Digestive system involvement and clinical outcomes among COVID-19 patients: A retrospective cohort study from Qatar

doi:10.3748/wjg.v27.i46.7995

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World Journal of Gastroenterology

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Retrospective Cohort Study

World J Gastroenterol. Dec 14, 2021; 27(46): 7995-8009
Published online Dec 14, 2021. doi: 10.3748/wjg.v27.i46.7995

Table 1 Demographic and epidemiological characteristics and presenting symptoms of coronavirus disease 2019 patients with and without gastrointestinal symptoms, n (%)

Characteristics	Overall (n = 601)	With GI (n = 163)	Without GI (n = 438)	P value
Age (yr)	46.20 13.66	46.45 13.76	46.12 13.64	0.728
Sex, male	513 (85.4)	136 (83.4)	377 (85.9)	0.515
BMI (kg/m²)	27.55 (24.90-31.00)	27.49 (24.40-30.60)	27.55 (24.90-31.00)	0.811
Duration of symptoms (d)	4.24 2.53	4.81 2.51	4.04 2.51	0.002^a
Nationality				0.765
Qatar	67 (11.1)	17 (25.4)	50 (74.6)
India	127 (21.1)	27 (21.3)	100 (78.7)
Nepal	89 (14.8)	23 (25.8)	66 (74.2)
Bangladesh	105 (17.5)	33 (31.4)	72 (68.6)
Pakistan	48 (8.0)	14 (29.2)	43 (70.8)
Philippines	56 (9.3)	18 (32.1)	38 (67.9)
Arab countries	60 (9.9)	16 (26.7)	44 (73.3)
Others	49 (8.15)	15 (30.6)	34 (69.4)
Presenting symptoms
Fever	478 (79.7)	130 (79.7)	348 (79.1)	0.147
Cough	455 (75.7)	112 (68.7)	343 (77.8)	0.016^a
Sputum	75 (12.5)	23 (14.1)	52 (11.8)	0.483
Shortness of breath	303 (50.2)	84 (51.5)	219 (49.7)	0.412
Sore throat	146 (24.3)	37 (22.7)	109 (24.7)	0.747
Nasal obstruction	51 (8.5)	18 (11.0)	33 (7.5)	0.359
Fatigue	163 (27.1)	79 (48.5)	84 (19.1)	< 0.001^a
Myalgia	182 (30.3)	63 (38.7)	119 (27.0)	0.007^a
Anosmia	303 (50.2)	86 (52.8)	217 (49.5)	0.424
Exposure history
Smoking	62 (10.1)	24 (14.9)	38 (8.7)	0.199
Ex-smoker	7 (1.2)	3 (1.9)	4 (0.9)
Alcohol	44 (7.3)	9 (5.6)	35 (8.3)	0.28
Travel history	43 (7.2)	9 (5.6)	34 (7.8)	0.456
Sick contact	142 (23.6)	34 (20.9)	108 (24.6)	0.533
Family cluster	27 (4.6)	10 (6.3)	17 (3.4)	0.477
Pre-existing conditions
No. of comorbid conditions				0.39
0	261 (43.4)	72 (43.6)	189 (43.0)
1-2	203 (33.8)	53 (32.1)	150 (32.2)
> 2	137 (22.8)	38 (24.9)	99 (22.1)
Diabetes mellitus	242 (40.3)	72 (44.2)	170 (38.6)	0.327
Hypertension	209 (34.6)	52 (31.9)	157 (35.6)	0.536
Coronary artery disease	46 (7.7)	6 (3.7)	40 (9.1)	0.622
Chronic kidney disease	47 (7.8)	12 (7.4)	35 (8.0)	0.882
Chronic liver disease	6 (1.0)	2 (1.2)	4 (0.9)	< 0.001^a
Malignancy	12 (2.0)	4 (2.5)	8 (1.8)	< 0.001^a
Lung disease	35 (5.8)	8 (4.9)	27 (6.1)	< 0.001^a
Immunosuppression	20 (3.3)	7 (4.3)	13 (3.0)	< 0.001^a
Disease severity at admission				0.0024^a
Asymptomatic	48 (8.0)	2 (1.2)	46 (10.5)
Mild	109 (18.1)	32 (19.6)	77 (17.7)
Moderate	291 (48.4)	75 (46.0)	216 (49.1)
Severe	70 (11.6)	26 (15.9)	44 (10.0)
Critical	83 (13.8)	28 (17.2)	55 (12.5)
Severe–non severe	153(25.5)	54 (33.1)	99 (22.5)	< 0.001^a

^aStatistically significant P value.

BMI: Body mass index; GI: Gastrointestinal.

Table 2 Frequency of gastrointestinal symptoms in coronavirus disease 2019 patients at admission and during hospital stay, n (%)

GI symptoms at admission (n = 601)	Frequency	During hospital stay (n = 438)	Frequency
Diarrhea	76 (12.6)	Diarrhea	42 (7.0)
Nausea	98 (16.2)	Nausea	94 (15.6)
Vomiting	73 (12.1)	Vomiting	87 (14.5)
Epigastric pain	69 (11.4)	Epigastric pain	22 (3.6)
GERD	6 (1.0)	GERD	2 (0.3)
Anorexia	66 (10.9)	Anorexia	26 (4.3)
GI bleeding	4 (0.7)	GI bleeding	6 (1.0)
Any GI symptoms	163 (27.1)	Any GI symptoms	119 (19.8)
Any nausea, vomiting, diarrhea	140 (19.0)

GI: Gastrointestinal; GERD: Gastro-esophageal reflux disease.

Table 3 Laboratory and radiological findings of coronavirus disease 2019 patients with and without gastrointestinal symptoms, n (%)

Parameters	Total	With GI symptoms (n = 163)	Without GI symptoms (n = 438)	P value
Hematological parameters
Hemoglobin gm/dL	14.0 (12.7-15.0)	13.9 (12.7-15.0)	14.0 (12.7-15.1)	0.590
Hematocrit	42.1 (39.0-45.2)	42.0 (38.7-45.0)	42.3 (39.1-45.3)	0.010
WBC (10³/L)	6.3 (4.9-8.6)	6.2 (4.6-8.6)	6.4 (5.0-8.5)	0.595
Neutrophils (10³/L)	4.3 (3.1-6.6)	4.4 (2.9-6.5)	4.3 (3.1-6.6)	0.617
Lymphocytes (10³/L)	1.2 (0.8-1.6)	1.1 (0.8-1.6)	1.2 (0.8-1.6)	0.987
Eosinophils (10³/L)	0 (0-0.02)	0 (0-0)	0 (0-0.05)	0.643
Monocytes (10³/L)	0.4 (0.3-0.6)	0.4 (0.3-0.6)	0.4 (0.3-0.6)	0.919
Platelets (10³/L)	211 (169-261)	202 (155-257)	215 (170-261)	0.961
Coagulation function
INR	1.1 (1.0-1.2)	1.1 (1.0-1.2)	1.1 (1.0-1.2)	0.486
Blood biochemistry
BUN (mmol/L)	4.0 (3.0-5.3)	3.8 (2.4-5.2)	4.1 (3.1-5.3)	0.758
Creatinine (mol/L)	85 (70-102)	86 (69-101)	84 (70-103)	0.407
Sodium (mmol/L)	136 (133-138)	135 (132-137)	136 (133-138)	0.225
ALT (U/L)	32 (22-51)	34 (22-56)	32 (22-49)	0.043^a
AST (U/L)	37 (25-59)	42 (28-69)	36 (24-55)	0.116
ALK-P (U/L)	70 (57-88)	71 (58-88)	70 (57-89)	0.199
Bilirubin (mol/L)	9 (6-12)	8 (7-12)	9 (6-12)	0.438
Albumin (gm/L)	36 (31-39)	35 (30-38)	36 (32-39)	0.058
Glucose (mmol/L)	6.6 (5.4-9.0)	6.7 (5.5-9.0)	6.6 (5.4-9.0)	0.708
Lactate (mmol/L)	1.3 (1.0-1.8)	1.4 (1.1-1.9)	1.2 (1.1-1.8)	0.297
CK (U/L)	218 (72-481)	147 (84-518)	237 (68-477)	0.455
Amylase (U/L)	48 (25-124)	47 (23-119)	47 (28-109)	0.604
Lipase (U/L)	55 (35-129)	56 (35-152)	54 (36-103)	0.648
Troponin-T (ng/L)	10 (6-26)	10 (6-17)	11 (6-26)	0.296
LDH (U/L)	436 (305-559)	446 (337-578)	435 (302-547)	0.167
Infection-related biomarkers
CRP (mg/L)	55.3 (16.0-113.7)	55.5 (24.9-113.7)	55.3 (13.2-113.7)	0.614
Procalcitonin (ng/ml)	0.21 (0.10-0.68)	0.21 (0.10-0.50)	0.21 (0.10-0.70)	0.789
Ferritin (g/L)	659 (327-1229)	805 (450-1475)	618 (289-1154)	0.561
Liver injury at admission				0.059
None	272 (45.87)	65 (40.37)	207 (47.92)
Abnormality < 2 × ULN	218 (36.76)	61 (37.89)	157 (36.34)
Mild	85 (14.33)	30 (18.63)	55 (12.73)
Moderate	15 (2.53)	5 (3.11)	10 (2.31)
Severe	2 (0.34)	0 (0.00)	2 (0.46)
Liver injury during hospitalization				0.302
None	107 (19.60)	26 (16.56)	81 (20.88)
Abnormality < 2 × ULN	163 (29.91)	51 (32.48)	112 (28.87)
Mild 2-5 ×	171 (31.40)	44 (28.03)	127 (32.73)
Moderate 5-10 ×	63 (11.56)	21 (13.38)	42 (10.82)
Severe > 10 ×	41 (7.52)	15 (9.55)	26 (6.70)
Radiological findings
X-ray chest				0.286
Not done	2 (0.3)	0 (0.0)	2 (0.5)
Normal	141 (23.5)	35 (21.6)	107 (24.3)
Unilateral PNA	100 (16.6)	24 (14.8)	76 (17.2)
Bilateral PNA	328 (54.6)	96 (59.3)	232 (52.6)
Ground glass	29 (4.8)	7 (4.3)	22 (5.0)

WBC: White blood cells; BUN: Blood urea nitrogen; INR: International normalized ratio; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase, ALK-P: Alkaline phosphatase; CK: Creatine Kinase; LDH: Lactate dehydrogenase; CRP: C-reactive protein; ULN: Upper limit of normal; PNA: Pneumonia; GI: Gastrointestinal.

Table 4 Clinical outcomes and treatment in coronavirus disease 2019 patients with and without gastrointestinal symptoms, n (%)

	Total	With GI symptoms n = 163	Without GI symptoms n = 438	P value
Outcomes
ICU admission	260 (43.55)	78 (48.45)	182 (41.74)	0.143
ARDS	206 (34.30)	61 (38.12)	145 (33.30)	0.268
Shock	130 (21.60)	40 (25.00)	90 (20.64)	0.254
MOF	48 (8.00)	15 (9.32)	33 (7.59)	0.491
ALF	7 (1.20)	1 (0.62)	6 (1.38)	0.447
MV	185 (30.80)	55 (34.80)	130 (29.90)	0.252
ECMO	4 (0.70)	1 (0.62)	3 (0.69)	0.929
CRRT	29 (4.80)	6 (3.73)	23 (5.28)	0.610
Death	34 (5.70)	10 (6.21)	24 (5.50)	0.741
LOS (d)	15 (8-21)	15 (10-22)	14 (7-21)	0.036^a
Treatment
Azithromycin	538 (90.12)	151 (93.80)	387 (88.80)	0.068
HCQ	540 (90.45)	150 (93.20)	390 (89.40)	0.170
Chloroquine	38 (6.30)	7 (4.35)	31 (7.11)	0.388
Antibiotics	493 (82.6)	149 (92.6)	344 (78.9)	< 0.001^a
Steroids	248 (41.61)	67 (41.60)	181 (41.60)	0.831
IFN	62 (10.30)	21 (13.04)	41 (9.43)	0.368
RBV	91 (15.10)	31 (19.25)	60 (13.80)	0.097
Tocilizumab	236 (39.50)	66 (40.99)	170 (38.99)	0.657
Lopinavir/ritonavir	340 (56.6)	96 (59.6)	244 (56.0)	0.422
Oseltamivir	510 (85.43)	139 (86.30)	371 (85.09)	0.702
Darunavir	48 (8.0)	14 (8.7)	34 (7.8)	0.782
Treatment groups
Group 1	524 (87.2)	150 (92.0)	374 (85.4)	0.039^a
Group 2	431 (71.7)	128 (78.5)	303 (69.2)	0.025^a
Group 3	307 (51.1)	88 (54.0)	219 (50.0)	0.409
Group 4	181 (30.1)	50 (30.7)	131 (29.9)	0.920
Group 5	61 (10.1)	22 (13.5)	39 (8.9)	0.128
Group 6	56 (9.3)	20 (12.3)	36 (8.2)	0.155

^aStatistically significant P value.

Group 1: Hydroxychloroquine + Azithromycin; Group 2: Hydroxychloroquine + Azithromycin + Oseltamivir + Antibiotics; Group 3: Hydroxychloroquine + Azithromycin + Oseltamivir + Antibiotics + Lopinavir/ritonavir; Group 4: Hydroxychloroquine + Azithromycin + Oseltamivir + Antibiotics + Lopinavir/ritonavir + Steroids; Group 5: Hydroxychloroquine + Azithromycin + Oseltamivir + Antibiotics + Lopinavir/ritonavir + Steroids + Interferon/ribavirin; Group 6: Hydroxychloroquine + Azithromycin + Oseltamivir + Antibiotics + Lopinavir/ritonavir + Steroids + Interferon/ribavirin + Tocilizumab.

ARDS: Acute respiratory distress syndrome; MOF: Multiorgan failure; ALF: Acute liver failure; MV: Mechanical ventilation; ECMO: Extra-corporal membrane oxygenation; CRRT: Continuous renal replacement therapy; LOS: Length of stay; HCQ: Hydroxychloroquine; IFN: Interferon; RBV: Ribavirin; GI: Gastrointestinal; ICU: Intensive care unit.

Table 5 Association of gastrointestinal symptoms with individual drugs, n (%)

	Azithromycin (n = 538)	HCQ (n = 540)	*Antibiotics (n =* 493)**	*Steroids (n =* 248)**	*RBV (n =* 91)**	*Tocilizumab (n =* 236)**	*L/r (n =* 340)**	*Oseltamivir (n =* 510)**
Diarrhea	78 (14.50)	79 (14.63)	70 (14.20)	37 (14.92)	24 (26.37)P < 0.001^a	35 (14.83)	44 (12.94)	75 (14.71)
Nausea	160 (29.74)	165 (30.60)	147 (29.82)	74 (29.84)	26 (8.57)	66 (27.97)	111 (32.65)P = 0.049^a	153 (30.00)
Vomiting	148 (27.51)	154 (28.52)P = 0.009^a	135 (27.38)	68 (27.42)	22 (24.18)	64 (27.12)	107 (31.47)P = 0.004^a	140 (27.45)
Epigastric pain	57 (10.59)	60 (11.11)	54 (10.95)	29 (11.69)	13 (14.29)	24 (10.17)	43 (12.65)P = 0.048^a	55 (10.78)
Anorexia	55 (10.22)	58 (10.74)	50 (10.14)	30 (12.10)	16 (17.58)P = 0.022^a	28 (11.86)	41 (12.06)	56 (10.98)
Any GI symptoms	208 (38.66)	209 (38.70)	191 (38.74)	95 (38.31)	41 (45.05)	92 (38.98)	138 (40.59)	194 (38.04)

^aStatistically significant P value.

HCQ: Hydroxychloroquine; RBV: Ribavirin; L/r: Lopinavir/ritonavir; GI: Gastrointestinal

Table 6 Multivariate analysis of risk factors for severe coronavirus disease 2019 at presentation and clinical outcomes, n (%)

	Multivariate analysis
Risk factors	Adjusted odds ratio	P value
	Death
Age > 65 yr	7.53 (3.09-18.29)	< 0.001
	Disease severity at presentation
Hypertension	1.68 (1.08-2.60)	0.021
Diabetes mellitus	1.92 (1.28-2.87)	0.002
GI symptoms	1.66 (1.09-2.52)	0.017
Smoking	1.62 (1.01-2.63)	0.049
	ICU admission
Age > 65 yr	1.79 (1.13-2.83)	0.012
Sex	1.82 (1.05-3.15)	0.033
Fever	2.14 (1.24-3.69)	0.006
Shortness of breath	2.90 (1.99-4.24)	< 0.001
Hypertension	1.82 (1.17-2.84)	0.008
	Mechanical ventilation
Age > 65 yr	1.89 (1.94-2.99)	0.007
Sex	1.88 (1.02-3.45)	0.043
Fever	3.16 (1.63-6.09)	0.001
Shortness of breath	2.36 (1.57-3.55)	< 0.001
Hypertension	1.66 (1.05-2.62)	0.028
Vomiting	2.03 (1.10-3.75)	0.023

GI: Gastrointestinal; ICU: Intensive care unit.

Citation: Khan MU, Mushtaq K, Alsoub DH, Iqbal P, Ata F, Chaudhry HS, Iqbal F, Balaraju G, Maslamani MAA, Varughese B, Singh R, Ejji KA, Kaabi SA, Kamel YM, Butt AA. Digestive system involvement and clinical outcomes among COVID-19 patients: A retrospective cohort study from Qatar. World J Gastroenterol 2021; 27(46): 7995-8009
URL: https://www.wjgnet.com/1007-9327/full/v27/i46/7995.htm
DOI: https://dx.doi.org/10.3748/wjg.v27.i46.7995