Clinical Features and Factors Associated with Occult Gastrointestinal Bleeding in COVID-19 Patients

Figures & data

Table 1 Baseline Characteristics, Treatments, and Outcomes of Patients with COVID-19 with and without Occult Gastrointestinal Bleeding

	Total (N=368)	GIB (n=43)	Non-GIB (n=325)	p value
Demographic characteristics
Age, years	57.0 (39.0–68.0)	67.0 (57.0–71.0)	55.0 (38.5–67.0)	<0.001
Male	191 (51.9%)	30 (69.8%)	161 (49.5%)	0.013
Comorbidities
Diabetes	53 (14.4%)	10 (23.3%)	43 (13.2%)	0.078
Hypertension	96 (26.1%)	17 (39.5%)	79 (24.3%)	0.033
Cardiovascular disease	34 (9.2%)	8 (18.6%)	26 (8.0%)	0.043
COPD	11 (3.0%)	3 (7.0%)	8 (2.5%)	0.126
Chronic liver disease	31 (8.4%)	9 (20.9%)	22 (6.8%)	0.005
Chronic kidney disease	5 (1.4%)	1 (2.3%)	4 (1.2%)	0.465
Malignancy	17 (4.6%)	6 (14.0%)	11 (3.4%)	0.008
Immunodeficiency disease	4 (1.1%)	1 (2.3%)	3 (0.9%)	0.393
Symptoms
Fever	329 (89.4%)	40 (93.0%)	289 (88.9%)	0.598
Chills	50 (13.6%)	6 (14.0%)	44 (13.5%)	0.941
Cough	251 (68.2%)	31 (72.1%)	220 (67.7%)	0.560
Chest tightness/chest Pain	97 (26.4%)	9 (20.9%)	88 (27.1%)	0.390
Dyspnea	59 (16.0%)	8 (18.6%)	51 (15.7%)	0.625
Fatigue	115 (31.3%)	10 (23.3%)	105 (32.3%)	0.229
Myalgia	54 (14.7%)	2 (4.7%)	52 (16.0%)	0.048
Anorexia	161 (43.8%)	22 (51.2%)	139 (42.8%)	0.297
Diarrhea	101 (27.4%)	8 (18.6%)	93 (28.6%)	0.167
Nausea or vomiting	29 (7.9%)	6 (14.0%)	23 (7.1%)	0.130
Other	122 (33.2%)	14 (32.6%)	108 (33.2%)	0.930
Disease severity status
Non-severe	221 (60.1%)	8 (18.6%)	213 (65.5%)
Severe	147 (39.9%)	35 (81.4%)	112 (34.5%)	<0.001
Complications
Sepsis	10 (2.7%)	5 (11.6%)	5 (1.5%)	0.003
ARDS	40 (10.9%)	17 (39.5%)	23 (7.1%)	<0.001
Acute liver injury	146 (39.7%)	28 (65.1%)	118 (36.3%)	<0.001
Acute kidney injury	54 (14.7%)	16 (37.2%)	38 (11.7%)	<0.001
Acute cardiac injury	34 (9.2%)	20 (46.5%)	14 (4.3%)	<0.001
Coagulopathy	48 (13.0%)	20 (46.5%)	28 (8.6%)	<0.001
Hypotension	24 (6.5%)	10 (23.3%)	14 (4.3%)	<0.001
Treatments
Mechanical ventilation	63 (17.1%)	32 (74.4%)	31 (9.5%)	<0.001
Antibiotic therapy	332 (90.2%)	41 (95.3%)	291 (89.5%)	0.286
Antiviral therapy	355 (96.5%)	37 (86.0%)	318 (97.8%)	0.002
Glucocorticoid therapy	153 (41.6%)	32 (74.4%)	121 (37.2%)	<0.001
Outcomes
ICU	37 (10.1%)	23 (53.5%)	14 (4.3%)	<0.001
Death	65 (17.7%)	32 (74.4%)	33 (10.2%)	<0.001

Note: Data are presented as median (interquartile range) or as n (%).

Abbreviations: COVID-19, coronavirus disease 2019; COPD, Chronic obstructive pulmonary disease; ARDS, acute respiratory distress syndrome.

Figure 1 Gastroscopy of seven patients with SARS-CoV-2 infection. The images showed different parts of the stomach under the endoscopy. (A–E) Scattered bleeding and congestion of the gastric fundus. (F–M) Scattered bleeding of the gastric body. (N and O) Scattered bleeding of the antrum.

Table 2 Laboratory Findings of Patients with COVID-19 with and without Occult Gastrointestinal Bleeding

Baseline	Total (N=368)	GIB (n=43)	Non-GIB (n=325)	p value
CRP, mg/L	16.8 (3.1–57.3)	79.3 (33.2–151.6)	12.8 (3.1–48.5)	<0.001
White blood cell count, ×10^9/L	5.1 (3.9–6.9)	7.8 (4.4–15.6)	5.0 (3.8–6.5)	<0.001
Lymphocyte count, ×10^9/L	1.1 (0.7–1.5)	0.6 (0.4–0.7)	1.2 (0.8–1.6)	<0.001
Platelet count, ×10^9/L	195.0 (147.0–256.3)	161.0 (113.0–238.0)	197.0 (151.0–265.0)	0.001
Hemoglobin, g/L	129.0 (117.0–138.0)	126.0 (117.0–144.0)	129.0 (117.0–137.0)	0.839
<60	1 (0.3%)	1 (2.3%)	0 (0.0%)	0.117
ALT, U/L	21.0 (15.0–34.0)	26.0 (16.0–42.0)	21.0 (15.0–33.0)	0.158
AST, U/L	26.0 (19.0–37.8)	42.0 (29.0–59.0)	25.0 (19.0–35.0)	<0.001
Albumin, g/L	36.2 (31.7–40.0)	30.9 (28.7–33.6)	36.9 (32.6–40.2)	<0.001
<35	153/365 (41.9%)	34/43 (79.1%)	119/322 (37.0%)	<0.001
Total bilirubin, µmol/L	9.3 (6.8–12.6)	14.0 (9.3–19.0)	8.9 (6.6–11.9)	<0.001
ALP, U/L	65.0 (53.3–79.0)	66.0 (55.0–88.0)	65.0 (53.0–78.0)	0.197
GGT, U/L	24.0 (16.0–46.8)	28.0 (19.0–54.0)	24.0 (16.0–45.0)	0.214
LDH, U/L	247.0 (194.0–336.0)	480.0 (284.0–655.0)	233.5 (187.5–307.8)	<0.001
Creatine kinase, U/L	68.0 (48.0–129.8)	106.0 (56.0–246.0)	67.0 (48.0–120.0)	0.013
Creatinine, µmol/L	69.2 (58.0–84.0)	80.0 (63.0–96.0)	69.0 (57.9–82.3)	0.005
PT, s	13.3 (12.4–14.1)	14.2 (12.9–15.7)	13.3 (12.3–14.0)	<0.001
≥16	17/359 (4.7%)	10/42 (23.8%)	7/317 (2.2%)	<0.001
APTT, s	36.6 (30.9–40.8)	37.9 (31.8–41.8)	36.4 (30.5–40.8)	0.094
D-dimer, ug/mL	0.6 (0.3–1.4)	2.1 (0.9–11.4)	0.5 (0.3–1.2)	<0.001
Extremum
CRP, mg/L	21.1 (3.6–64.6)	157.3 (59.5–200.3)	16.8 (3.2–51.6)	<0.001
White blood cell count, ×10^9/L	6.8 (5.2–9.6)	15.6 (7.7–24.8)	6.5 (5.0–8.5)	<0.001
Lymphocyte count, ×10^9/L	1.0 (0.6–1.4)	0.4 (0.2–0.6)	1.0 (0.7–1.5)	<0.001
Platelet count, ×10^9/L	246.0 (187.0–316.0)	176.0 (87.0–273.0)	248.0 (197.0–327.0)	<0.001
Hemoglobin, g/L	122.0 (109.0–132.0)	117.0 (87.0–129.0)	122.0 (111.0–132.0)	0.008
<60	1 (0.3%)	1 (2.3%)	0 (0.0%)	0.117
ALT, U/L	32.0 (20.0–57.0)	41.0 (21.0–74.0)	32.0 (19.5–51.0)	0.072
AST, U/L	31.0 (21.0–46.0)	52.0 (36.0–84.0)	29.0 (21.0–41.5)	<0.001
Albumin, g/L	33.7 (29.9–38.0)	26.8 (22.8–31.7)	34.8 (30.8–38.3)	<0.001
<35	205 (55.7%)	39 (90.7%)	166 (51.1%)	<0.001
Total bilirubin, µmol/L	11.5 (8.5–15.9)	17.7 (13.5–35.9)	11.1 (8.2–14.8)	<0.001
ALP, U/L	74.0 (60.0–94.8)	94.0 (74.0–142.0)	71.0 (58.0–88.0)	<0.001
GGT, U/L	32.0 (19.0–58.0)	48.0 (27.0–96.0)	31.0 (19.0–57.0)	0.003
LDH, U/L	262.5 (200.8–373.5)	651.0 (417.0–1093.0)	249.0 (197.0–326.0)	<0.001
Creatine kinase, U/L	72.0 (49.8–146.3)	163.0 (67.0–495.5)	67.0 (48.0–129.3)	<0.001
Creatinine, µmol/L	75.0 (61.0–92.0)	96.0 (76.0–175.0)	73.0 (61.0–87.6)	<0.001
PT, s	13.6 (12.8–14.5)	16.0 (13.6–20.3)	13.4 (12.5–14.3)	<0.001
≥16	48/363 (13.2%)	22/43 (51.2%)	26/320 (8.1%)	<0.001
APTT, s	37.8 (33.1–42.9)	44.8 (40.0–56.6)	37.1 (32.4–42.0)	<0.001
D-dimer, ug/mL	0.7 (0.3–2.2)	16.2 (1.7–21.0)	0.6 (0.3–1.5)	<0.001

Notes: Data are presented as median (interquartile range) or as n (%). Baseline laboratory findings were the results on admission, while the extremum were the maximum or minimum results after hospitalization.

Abbreviations: COVID-19, coronavirus disease 2019; CRP, C-reactive protein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, γ-glutamyl transpeptidase; LDH, lactate dehydrogenase; PT, prothrombin time; APTT, activated partial thromboplastin time.

Table 3 Multivariable Logistic Regression Identifying Independent Factors Associated with Occult Gastrointestinal Bleeding

	Univariable Analysis	p value	Multivariable Analysis	p value
	Odds Ratio (95% CI)		Odds Ratio (95% CI)
Baseline characteristics
Age, years	1.043 (1.020–1.067)	<0.001
Male	2.351 (1.184–4.669)	0.015
Severe	8.320 (3.733–18.543)	<0.001	4.157 (1.765–9.791)	0.001
Comorbidities
Diabetes	1.987 (0.914–4.322)	0.083
Hypertension	1.050 (2.036–3.946)	0.035
Cardiovascular disease	2.629 (1.105–6.251)	0.029
COPD	2.972 (0.757–11.661)	0.118
Chronic liver disease	3.646 (1.554–8.553)	0.003
Chronic kidney disease	1.911 (0.209–17.501)	0.567
Malignancy	4.629 (1.618–13.247)	0.004
Immunodeficiency disease	2.556 (0.260–25.133)	0.421
Baseline laboratory findings
CRP, mg/L	1.016 (1.011–1.022)	<0.001
White blood cell count, ×10^9/L	1.300 (1.191–1.419)	<0.001
Lymphocyte count, ×10^9/L	0.109 (0.046–0.257)	<0.001
Platelet count, ×10^9/L	0.991 (0.986–0.996)	0.001
Hemoglobin, g/L	1.000 (0.984–1.017)	0.991
ALT, U/L	1.005 (0.995–1.014)	0.313
AST, U/L	1.023 (1.012–1.035)	<0.001
Albumin, g/L	0.824 (0.767–0.885)	<0.001	0.856 (0.793–0.924)	<0.001
Total bilirubin, µmol/L	1.093 (1.045–1.143)	<0.001
ALP, U/L	1.007 (1.000–1.015)	0.054
GGT, U/L	1.001 (0.998–1.005)	0.509
LDH, U/L	1.004 (1.003–1.006)	<0.001
Creatine kinase, U/L	1.002 (1.001–1.003)	0.002
Creatinine, µmol/L	1.016 (1.006–1.025)	0.001
PT, s	1.423 (1.201–1.685)	<0.001	1.267 (1.089–1.475)	0.002
APTT, s	1.038 (0.993–1.086)	0.095
D-dimer, ug/mL	1.068 (1.027–1.111)	0.001
Treatments
Antiviral therapy	0.136 (0.043–0.425)	0.001	0.416 (0.104–1.666)	0.215
Glucocorticoid therapy	4.905 (2.385–10.086)	<0.001	1.553 (0.512–4.707)	0.437

Note: Baseline laboratory findings were the results on admission.

Abbreviations: CI, confidence interval; COPD, Chronic obstructive pulmonary disease; CRP, C-reactive protein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, γ-glutamyl transpeptidase; LDH, lactate dehydrogenase; PT, prothrombin time; APTT, activated partial thromboplastin time.