Derivation and Validation of a Predictive Score for Disease Worsening in Patients with COVID-19

Abstract

The prospective observational cohort study COMPASS-COVID-19 aimed to develop a risk assessment model for early identification of hospitalized COVID-19 patients at risk for worsening disease. Patients with confirmed COVID-19 (n = 430) hospitalized between March 18 and April 21, 2020 were divided in derivation (n = 310) and validation (n = 120) cohorts. Two groups became evident: (1) good prognosis group (G-group) with patients hospitalized at the conventional COVID-19 ward and (2) Worsening disease group (W-group) with patients admitted to the intensive care unit (ICU) from the emergency departments. The study end point was disease worsening (acute respiratory failure, shock, myocardial dysfunction, bacterial or viral coinfections, and acute kidney injury) requiring ICU admission. All patients were routinely evaluated for full blood count, prothrombin time, fibrinogen, D-dimers, antithrombin (AT), and protein C activity. Data from the first hospitalization day at the conventional ward or the ICU were analyzed. Cardiovascular risk factors and comorbidities were routinely registered. Obesity, hypertension, diabetes and male gender, increased fibrinogen and D-dimers, thrombocytopenia, AT deficiency, lymphopenia, and an International Society on Thrombosis and Haemostasis (ISTH) score for compensated disseminated intravascular coagulation score (cDIC-ISTH) ≥5 were significant risk factors for worsening disease. The COMPASS-COVID-19 score was derived from multivariate analyses and includes obesity, gender, hemoglobin, lymphocyte, and the cDIC-ISTH score (including platelet count, prothrombin time, D-dimers, AT, and protein C levels). The score has a very good discriminating capacity to stratify patients at high and low risk for worsening disease, with an area under the receiver operating characteristic curve value of 0.77, a sensitivity of 81%, and a specificity of 60%. Application of the COMPASS-COVID-19 score at the validation cohort showed 96% sensitivity. The COMPASS-COVID-19 score is an accurate clinical decision-making tool for an easy identification of COVID-19 patients being at high risk for disease worsening.

Keywords

COVID-19 - SARS-CoV-2 - disseminated intravascular coagulation - antithrombin - D-dimers

Data Sharing

After approval from the legal authorities of the Assistance Publique-Hôpitaux de Paris (APHP), data can be shared—after contacting the corresponding author ([e-mail])—with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.

Authors' Contributions

G.T.G. as principal investigator has made substantial contributions to the conception and design of the study and analysis and interpretation of the data, wrote the manuscript and has given the final approval of the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. T.N.S. has made substantial contribution by doing the statistical plan and the statistical analysis. G.V. has made substantial contribution in the enrolment of the patients and participated in the design of the study. L.L. has made substantial contribution in the enrolment of the patients. C.P. has made substantial contribution in data acquisition, data interpretation, and critical revision of the manuscript. A.E. participated in the enrollment of the patients and data acquisition. M.T. participated in the enrollment of the patients and data acquisition. P.V. participated in the critical revision and editing of the manuscript. L.P. participated in the critical revision and editing of the manuscript. T.P. participated in the statistical analysis. E.T. critically revised the manuscript. M-.A.D. gave valuable suggestions for data analysis and critically revised the manuscript. A.P., J.C., and G.P. have made substantial contribution in the enrollment of the patients and critically revised the manuscript. M.F. made substantial contribution to the design of the study, the interpretation of the data, and critically revised the manuscript. I.E. critically revised the manuscript.

Publikationsverlauf

Eingereicht: 18. Mai 2020

Angenommen: 13. August 2020

Artikel online veröffentlicht:
22. September 2020

• References

• 1 Wu F, Zhao S, Yu B. et al. A new coronavirus associated with human respiratory disease in China. Nature 2020; 579 (7798): 265-269
• 2 Lu R, Zhao X, Li J. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395 (10224): 565-574
• 3 Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020; 94 (07) e00127-20
• 4 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
• 5 Chen N, Zhou M, Dong X. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395 (10223): 507-513
• 6 Driggin E, Madhavan MV, Bikdeli B. et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol 2020; 75 (18) 2352-2371
• 7 Bangash MN, Patel J, Parekh D. COVID-19 and the liver: little cause for concern. Lancet Gastroenterol Hepatol 2020; 5 (06) 529-530
• 8 Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395 (10229): 1033-1034
• 9 Bikdeli B, Madhavan MV, Jimenez D. et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75 (23) 2950-2973
• 10 Thachil J, Tang N, Gando S. et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020; 18 (05) 1023-1026
• 11 Kollias A, Kyriakoulis KG, Dimakakos E, Poulakou G, Stergiou GS, Syrigos K. Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action. Br J Haematol 2020; 189 (05) 846-847
• 12 Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 2020; 323 (18) 1775-1776
• 13 Poston JT, Patel BK, Davis AM. Management of critically ill adults with COVID-19. JAMA 2020; 323 (18) 1839-1841
• 14 Terpos E, Ntanasis-Stathopoulos I, Elalamy I. et al. Hematological findings and complications of COVID-19. Am J Hematol 2020; 95 (07) 834-847
• 15 Li X, Xu S, Yu M. et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol 2020; 146 (01) 110-118
• 16 Phua J, Weng L, Ling L. et al. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations. Lancet Respir Med 2020; 8 (05) 506-517
• 17 Cao B, Wang Y, Wen D. et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020; 382 (19) 1787-1799
• 18 Shen C, Wang Z, Zhao F. et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020; 323 (16) 1582-1589
• 19 Alexander PE, Debono VB, Mammen MJ. COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine. J Clin Epidemiol 2020; 123: 120-126
• 20 Baden LR, Rubin EJ. Covid-19–the search for effective therapy. N Engl J Med 2020; 382 (19) 1851-1852
• 21 Grein J, Ohmagari N, Shin D. et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med 2020; 382 (24) 2327-2336
• 22 Rubin GD, Ryerson CJ, Haramati LB. et al. The role of chest imaging in patient management during the COVID-19 Pandemic: a multinational consensus statement from the Fleischner Society. Radiology 2020; 296 (01) 172-180
• 23 Taylor FB, Toh CH, Hoots WK, Wada H, Levi M. Scientific subcommittee on disseminated intravascular coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86 (05) 1327-1330
• 24 Hendriksen JM, Geersing GJ, Moons KG, de Groot JA. Diagnostic and prognostic prediction models. J Thromb Haemost 2013; 11 (Suppl. 01) 129-141
• 25 Harrell Jr FE, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996; 15 (04) 361-387
• 26 Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 1996; 49 (12) 1373-1379
• 27 Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (04) 844-847
• 28 Wu C, Chen X, Cai Y. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020; 180 (07) 1-11
• 29 Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395 (10234): 1417-1418
• 30 Du Y, Tu L, Zhu P. et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan. A retrospective observational study. Am J Respir Crit Care Med 2020; 201 (11) 1372-1379
• 31 Cattaneo M, Bertinato EM, Birocchi S. et al. Pulmonary embolism or pulmonary thrombosis in COVID-19? Is the recommendation to use high-dose heparin for thromboprophylaxis justified?. Thromb Haemost 2020; 120 (08) 1230-1232
• 32 Moons KGM, Altman DG, Reitsma JB. et al. Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med 2015; 162 (01) W1-73
• 33 Wynants L, Van Calster B, Collins GS. et al. Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal. BMJ 2020; 369: m1328
• 34 Richardson S, Hirsch JS, Narasimhan M. et al; and the Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA 2020; 323 (20) 2052-2059
• 35 Garg S, Kim L, Whitaker M. et al. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 states, March 1-30, 2020. MMWR Morb Mortal Wkly Rep 2020; 69 (15) 458-464
• 36 Zheng Z, Peng F, Xu B. et al. Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis. J Infect 2020; 81 (12) e16-e25
• 37 Mehra MR, Desai SS, Kuy S. et al. Cardiovascular disease, drug therapy, and mortality in Covid-19. N Engl J Med 2020; 382: e102
• 38 Miyara M, Tubach F, Pourcher V. et al. Low incidence of daily active tobacco smoking in patients with symptomatic COVID-19. Qeios 2020;
• 39 Bai X, Fang C, Zhou Y. et al. Predicting COVID-19 malignant progression with AI techniques. medRxiv 2020;
• 40 Gong J, Ou J, Qiu X. et al. A tool for early prediction of severe coronavirus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clin Infect Dis 2020; 71 (15) 833-840
• 41 Li DL, Shen F, Yin Y, Peng JX, Chen PY. Weighted Youden index and its two-independent-sample comparison based on weighted sensitivity and specificity. Chin Med J (Engl) 2013; 126 (06) 1150-1154
• 42 Wang Y, Zhang D, Du G. et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020; 395 (10236): P1569-P1578