Table 1.
Baseline characteristics, comorbidities, clinical illness severity, respiratory support at hospital admission; treatments and outcomes of patients stratified by subphenotypes
| Overall | Subphenotype 1 | Subphenotype 2 | p value | |
|---|---|---|---|---|
| Reason of hospital admission | ||||
| Respiratory failure, n (%) | 559 (100) | 156 (28) | 403 (72) | – |
| Baseline characteristics | ||||
| BMI, kg/m2; mean (standard deviation), N = 171 | 27.7 (4.6) | 27.4 (5.2) | 27.8 (4.3) | 0.572 |
| Sex, F (%) | 196 (35) | 58 (37) | 138 (34) | 0.514 |
| Time between admission and CT scan, days; median (IQR) | 0 (0;0) | 0 (0;0) | 0 (0;0) | 0.138 |
| Comorbidities | ||||
| COPD, n (%) | 28 (5) | 12 (8) | 16 (4) | 0.070 |
| Asthma, n (%) | 27 (5) | 7 (5) | 20 (5) | 0.814 |
| Congestive heart failure, n (%) | 26 (5) | 12 (8) | 14 (4) | 0.034 |
| Chronic kidney disease, n (%) | 37 (7) | 31 (20) | 6 (2) | < 0.001 |
| Chronic liver failure, n (%) | 3 (1) | 0 (0) | 3 (1) | 0.280 |
| Solid cancer, n (%) | 14 (3) | 6 (4) | 8 (2) | 0.207 |
| Hematologic malignancy, n (%) | 9 (2) | 1 (1) | 8 (2) | 0.257 |
| Immune mediated disease, n (%) | 20 (4) | 4 (3) | 16 (4) | 0.422 |
| Diabetes, n (%) | 97 (17) | 39 (25) | 58 (14) | 0.003 |
| Systemic hypertension, n (%) | 284 (51) | 99 (63) | 185 (46) | < 0.001 |
| Antihypertensive drugs, n (%) N = 549 | ||||
| ACE-inhibitors | 346 (63) | 81 (53) | 256 (67) | 0.004 |
| ARBs | 90 (16) | 27 (18) | 63 (16) | |
| Others/unknown | 113 (21) | 46 (30) | 67 (17) | |
| Pulmonary hypertension, n (%) | 3 (1) | 3 (2) | 0 (0) | 0.005 |
| Atrial fibrillation, n (%) | 57 (10) | 22 (14) | 35 (9) | 0.058 |
| OSAS, n (%) | 6 (1) | 2 (1) | 4 (1) | 0.766 |
| cPAP at home, n (%) | 4 (1) | 1 (1) | 3 (1) | 0.896 |
| Pacing, n (%) | 10 (2) | 6 (4) | 4 (1) | 0.022 |
| Any comorbidities, n (%) | 404 (72) | 128 (82) | 276 (69) | 0.001 |
| Clinical illness severity | ||||
| pH, mean (standard deviation) | 7.47 (0.05) | 7.45 (0.06) | 7.47 (0.04) | < 0.001 |
| PaO2/FiO2, mean (standard deviation), mmHg | 252 (103) | 188 (95) | 277 (95) | < 0.001 |
| HCO3−, mean (standard deviation), mEq/L | 23 (4) | 23 (4) | 23 (3) | 0.168 |
| D-dimer, mean (standard deviation), mg/L, n = 287 | 2.7 (5.9) | 4.5 (7.8) | 1.8 (4.6) | < 0.001 |
| Respiratory support, N = 559 | ||||
| Oxygen delivery, n (%) | ||||
| Room air | 367 (66) | 61 (39) | 306 (76) | < 0.001 |
| LFO | 189 (34) | 93 (60) | 96 (24) | |
| Non-invasive ventilation, n (%) | ||||
| cPAP | 2 (0) | 1 (1) | 1 (0) | |
| Pharmacological treatments | ||||
| Antivirals; N = 557 | 202 (36) | 47 (30) | 155 (39) | 0.060 |
| Antibiotic treatment; N = 556 | 491 (88) | 149 (96) | 342 (86) | < 0.001 |
| Steroids; N = 553 | 128 (23) | 39 (25) | 89 (22) | 0.483 |
| Hydroxycloroquine; N = 555 | 406 (73) | 131 (85) | 275 (69) | < 0.001 |
| Cloroquine phosphate; N = 554 | 48 (9) | 1 (1) | 47 (12) | < 0.001 |
| Immunoglobulins IV; N = 553 | 2 (0) | 0 (0) | 2 (1) | 0.377 |
| Tocilizumab; N = 553 | 30 (5) | 9 (6) | 21 (5) | 0.805 |
| Anakinra; N = 552 | 4 (1) | 1 (1) | 3 (1) | 0.897 |
| Thrombolysis; N = 553 | 2 (0) | 2 (1) | 0 (0) | 0.023 |
| Anticoagulation; N = 552 | 379 (69) | 135 (87) | 244 (62) | < 0.001 |
| Anticoagulant; N = 550 | ||||
| None | 149 (27) | 20 (13) | 129 (33) | < 0.001 |
| LMWH | 371 (68) | 128 (82) | 243 (62) | |
| UFH | 2 (0) | 1 (1) | 1 (0) | |
| Argatroban | 16 (3) | 4 (3) | 12 (3) | |
| Fondaparinux | 2 (0) | 0 (0) | 2 (1) | |
| Salicilic acid | 10 (2) | 3 (2) | 7 (2) | |
| Organ support techniques | ||||
| CRRT; N = 553 | 9 (2) | 5 (3) | 4 (1) | 0.064 |
| Complications | ||||
| All Bacterial overinfections; N = 556 | 57 (10) | 28 (18) | 29 (7) | < 0.001 |
| Lung overinfection; N = 556 | 33 (6) | 18 (12) | 15 (4) | < 0.001 |
| Blood overinfection; N = 555 | 17 (3) | 5 (3) | 12 (3) | 0.890 |
| Urinary tract overinfection; N = 555 | 9 (2) | 3 (2) | 6 (2) | 0.716 |
| Soft tissues overinfection; N = 555 | 4 (1) | 1 (1) | 3 (1) | 0.896 |
| Abdominal overinfection; N = 555 | 2 (0) | 1 (1) | 1 (0) | 0.486 |
| Stroke; N = 552 | 6 (1) | 2 (1) | 4 (1) | 0.773 |
| Venous thromboembolism; N = 552 | 7 (1) | 3 (2) | 4 (1) | 0.381 |
| Pulmonary thromboembolism; N = 552 | 9 (2) | 6 (4) | 3 (1) | 0.009 |
| Tracheostomy | 7 (1) | 2 (1) | 5 (1) | 0.969 |
| Outcomes | ||||
| MV duration (days); N = 49 | 14 (12) | 15 (15) | 13 (11) | 0.544 |
| Limitation of life sustaining measures; N = 549 | 132 (24) | 71 (46) | 61 (15) | < 0.001 |
| ICU admission—N = 59 | 59 (11) | 22 (14) | 37 (9) | 0.089 |
| ICU mortality—N = 59 | 35 (57) | 15 (63) | 20 (54) | 0.515 |
| ICU LOS; N = 57 | 17 (14) | 16 (14) | 18 (14) | 0.639 |
| Survivors; N = 23 | 22 (16) | 20 (22) | 23 (14) | 0.794 |
| Dead; N = 34 | 14 (10) | 14 (8) | 14 (12) | 0.997 |
| Hospital mortality | 180 (32) | 91 (58) | 89 (22) | < 0.001 |
| Hospital LOS; N = 554 | 13 (15) | 14 (13) | 13 (15) | 0.305 |
| Survivors; N = 371 | 14 (16) | 21 (15) | 13 (16) | < 0.001 |
| Dead; N = 180 | 10 (10) | 9 (7) | 12 (11) | 0.093 |
Differences between the 2 subphenotypes were assessed and reported in p value column. Continuous data are expressed as mean (standard deviation), categorical variables as count (relative frequency %). In the presence of missing data, sample size was reported
ACE angiotensin converting enzyme, ARB angiotensin receptor blockers, BMI body mass index, COPD chronic obstructive pulmonary disease, cPAP continuous positive airway pressure, ICU intensive care unit, LFO low-flow oxygen, LMWH low molecular weight heparin, LOS length of stay, OSAS obstructive sleep apnea syndrome, UFH unfractionated heparin