Table 3.
Summary of patient characteristics by latent class analysis subtype assignment
| Subtype 1 (N = 292) |
Subtype 2 (N = 108) |
P-value* | |
|---|---|---|---|
| Variables included in LCA model | |||
| Age | 57.7 ± 13.8 | 65.7 ± 13.5 | < 0.0001 |
| Male sex | 192 (66%) | 75 (69%) | 0.56 |
| BMI (median (IQR)) | 32 (28 to 37) | 32 (27 to 38) | 0.47 |
| Race | 0.91 | ||
| Not White or Caucasian | 88 (30%) | 30 (28%) | |
| White or Caucasian | 157 (54%) | 57 (53%) | |
| Unknown | 47 (16%) | 21 (19%) | |
| Respiratory support | < 0.0001 | ||
| ≤ 15 LPM oxygen | 32 (11%) | 10 (9%) | |
| > 15 LPM oxygen | 204 (70%) | 51 (47%) | |
| Noninvasive mechanical ventilation | 30 (10%) | 10 (9%) | |
| Invasive Mechanical ventilation | 26 (9%) | 36 (33%) | |
| Labs† | |||
| Platelets (109/L) | 275 ± 91 | 225 ± 84 | < 0.0001 |
| Bicarbonate (mmol/L) | 25.1 ± 5.8 | 21.8 ± 3.3 | < 0.0001 |
| Hematocrit (%) | 40 ± 5 | 36 ± 6 | < 0.0001 |
| Bilirubin (mg/dL) | 0.5 (0.4 to 0.7) | 0.6 (0.4 to 0.9) | 0.13 |
| Creatinine (mg/dL) | 0.8 (0.7 to 1) | 1.4 (1.1 to 2.3) | < 0.0001 |
| WBC (109/L) | 8.7 (6.2 to 11.9) | 10.9 (7.7 to 14.9) | 0.0002 |
| Neutrophil:Lymphocyte | 8.9 (5.7 to 14.9) | 14.9 (8.8 to 27.3) | < 0.0001 |
| PTT (s) | 28.7 (26 to 32) | 33 (28.3 to 45.1) | < 0.0001 |
| CRP (mg/L) | 54.3 (13.7 to 129) | 108 (21 to 169) | 0.01 |
| BNP (pg/mL) | 71 (32 to 177) | 563 (174 to 1477) | < 0.0001 |
| Biomarkers (median (IQR)) | |||
| SARS-CoV-2 viral antigen protein (pg/mL) | 732 (81 to 5,918) | 1,358 (123 to 13,784) | 0.01 |
| Protein C (% normal) | 118 (95 to 140) | 89 (66 to 109) | < 0.0001 |
| PAI-1 (ng/mL) | 6.5 (4.4 to 9.3) | 6.6 (4.7 to 13.3) | 0.17 |
| ICAM-1 (pg/mL) | 660,243 (424,368 to 940,689) | 724,537 (485,815 to 921,318) | 0.44 |
| sTNFR-1 (pg/mL) | 2,492 (1,851 to 3,259) | 4,757 (3,605 to 6,627) | < 0.0001 |
| IL-6 (pg/mL) | 15.5 (6.3 to 61.2) | 28.9 (12.8 to 72.7) | < 0.0001 |
| IL-8 (pg/mL) | 11.4 (7.0 to 17.7) | 14.8 (8.8 to 26.5) | 0.0002 |
| Ang-2 (pg/mL) | 1,616 (1,035 to 2,552) | 3,142 (1,948 to 5,272) | < 0.0001 |
| sRAGE (pg/mL) | 5,965 (3,272 to 10,643) | 12,323 (7,368 to 18,280) | < 0.0001 |
| IP-10 (pg/mL) | 394 (175 to 646) | 850 (364 to 1,870) | < 0.0001 |
| VEGF (pg/mL) | 42.7 (21.6 to 82.8) | 28.2 (15.7 to 52.2) | 0.0003 |
| MMP-8 (pg/mL) | 2,239 (1,302 to 4,046) | 3,540 (1,990 to 6,337) | < 0.0001 |
| SP-D (pg/mL) | 15,883 (7,667 to 26,658) | 20,851 (9,970 to 38,126) | 0.005 |
| Ang-1 (pg/mL) | 8,208 (4,875 to 15,454) | 5,745 (2,742 to 11,023) | 0.0001 |
| IL-18 (pg/mL) | 401 (310 to 543) | 544 (412 to 703) | < 0.0001 |
| Variables not included in LCA model | |||
| Time from symptom onset, days | 8.8 ± 3.7 | 9.0 ± 5.3 | 0.70 |
| Dexamethasone ≥ 6 mg‡ | 282 (97%) | 105 (97%) | 0.99 |
| Other COVID-19 treatments | |||
| Tocilizumab | 56 (19%) | 12 (11%) | 0.08 |
| Convalescent plasma | 13 (5%) | 7 (7%) | 0.57 |
| Inhaled nitric oxide | 24 (8%) | 12 (11%) | 0.48 |
| Epoprostenol | 54 (19%) | 24 (22%) | 0.49 |
| Neuromuscular blockade | 82 (28%) | 42 (39%) | 0.05 |
| Baricitinib | 8 (3%) | 0 | 0.11 |
| Investigational arm | 0.08 | ||
| Apremilast | 20 (7%) | 11 (10%) | |
| Aviptadil | 15 (5%) | 5 (5%) | |
| Celecoxib/Famotidine | 16 (5%) | 2 (2%) | |
| Cenicriviroc | 31 (11%) | 12 (11%) | |
| Control | 101 (35%) | 41 (38%) | |
| Cyclosporine | 9 (3%) | 0 | |
| Cyproheptadine | 5 (2%) | 1 (1%) | |
| IC14 | 30 (10%) | 10 (9%) | |
| Icatibant | 24 (8%) | 14 (13%) | |
| Narsoplimab | 19 (7%) | 3 (3%) | |
| Pulmozyme | 18 (6%) | 3 (3%) | |
| Razuprotafib | 4 (1%) | 6 (6%) | |
| 28-day mortality | 57 (20%) | 44 (41%) | < 0.0001 |
| 60-day mortality | 69 (24%) | 49 (45%) | < 0.0001 |
Numbers are presented as n(%) or mean ± SD unless stated otherwise
Ang = angiopoietin; BMI = body mass index; BNP = brain natriuretic peptide; CRP = C reactive protein; ICAM = intercellular adhesion molecule; IL = interleukin; IP = interferon-gamma induced protein; IQR = interquartile range. MMP = matrix metalloproteinase; PAI = plasminogen activator inhibitor; PTT = partial thromboplastin time; SP-D = surfactant protein D; sRAGE = soluble receptor for advanced glycation end products; sTNFR = soluble tumor necrosis factor receptor; TREM = triggering receptor expressed on myeloid cells; VEGF = vascular endothelial growth factor; WBC = white blood cell.
*Determined via Welch’s t-test for normally distributed continuous variables, Wilcoxon rank-sum for non-normally distributed continuous variables, and Chi-squared test or Fisher’s exact test for categorical variables
†Presented as mean ± SD or median(IQR) if variable demonstrated a skewed distribution
‡Completed course of steroid therapy prior to trial enrollment or receiving dexamethasone at the time of trial enrollment