Key messages
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The National Early Warning Score (NEWS2), currently recommended for stratification of severe COVID-19 disease in the UK, showed poor-to-moderate discrimination for medium-term outcomes (14-day transfer to intensive care unit (ICU) or death) amongst COVID-19 patients.
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Risk stratification was improved by the addition of routinely measured blood and physiological parameters routinely at hospital admission (supplemental oxygen, urea, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) which provided moderate improvements in a risk stratification model for 14-day ICU/death.
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This improvement over NEWS2 alone was maintained across multiple hospital trusts, but the model tended to be miscalibrated with risks of severe outcomes underestimated in most sites.
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We benefited from existing pipelines for informatics at King’s College Hospital such as CogStack that allowed rapid extraction and processing of electronic health records. This methodological approach provided rapid insights and allowed us to overcome the complications associated with slow data centralisation approaches.
Background
Methods
Study cohorts
Measures
Outcome
Blood and physiological parameters
Demographics and comorbidities
Data processing
King’s College Hospital
Guy’s and St Thomas’ NHS Foundation Trust
University Hospitals Southampton
University Hospitals Bristol and Weston NHS Foundation Trust
University College Hospital London
Wuhan cohort
University Hospitals Birmingham
Oslo University Hospital
Statistical analyses
Sensitivity analyses
Results
Descriptive analyses
Training cohort | Validation cohorts (n = 6237) | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
KCH (n = 1276) | UHS (n = 633) | UCH (n = 411) | GSTT (n = 988) | UHBW (n = 190) | Wuhan (n = 2815) | UHB (n = 1037) | Oslo (n = 163) | |||||||||
COVID-19 WHO Score 6–8 (ICU/death) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) |
3 days | 1276 | 163 (12.8%) | 633 | 109 (17.2%) | 411 | 120 (29.0%) | 988 | 289 (29.3%) | 190 | 32 (16.8%) | 2815 | 58 (2.1%) | 1037 | 169 (16.3%) | 163 | 27 (16.3%) |
14 days | 1276 | 389 (30.5%) | 633 | 223 (35.2%) | 411 | 171 (42.0%) | 988 | 391 (39.6%) | 190 | 56 (29.5%) | 2815 | 118 (4.2%) | 1037 | 310 (29.9%) | 163 | 39 (23.9%) |
Demographics | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) |
Age (median [IQR]) | 1276 | 71.5 [57.1, 82.6] | 633 | 73.0 [56.0, 84.0] | 411 | 66.0 [53.0, 79.0] | 988 | 59.0 [46.0,75.0] | 190 | 73.5 [59.3, 82.0] | 2815 | 60.0 [50.0, 68.0] | 1037 | 70.0 [57.0, 82.0] | 163 | 60.0 [48.0–74.0] |
Sex (male) | 1276 | 742 (58.2%) | 633 | 364 (57.5%) | 411 | 252 (61.0%) | 988 | 581 (58.8%) | 190 | 120 (63.1%) | 2815 | 1437 (51.0%) | 1037 | 573 (55.3%) | 163 | 95 (58.3%) |
Non-White ethnicity | 960 | 379 (39.5%) | 546 | 55 (10.0%) | 390 | 156 (40.0%) | 817 | 607 (74.3%) | 190 | 46 (24.2%) | 2815 | 2815 (100.0%) | 892 | 306 (34.3%) | – | – |
Comorbidities | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) | N avail. | N (%) |
Hypertension | 1276 | 695 (54.5%) | 633 | 321 (50.7%) | 411 | 172 (42.0%) | 988 | 309 (31.3%) | 190 | 117 (61.6%) | 2815 | 821 (29.2%) | 1037 | 637 [61.4%) | 163 | 55 (33.7%) |
Diabetes mellitus | 1276 | 439 (34.4%) | 633 | 163 (25.8%) | 411 | 105 (26.0%) | 988 | 286 (28.9%) | 190 | 71 (37.4%) | 2815 | 371 (13.2%) | 1037 | 358 (34.5%) | 163 | 27 (16.6%) |
Heart failure | 1276 | 117 (9.2%) | 633 | 137 (21.6%) | 410 | – | 988 | 52 (5.3%) | 190 | 33 (17.4%) | 2815 | 236 (8.4%)2 | 1037 | 178 (17.2%) | 163 | 15 (9.2%) |
Ischaemic heart diseases | 1276 | 185 (14.5%) | 633 | 152 (24.0%) | 409 | 108 (26.0%)1 | – | – | 190 | 52 (27.4%) | – | – | 1037 | 245 (23.6%) | 163 | 21 (12.9%) |
COPD | 1276 | 141 (11.1%) | 633 | 115 (18.2%) | 409 | 27 (6.6%) | 988 | 64 (6.5%) | 190 | 41 (21.6%) | 2815 | 17 (0.6%) | 1037 | 152 (14.7%) | – | – |
Asthma | 1276 | 174 (13.6%) | 633 | 112 (17.7%) | 409 | 41 (10.0%) | 988 | 85 (8.6%) | 190 | 27 (14.2%) | – | – | 1037 | 169 (16.3%) | – | – |
Chronic kidney disease | 1276 | 234 (18.3%) | 633 | 111 (17.5%) | 410 | 40 (9.8%) | 988 | 110 (11.1%) | 190 | 59 (31.1%) | 2815 | 56 (2.0%) | 1037 | 274 (26.4%) | 163 | 9 (5.5%) |
Blood biomarker | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] |
Albumin (g/L) | 1153 | 37.0 [33.0, 40.0] | 501 | 32.0 [29.0, 36.0] | 390 | 38.0 [35.0, 42.0] | 863 | 36.0 [31.0, 40.0] | 190 | 30.0 [27.0, 33.0] | 2404 | 38.1 [35.1, 40.5] | 993 | 32.0 [28.0, 35.0] | 120 | 39.0 [36.0–43.0] |
C-reactive protein (CRP, mg/L) | 1240 | 80.0 [36.0, 141.6] | 545 | 75.0 [25.0, 150.0] | 403 | 97.0 [45.0, 179.0] | 974 | 76.5 [25.0, 153.8] | 190 | 77.0 [36.3, 138.3] | 2393 | 2.3 [0.8, 9.0] | 970 | 89.0 [33.2, 157.0] | 163 | 48.0 [16.0–113.0] |
Urea (mmol/L) | 1221 | 7.1 [4.6, 11.7] | 563 | 6.95 [4.8, 10.6] | 375 | 6.0 [4.0, 9.4] | 489 | 7.4 [4.6, 12.5] | – | – | – | – | 1018 | 6.8 [4.6, 11.8] | 154 | 5.5 [4.3–7.5] |
Estimated GFR | 1254 | 65.0 [41.0, 86.0] | 377 | 62.0 [40.0, 81.0] | 407 | 77.0 [54.0, 96.0] | 965 | 74.0 [49.0, 100.0] | 190 | 68.0 [43.3. 88.0] | 2433 | 103.1 [88.2, 117.5] | 757 | 54.0 [29.0, 72.0] | 163 | 84.0 [57.0–99.0] |
Haemoglobin (g/L) | 1223 | 127.0 [112.0, 141.0] | 561 | 128.0 [111.0, 143.0] | 410 | 130.0 [112.0, 143.0] | 987 | 125.0 [108.0, 139.0] | 190 | 129.0 [110.0, 141.0] | 2584 | 124.0 [113.0, 135.0] | 1009 | 130.0 [113.0, 144.0] | 163 | 139.0 [129.0–148.0] |
Lymphocyte count (× 109/L) | 1221 | 0.9 [0.7, 1.3] | 561 | 1.0 [0.7, 1.4] | 410 | 0.9 [0.6, 1.4] | 987 | 0.9 [0.6, 1.3] | 190 | 0.9 [0.6, 1.2] | 2584 | 1.5 [1.1, 1.9] | 1011 | 0.9 [0.7, 1.4] | 153 | 1.1 [0.8–1.5] |
Neutrophil count (× 109/L) | 1220 | 5.4 [3.8, 7.7] | 560 | 5.8 [4.2, 8.8] | 410 | 5.9 [3.9, 8.2] | 986 | 5.0 [3.5, 8.1] | 190 | 5.2 [3.5, 7.4] | 2584 | 3.5 [2.7, 4.7] | 1011 | 5.5 [3.8, 8.2] | 153 | 4.4 [3.0–7.1] |
Neutrophil/lymphocyte ratio | 1218 | 5.6 [3.4, 9.5] | 559 | 5.8 [3.4, 10] | 410 | 6.0 [4.0, 10.0] | 986 | 5.6 [3.2, 10.1] | 190 | 5.7 [3.6, 9.8] | 2584 | 2.3 [1.7, 3.5] | 1011 | 5.6 [3.2, 10.2] | 153 | 4.3 [2.4–7.7] |
Lymphocyte/CRP ratio | 1196 | 1.2 [0.6, 3.2] | 559 | 1.3 [0.5, 4.6] | 402 | 1.0 [0.4, 2.4] | 0.0 [0.0, 0.0] | 190 | 1.1 [0.5, 2.7] | 2362 | 0.7 [0.1, 2.0] | 962 | 1.1 [0.5, 3.3] | – | – | |
Platelet count (× 109/L) | 1224 | 213.0 [161.8, 274.0] | 560 | 231 [176.8, 303.5] | 409 | 221.0 [169.0, 280.0] | 986 | 209.0 [161.0, 275.8] | 190 | 207.5 [150.3, 268.5] | 2584 | 223.0 [179.8, 273.0] | 1008 | 218.0 [165.0, 287.2] | 163 | 205.0 [160.0–279.0] |
Physiological parameters | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] | N avail. | Median [IQR] |
NEWS2 Total Score | 1262 | 2.0 [1.0, 4.0] | 529 | 3.0 [2.0, 5.0] | 404 | 5.0 [3.0, 7.0] | 744 | 3.0 [1.0, 5.0] | 190 | 3.0 [2.0, 5.0] | 2804 | 1.0 [0.0, 3.0] | 1019 | 4.0 [2.0, 7.0] | 163 | 5.0 [3.0–7.0] |
Heart rate | 1273 | 85.0 [75.0, 94.0] | 560 | 90.5 [82.0, 102.0] | 410 | 94.0 [81.0, 107.0] | 752 | 85.0 [75.0, 95.0] | 190 | 82.0 [71.0, 95.0] | 2812 | 81.0 [76.9, 85.8] | 1028 | 90.0 [79.0, 104.0] | 160 | 89.5 [75.3–100.8] |
Oxygen saturation | 1273 | 96.0 [95.0, 98.0] | 561 | 97.0 [96.0, 99.0] | 410 | 96.0 [94.0, 98.0] | 712 | 96.0 [95.0, 97.0] | 190 | 95.0 [94.0, 96.0] | 2797 | 97.8 [97.0, 98.2] | 1029 | 96.0 [94.0, 98.0] | 163 | 95.0 [92.0–97.0] |
Oxygen flow rate (L/min) | 1271 | 0.0 [0.0, 4.0] | 260 | 3.0 [2.0, 8.0] | 403 | 2.0 [0.0, 10.0] | 978 | 0.0 [0.0, 0.0] | 190 | 2.0 [0.0, 3.0] | – | – | 1017 | 0.0 [0.0, 4.0] | 125 | 1.0 [0.0–2.0] |
Respiration rate | 1273 | 19.0 [18.0, 21.0] | 561 | 20.0 [19.0, 24.0] | 410 | 24.0 [20.0, 28.0] | 755 | 19.0 [18.0, 22.0] | 190 | 20.0 [18.0, 21.0] | 2811 | 20.0 [19.0, 21.0] | 1020 | 20.0 [18.0, 25.0] | 160 | 24.0 [20.0–28.0] |
Systolic blood pressure | 1273 | 125.0 [112.0, 139.0] | 555 | 137.0 [123.0, 152.0] | 411 | 131.0 [115.0, 143.0] | 751 | 125.0 [115.0, 140.0] | 190 | 123.0 [111.0, 140.8] | 1431 | 120.0 [110.0, 128.0] | 1022 | 128.0 [113.0, 144.0] | 160 | 129 [116.0–142.8] |
Diastolic blood pressure | 1273 | 71.0 [62.0, 80.0] | 555 | 78.0 [70.0, 85.0] | 411 | 73.0 [64.0, 81.0] | 751 | 74.0 [66.0, 81.0] | 190 | 72.0 [64.3, 82.0] | 1433 | 71.0 [65.0, 78.0] | 1022 | 75.0 [67.0, 84.0] | 160 | 77.0 [69.0–87.0] |
Temperature | 1273 | 36.9 [36.6, 37.4] | 558 | 36.9 [36.7, 37.5] | 410 | 37.3 [36.8, 38.1] | 750 | 36.9 [36.4, 37.5] | 190 | 37.2 [36.7, 37.9] | 2815 | 36.5 [36.3, 36.7] | 1029 | 36.8 [36.2, 37.5] | 162 | 37.2 [36.5–38.3] |
Evaluating NEWS2 score for prediction of severe COVID-19 outcome
NEWS2 + age, mean (95% CI) | All features, mean (95% CI) | ||
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14-day ICU/death | AUC | 0.700 [0.680, 0.722] | 0.735 [0.715, 0.757] |
Brier score | 0.192 [0.186, 0.197] | 0.183 [0.177, 0.189] | |
Sensitivity1 | 0.778 [0.747, 0.815] | 0.735 [0.702, 0.772] | |
Specificity1 | 0.478 [0.445, 0.509] | 0.592 [0.562, 0.621] |