Use of Proton-Pump Inhibitor Is Not Associated with Adverse Clinical Outcomes in COVID-19 Patients: A Territory-Wide Cohort Study

Table 1

Baseline clinical characteristics of patients with SARS-CoV-2 infection/COVID-19 who were or were not PPI users before multiple imputation.

Clinical characteristics	All	PPI nonuser	PPI user	value
Age (years)				<0.001
Male gender (, %)	4,207 (48.5)	3,915 (48.4)	292 (50.4)	0.335
Comorbidities (, %)
Cardiovascular diseases	2,139 (24.7)	1,758 (21.7)	381 (65.8)	<0.001
Hypertension	2,030 (23.4)	1,669 (20.6)	361 (62.3)	<0.001
Ischemic heart disease	226 (2.6)	106 (1.3)	120 (20.7)	<0.001
Cardiac dysrhythmias	243 (2.8)	172 (2.1)	71 (12.3)	<0.001
Heart failure	69 (0.8)	32 (0.4)	37 (6.4)	<0.001
Digestive diseases	831 (9.6)	673 (8.3)	158 (27.3)	<0.001
Peptic ulcer	107 (1.2)	61 (0.8)	46 (7.9)	<0.001
Chronic liver disease	494 (5.7)	439 (5.4)	55 (9.5)	<0.001
Liver failure, cirrhosis, or cirrhotic complications	45 (0.5)	29 (0.4)	16 (2.8)	<0.001
Biliary disease	116 (1.3)	73 (0.9)	43 (7.4)	<0.001
Gastrointestinal haemorrhage	220 (2.5)	153 (1.9)	67 (11.6)	<0.001
Diabetes mellitus	1,348 (15.5)	1,104 (13.6)	244 (42.1)	<0.001
Malignant tumour	263 (3.0)	201 (2.5)	62 (10.7)	<0.001
Nervous system diseases	308 (3.6)	228 (2.8)	80 (13.8)	<0.001
Cerebrovascular events	216 (2.5)	153 (1.9)	63 (10.9)	<0.001
Other nervous system diseases ^†	137 (1.6)	104 (1.3)	33 (5.7)	<0.001
Respiratory disease ^‡	307 (3.5)	247 (3.1)	60 (10.4)	<0.001
Kidney disease	150 (1.7)	90 (1.1)	60 (10.4)	<0.001
Human immunodeficiency virus infection	12 (0.1)	12 (0.1)	0 (0)	1.000
Nosocomial infection	224 (2.6)	185 (2.3)	39 (6.7)	<0.001
Laboratory results
Creatinine (μmol/L)	69 (58-83)	68 (57-82)	75 (63-100)	<0.001
Urea (mmol/L)				<0.001
Sodium (mmol/L)				0.001
Potassium (mmol/L)				0.385
Albumin (g/L)				<0.001
Alanine aminotransferase (U/L)				0.691
Total bilirubin (μmol/L)				0.021
Lactate dehydrogenase (U/L)				<0.001
C-reactive protein (mg/dL)				<0.001
International normalised ratio				0.026
Haemoglobin (g/dL)				<0.001
WCC (×10^9/L)				0.138
WCC </L (, %)	840 (10.0)	784 (10.0)	56 (9.7)	0.806
Lymphocyte (×10^9/L)				<0.001
Lymphocyte </L (, %)	2,308 (27.5)	2,074 (26.6)	234 (40.5)	<0.001
Neutrophil (×10^9/L)				<0.001
Neutrophil-lymphocyte ratio				<0.001
Platelet (×10^9/L)				<0.001
Platelet </L (n, %)				<0.001
SpO2 (%)				0.001
Respiratory rate (/min)				0.142
Treatment before baseline (, %)
H2RA	1,027 (11.8)	843 (10.4)	184 (31.8)	<0.001
NSAID	774 (8.9)	547 (6.8)	227 (39.2)	<0.001
Aspirin	432 (5.0)	236 (2.9)	196 (33.9)	<0.001
Other antiplatelets ^§	95 (1.1)	33 (0.4)	62 (10.7)	<0.001
Anticoagulants	180 (2.1)	111 (1.4)	69 (11.9)	<0.001
Antihypertensive drugs ^¶	1,554 (17.9)	1,214 (15.0)	340 (58.7)	<0.001
Statins	1,052 (12.1)	780 (9.6)	272 (47.0)	<0.001
Treatment during follow-up (, %)
Antiviral treatment
Ribavirin	1,878 (21.6)	1,713 (21.2)	165 (28.5)	<0.001
Lopinavir-ritonavir	1,814 (20.9)	1,662 (20.5)	152 (26.3)	0.001
Interferon beta	2,947 (34.0)	2,638 (32.6)	309 (53.4)	<0.001
Oseltamivir	81 (0.9)	76 (0.9)	5 (0.9)	0.856
Ganciclovir	0 (0)	0 (0)	0 (0)	—
Aciclovir/famciclovir/valaciclovir	9 (0.1)	8 (0.1)	1 (0.2)	0.463
Antibiotic treatment	2,626 (30.3)	2,321 (28.7)	305 (52.7)	<0.001
Antifungal treatment	8 (0.1)	4 (0.05)	4 (0.7)	0.001
Corticosteroid	1,180 (13.6)	993 (12.3)	187 (32.3)	<0.001
(i) Dexamethasone	1,087 (12.5)	920 (11.4)	167 (28.8)	<0.001
(ii) Hydrocortisone	97 (1.1)	78 (1.0)	19 (3.3)	<0.001
(iii) Prednisolone	58 (0.7)	43 (0.5)	15 (2.6)	<0.001
(iv) Methylprednisolone	5 (0.1)	5 (0.1)	0 (0)	1.000
Intravenous immunoglobulin therapy	4 (0.05)	3 (0.04)	1 (0.2)	0.241
Clinical outcomes in 60 days (n, %)
Primary endpoint	500 (5.8)	398 (4.9)	102 (17.6)	<0.001
(i) Death	144 (1.7)	97 (1.2)	47 (8.1)	<0.001
(ii) Intensive care unit admission	407 (4.7)	338 (4.2)	69 (11.9)	<0.001
(iii) Invasive mechanical ventilation	181 (2.1)	148 (1.8)	33 (5.7)	<0.001
Follow-up duration (days)	11 (7-16)	11 (7-16)	12 (7-18)	0.001

All comorbidities were represented as binary parameters. Categorical variables were presented as number (percentage). Creatinine, alanine aminotransferase, and follow-up duration were expressed in median (interquartile range), whereas other continuous variables were expressed in . Qualitative and quantitative differences between subgroups were analysed by Chi-square or Fisher’s exact tests for categorical parameters and Student’s -test or Mann–Whitney test for continuous parameters, as appropriate. ^†Other nervous system disease was defined by ICD-9-CM diagnosis codes for inflammatory diseases of the central nervous system (ICD-9-CM codes: 320-327), hereditary and degenerative diseases of the central nervous system (ICD-9-CM codes: 330-337), and other disorders of the central nervous system (ICD-9-CM codes: 340-345). ^‡Respiratory system disease was defined by ICD-9-CM diagnosis codes for pneumonia other than SARS-related pneumonia (ICD-9-CM codes: 480-487·0) in previous 3 months, chronic obstructive pulmonary disease and allied conditions (ICD-9-CM codes: 490-496), pneumoconioses and other lung diseases due to external agents (ICD-9-CM codes: 500-508) in previous 3 months, and other diseases of respiratory system (ICD-9-CM codes: 510-519) in previous 3 months. ^§Other antiplatelet included clopidogrel, dipyridamole, eptifibatide, and ticagrelor. ^¶Antihypertensive drugs included angiotensin-converting-enzyme inhibitors, angiotensin receptor beta blockers, calcium channel blockers, and thiazide diuretics. H2RA: H2 receptor antagonist; NSAID: nonsteroidal anti-inflammatory drug; PPI: proton-pump inhibitor; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SpO₂: peripheral oxygen saturation; WCC: white cell counts.