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The Predictive Potential of Elevated Serum Inflammatory Markers in Determining the Need for Intubation in CoVID-19 Patients

Samuel Windham

Samuel Windham

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Windham, Samuel
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Kellen Hirsch

Kellen Hirsch

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Hirsch, Kellen
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Ryan Peterson

Ryan Peterson

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Peterson, Ryan
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David Douin

David Douin

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Douin, David
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Lakshmi Chauhan

Lakshmi Chauhan

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Chauhan, Lakshmi
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Lauren Heery

Lauren Heery

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Heery, Lauren
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Connor Fling

Connor Fling

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Fling, Connor
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Nemanja Vukovic

Nemanja Vukovic

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Vukovic, Nemanja
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Fernando Holguin

Fernando Holguin

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Holguin, Fernando
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Shanta Zimmer

Shanta Zimmer

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Zimmer, Shanta
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Kristine Erlandson

Kristine Erlandson

University of Colorado Anschutz Medical CampusDenver, CO, USA
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Erlandson, Kristine
  
13 nov 2021
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Categoria dell'articolo: Research article
Pubblicato online: 13 nov 2021
Pagine: 14 - 22
Ricevuto: 15 dic 2020
Accettato: 31 ago 2021
DOI: https://doi.org/10.2478/jccm-2021-0035
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© 2022 Samuel Windham, Kellen Hirsch, Ryan Peterson, David Douin, Lakshmi Chauhan, Lauren Heery, Connor Fling, Nemanja Vukovic, Fernando Holguin, Shanta Zimmer, Kristine Erlandson, published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

Fig.1

Kaplan-Meier curves for intubation-free survival of hospitalized CoVID-19 patients stratified by C-reactive protein (CRP). Patients with low CRP (<100 mg/L) have a significantly higher probability of iuntubation-free survival, as compared to patients with high CRP (≥100 mg/L) (p<0.001)
Kaplan-Meier curves for intubation-free survival of hospitalized CoVID-19 patients stratified by C-reactive protein (CRP). Patients with low CRP (<100 mg/L) have a significantly higher probability of iuntubation-free survival, as compared to patients with high CRP (≥100 mg/L) (p<0.001)

Fig. 2

Predictive model for intubation and mechanical ventilation fit via the Minimax Concave Penalty. (A) Cross-validation deviance indicates optimal model has 3 predictors, including (B) C-reactive protein (CRP), lactate dehydrogenase (LDH), and type 2 diabetes mellitus as most predictive covariates. (C) Cross validated ROC curve of logistic model (CV) along with ROC curve on the validation cohort (EV). (D) Optimal model shown as probability formula where coviariates are centered and scaled using observed mean and standard deviation. DM signifies patient has type 2 diabetes (yes=1, no=0). Both logistic regression and linear approximation formulas presented.
Predictive model for intubation and mechanical ventilation fit via the Minimax Concave Penalty. (A) Cross-validation deviance indicates optimal model has 3 predictors, including (B) C-reactive protein (CRP), lactate dehydrogenase (LDH), and type 2 diabetes mellitus as most predictive covariates. (C) Cross validated ROC curve of logistic model (CV) along with ROC curve on the validation cohort (EV). (D) Optimal model shown as probability formula where coviariates are centered and scaled using observed mean and standard deviation. DM signifies patient has type 2 diabetes (yes=1, no=0). Both logistic regression and linear approximation formulas presented.

Baseline Characteristics of Hospitalised CoVID-19 Patients

Overall (N=158)
Clinical Characteristics
          Age 56.2 (16.8)
          BMI 31.3 (8.0)
          Male 81 (51.3%)
          Active Tobacco Use 9 (5.8%)
          White, non-Hispanic 30 (19.5%)
          Black 53 (34.4%)
          Hispanic 45 (29.2%)
          Asian 11 (7.1%)
          Other 15 (9.7%)
          Diabetes 47 (30.3%)
          Hypertension 87 (56.1%)
          COPD 11 (7.1%)
          Creatinine >2 mg/dL on Admission 4 (2.5%)
          Cirrhosis 3 (1.9%)
          Coronary Artery Disease 18 (11.6%)
          Active Cancer 11 (7.1%)
          Immunosuppressed 10 (6.5%)
Presenting Symptoms
          Subjective Fever 111 (74.0%)
          Cough 126 (82.4)
          Diarrhoea 40 (26.8%)
          Nausea/Vomiting 42 (28.2%)
          Myalgia 34 (22.8%)
          Dyspnoea 116 (75.3%)
          Duration of Symptoms 6.7 (4.6)
Chest X-Ray Findings*
          Unilateral Infiltrate 28 (17.8%)
          Bilateral Infiltrate 102 (65%)
          Other Findings 28 (17.8%)
Clinical Course
          Intubation Indicated 64 (40.5%)
          Vasopressors Indicated 42 (26.6%)
          Prone Positioned 24 (15.2%)
          Deceased 4 (2.5%)
          Discharge 55 (36.9%)

Characteristics of Intubated CoVID-19 Patients

Overall (N=64)
Clinical Characteristics
          Oxygen Requirement on Admission in Litres of Oxygen 5.6 (13.2)
          Highest Oxygen Requirement Stable >1 Hour within 24 Hours of Admission in Litres of Oxygen 5.0 (4.1)
          Use of Non-Invasive Ventilation Before Intubation 1 (1.6%)
          Oxygen Requirement within one hour of Intubation in Litres of Oxygen 12.9 (12.7)
          SOFA on Intubation 4.5 (2.1)
          Days Intubated 11.926 (8.519)
Pa02 to Fi02 at 8 Hour Intervals
          P:F Ratio at 8h 146.3 (84.1)
          P:F Ratio at 16h 194.9 (69.1)
          P:F Ratio at 24h 204.0 (63.4)
          P:F Ratio at 32h 216.8 (65.5)
          P:F Ratio at 40h 216.2 (65.9)
          P:F Ratio at 48h 204.7 (75.3)
          P:F Ratio at 56h 212.5 (73.9)
          P:F Ratio at 64h 217.0 (71.2)
          P:F Ratio at 72h 219.9 (81.4)
Pa02 to (Fi02*PEEP) at 8 Hour Intervals
          P:FP Ratio at 8h 12.3 (7.4)
          P:FP Ratio at 16h 17.3 (9.8)
          P:FP Ratio at 24h 17.5 (8.0)
          P:FP Ratio at 32h 19.1 (8.8)
          P:FP Ratio at 40h 20.1 (10.8)
          P:FP Ratio at 48h 18.2 (13.7)
          P:FP Ratio at 56h 19.1 (9.5)
          P:FP Ratio at 64h 20.6 (12.8)
          P:FP Ratio at 72h 21.2 (13.0)

Characteristics of Hospitalised CoVID-19 Patients Stratified by Intubation Status

Not Intubated (N=94) Intubated (N=64) N-Missing (Not intubated/ Intubated) p-value
Clinical Characteristics
          Age 55.36 (17.33) 57.32 (15.90) 0/1 0.415
          BMI 30.85 (7.84) 32.01 (8.2) 5/0 0.436
          Male 45 (47.9%) 36 (56.2%) NA 0.333
          Active Tobacco Use 4 (4.3%) 5 (8.1%) NA 0.485
          Non-White Race and/or Hispanic 71 (76.3%) 53 (86.9%) NA 0.145
          Ethnicity
          Diabetes 21 (22.3%) 26 (42.6%) NA 0.012
          Hypertension 52 (55.3%) 35 (57.4%) NA 0.869
          COPD 6 (6.4%) 5 (8.2%) NA 0.753
          Creatinine >2 mg/dL on Admission 1 (1.1%) 3 (4.8%) NA 0.303
          Cirrhosis 1 (1.1%) 2 (3.3%) NA 0.562
          Coronary Artery Disease 12 (12.8%) 6 (9.8%) NA 0.620
          Active Cancer 6 (6.4%) 5 (8.2%) NA 0.753
          Immunosuppressed 8 (8.6%) 2 (3.3%) NA 0.317
Presenting Symptoms
          Subjective Fever 72 (77.4%) 39 (68.4%) NA 0.253
          Cough 75 (79.8%) 51 (86.4%) NA 0.385
          Diarrhoea 30 (32.3%) 10 (17.9%) NA 0.059
          Nausea/Vomiting 33 (35.5%) 9 (16.1%) NA 0.014
          Myalgia 20 (21.5%) 14 (25%) NA 0.688
          Dyspnoea 74 (78.7%) 42 (70%) NA 0.253
          Duration of Symptoms 6.7 (4.53) 6.57 (4.81) 1/6 0.796
Chest X-Ray Findings*
          Clear 12 (13.8%) 4 (6.3%) NA 0.192
          Unilateral Infiltrate 21 (22.3%) 7 (11.1%) NA 0.090
          Bilateral Infiltrate 51 (54.3%) 51 (81%) NA <0.001
          Pleural Effusion 0 (0%) 2 (3.2%) NA 0.159
          Other Finding 6 (6.4%) 3 (4.8%) NA 0.741
Laboratory Findings*
          CRP mg/L 70.34 (60.5) 142.50 (83.36) 2/6 <0.001
          LDH U/L 311.53 (102.3) 415.37 (160.22) 5/13 <0.001
          D-dimer FEU 1199.23 (1692.86) 4475.20 (14140.16) 15/14 0.033
          Ferritin ng/mL 428.47 (426.81) 790.62 (1236.12) 7/17 0.079
          Neutrophils x10^9/L 4.55 (2.11) 7.20 (3.68) 59/24 <0.001
          Lymphocytes x10^9/L 3.60 (14.03) 1.08 (0.63) 59/24 0.067
          NLR 4.20 (2.41) 8.33 (6.51) 59/24 <0.001
Clinical Course
          Deceased 2 (2.1%) 2 (3.1%) NA 1.00
          Discharged 53 (57.6%) 2 (3.5%) NA <0.001

Covariate Effects on Odds of Intubation

Unadjusted Adjusted *
Term OR 95% CI p-value OR 95% CI p-value
1 SD change in CRP (78.0 mg/L) 3.05 (1.9, 4.8) <0.001 2.81 (1.8, 4.5) <0.001
1 SD change in LDH (135.6 U/L) 2.31 (1.5, 3.6) <0.001 2.10 (1.3, 3.3) 0.002
1 SD change in Log D-Dimer (0.94 log FEU) 1.47 (1, 2.2) 0.048 1.33 (0.8, 2.1) 0.22
1 SD change in NLR (5.4) 1.94 (1.1, 3.5) 0.031 2.21 (1.1, 4.5) 0.033
1 SD change in Log Ferritin (1.12 log ng/mL) 1.45 (1, 2.1) 0.055 1.29 (0.9, 1.9) 0.23
1 SD change in BMI (8.0 kg/m2) 1.15 (0.8, 1.6) 0.39 1.07 (0.7, 1.6) 0.71
1 SD change in age (16.8 years) 1.13 (0.8, 1.6) 0.45 1.15 (0.8, 1.7) 0.48
Symptom Duration 0.99 (0.9, 1.1) 0.86 0.99 (0.9, 1.1) 0.72
DM 2.52 (1.3, 5.1) 0.010 1.98 (0.9, 4.3) 0.081
Ethnicity/Race is Non-White 2.08 (0.9, 5) 0.10 1.96 (0.8, 5.1) 0.17
Bilateral Infiltrate on X-Ray 3.6 (1.7, 7.6) 0.001 3.39 (1.5, 7.6) 0.003
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