 (33.3%) | NA | NA | NA |
7 | Chen T et al. | 274 | 113 (41.2%) | 77 (28.1%) | 77 (28.1%) | 24(8.8%) | 19(6.9%) |
8 | Comoglu Ş et al. | 1086 | 38 (3.5%) | 78 (7.2%) | 78 (7.2%) | NA | NA |
9 | Crespo M et al. | 414 | 109 (26.3%) | 152 (36.7%) | NA | NA | NA |
10 | Doganci S et al. | 397 | 34 (8.6%) | 292 (73.6%) | NA | NA | NA |
11 | Du H et al. | 182 | 1 (0.5%) | 20 (11.0%) | 9 (4.9%) | 7(3.8%) | 7(3.8%) |
12 | Elimian K et al. | 3215 | 295 (9.2%) | 132 (4.1%) | 132 (4.1%) | 103(3.2%) | 20(0.6%) |
13 | Ferm S et al. | 877 | 208 (23.7%) | 219 (25.0%) | NA | NA | NA |
14 | Gayam V et al. | 408 | 132 (32.4%) | 111 (27.2%) | NA | NA | NA |
15 | Ghoshal U et al. | 252 | 5 (2.0%) | 26 (10.3%) | NA | NA | NA |
16 | Hajifathalian K et al. | 1059 | 147 (13.9%) | 349 (33.0%) | NA | NA | NA |
17 | Huang H et al. | 49 | 9 (18.4%) | 3 (6.1%) | 3 (6.1%) | 1 (2.0%) | NA |
18 | Jiang Y et al. | 281 | 114 (40.6%) | 33 (11.7%) | 33 (11.7%) | 13 (4.6%) | NA |
19 | Jin X et al. | 651 | 1 (0.2%) | 74(11.4%) | NA | NA | NA |
20 | Kang M et al. | 118 | 6 (5.1%) | 54 (45.8%) | 54(45.8%) | NA | NA |
21 | Kim D et al. | 867 | 121 (14.0%) | 181 (20.9%) | 181 (20.9%) | 175 (20.2%) | NA |
22 | Lanthier N et al. | 50 | 26 (52.0%) | 15 (30.0%) | 12 (24.0%) | 3 (6.0%) | 3 (6.0%) |
23 | Laszkowska M et al. | 2804 | 542 (19.3%) | 1084 (38.7%) | NA | NA | NA |
24 | Leal T et al. | 201 | 55 (27.4%) | 60 (29.9%) | NA | NA | NA |
25 | Liang J et al. | 109 | 23 (21.1%) | 26 (23.9%) | 26 (23.9%) | 10 (9.2%) | 5 (4.6%) |
26 | Liu J et al. | 29,393 | 711 (2.4%) | 2289 (7.8%) | NA | NA | NA |
27 | Livanos A et al. | 634 | 151 (23.8%) | 299 (47.2%) | NA | NA | NA |
28 | Luo S et al. | 1411 | 66 (4.7%) | 183 (13.0%) | NA | NA | NA |
29 | Ma X et al. | 467 | 16 (3.4%) | 25 (5.4%) | 25(5.4%) | NA | NA |
30 | Montazeri M et al. | 611 | 104 (17.0%) | 155 (25.4%) | NA | NA | NA |
31 | Moura D et al. | 400 | 89 (22.3%) | 133 (33.3%) | NA | NA | NA |
32 | Nobel Y et al. | 278 | 9 (3.2%) | 97 (34.9%) | 56 (20.1%) | 63 (22.7%) | NA |
33 | Pan L et al. | 204 | 36 (17.6%) | 103 (50.5%) | NA | NA | NA |
34 | Peng X et al. | 49 | 16 (32.7%) | 22 (44.9%) | 11 (22.4%) | 15 (30.6%) | 3(6.1%) |
35 | Ramachandran P et al. | 150 | 58 (38.7%) | 31 (20.7%) | NA | NA | NA |
36 | Redd W et al. | 318 | 32 (10.1%) | 195 (61.3%) | NA | NA | NA |
37 | Renelus B et al. | 734 | 237 (32.3%) | 231 (31.5%) | NA | NA | NA |
38 | Russell B et al. | 156 | 34 (21.8%) | 25 (16.0%) | NA | NA | NA |
39 | Schettino M et al. | 190 | 41 (21.6%) | 138 (72.6%) | NA | NA | NA |
40 | Shang H et al. | 564 | 51 (9.0%) | 157 (27.8%) | 157 (27.8%) | NA | NA |
41 | Soares R et al. | 1152 | 456 (39.6%) | 126 (10.9%) | 126 (10.9%) | NA | NA |
42 | Sulaiman T et al. | 140 | 12 (8.6%) | 78 (55.7%) | NA | NA | NA |
43 | Tsibouris P et al. | 61 | 16 (26.2%) | 11 (18.0%) | 11 (18.0%) | 4 (6.6%) | 2 (3.3%) |
44 | Vena A et al. | 275 | 120 (43.6%) | 14 (5.1%) | 14(5.1%) | 11(4.0%) | NA |
45 | Villanego F et al. | 1011 | 220 (21.8%) | 323 (31.9%) | NA | NA | NA |
46 | Vrillon A et al. | 52 | 17 (32.7%) | 17 (32.7%) | NA | NA | NA |
47 | Wan, Y et al. | 230 | 6 (2.6%) | 49 (21.3%) | 49 (21.3%) | NA | NA |
48 | Wang Z et al. | 59 | 41 (69.5%) | 22 (37.3%) | 22 (37.3%) | 4 (6.8%) | NA |
49 | Yang X et al. | 52 | 32 (61.5%) | 2 (3.8%) | NA | 2 (3.8%) | NA |
50 | Zhang J et al. | 663 | 25 (3.8%) | 61
(9.2%) | 61 (9.2%) | 31 (4.7%) | 5 (0.8%) |
51 | Zhang L et al. | 409 | 102 (24.9%) | 91 (22.2%) | 91 (22.2%) | 50 (12.2%) | 28 (6.8%) |
52 | Zhou F et al. | 191 | 54 (28.3%) | 9 (4.7%) | 9 (4.7%) | 7 (3.7%) | NA |
53 | Zhou Z et al. | 254 | 16 (6.3%) | 66 (26.0%) | NA | NA | NA |
Cumulative incidence | 25% | 16% | 7.5% | 3.6% |
Association of GI symptoms with the mortality of COVID-19
Subgroup Analysis
Subgroups | No. of studies | No. of patients | OR and P value for mortality of different symptoms | ||||
---|---|---|---|---|---|---|---|
GI symptom | I 2 for GI symptom | Diarrhea | Nausea/vomiting | Abdominal pain | |||
1. Study location | |||||||
1.1 Asia | 28 | 39,501 (72%) | 1.43, P=0.01 | 54.7% | 1.32, P=0.21 | 1.3, P=0.36 | 1.07, P=0.85 |
Sub-subgroups for studies in Asia: | |||||||
1.1.1 GI group older than non-GI group | 7 | 32,894 | 2.43, P<0.01 | 66.9% | |||
1.1.2 GI group younger than non-GI group | 6 | 3048 | 1.2, P=0.29 | 15.8% | |||
1.2 America | 12 | 8324 (15%) | 0.64, P<0.01 | 42.7% | 0.81, P=0.37 | 0.84, P=0.8 | NA |
Sub-subgroups for studies in America: | |||||||
1.2.1 GI group older than non-GI group | NA | NA | NA | NA | |||
1.2.2 GI group younger than non-GI group | 5 | 3990 | 0.55, P<0.01 | 30.6% | |||
1.3 Europe | 10 | 2653 (5%) | 0.4, P<0.01 | 77% | 0.51, P=0.07 | 0.7, P=0.51 | 0.61, P=0.76 |
Sub-subgroups for studies in Europe: | |||||||
1.3.1 GI group older than non-GI group | NA | NA | NA | NA | |||
1.3.2 GI group younger than non-GI group | 3 | 805 | 0.23, P<0.01 | 84% | |||
1.4 Other | 3 | 4767(8%) | 0.92, P=0.83 | 87.8% | 0.93, P=0.92 | NA | NA |
2. Only include critically ill patients? | |||||||
3.1 Yes | 6 | 1124(2%) | 1.42, P=0.36 | 74.6% | 1.3, P=0.45 | 0.92, P=0.71 | 0.75, P=0.45 |
3.2 No | 47 | 54,121 (98%) | 0.83, P=0.1 | 78.3% | 0.92, P=0.69 | 1.37, P=0.28 | 2.67, P=0.05 |
3. Population size | |||||||
4.1 <500 | 36 | 7436 (13%) | 0.93, P=0.66 | 72.1% | 1.05, P=0.82 | 1.19, P=0.51 | 1.04, P=0.92 |
4.2 >=500 | 17 | 47,809 (87%) | 0.84, P=0.25 | 85.7% | 0.94, P=0.83 | 1.16, P=0.68 | NA |
4. Average age of GI group and non-GI group | |||||||
4.1 GI group older than non-GI group | 8 | 33,294 (60%) | 1.89, P=0.02 | 69% | |||
4.2 GI group younger than non-GI group | 14 | 7843 (14%) | 0.61, P=0.01 | 80% | |||
4.3 Unknown | 31 | 14,058 (26%) | 0.89, P=0.36 | 64% |
Age stratification analysis
Age stratification | No. of studies | OR and 95% CI of GI symptom for mortality | P value of OR | No. of studies that average age: GI group >non GI group | No. of studies that average age: GI group <non-GI group |
---|---|---|---|---|---|
0–39 | 3 | 2.36 [0.88; 6.33] | 0.088 | NA | NA |
40–49 | 8 | 2.22 [0.96; 5.11] | 0.061 | 5 (83.3%) | 1 (16.7%) |
50–59 | 15 | 1.09 [0.85; 1.40] | 0.517 | 3 (33.3%) | 6 (66.7%) |
60–69 | 18 | 0.71 [0.54; 0.95] | 0.02 | 0 (0%) | 6 (100%) |
70~ | 7 | 0.40 [0.21; 0.76] | 0.006 | 0 | 1 (100%) |
Publication bias analysis
No. of included literatures | OR | P value for OR | P value of Egger’s test | |
---|---|---|---|---|
Original data | ||||
GI symptom | 53 | 0.88 | 0.23 | 0.05 |
Diarrhea | 24 | 1.01 | 0.96 | 0.55 |
Nausea/vomiting | 18 | 1.16 | 0.46 | 0.04 |
Abdominal pain | 9 | 1.55 | 0.3 | 0.61 |
After trim-and-fill | ||||
GI symptom | 56 | 0.84 | 0.11 | 0.82 |
Diarrhea | 24 | 1.01 | 0.96 | 0.55 |
Nausea/vomiting | 21 | 1.02 | 0.91 | 0.9 |
Abdominal pain | 11 | 1.28 | 0.51 | 0.94 |
Sensitivity analysis
OR and P value for mortality of different symptoms | ||||
---|---|---|---|---|
Study omitted | GI symptom | Diarrhea | Nausea/vomiting | Abdominal pain |
Omitting Alizadehsani R et al. | 0.88, P=0.25 | NA | NA | NA |
Omitting An P et al. | 0.86, P=0.17 | NA | NA | NA |
Omitting Atalla E et al. | 0.87, P=0.22 | 1, P=1 | 1.13, P=0.55 | NA |
Omitting Caillard S et al. | 0.89, P=0.28 | 1.04, P=0.81 | NA | NA |
Omitting Chadalavada P et al. | 0.88, P=0.25 | NA | NA | NA |
Omitting Chen R et al. | 0.87, P=0.2 | NA | NA | NA |
Omitting Chen T et al. | 0.89, P=0.27 | 1.04, P=0.83 | 1.23, P=0.33 | 1.91, P=0.17 |
Omitting Comoglu Ş et al. | 0.88, P=0.25 | 1.02, P=0.9 | NA | NA |
Omitting Crespo M et al. | 0.9, P=0.31 | NA | NA | NA |
Omitting Doganci S et al. | 0.86, P=0.15 | NA | NA | NA |
Omitting Du H et al. et al | 0.87, P=0.18 | 0.99, P=0.96 | 1.08, P=0.63 | 1.42, P=0.42 |
Omitting Elimian K et al. | 0.86, P=0.16 | 0.96, P=0.82 | 1.05, P=0.82 | 1.05, P=0.9 |
Omitting Ferm S et al. | 0.88, P=0.28 | NA | NA | NA |
Omitting Gayam V et al. | 0.88, P=0.23 | NA | NA | NA |
Omitting Ghoshal U et al. | 0.86, P=0.15 | NA | NA | NA |
Omitting Hajifathalian K et al. | 0.9, P=0.32 | NA | NA | NA |
Omitting Huang H et al. | 0.87, P=0.21 | 1, P=0.98 | 1.12, P=0.57 | NA |
Omitting Jiang Y et al. | 0.89, P=0.29 | 1.05, P=0.77 | 1.23, P=0.3 | NA |
Omitting Jin X et al. | 0.87, P=0.18 | NA | NA | NA |
Omitting Kang M et al. | 0.89, P=0.27 | 1.04, P=0.83 | NA | NA |
Omitting Kim D et al. | 0.88, P=0.26 | 1.03, P=0.88 | 1.25, P=0.32 | NA |
Omitting Lanthier N et al. | 0.9, P=0.31 | 1.06, P=0.72 | 1.15, P=0.5 | 1.77, P=0.16 |
Omitting Laszkowska M et al. | 0.9, P=0.32 | NA | NA | NA |
Omitting Leal T et al. | 0.9, P=0.34 | NA | NA | NA |
Omitting Liang J et al. | 0.87, P=0.22 | 1, P=0.99 | 1.14, P=0.54 | 1.46, P=0.42 |
Omitting Liu J et al. | 0.86, P=0.14 | NA | NA | NA |
Omitting Livanos A et al. | 0.9, P=0.33 | NA | NA | NA |
Omitting Luo S et al. | 0.88, P=0.25 | NA | NA | NA |
Omitting Ma X et al. | 0.87, P=0.19 | 0.98, P=0.9 | NA | NA |
Omitting Montazeri M et al. | 0.87, P=0.19 | NA | NA | NA |
Omitting Moura D et al. | 0.88, P=0.24 | NA | NA | NA |
Omitting Nobel Y et al. | 0.89, P=0.27 | 1.03, P=0.87 | 1.19, P=0.37 | NA |
Omitting Pan L et al. | 0.87, P=0.22 | NA | NA | NA |
Omitting Peng X et al. | 0.85, P=0.13 | 0.97, P=0.84 | 1.1, P=0.64 | 1.42, P=0.44 |
Omitting Ramachandran P et al. | 0.87, P=0.21 | NA | NA | NA |
Omitting Redd W et al. | 0.89, P=0.28 | NA | NA | NA |
Omitting Renelus B et al. | 0.89, P=0.29 | NA | NA | NA |
Omitting Russell B et al. | 0.86, P=0.18 | NA | NA | NA |
Omitting Schettino M et al. | 0.92, P=0.43 | NA | NA | NA |
Omitting Shang H et al. | 0.86, P=0.17 | 0.97, P=0.85 | NA | NA |
Omitting Soares R et al. | 0.9, P=0.32 | 1.08, P=0.66 | NA | NA |
Omitting Sulaiman T et al. | 0.88, P=0.24 | NA | NA | NA |
Omitting Tsibouris P et al. | 0.89, P=0.27 | 1.04, P=0.83 | 1.17, P=0.45 | 1.49, P=0.38 |
Omitting Vena A et al. | 0.88, P=0.23 | 1.01, P=0.95 | 1.23, P=0.32 | NA |
Omitting Villanego F et al. | 0.89, P=0.29 | NA | NA | NA |
Omitting Vrillon A et al. | 0.89, P=0.3 | NA | NA | NA |
Omitting Wan Y et al. | 0.86, P=0.15 | 0.96, P=0.78 | NA | NA |
Omitting Wang Z et al. | 0.86, P=0.16 | 0.96, P=0.8 | 1.13, P=0.53 | NA |
Omitting Yang X et al. | 0.88, P=0.24 | NA | 1.18, P=0.43 | NA |
Omitting Zhang J et al. | 0.89, P=0.26 | 1.03, P=0.86 | 1.18, P=0.43 | 1.52, P=0.35 |
Omitting Zhang L et al. | 0.86, P=0.17 | 0.97, P=0.86 | 1.21, P=0.4 | 1.91, P=0.17 |
Omitting Zhou F et al. | 0.88, P=0.24 | 1.02, P=0.91 | 1.13, P=0.56 | NA |
Omitting Zhou Z et al. | 0.88, P=0.23 | NA | NA | NA |