Table 1.
Overall Population and Cluster Characteristics
| Overall (N = 96) | Cluster 1 (n = 34) | Cluster 2 (n = 20) | Cluster 3 (n = 42) | P | |
|---|---|---|---|---|---|
| Demographics | |||||
| Age, y | 58 [53-67] | 57 [50-67] | 61 [55-67] | 60 [53-66] | .638 |
| BMI | 28 [23-31] | 25 [23-31] | 27 [26-31] | 28 [25-31] | .268 |
| Male | 69 (72) | 25 (74) | 18 (90) | 26 (62) | .068 |
| Underlying conditions | |||||
| Hypertension | 52 (55) | 16 (49) | 12 (60) | 24 (57) | .693 |
| Diabetes mellitus | 28 (30) | 10 (30) | 5 (25) | 13 (31) | .916 |
| Cardiovascular disease | 11 (12) | 5 (15) | 3 (15) | 3 (7) | .499 |
| Solid organ transplant | 10 (10.4) | 6 (17.6) | 3 (15.0) | 1 (2.4) | .048 |
| Past history of malignancy | 16 (16.8) | 12 (35.3) | 2 (10.0) | 2 (4.9) | .002 |
| Active malignancya | 6 (6.2) | 6 (17.6) | 0 (0) | 0 (0) | <.005 |
| Clinical characteristics | |||||
| SAPS-II score | 28 [21-39] | 29 [22-37] | 36 [25-49] | 25 [18-34] | .04 |
| SOFA score | 4 [2-7] | 5 [2.25-8] | 5.5 [2.75-8.25] | 2 [2-6] | .019 |
| Respiratory | 2 [2-3] | 2 [2-3] | 2 [2-4] | 2 [1.25-3] | .221 |
| Hemodynamic | 0 [0-3] | 0 [0-3] | 3 [0-3] | 0 [0-3] | .131 |
| Renal | 0 [0-1] | 0 [0-1] | 0.5 [0-1.25] | 0 [0-0] | .042 |
| Liver | 0 [0-0] | 0 [0-0] | 0 [0-0] | 0 [0-0] | NS |
| Neurologic | 0 [0-0] | 0 [0-0] | 0 [0-0] | 0 [0-0] | NS |
| Coagulation | 0 [0-0] | 0 [0-1] | 0 [0, 0] | 0 [0, 0] | .009 |
| Time from symptom onset, days | 8 [6-12] | 6 [3-12] | 7 [4-8] | 9 [5-12] | .12 |
| Oxygen flow on arrival, L/min | 9 [6-12] | 9 [6-10] | 12 [6-15] | 9 [6-12] | .292 |
| RR, breaths/min | 28 [23-34] | 29 [20-30] | 30 [25-35] | 28 [24-34] | .483 |
| Oxygenation strategies on day 1 | |||||
| Standard oxygen alone | 51 (53.1) | 18 (52.9) | 8 (40.0) | 25 (59.5) | .36 |
| HFNC | 30 (31.2) | 12 (35.3) | 6 (30.0) | 12 (28.6) | .846 |
| Mechanical ventilation | 15 (15.6) | 4 (11.8) | 6 (30.0) | 5 (11.9) | .173 |
| Biological markers | |||||
| LDH, U/L | 809 [634-908] | 696 [558-842] | 870 [799-935] | 850 [710-903] | .036 |
| D-dimers, μg/L | 1,360 [780-2,840] | 1,230 [730-1,960] | 1,780 [955-3,155] | 1,360 [820-2,740] | .646 |
| CRP, mg/L | 181 [84-261] | 132 [77-226] | 263 [133-322] | 179 [94-238] | .075 |
| Ferritin, μg/L | 1,272 [636-2,234] | 1,238 [523-2,272] | 1,658 [1,183-2,099] | 1,045 [641-1,644] | .128 |
| Cytokine release | |||||
| TNF⍺, pg/mL | 22.7 [18.7-28.0] | 18.2 [14.4-23.8] | 29.7 [23.4-36.7] | 22.2 [19.2-26.5] | <.001 |
| IL-1β, pg/mL | 0.44 [0.32-0.86] | 0.44 [0.32-0.59] | 1.01 [0.75-1.27] | 0.36 [0.32-0.52] | <.001 |
| IL-6, pg/mL | 74 [41-137] | 89 [54-147] | 135 [79-220] | 46.7 [29.7-76.5] | <.001 |
| IL-8, pg/mL | 50 [31-78] | 44 [28-59] | 57 [47-90] | 42 [31-74] | .048 |
| Lymphocytes typing | |||||
| Total lymphocytes, cells/mm3 | 790 [580-1,170] | 710 [550-960] | 750 [340-1,240] | 960 [720-1,380] | .023 |
| T lymphocytes, cells/mm3 | 539 [343-764] | 567 [370-752] | 344 [244-525] | 637 [392-799] | .087 |
| CD8+ T lymphocytes, cells/mm3 | 182 [114-269] | 235 [170-356] | 101 [67-201] | 177 [134-238] | .027 |
| CD4+ T lymphocytes, cells/mm3 | 332 [184-464] | 322 [162-395] | 186 [168-375] | 413 [239-539] | .016 |
| NK cells, cells/mm3 | 106 [76-153] | 93 [57-117] | 139 [94-299] | 103 [73-156] | .011 |
| B lymphocytes, cells/mm3 | 104 [54-184] | 49 [14-82] | 100 [65-130] | 183 [143-283] | <.001 |
| Gamma globulins, g/L | 9.1 [7.4-11.5] | 7.7 [6.9-8.9] | 8.8 [7.1-12.3] | 10.9 [9.1-12.0] | <.001 |
| HLA-DR/monocyte, count | 8,631 [6,828-13,962] | 7,712 [5,939-11,668] | 7,852 [6,701-10,265] | 1,1073 [8,533-16,559] | .144 |
| Complement pathway | |||||
| C3, mg/L | 1,305 [1,173-1,550] | 1,260 [1,150-1,540] | 1,230 [1,160-1,340] | 1,445 [1,243-1,630] | .072 |
| sC5b-9, ng/mL | 373 [270-471] | 292 [217-449] | 368 [330-442] | 392 [357-492] | .034 |
| SC5b-9 > 360, ng/mL | 43 (56) | 10 (35) | 9 (56) | 24 (75) | .006 |
| ICU outcome | |||||
| Time of follow-up, days | 15 [7-20.25] | 17 [12-21] | 13 [7-19] | 15 [7-19] | .609 |
| Mechanical ventilation | 53 (55) | 18 (53) | 15 (75) | 20 (48) | .123 |
| Noninvasive ventilation (NIV) | 4 (4.2) | 0 (0.0) | 1 (5.0) | 3 (7.1) | .338 |
| ECMO | 4 (4.3) | 1 (2.9) | 1 (5.3) | 2 (4.9) | NS |
| AKI in ICU | 42 (44) | 12 (35) | 15 (75) | 15 (36) | .007 |
| Renal replacement therapy | 13 (13.5) | 3 (8.8) | 5 (25.0) | 5 (11.9) | .269 |
| Venous thromboembolic events | 13 (13.5) | 3 (8.8) | 2 (10.0) | 8 (19.5) | .4 |
| In-ICU mortality | 29 (31) | 11 (32.4) | 11 (55) | 7 (17.5) | .015 |
Values are given in No. (%) or median [interquartile range (IQR)]. Univariate analysis according to cluster status was done using Fisher exact test for categorical variables, and Kruskal-Wallis test for continuous nonnormal variables. AKI was defined using the Kidney Disease Improving Global Outcome (KDIGO) classification. Mechanical ventilation status was defined as any requirement for mechanical ventilation during ICU stay. AKI = acute kidney injury; CRP = C-reactive protein; ECMO = extracorporeal membrane oxygenation; HFNC = high-flow nasal canula; LDH = lactate dehydrogenase; NIV = noninvasive ventilation; NK = natural killer; RR = respiratory rate; RRT = renal replacement therapy; SAPS-II = simplified acute physiology score (SAPS II); sC5b-9 = soluble membrane attack complex; SOFA = Sequential Organ Failure Assessment; TNF-⍺ = tumor necrosis factor-alpha.
Chemotherapy during the last 6 months.