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Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Luis Felipe Reyes, Srinivas Murthy, Esteban Garcia-Gallo, Mike Irvine, Laura Merson, Ignacio Martin-Loeches, Jordi Rello, Fabio S. Taccone, Robert A. Fowler, Annemarie B. Docherty, Christiana Kartsonaki, Irene Aragao, Peter W. Barrett, Abigail Beane, Aidan Burrell, Matthew Pellan Cheng, Michael D. Christian, Jose Pedro Cidade, Barbara Wanjiru Citarella, Christl A. Donnelly, Susana M. Fernandes, Craig French, Rashan Haniffa, Ewen M. Harrison, Antonia Ying Wai Ho, Mark Joseph, Irfan Khan, Michelle E. Kho, Anders Benjamin Kildal, Demetrios Kutsogiannis, François Lamontagne, Todd C. Lee, Gianluigi Li Bassi, Jose Wagner Lopez Revilla, Catherine Marquis, Jonathan Millar, Raul Neto, Alistair Nichol, Rachael Parke, Rui Pereira, Sergio Poli, Pedro Povoa, Kollengode Ramanathan, Oleksa Rewa, Jordi Riera, Sally Shrapnel, Maria Joao Silva, Andrew Udy, Timothy Uyeki, Steve A. Webb, Evert-Jan Wils, Amanda Rojek, Piero L. Olliaro, ISARIC Clinical Characterisation Group on behalf of the ISARIC Clinical Characterisation Group
ERJ Open Research 2022 8: 00552-2021; DOI: 10.1183/23120541.00552-2021
Luis Felipe Reyes
1Universidad de La Sabana, Chía, Colombia
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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  • For correspondence: luis.reyes5@unisabana.edu.co
Srinivas Murthy
3British Columbia Children's Hospital, Vancouver, BC, Canada
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Esteban Garcia-Gallo
1Universidad de La Sabana, Chía, Colombia
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Mike Irvine
4British Columbia Centre for Disease Control, Vancouver, BC, Canada
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Laura Merson
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Ignacio Martin-Loeches
5Intensive Care Medicine, St James's Hospital, Dublin, Ireland
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Jordi Rello
6Vall d'Hebron Institute of Research, Barcelona, Spain
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Fabio S. Taccone
7Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
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Robert A. Fowler
8Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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Annemarie B. Docherty
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Christiana Kartsonaki
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Irene Aragao
9Centro Hospitalar Universitário do Porto, Porto, Portugal
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Peter W. Barrett
10Piedmont Atlanta Hospital, Atlanta, GA, USA
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Abigail Beane
11Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand
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Aidan Burrell
12Monash University, Melbourne, Australia
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Matthew Pellan Cheng
13McGill University, Hamilton, ON, Canada
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Michael D. Christian
14Bart's NHS Health Trust, London, UK
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Jose Pedro Cidade
15Hospital São Francisco Xavier, Lisbon, Portugal
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Barbara Wanjiru Citarella
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Christl A. Donnelly
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Susana M. Fernandes
16Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
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Craig French
17Western Health, Melbourne, Australia
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Rashan Haniffa
11Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand
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Ewen M. Harrison
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Antonia Ying Wai Ho
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Mark Joseph
18Carilion Clinic, Roanoke, VA, USA
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Irfan Khan
19Presbyterian Hospital Services, Albuquerque, NM, USA
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Michelle E. Kho
13McGill University, Hamilton, ON, Canada
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Anders Benjamin Kildal
20University Hospital of North Norway, Tromsø, Norway
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Demetrios Kutsogiannis
21The University of Alberta, School of Medicine and Dentistry, Edmonton, AB, Canada
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François Lamontagne
22Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada
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Todd C. Lee
13McGill University, Hamilton, ON, Canada
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Gianluigi Li Bassi
23University of Queensland, Brisbane, Australia
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Jose Wagner Lopez Revilla
24Instituto Nacional del Niño San Borja, Lima, Peru
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Catherine Marquis
22Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada
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Jonathan Millar
25Roslin Institute, University of Edinburgh, Edinburgh, UK
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Raul Neto
26Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
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Alistair Nichol
27St Vincent's University Hospital, Dublin, Ireland
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Rachael Parke
28Auckland City Hospital, Auckland, New Zealand
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Rui Pereira
29Hospital Curry Cabral, Lisbon, Portugal
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Sergio Poli
30Mount Sinai Medical Center, Miami, FL, USA
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Pedro Povoa
15Hospital São Francisco Xavier, Lisbon, Portugal
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Kollengode Ramanathan
31National University of Singapore, Singapore, Singapore
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Oleksa Rewa
21The University of Alberta, School of Medicine and Dentistry, Edmonton, AB, Canada
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Jordi Riera
6Vall d'Hebron Institute of Research, Barcelona, Spain
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Sally Shrapnel
23University of Queensland, Brisbane, Australia
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Maria Joao Silva
9Centro Hospitalar Universitário do Porto, Porto, Portugal
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Andrew Udy
12Monash University, Melbourne, Australia
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Timothy Uyeki
32Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Steve A. Webb
12Monash University, Melbourne, Australia
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Evert-Jan Wils
33Franciscus Gasthuis en Vlietland, Rotterdam, The Netherlands
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Amanda Rojek
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Piero L. Olliaro
2Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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  • Article
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  • FIGURE 1
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    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
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    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
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    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
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    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

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  • Supplementary Materials
  • 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)

    AllPatients admitted to the ICUp-value
    YesNo
    Patients, n40 44020 04420 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 hypertension11 910 (29.5)5712 (28.5)6198 (30.4)<0.0001
     Chronic cardiac disease8161 (20.2)2493 (12.4)5668 (27.8)<0.0001
     Chronic cardiac arrhythmia38 (0.1)34 (0.2)4 (0.0)<0.0001
     Chronic pulmonary disease4848 (12.0)1423 (7.1)3425 (16.8)<0.0001
     Asthma3920 (9.7)1857 (9.3)2063 (10.1)<0.0001
     Other chronic respiratory disease873 (2.2)148 (0.7)725 (3.6)<0.0001
     Chronic neurological disorder2898 (7.2)798 (4.0)2100 (10.3)<0.0001
     Chronic rheumatic disorder2736 (6.8)794 (4.0)1942 (9.5)<0.0001
     Chronic kidney disease4151 (10.3)1252 (6.2)2899 (14.2)<0.0001
     Mild liver disease413 (1.0)187 (0.9)226 (1.1)0.08
     Moderate or severe liver disease454 (1.1)163 (0.8)291 (1.4)<0.0001
     Diabetes mellitus9141 (22.6)4343 (21.7)4798 (23.5)<0.0001
     Chronic haematological disorder1069 (2.6)354 (1.8)715 (3.5)<0.0001
     Chronic immunosuppressive disorders44 (0.1)44 (0.2)0 (0.0)<0.0001
     Chronic immunosuppressive medication537 (1.3)194 (1.0)343 (1.7)<0.0001
     Cancer680 (1.7)197 (1.0)483 (2.4)<0.0001
     Malignant neoplasm2453 (6.1)797 (4.0)1656 (8.1)<0.0001
     Solid organ transplant recipient192 (0.5)76 (0.4)116 (0.6)0.006
     AIDS/HIV178 (0.4)123 (0.6)55 (0.3)<0.0001
     Asplenia46 (0.1)45 (0.2)1 (0.0)<0.0001
     Dementia2774 (6.9)188 (0.9)2586 (12.7)<0.0001
     Obesity4623 (11.4)2802 (14.0)1821 (8.9)<0.0001
     Malnutrition628 (1.6)210 (1.0)418 (2.0)<0.0001
    Symptoms on admission, n (%)
     Fever21 115 (52.2)10 578 (52.8)10 537 (51.7)0.02
     Abdominal pain2386 (5.9)1143 (5.7)1243 (6.1)0.09
     Bleeding (haemorrhage)463 (1.1)173 (0.9)290 (1.4)<0.0001
     Fatigue/malaise12 391 (30.6)6317 (31.5)6074 (29.8)<0.0001
     Shortness of breath23 955 (59.2)11 924 (59.5)12 031 (59.0)0.30
     Sore throat2464 (6.1)1619 (8.1)845 (4.1)<0.0001
     Dry cough21 065 (52.1)10 230 (51.0)10 835 (53.1)<0.0001
     Cough – productive6693 (16.6)3132 (15.6)3561 (17.5)<0.0001
     Cough – with haemoptysis804 (2.0)444 (2.2)360 (1.8)0.0001
     Wheezing2294 (5.7)850 (4.2)1444 (7.1)<0.0001
     Seizures352 (0.9)148 (0.7)204 (1.0)0.005
     Altered consciousness/confusion5964 (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 dehydration1614 (4.0)538 (2.7)1076 (5.3)<0.0001
     Vomiting/nausea5006 (12.4)2469 (12.3)2537 (12.4)0.71
     Diarrhoea5335 (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 pain3823 (9.5)1951 (9.7)1872 (9.2)0.05
     Headache2918 (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 ulcers419 (1.0)77 (0.4)342 (1.7)<0.0001
     Lower chest wall indrawing528 (1.3)334 (1.7)194 (1.0)<0.0001
     Skin rash304 (0.8)140 (0.7)164 (0.8)0.24
     Conjunctivitis110 (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 pain95 (0.2)49 (0.2)46 (0.2)0.69
     Lymphadenopathy170 (0.4)59 (0.3)111 (0.5)<0.0001
     Inability to walk279 (0.7)226 (1.1)53 (0.3)<0.0001
     Anorexia349 (0.9)285 (1.4)64 (0.3)<0.0001
     Asymptomatic272 (0.7)93 (0.5)179 (0.9)<0.0001
    Physiological parameters on admission, median (IQR)
     Temperature, °C37.3 (36.7–38.2)37.4 (36.7–38.3)37.3 (36.6–38.1)<0.0001
     Heart rate, beats·min−193 (8–108)96 (84–110)91 (79–105)<0.0001
     Respiratory rate, breaths·min−124 (20–28)24 (20–30)22 (19–28)<0.0001
     Systolic blood pressure, mmHg130 (114–145)130 (115–144)130 (114–146)0.02
     Diastolic blood pressure, mmHg74 (65–83)75 (65–83)74 (64–84)0.0001
    Continent of admission, n (%)
     Europe34 456 (85.2)12 427 (61.9)20 029 (98.2)<0.0001
     Asia3292 (8.1)3140 (15.6)152 (0.7)<0.0001
     South America1408 (3.5)1308 (6.5)100 (0.5)<0.0001
     North America2614 (6.4)2505 (12.5)109 (0.5)<0.0001
     Africa164 (0.4)159 (0.6)5 (0.0)<0.0001
     Oceania506 (1.3)505 (2.5)1 (0.0)<0.0001
    Regional income stratification, n (%)
     High-income country35 956 (88.9)15 810 (78.8)20 146 (98.7)<0.0001
     Upper middle-income country1976 (4.8)1821 (9.1)155 (0.8)<0.0001
     Lower middle-income country2496 (6.2)2401 (11.9)96 (0.5)<0.0001
    Clinical outcomesn=38 126n=18 831n=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)

      AllPatients admitted to the ICUp-value
      YesNo
      Patients, n40 44020 04420 396
      Invasive mechanical ventilation12 462 (30.8)11 957 (59.6)505 (2.5)<0.0001
      Noninvasive mechanical ventilation15 522 (38.4)9127 (45.5)6395 (31.4)<0.0001
      High-flow nasal cannula25 433 (62.9)8891 (44.4)16 542 (81.1)<0.0001
      Inotropes or vasopressors16 542 (40.7)8375 (41.8)175 (0.9)<0.0001
      Antibiotics35 316 (87.3)17 800 (88.8)17 516 (85.9)<0.0001
      Prone positioning7825 (19.3)7390 (36.9)435 (2.1)<0.0001
      Neuraminidase inhibitors231 (0.6)118 (0.6)113 (0.6)0.69
      Neuromuscular blocking agents3647 (9.0)3597 (17.9)50 (0.2)<0.0001
      Dialysis/haemofiltration3191 (7.9)2953 (14.7)238 (1.2)<0.0001
      Corticosteroids11 435 (28.3)7627 (38.1)3808 (18.7)<0.0001
      Antivirals8025 (19.8)5925 (29.6)2100 (10.3)<0.0001
      Tracheostomy2461 (6.1)2422 (12.1)39 (0.2)<0.0001
      ECMO706 (1.7)706 (3.5)0 (0.0)<0.0001
      ACE inhibitors4399 (10.9)1991 (9.9)2408 (11.8)<0.0001
      Antifungal3200 (7.9)2384 (11.9)816 (4.0)<0.0001
      Angiotensin II receptor blockers2865 (7.1)1674 (8.4)1191 (5.8)<0.0001
      Therapeutic anticoagulants532 (1.3)510 (2.5)22 (0.1)<0.0001
      Lopinavir/ritonavir651 (1.6)397 (2.0)254 (1.2)<0.0001
      Nonsteroidal anti-inflammatory2317 (5.7)1191 (5.9)1126 (5.5)0.07
      Inhaled nitric oxide505 (1.2)491 (2.4)14 (0.1)<0.0001
      Chloroquine/hydroxychloroquine946 (2.3)718 (3.6)228 (1.1)<0.0001
      Convalescent plasma398 (1.0)248 (1.2)150 (0.7)<0.0001
      Macrolides83 (0.2)66 (0.3)17 (0.1)<0.0001
      Dexamethasone4174 (10.3)1992 (9.9)2182 (10.7)0.01
      Interferon-β131 (0.3)118 (0.6)13 (0.1)<0.0001
      Oral steroids311 (0.8)275 (1.4)36 (0.2)<0.0001
      Remdesivir2009 (5.0)1092 (5.4)917 (4.5)<0.0001
      IL-6 inhibitor122 (0.3)90 (0.4)32 (0.2)<0.0001
      Tocilizumab51 (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)

        AllPatients admitted to the ICUp-value
        YesNo
        Patients, n40 44020 04420 396
        Neurological, n (%)
         Seizures393 (1.0)240 (1.2)153 (0.8)<0.0001
         Stroke489 (1.2)281 (1.4)208 (1.0)<0.0001
         Meningitis or encephalitis113 (0.3)93 (0.5)20 (0.1)<0.0001
         Other neurological complications490 (1.2)228 (1.1)262 (1.3)0.19
        Cardiovascular, n (%)
         Congestive heart failure1183 (2.9)432 (2.2)751 (3.7)<0.0001
         Endocarditis, myocarditis, pericarditis223 (0.6)191 (1.0)32 (0.2)<0.0001
         Cardiac arrhythmia2992 (7.4)1995 (10.0)997 (4.9)<0.0001
         Cardiac arrest1457 (3.6)1012 (5.0)445 (2.2)<0.0001
         Cardiac ischaemia556 (1.4)303 (1.5)253 (1.2)0.021
         Cardiomyopathy195 (0.5)138 (0.7)57 (0.3)<0.0001
         Myocardial infarction34 (0.1)31 (0.2)3 (0.0)<0.0001
        Pulmonary, n (%)
         Bacterial pneumonia4695 (11.6)2591 (12.9)2104 (10.3)<0.0001
         Acute respiratory distress syndrome7928 (19.6)5747 (28.7)2181 (10.7)<0.0001
         Pneumothorax555 (1.4)447 (2.2)108 (0.5)<0.0001
         Pleural effusion2198 (5.4)1093 (5.5)1105 (5.4)0.89
         Pulmonary embolism272 (0.7)237 (1.2)35 (0.2)<0.0001
         Cryptogenic organising pneumonia122 (0.3)95 (0.5)27 (0.1)<0.0001
        Gastrointestinal, n (%)
         Pancreatitis138 (0.3)103 (0.5)35 (0.2)<0.0001
         Liver dysfunction2385 (5.9)1703 (8.5)682 (3.3)<0.0001
         Gastrointestinal haemorrhage393 (1.0)221 (1.1)172 (0.8)0.008
        Renal, n (%)
         Acute kidney injury6566 (16.2)4030 (20.1)2536 (12.4)<0.0001
        Metabolic, n (%)
         Hyperglycaemia3232 (8.0)2265 (11.3)967 (4.7)<0.0001
         Hypoglycaemia757 (1.9)355 (1.8)402 (2.0)0.14
        Haematological, n (%)
         Anaemia5057 (12.5)3203 (16.0)1854 (9.1)<0.0001
         Disseminated intravascular coagulation1296 (3.2)844 (4.2)452 (2.2)<0.0001
         Bleeding84 (0.2)80 (0.4)4 (0.0)<0.0001
        Others, n (%)
         Other complication6321 (15.6)2883 (14.4)3438 (16.9)<0.0001
         Bacteraemia1848 (4.6)1366 (6.8)482 (2.4)<0.0001
         Rhabdomyolysis or myositis246 (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 admission0.70 (0.65–0.75)<0.0001
        High-flow nasal cannula1.05 (1.00–1.11)0.052
        Noninvasive respiratory support1.37 (1.31–1.44)<0.0001
        Invasive mechanical ventilation1.97 (1.81–2.14)<0.0001
        Vasopressors or inotropes1.56 (1.44–1.70)<0.0001
        Number of comorbidities1.07 (1.06–1.09)<0.0001
        Temperature on hospital admission0.92 (0.90–0.94)<0.0001
        Heart rate on hospital admission1.01 (1.00–1.01)<0.0001
        Respiratory rate on hospital admission1.03 (1.02–1.03)<0.0001
        Systolic blood pressure on hospital admission1.00 (1.00–1.01)<0.0001
        Diastolic blood pressure on hospital admission0.99 (0.99–0.99)<0.0001
        Acute respiratory distress syndrome1.47 (1.39–1.56)<0.0001
        Male1.25 (1.19–1.31)<0.0001
        Month of hospital admission0.98 (0.96–0.99)<0.0001
        New cases per million1.00 (1.00–1.00)<0.0001
        Age (years)
         207.1% (5.8–8.7%)
         409.1% (8.3–9.9%)
         6019.8% (19.0–20.6%)
         8051.8% (50.7–52.9%)

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        Supplementary material 00552-2021.supplement

        Case report form 00552-2021.CRF

        Protocol 00552-2021.protocol

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      Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study
      Luis Felipe Reyes, Srinivas Murthy, Esteban Garcia-Gallo, Mike Irvine, Laura Merson, Ignacio Martin-Loeches, Jordi Rello, Fabio S. Taccone, Robert A. Fowler, Annemarie B. Docherty, Christiana Kartsonaki, Irene Aragao, Peter W. Barrett, Abigail Beane, Aidan Burrell, Matthew Pellan Cheng, Michael D. Christian, Jose Pedro Cidade, Barbara Wanjiru Citarella, Christl A. Donnelly, Susana M. Fernandes, Craig French, Rashan Haniffa, Ewen M. Harrison, Antonia Ying Wai Ho, Mark Joseph, Irfan Khan, Michelle E. Kho, Anders Benjamin Kildal, Demetrios Kutsogiannis, François Lamontagne, Todd C. Lee, Gianluigi Li Bassi, Jose Wagner Lopez Revilla, Catherine Marquis, Jonathan Millar, Raul Neto, Alistair Nichol, Rachael Parke, Rui Pereira, Sergio Poli, Pedro Povoa, Kollengode Ramanathan, Oleksa Rewa, Jordi Riera, Sally Shrapnel, Maria Joao Silva, Andrew Udy, Timothy Uyeki, Steve A. Webb, Evert-Jan Wils, Amanda Rojek, Piero L. Olliaro, ISARIC Clinical Characterisation Group
      ERJ Open Research Jan 2022, 8 (1) 00552-2021; DOI: 10.1183/23120541.00552-2021

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      Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study
      Luis Felipe Reyes, Srinivas Murthy, Esteban Garcia-Gallo, Mike Irvine, Laura Merson, Ignacio Martin-Loeches, Jordi Rello, Fabio S. Taccone, Robert A. Fowler, Annemarie B. Docherty, Christiana Kartsonaki, Irene Aragao, Peter W. Barrett, Abigail Beane, Aidan Burrell, Matthew Pellan Cheng, Michael D. Christian, Jose Pedro Cidade, Barbara Wanjiru Citarella, Christl A. Donnelly, Susana M. Fernandes, Craig French, Rashan Haniffa, Ewen M. Harrison, Antonia Ying Wai Ho, Mark Joseph, Irfan Khan, Michelle E. Kho, Anders Benjamin Kildal, Demetrios Kutsogiannis, François Lamontagne, Todd C. Lee, Gianluigi Li Bassi, Jose Wagner Lopez Revilla, Catherine Marquis, Jonathan Millar, Raul Neto, Alistair Nichol, Rachael Parke, Rui Pereira, Sergio Poli, Pedro Povoa, Kollengode Ramanathan, Oleksa Rewa, Jordi Riera, Sally Shrapnel, Maria Joao Silva, Andrew Udy, Timothy Uyeki, Steve A. Webb, Evert-Jan Wils, Amanda Rojek, Piero L. Olliaro, ISARIC Clinical Characterisation Group
      ERJ Open Research Jan 2022, 8 (1) 00552-2021; DOI: 10.1183/23120541.00552-2021
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