The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients

Table 1

Baseline demographic, clinical, and laboratory characteristics, inpatient treatment, and outcome comparison in regard to RASi exposure.

	Total; n = 279	RASi; n = 133	Non-RASi; n = 146
Demographics
Male sex	159 (57)	77 (57.9)	82 (56.2)	0.771
Age, years	69 ± 26	76 ± 21	64 ± 30	<0.001
Caucasian ethnic	223/269 (82.9)	113/128 (88.3)	110/141 (78.0)	0.026
Comorbid conditions
High blood pressure	185 (66.3)	127 (95.5)	58 (39.7)	<0.001
Dyslipidaemia	93 (33.3)	62 (46.6)	31 (21.2)	<0.001
Diabetes mellitus	76 (27.2)	53 (39.9)	23 (15.8)	<0.001
Cardiovascular disease^•	74 (26.5)	48 (36.1)	26 (17.8)	0.001
Obesity^+	71 (25.5)	43 (32.6)	28 (19.2)	0.011
Chronic kidney disease^♦	51 (18.4)	31 (23.3)	20 (13.8)	0.041
Cerebrovascular disease^°	49 (17.6)	24 (18.2)	25 (17.1)	0.817
Chronic obstructive pulmonary disease	37 (13.3)	21 (15.8)	16 (11)	0.235
Active cancer^⋄	23 (8.2)	9 (6.8)	14 (9.6)	0.392
Asthma	15 (5.4)	8 (6.0)	7 (4.8)	0.652
Rheumatic/autoimmune disease^∴	15 (5.4)	7 (5.3)	8 (5.5)	0.936
HIV/AIDS	5 (1.8)	1 (0.8)	4 (2.7)	0.211
Other antihypertensive drugs
Diuretic	95 (34.1)	70 (52.6)	25 (17.1)	<0.001
Calcium channel blocker	77 (27.6)	56 (42.1)	21 (14.4)	<0.001
Beta-blocker	62 (22.3)	36 (27.1)	26 (17.8)	0.063
Signs and symptoms
Fever	206/277 (74.4)	97/132 (74.5)	109/145 (75.2)	0.748
Cough	185/276 (67.0)	77/131 (58.8)	108/145 (74.5)	0.006
Dyspnoea	166/277 (59.9)	82/132 (62.1)	84/145 (57.9)	0.477
Asthenia	146/275 (53.1)	65/130 (50.0)	81/145 (55.9)	0.331
Myalgia	84/273 (30.8)	35/130 (26.9)	49/143 (34.3)	0.189
Diarrhoea	64/276 (23.2)	31/131 (23.7)	33/145 (22.8)	0.859
Headache	40/273 (14.7)	10/130 (7.7)	30/143 (21)	0.002
Chest pain	37/273 (13.6)	18/130 (13.9)	19/143 (13.3)	0.893
Anorexia	33/273 (12.1)	13/130 (10.0)	20/143 (14)	0.313
Nausea/vomiting	32/276 (11.6)	15/131 (11.5)	17/145 (11.7)	0.943
Ageusia	21/271 (7.8)	5/129 (3.9)	16/142 (11.3)	0.024
Sore throat	18/272 (6.6)	8/129 (6.2)	10/143 (7)	0.813
Anosmia	17/271 (6.3)	4/129 (3.1)	13/142 (9.2)	0.046
Rhinorrhoea	8/273 (2.9)	4/129 (3.1)	4/144 (2.8)	1.000
Abdominal pain	8/274 (2.9)	2/130 (1.5)	6/144 (4.2)	0.287
Arthralgia	2/273 (0.7)	1/130 (0.8)	1/143 (0.7)	1.000
Laboratory results
Hb, M: <13.0 g/dL/F: <12.0 g/dL	90/278 (32.4)	44/132 (33.3)	46 (31.5)	0.745
Leucocyte, >11000 × 10^6/L	40/278 (14.4)	21/132 (15.9)	19 (13.0)	0.492
Neutrophil, >7500 × 10^6/L	75/278 (27)	39/132 (29.6)	36 (24.7)	0.359
Lymphocyte, <1000 × 10^6/L	126/276 (45.7)	65/132 (49.2)	61 (42.4)	0.252
500–1000 × 10^6/L	103/276 (37.3)	56/132 (42.4)	47/144 (32.6)	0.093
≤500 × 10^6/L	23/276 (8.3)	9/132 (6.8)	14/144 (9.7)	0.383
Absolute value, ×10^6/L	1060 ± 600	1050 ± 630	1060 ± 560	0.761
Monocyte, >1000 × 10^6/L	10/272 (3.7)	6/130 (4.6)	4/142 (2.8)	0.527
Platelet count, <150 × 10^9/L	67/276 (24.3)	33/131 (25.2)	34/145 (23.5)	0.736
100–150 × 10^9/L	58/276 (21.0)	30/131 (22.9)	28/145 (19.3)	0.465
≤100 × 10^9/L	9/176 (3.3)	3/131 (2.3)	6/145 (4.1)	0.506
D-dimer, >0.25 µg/mL	190/257 (73.9)	96/125 (76.8)	94/132 (71.2)	0.308
≤0.5 µg/mL	78/257 (30.4)	40/125 (32.0)	38/132 (28.8)	0.576
0.5–1 µg/mL	58/257 (22.6)	25/125 (20.0)	33/132 (25.0)	0.338
≥1 µg/mL	54/257 (21.0)	31/125 (24.8)	23/132 (17.4)	0.147
Acute kidney injury	94/269 (34.9)	54/127 (42.5)	40/142 (28.2)	0.014
Sodium, <135 mmol/L	85/275 (30.9)	47/132 (35.6)	38/143 (26.6)	0.105
AST, >40 U/L	103/274 (37.6)	47/130 (36.2)	56/144 (38.9)	0.641
ALT, >41 U/L	60/274 (21.9)	23/130 (17.7)	37/144 (25.7)	0.110
Total bilirubin, >1.2 mg/dL	9/242 (3.7)	6/115 (5.2)	3/127 (2.4)	0.315
Creatin kinase, >300 U/L	53/246 (21.5)	28/119 (23.5)	25/127 (19.7)	0.464
LDH, >250 U/L	223/272 (82)	100/130 (76.9)	123/142 (86.6)	0.038
Albumin, <3 g/dL	27/215 (12.6)	12/102 (11.8)	15/113 (13.3)	0.739
Troponin T, >14 ng/L	121/226 (53.5)	78/112 (69.6)	43/114 (37.7)	<0.001
CRP, >5 mg/dL	208/278 (74.8)	90/132 (68.2)	118 (80.8)	0.015
≤10 mg/dL	83/278 (29.9)	36/132 (27.3)	47 (32.2)	0.371
10–20 mg/dL	76/278 (27.3)	31/132 (23.5)	45 (30.8)	0.170
≥20 mg/dL	49/278 (17.6)	22/132 (16.7)	27 (18.5)	0.690
Absolute value, mg/dL	9.3 ± 12.4	7.9 ± 12.5	9.8 ± 11.9	0.018
Procalcitonin, >2 ng/mL	18/261 (6.9)	10/125 (8.0)	8/136 (5.9)	0.626
Ferritin, >300 ng/mL	158/183 (86.3)	71/85 (83.5)	87/98 (88.8)	0.303
300–1000 ng/mL	85/183 (46.5)	43/85 (50.6)	42/98 (42.9)	0.296
>1000 ng/mL	73/183 (39.9)	28/85 (32.9)	45/98 (45.9)	0.074
Absolute value, ng/mL	789.0 ± 1104.0	675.0 ± 935.0	912.0 ± 1148.0	0.171
IL-6, >40 pg/mL	46/76 (60.5)	16/29 (55.2)	30/47 (63.8)	0.453
Absolute value, pg/mL	54.0 ± 73.0	51.4 ± 82.6	54.0 ± 53.5	0.531
Inpatient treatment
Hydroxychloroquine	143/271 (52.8)	74/128 (57.8)	69/143 (48.3)	0.116
Antiviral therapy (total)	193/270 (71.5)	93/127 (73.2)	100/143 (69.9)	0.549
Lopinavir/ritonavir	177/270 (65.6)	86/127 (67.7)	91/143 (63.6)	0.481
Remdesivir	21/270 (7.8)	9/127 (7.1)	12/143 (8.4)	0.689
Antibiotics	135/273 (49.5)	62/129 (48.1)	73/144 (50.7)	0.664
Tocilizumab	15/272 (5.5)	5/129 (3.9)	10/143 (7)	0.298
Steroids	78/269 (29.0)	35/127 (27.6)	43/142 (30.3)	0.623
Timeframes^×
Time from disease onset to admission, days	5 ± 4	4 ± 4	6 ± 5	0.041
Time from disease onset to outcome, days	17 ± 12	17 ± 14	17 ± 12	0.792
Time from admission to outcome, days	10 ± 13	11 ± 13	10 ± 10.5	0.669
Outcomes
Death	48/277 (17.3)	25/132 (18.9)	23/145 (15.9)	0.499
Time from disease onset to death, days	12 ± 22	12 ± 19	13 ± 22	0.732
Time from admission to death, days	7.5 ± 16	8 ± 14	7 ± 18	0.959
ARDS/ALI	87/269 (32.3)	43/128 (33.6)	44/141 (31.2)	0.676
Time from disease onset to ARDS, days	9 ± 7	7 ± 5	11 ± 6	0.002
Time from admission to ARDS, days	4 ± 5	3 ± 5	5 ± 5	0.166
ICU	89 (31.9)	44 (33.1)	45 (30.8)	0.686
Time from disease onset to ICU, days	8 ± 5	7 ± 5	8 ± 3.5	0.044
Time from admission to ICU, days	2 ± 3	1.5 ± 3	2 ± 1	0.939
Duration, days	12 ± 25	12 ± 23	14 ± 29	0.384
IMV	58 (20.8)	28 (21.1)	30 (20.6)	0.917
Time from disease onset to IMV, days	8 ± 5	6 ± 5	9 ± 4	0.002
Time from admission to IMV, days	2 ± 4	2 ± 4	3 ± 3	0.126
Duration, days	16 ± 21	12.5 ± 31	20 ± 19	0.593

Data are shown as number (%) for categorical variables and median ± interquartile range for continuous variables. The denominators of patients who were included in the analysis are provided if they differed from the overall numbers within the group. ^•Cardiovascular disease included the following: aortic aneurysm disease, cardiomyopathy of any cause, coronary artery disease, heart failure of any cause, heart valve disease, peripheral artery disease, and pulmonary hypertension. ⁺Obesity was defined as body mass index equal to or higher than 30 kg/m². ^♦Chronic kidney disease was diagnosed according to the Kidney Disease: Improving Global Outcomes position statement. ^°Cerebrovascular disease included the following: ischemic and/or haemorrhagic stroke and cerebral microvascular disease. ^⋄Cancer included any type of active solid and/or haematological cancer under active surveillance and/or treatment. ^∴Rheumatic/autoimmune disease included the following: rheumatoid arthritis, systemic lupus erythematosus, and psoriatic arthritis Fever was defined as tympanic temperature of at least 38.0°C. Acute kidney injury was diagnosed according to Acute Kidney Injury Network criteria. ^×The outcome date is the time the patient died or was clinically discharged (see Materials and Methods section). ALT, alanine aminotransferase; ARDS/ALI, acute respiratory distress syndrome/acute lung injury; AST, aspartate aminotransferase; CRP, c-reactive protein; F, female; Hb, haemoglobin; HIV/AIDS, human immunodeficiency virus/acquired immunodeficiency syndrome; ICU, intensive care unit; IL-6, interleukin 6; IMV, invasive mechanical ventilation; M, male; RASi, renin-angiotensin system inhibitors.