Article Figures & Data
- Figure 1
Subject flow diagram for the derivation and test sets.
- Figure 2
Risk prediction of progression to critical disease status by 10 days post admission. (A) Receiver operating curve for best multivariable logistic regression and subcomponent models. The best multivariate model consists of lymphocyte (%) at baseline and the change in albumin from baseline to nadir. The triangle indicates the sensitivity (0.78) and specificity (0.71) at a probability cut-off at the event rate of 0.18. (B) Predicted risk based on the best multivariable logistic model with baseline lymphocyte (%) and delta albumin (change from baseline to lowest level within 5 days, g/dL). Predicted risk above 0.18 (dashed line) indicates high risk for progression to critical disease (ie, a patient with a −1 g/dL drop in albumin from baseline and baseline lymphocyte of 20% has a high risk probability of 0.34 (>0.18) of progression to critical disease). AUC, area under the receiver-operator characteristic curve.
- Figure 3
Association of the decrease in mean albumin from baseline within 7 days postadmission. (A,B) Observed subject-specific profiles by patients who progressed to (A) critical disease and (B) those who did not with an overall mean between subsequent albumin change from baseline measures. (C) Predicted decrease from baseline and rate of change in albumin by time from admission and progression to critical disease subgroups. The change in albumin from baseline decreases by 0.06 g/dL (0.02, 0.10; p=0.003) per day faster in the critical progression group compared with those who do not progress. In fact, the mean change from baseline in albumin does not decrease significantly from the initial change following admission in the non-progression group (slope: −0.02 (–0.03, 0.01); p=0.01) compared with a rate of change of –0.08 (−0.11 to –0.04) g/dL in the progression group. (D) Association of change from baseline to nadir albumin within 5 days with progression to critical disease status. The median fall in albumin is significantly larger in patients who progress to critical disease (–0.8 (–1.1, –0.5) vs –0.5 (–0.7, –0.3) g/dL; p<0.001).
- Table 1
Baseline results
Variable Disease severity on admission P value Moderate Serious Critical (n=59) (n=34) (n=10) Demographics Age (years) 58.3 (50.0 to 65.1) 52.5 (48.9 to 70.5) 48.8 (40.3 to 70.3) 0.69 BMI (kg m-2) 30.7 (27.3 to 35.4) 31.0 (24.7 to 36.5) 35.0 (29.5 to 38.6) 0.52 Ethnicity, Hispanic or Latino 13 (22.0%) 9 (26.5%) 4 (40%) 0.47 Male, gender 30 (50.9%) 26 (76.5%) 5 (50%) 0.04 Race 0.74 Black or African American 22 (37.3%) 10 (29.4%) 3 (30%) White or Caucasian 30 (50.9%) 22 (64.7%) 6 (60%) Other 7 (11.9%) 2 (5.9%) 1 (10%) Clinical presentation Blood pressure, systolic (mm Hg) 131 (116 to 148) 129 (119 to 147) 128 (114 to 132) 0.74 Blood pressure, diastolic (mm Hg) 75 (69 to 86) 78 (69 to 88) 65 (56 to 69) 0.04 Clinical Score 3 (3 to 5) 4 (3 to 5) 3 (2 to 4) 0.61 Respiratory rate 20 (18 to 20) 20 (18 to 26) 23 (19 to 25) 0.07 SpO2 (%) 97 (95 to 98) 93 (90 to 94) 89 (87 to 94) <0.001 Comorbidities Comorbidity Score 1 (1 to 3) 2 (1 to 2) 2 (1 to 2) 0.96 Asthma 8 (13.6%) 2 (5.9%) 0 (0%) 0.36 CAD 5 (8.5%) 3 (8.8%) 2 (20%) 0.47 Cancer 8 (13.6%) 2 (5.9%) 0 (0%) 0.36 COPD 6 (10.2%) 1 (2.9%) 0 (0 %) 0.41 Diabetes 19 (32.2%) 12 (35.3%) 3 (30%) 0.95 Hypertension 36 (61.0%) 17 (50.0%) 6 (60%) 0.61 Renal disease 9 (15.3%) 9 (26.5%) 0 (0%) 0.14 Smoker 15 (25.4%) 13 (38.2%) 4 (40.0%) 0.36 Laboratory features Albumin (on admission) (g/dL) 3.4 (3.2 to 3.9) 3.6 (3.0 to 3.9) 2.8 (2.3 to 3.3) 0.02 Albumin change (baseline to nadir) (g/dL) −0.5 (–0.7 to −0.4) −0.6 (−1.0 to –0.4) −0.7 (−1.0 to −0.4) 0.18 Alkaline phosphatase (U/L) 81 (61 to 103) 78 (55 to 96) 70 (54 to 85) 0.66 ALT (U/L) 32 (23 to 59) 33 (27 to 48) 44 (37 to 63) 0.79 AST (U/L) 39 (23 to 58) 41 (29 to 55) 60 (41 to 134) 0.23 BNP (pg/mL) 51 (18 to 118) 48 (22 to 124) 82 (48 to 129) 0.61 Creatinine (mg/dL) 1.0 (0.5 to 3.0) 1.5 (1.0 to 2.0) 1.5 (1.0 to 2.0) 0.96 C reactive protein (mg/dL) 5.9 (2.5 to 10.1) 11.1 (4.0 to 16.2) 16.2 (6.8 to 17.2) 0.03 Ferritin (ng/mL) 360 (166 to 707) 531 (302 to 1183) 761 (210 to 1682) 0.27 Lymphocytes (%) 20 (13 to 29) 12 (9 to 19) 12 (9 to 18) 0.006 Neutrophils (%) 69 (61 to 79) 74 (70 to 85) 80 (72 to 84) 0.007 Admission details DNAR status 3 (5.1%) 2 (5.9%) 1 (10.0%) 0.63 ICU admission 20 (33.9%) 19 (55.9%) 10 (100%) <0.001 Critical outcomes Invasive mechanical ventilation 4 (6.8%) 14 (41.2%) 6 (60.0%) <0.001 Multiorgan failure 5 (8.5%) 13 (38.2%) 7 (70%) <0.001 Heart failure 3 (5.1%) 9 (26.5%) 6 (60%) <0.001 Hepatic failure 5 (8.5%) 3 (8.8%) 1 (10%) 1.00 Kidney failure 3 (5.1%) 7 (20.6%) 3 (30.0%) 0.01 Respiratory failure 7 (11.9%) 15 (44.1%) 7 (70%) <0.001 Shock 4 (7.0%) 9 (25.0%) 10 (100%) <0.001 Mortality, inpatient 4 (6.8%) 7 (20.6%) 5 (50%) 0.003 ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BNP, B-type natriuretic peptide; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; DNAR, do not attempt resuscitation; ICU, intensive care unit; NAA, nucleic acid amplification test; SpO2, pulse oximeter oxygen saturation.
- Table 2
Comparison of demographic, clinical, and laboratory factors by progression of disease
Variable Disease progression P value Remained non-critical (n=75) Progressed to critical (n=18) Demographics Age (years) 57 (49 to 65) 60 (52 to 69) 0.48 BMI (kg m-2) 30.9 (26.9 to 35.9) 30.9 (24.6 to 35.5) 0.67 Ethnicity, Hispanic or Latino 17 (22.7%) 5 (27.8%) 0.76 Male gender 42 (56.0%) 14 (77.8%) 0.15 Race 0.39 Black or African American 28 (37.3%) 4 (22.2%) White or Caucasian 39 (52.0%) 13 (72.2%) Other 8 (10.7%) 1 (5.6%) Admission clinical presentation Blood pressure, systolic (mm Hg) 129 (116 to 144) 142 (123 to 155) 0.27 Blood pressure, diastolic (mm Hg) 76 (68 to 87) 81 (73 to 85) 0.51 Clinical Score 3 (3 to 5) 4 (3 to 4) 0.60 Anorexia 11 (14.7%) 7 (38.9%) 0.04 Chest pain 13 (17.3%) 0 (0%) 0.07 Cough 58 (77.3%) 16 (88.9%) 0.35 Diarrhea 20 (26.7%) 3 (16.7%) 0.55 Fever 61 (81.3%) 14 (77.8%) 0.74 Headache 12 (16.0%) 3 (16.7%) 1.00 Myalgia 22 (29.3%) 7 (38.9%) 0.62 Rash 0 (0%) 1 (5.6%) 0.19 Shortness of breath 53 (70.7%) 12 (66.7%) 0.96 Nausea/Vomiting 18 (24%) 5 (27.8%) 0.77 Respiratory rate 19 (18 to 22) 20 (18 to 22) 0.36 SpO2 (%) 96 (95 to 97) 94 (90 to 96) 0.001 Comorbidities Comorbidity Score 1 (1 to 3) 2 (1 to 4) 0.36 Asthma 10 (13.3%) 0 (0%) 0.20 CAD 6 (8.0%) 2 (11.1%) 0.65 Cancer 9 (12.0%) 1 (5.6%) 0.68 COPD 5 (6.7%) 2 (11.1%) 0.62 Diabetes 21 (28.0%) 10 (55.6%) 0.05 Hypertension 42 (56.0%) 11 (61.1%) 0.90 Renal disease 14 (18.7%) 4 (22.2%) 0.74 Smoker 21 (28.0%) 7 (38.9%) 0.54 Disease severity on admission <0.001 Moderate 55 (73.3%) 4 (22.2%) Serious 20 (26.7%) 14 (77.8%) Laboratory results Albumin (on admission) (g/dL) 3.5 (3.1 to 3.9) 3.4 (3.0 to 3.9) 0.72 Albumin change (baseline to nadir) (g/dL) −0.5 (–0.7 to –0.3) −0.9 (–1.1 to –0.5) 0.001 Alkaline phosphatase (U/L) 81 (60 to 99) 73 (57 to 106) 0.91 ALT (U/L) 32 (24 to 52) 39 (27 to 80) 0.32 AST (U/L) 39 (25 to 56) 42 (31 to 124) 0.15 BNP (pg/mL) 53 (20 to 123) 38 (21 to 76) 0.46 Creatinine (mg/dL) 1.0 (0.8 to 1.3) 1.1 (1.0 to 1.8) 0.28 C reactive protein (mg/dL) 4.7 (2.4 to 9.0) 16.2 (12.6 to 21.4) <0.001 Ferritin (ng/mL) 391 (170 to 576) 970 (369 to 1741) 0.03 Lymphocytes (%) 19 (12 to 27) 11 (9 to 19) 0.01 Neutrophils (%) 70 (62 to 79) 79 (71 to 87) 0.006 Total bilirubin (mg/dL) 0.5 (0.4 to 0.7) 0.6 (0.6 to 0.9) 0.04 Troponin-I (ng/mL) 0.02 (0.02 to 0.03) 0.02 (0.01 to 0.04) 0.90 ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BNP, B-type natriuretic peptide; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; SpO2, pulse oximeter oxygen saturation.
- Table 3
Multivariable logistic model estimates of risk for development of critical disease
Variable Estimate SE OR (95% CI) P value Intercept −1.77 0.94 0.17 (0.02 to 0.99) 0.06 Baseline lymphocyte (%) −0.10 0.04 0.91 (0.83 to 0.97) 0.01 Total albumin change (baseline to nadir) (g/dL) −3.07 0.98 0.05 (0.01 to 0.26) 0.002
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