Figures
- FIGURE 1
Study flow chart. ISARIC: International Severe Acute Respiratory and Emerging Infection Consortium; WHO: World Health Organization; COVID-19: coronavirus disease 2019; ICU: intensive care unit.
- FIGURE 2
Patients with severe coronavirus disease 2019 were enrolled in six continents. The colour scale shows the number of patients included in each country. Grey shading represents countries with no patients included in this analysis.
- FIGURE 3
Patients admitted to the intensive care unit (ICU) have lower cumulative deaths over time. a) The cumulative number of cases included in the study, stratified by b) patients admitted to the ICU and c) patients who were not admitted to the ICU. Proportions of patients still hospitalised at the moment of data extraction, discharged alive and reported dead are shown.
- FIGURE 4
Estimation of the non-linear effect on 28-day fatality ratio using a generalised additive model in patients with severe coronavirus disease 2019 (COVID-19) stratified by intensive care unit (ICU) admission. a) Age is shown to be an essential factor for higher fatality ratio in patients with severe COVID-19; however, patients admitted to the ICU have a lower fatality ratio independent of age. Even after adjusting by b) the number of new cases per million at the moment of hospital admission and c) the interaction over time, the marginal 28-day fatality ratio was lower in patients admitted to the ICU.
Tables
- TABLE 1
Baseline characteristics of patients with confirmed severe acute respiratory syndrome coronavirus 2 infection who developed severe coronavirus disease 2019 stratified by patients admitted to the intensive care unit (ICU)
All Patients admitted to the ICU p-value Yes No Patients, n 40 440 20 044 20 396 Demographics Age, median (IQR) 67 (55–78) 61 (50–70) 75 (62–84) <0.0001 Female, n (%) 14 939 (36.9) 6473 (32.2) 8466 (41.5) <0.0001 Chronic comorbidities, n (%) Number of comorbidities, median (IQR) 2.0 (0.0–3.0) 1.0 (0.0–2.0) 2.0 (0.0–4.0) <0.0001 Chronic arterial hypertension 11 910 (29.5) 5712 (28.5) 6198 (30.4) <0.0001 Chronic cardiac disease 8161 (20.2) 2493 (12.4) 5668 (27.8) <0.0001 Chronic cardiac arrhythmia 38 (0.1) 34 (0.2) 4 (0.0) <0.0001 Chronic pulmonary disease 4848 (12.0) 1423 (7.1) 3425 (16.8) <0.0001 Asthma 3920 (9.7) 1857 (9.3) 2063 (10.1) <0.0001 Other chronic respiratory disease 873 (2.2) 148 (0.7) 725 (3.6) <0.0001 Chronic neurological disorder 2898 (7.2) 798 (4.0) 2100 (10.3) <0.0001 Chronic rheumatic disorder 2736 (6.8) 794 (4.0) 1942 (9.5) <0.0001 Chronic kidney disease 4151 (10.3) 1252 (6.2) 2899 (14.2) <0.0001 Mild liver disease 413 (1.0) 187 (0.9) 226 (1.1) 0.08 Moderate or severe liver disease 454 (1.1) 163 (0.8) 291 (1.4) <0.0001 Diabetes mellitus 9141 (22.6) 4343 (21.7) 4798 (23.5) <0.0001 Chronic haematological disorder 1069 (2.6) 354 (1.8) 715 (3.5) <0.0001 Chronic immunosuppressive disorders 44 (0.1) 44 (0.2) 0 (0.0) <0.0001 Chronic immunosuppressive medication 537 (1.3) 194 (1.0) 343 (1.7) <0.0001 Cancer 680 (1.7) 197 (1.0) 483 (2.4) <0.0001 Malignant neoplasm 2453 (6.1) 797 (4.0) 1656 (8.1) <0.0001 Solid organ transplant recipient 192 (0.5) 76 (0.4) 116 (0.6) 0.006 AIDS/HIV 178 (0.4) 123 (0.6) 55 (0.3) <0.0001 Asplenia 46 (0.1) 45 (0.2) 1 (0.0) <0.0001 Dementia 2774 (6.9) 188 (0.9) 2586 (12.7) <0.0001 Obesity 4623 (11.4) 2802 (14.0) 1821 (8.9) <0.0001 Malnutrition 628 (1.6) 210 (1.0) 418 (2.0) <0.0001 Symptoms on admission, n (%) Fever 21 115 (52.2) 10 578 (52.8) 10 537 (51.7) 0.02 Abdominal pain 2386 (5.9) 1143 (5.7) 1243 (6.1) 0.09 Bleeding (haemorrhage) 463 (1.1) 173 (0.9) 290 (1.4) <0.0001 Fatigue/malaise 12 391 (30.6) 6317 (31.5) 6074 (29.8) <0.0001 Shortness of breath 23 955 (59.2) 11 924 (59.5) 12 031 (59.0) 0.30 Sore throat 2464 (6.1) 1619 (8.1) 845 (4.1) <0.0001 Dry cough 21 065 (52.1) 10 230 (51.0) 10 835 (53.1) <0.0001 Cough – productive 6693 (16.6) 3132 (15.6) 3561 (17.5) <0.0001 Cough – with haemoptysis 804 (2.0) 444 (2.2) 360 (1.8) 0.0001 Wheezing 2294 (5.7) 850 (4.2) 1444 (7.1) <0.0001 Seizures 352 (0.9) 148 (0.7) 204 (1.0) 0.005 Altered consciousness/confusion 5964 (14.7) 1759 (8.8) 4205 (20.6) <0.0001 Disturbance or loss of smell (anosmia) 1047 (2.6) 614 (3.1) 433 (2.1) <0.0001 Disturbance or loss of taste (ageusia) 1275 (3.2) 631 (3.1) 644 (3.2) 0.95 Severe dehydration 1614 (4.0) 538 (2.7) 1076 (5.3) <0.0001 Vomiting/nausea 5006 (12.4) 2469 (12.3) 2537 (12.4) 0.71 Diarrhoea 5335 (13.2) 2872 (14.3) 2463 (12.1) <0.0001 Muscle aches (myalgia) 5562 (13.8) 3397 (16.9) 2165 (10.6) <0.0001 Chest pain 3823 (9.5) 1951 (9.7) 1872 (9.2) 0.05 Headache 2918 (7.2) 1747 (8.7) 1171 (5.7) <0.0001 Joint pain (arthralgia) 1495 (3.7) 739 (3.7) 756 (3.7) 0.91 Skin ulcers 419 (1.0) 77 (0.4) 342 (1.7) <0.0001 Lower chest wall indrawing 528 (1.3) 334 (1.7) 194 (1.0) <0.0001 Skin rash 304 (0.8) 140 (0.7) 164 (0.8) 0.24 Conjunctivitis 110 (0.3) 72 (0.4) 38 (0.2) 0.0001 Runny nose (rhinorrhoea) 927 (2.3) 665 (3.3) 262 (1.3) <0.0001 Ear pain 95 (0.2) 49 (0.2) 46 (0.2) 0.69 Lymphadenopathy 170 (0.4) 59 (0.3) 111 (0.5) <0.0001 Inability to walk 279 (0.7) 226 (1.1) 53 (0.3) <0.0001 Anorexia 349 (0.9) 285 (1.4) 64 (0.3) <0.0001 Asymptomatic 272 (0.7) 93 (0.5) 179 (0.9) <0.0001 Physiological parameters on admission, median (IQR) Temperature, °C 37.3 (36.7–38.2) 37.4 (36.7–38.3) 37.3 (36.6–38.1) <0.0001 Heart rate, beats·min−1 93 (8–108) 96 (84–110) 91 (79–105) <0.0001 Respiratory rate, breaths·min−1 24 (20–28) 24 (20–30) 22 (19–28) <0.0001 Systolic blood pressure, mmHg 130 (114–145) 130 (115–144) 130 (114–146) 0.02 Diastolic blood pressure, mmHg 74 (65–83) 75 (65–83) 74 (64–84) 0.0001 Continent of admission, n (%) Europe 34 456 (85.2) 12 427 (61.9) 20 029 (98.2) <0.0001 Asia 3292 (8.1) 3140 (15.6) 152 (0.7) <0.0001 South America 1408 (3.5) 1308 (6.5) 100 (0.5) <0.0001 North America 2614 (6.4) 2505 (12.5) 109 (0.5) <0.0001 Africa 164 (0.4) 159 (0.6) 5 (0.0) <0.0001 Oceania 506 (1.3) 505 (2.5) 1 (0.0) <0.0001 Regional income stratification, n (%) High-income country 35 956 (88.9) 15 810 (78.8) 20 146 (98.7) <0.0001 Upper middle-income country 1976 (4.8) 1821 (9.1) 155 (0.8) <0.0001 Lower middle-income country 2496 (6.2) 2401 (11.9) 96 (0.5) <0.0001 Clinical outcomes n=38 126 n=18 831 n=19 295 Hospital LOS, median (IQR) 10 (5–19) 12 (6–23) 8 (4–15) <0.0001 28-day fatality ratio, n (%) 13 329 (34.9) 5797 (30.7) 7532 (39.0) <0.0001 90-day fatality ratio, n (%) 14 394 (37.7) 6358 (33.7) 8036 (41.6) <0.0001 IQR: interquartile range; LOS: length of stay.
- TABLE 2
Treatments stratified by patients admitted to the intensive care unit (ICU)
All Patients admitted to the ICU p-value Yes No Patients, n 40 440 20 044 20 396 Invasive mechanical ventilation 12 462 (30.8) 11 957 (59.6) 505 (2.5) <0.0001 Noninvasive mechanical ventilation 15 522 (38.4) 9127 (45.5) 6395 (31.4) <0.0001 High-flow nasal cannula 25 433 (62.9) 8891 (44.4) 16 542 (81.1) <0.0001 Inotropes or vasopressors 16 542 (40.7) 8375 (41.8) 175 (0.9) <0.0001 Antibiotics 35 316 (87.3) 17 800 (88.8) 17 516 (85.9) <0.0001 Prone positioning 7825 (19.3) 7390 (36.9) 435 (2.1) <0.0001 Neuraminidase inhibitors 231 (0.6) 118 (0.6) 113 (0.6) 0.69 Neuromuscular blocking agents 3647 (9.0) 3597 (17.9) 50 (0.2) <0.0001 Dialysis/haemofiltration 3191 (7.9) 2953 (14.7) 238 (1.2) <0.0001 Corticosteroids 11 435 (28.3) 7627 (38.1) 3808 (18.7) <0.0001 Antivirals 8025 (19.8) 5925 (29.6) 2100 (10.3) <0.0001 Tracheostomy 2461 (6.1) 2422 (12.1) 39 (0.2) <0.0001 ECMO 706 (1.7) 706 (3.5) 0 (0.0) <0.0001 ACE inhibitors 4399 (10.9) 1991 (9.9) 2408 (11.8) <0.0001 Antifungal 3200 (7.9) 2384 (11.9) 816 (4.0) <0.0001 Angiotensin II receptor blockers 2865 (7.1) 1674 (8.4) 1191 (5.8) <0.0001 Therapeutic anticoagulants 532 (1.3) 510 (2.5) 22 (0.1) <0.0001 Lopinavir/ritonavir 651 (1.6) 397 (2.0) 254 (1.2) <0.0001 Nonsteroidal anti-inflammatory 2317 (5.7) 1191 (5.9) 1126 (5.5) 0.07 Inhaled nitric oxide 505 (1.2) 491 (2.4) 14 (0.1) <0.0001 Chloroquine/hydroxychloroquine 946 (2.3) 718 (3.6) 228 (1.1) <0.0001 Convalescent plasma 398 (1.0) 248 (1.2) 150 (0.7) <0.0001 Macrolides 83 (0.2) 66 (0.3) 17 (0.1) <0.0001 Dexamethasone 4174 (10.3) 1992 (9.9) 2182 (10.7) 0.01 Interferon-β 131 (0.3) 118 (0.6) 13 (0.1) <0.0001 Oral steroids 311 (0.8) 275 (1.4) 36 (0.2) <0.0001 Remdesivir 2009 (5.0) 1092 (5.4) 917 (4.5) <0.0001 IL-6 inhibitor 122 (0.3) 90 (0.4) 32 (0.2) <0.0001 Tocilizumab 51 (0.1) 42 (0.2) 9 (0.0) <0.0001 Data are presented as n (%), unless otherwise stated. ECMO: extracorporeal membrane oxygenation; ACE: angiotensin-converting enzyme; IL: interleukin.
- TABLE 3
Patients with severe coronavirus disease 2019 who developed complications stratified by patients admitted to the intensive care unit (ICU)
All Patients admitted to the ICU p-value Yes No Patients, n 40 440 20 044 20 396 Neurological, n (%) Seizures 393 (1.0) 240 (1.2) 153 (0.8) <0.0001 Stroke 489 (1.2) 281 (1.4) 208 (1.0) <0.0001 Meningitis or encephalitis 113 (0.3) 93 (0.5) 20 (0.1) <0.0001 Other neurological complications 490 (1.2) 228 (1.1) 262 (1.3) 0.19 Cardiovascular, n (%) Congestive heart failure 1183 (2.9) 432 (2.2) 751 (3.7) <0.0001 Endocarditis, myocarditis, pericarditis 223 (0.6) 191 (1.0) 32 (0.2) <0.0001 Cardiac arrhythmia 2992 (7.4) 1995 (10.0) 997 (4.9) <0.0001 Cardiac arrest 1457 (3.6) 1012 (5.0) 445 (2.2) <0.0001 Cardiac ischaemia 556 (1.4) 303 (1.5) 253 (1.2) 0.021 Cardiomyopathy 195 (0.5) 138 (0.7) 57 (0.3) <0.0001 Myocardial infarction 34 (0.1) 31 (0.2) 3 (0.0) <0.0001 Pulmonary, n (%) Bacterial pneumonia 4695 (11.6) 2591 (12.9) 2104 (10.3) <0.0001 Acute respiratory distress syndrome 7928 (19.6) 5747 (28.7) 2181 (10.7) <0.0001 Pneumothorax 555 (1.4) 447 (2.2) 108 (0.5) <0.0001 Pleural effusion 2198 (5.4) 1093 (5.5) 1105 (5.4) 0.89 Pulmonary embolism 272 (0.7) 237 (1.2) 35 (0.2) <0.0001 Cryptogenic organising pneumonia 122 (0.3) 95 (0.5) 27 (0.1) <0.0001 Gastrointestinal, n (%) Pancreatitis 138 (0.3) 103 (0.5) 35 (0.2) <0.0001 Liver dysfunction 2385 (5.9) 1703 (8.5) 682 (3.3) <0.0001 Gastrointestinal haemorrhage 393 (1.0) 221 (1.1) 172 (0.8) 0.008 Renal, n (%) Acute kidney injury 6566 (16.2) 4030 (20.1) 2536 (12.4) <0.0001 Metabolic, n (%) Hyperglycaemia 3232 (8.0) 2265 (11.3) 967 (4.7) <0.0001 Hypoglycaemia 757 (1.9) 355 (1.8) 402 (2.0) 0.14 Haematological, n (%) Anaemia 5057 (12.5) 3203 (16.0) 1854 (9.1) <0.0001 Disseminated intravascular coagulation 1296 (3.2) 844 (4.2) 452 (2.2) <0.0001 Bleeding 84 (0.2) 80 (0.4) 4 (0.0) <0.0001 Others, n (%) Other complication 6321 (15.6) 2883 (14.4) 3438 (16.9) <0.0001 Bacteraemia 1848 (4.6) 1366 (6.8) 482 (2.4) <0.0001 Rhabdomyolysis or myositis 246 (0.6) 185 (0.9) 61 (0.3) <0.0001 - TABLE 4
Generalised additive model fitted to assess the association of being admitted to the intensive care unit (ICU) with 28-day fatality ratio
OR (95% CI) Estimated marginal mean (range) p-value ICU admission 0.70 (0.65–0.75) <0.0001 High-flow nasal cannula 1.05 (1.00–1.11) 0.052 Noninvasive respiratory support 1.37 (1.31–1.44) <0.0001 Invasive mechanical ventilation 1.97 (1.81–2.14) <0.0001 Vasopressors or inotropes 1.56 (1.44–1.70) <0.0001 Number of comorbidities 1.07 (1.06–1.09) <0.0001 Temperature on hospital admission 0.92 (0.90–0.94) <0.0001 Heart rate on hospital admission 1.01 (1.00–1.01) <0.0001 Respiratory rate on hospital admission 1.03 (1.02–1.03) <0.0001 Systolic blood pressure on hospital admission 1.00 (1.00–1.01) <0.0001 Diastolic blood pressure on hospital admission 0.99 (0.99–0.99) <0.0001 Acute respiratory distress syndrome 1.47 (1.39–1.56) <0.0001 Male 1.25 (1.19–1.31) <0.0001 Month of hospital admission 0.98 (0.96–0.99) <0.0001 New cases per million 1.00 (1.00–1.00) <0.0001 Age (years) 20 7.1% (5.8–8.7%) 40 9.1% (8.3–9.9%) 60 19.8% (19.0–20.6%) 80 51.8% (50.7–52.9%)
Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary material 00552-2021.supplement
Case report form 00552-2021.CRF
Protocol 00552-2021.protocol
