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. 2022 Feb 25;3(3):100560.
doi: 10.1016/j.xcrm.2022.100560. eCollection 2022 Mar 15.

Development and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failure

Evangelos J Giamarellos-Bourboulis  1   2 , Garyfallia Poulakou  3 , Aline de Nooijer  4 , Haralampos Milionis  5 , Simeon Metallidis  6 , Michalis Ploumidis  7 , Pinelopi Grigoropoulou  8 , Aggeliki Rapti  9 , Francesco Vladimiro Segala  10 , Evangelos Balis  11 , Efthymia Giannitsioti  12 , Paola Rodari  13 , Ilias Kainis  14 , Zoi Alexiou  15 , Emanuele Focà  16 , Brollo Lucio  17 , Nikoletta Rovina  18 , Laura Scorzolini  19 , Maria Dafni  20 , Sofia Ioannou  21 , Alessandro Tomelleri  22 , Katerina Dimakou  23 , Glykeria Tzatzagou  24 , Maria Chini  25 , Matteo Bassetti  26 , Christina Trakatelli  27 , George Tsoukalas  28 , Carlo Selmi  29 , Charilaos Samaras  30 , Maria Saridaki  31 , Athina Pyrpasopoulou  32 , Elisabeth Kaldara  33 , Ilias Papanikolaou  34 , Aikaterini Argyraki  35 , Karolina Akinosoglou  36 , Marina Koupetori  37 , Periklis Panagopoulos  38 , George N Dalekos  39 , Mihai G Netea  4   40
Affiliations

Development and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failure

Evangelos J Giamarellos-Bourboulis et al. Cell Rep Med. .

Abstract

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

Keywords: C-reactive protein; COVID-19; D dimers; SARS-CoV-2; biomarkers; disease progression; ferritin; interleukin-6; soluble urokinase plasminogen activator receptor.

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Conflict of interest statement

E.J.G.-B. has received honoraria from Abbott CH, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi, and XBiotech, Inc.; independent educational grants from Abbott CH, AxisShield, bioMérieux, InflaRx GmbH, Johnson & Johnson, MSD, Sobi, and XBiotech, Inc.; and funding from the Horizon 2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens) and the Horizon 2020 European Grants ImmunoSep and RISCinCOVID (granted to the Hellenic Institute for the Study of Sepsis). G.P. has received independent educational grants from Pfizer, MSD, Angelini, and Bio-Rad. H.M. reports receiving honoraria, consulting fees, and non-financial support from health care companies, including Amgen, Angelini, Bayer, Mylan, MSD, Pfizer, and Servier. L.D. has received consultation honoraria from SOBI. M.B. has received funds for research grants from and/or has been an advisor/consultant and/or speaker/chairman for Angelini, Astellas, Bayer, bioMérieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Roche, Shionogi, and Nabriva. P.P. has received honoraria from GILEAD Sciences, Janssen, and MSD. G.N.D. is an advisor or lecturer for Ipsen, Pfizer, Genkyotex, Novartis, and Sobi; received research grants from Abbvie and Gilead; and has served as PI in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics, Inc., Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics, Inc., Sobi, and Intercept Pharmaceuticals. M.G.N. is supported by an ERC advanced grant (833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. M.G.N. is a scientific founder of TTxD and he has received independent educational grants from TTxD, GSK, Ono Pharma, and ViiV HealthCare. The other authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Flowchart of the discovery and the validation cohorts The discovery cohort was recruited from patients screened for eligibility for participation in the SAVE-MORE trial and for which the screening samples were available for the measurement of the SCOPE score. The samples of patients with suPAR of less than 6 ng/mL and of patients with suPAR of 6 ng/mL or more treated in the SAVE-MORE trial with placebo were analyzed for the primary endpoint, i.e., prediction of progression into severe respiratory failure or death within the first 14 days (302 total). Samples from all 639 patients were analyzed for the ability of the SCOPE score to predict suPAR levels; and 263 patients with SCOPE score of 6 or more were analyzed for the efficacy of anakinra treatment. The validation cohort I came from the SAVE trial and it was analyzed for the same endpoints as the discovery cohort. The validation cohort II came from the Netherlands and it was analyzed for the primary endpoint. SCOPE, Severe COvid Prediction Estimate; SoC, standard of care; suPAR, soluble urokinase plasminogen activator receptor; WHO-CPS, World Health Organization Clinical Progression Scale.
Figure 2
Figure 2
Discovery of the SCOPE score and comparative performance to that of suPAR for the prediction of progression into severe respiratory failure (SRF) or death within the first 14 days (A) ROC curves of the SCOPE score and suPAR to predict progression into SRF or death within the first 14 days. (B) Prognostic performance of SCOPE score of 6 or more to predict progression into SRF or death within the first 14 days. The odds for patients with a score of 6 or more to progress into SRF or death within the first 14 days are provided (calculation by Mantel Haenszel statistics). (C) Prognostic performance of suPAR values of 6 ng/mL or more to predict the progression into SRF or death within the first 14 days. The odds for patients with suPAR of 6 ng/mL or more to progress into SRF or death are provided (calculation by Mantel Haenszel statistics). (D) The p values of comparisons of the AUC of ROC, of sensitivity, of specificity, of PPV, and of NPV of the SCOPE score and of suPAR to predict progression into SRF or death within the first 14 days. AUC, area under the curve; CI, confidence intervals; NPV, negative predictive value; n, number of patients; OR, odds ratio; PPV, positive predictive value; SCOPE, Severe COvid Prediction Estimate; suPAR, soluble urokinase plasminogen activator receptor.
Figure 3
Figure 3
Estimates of SRF or death by SCOPE score and by suPAR levels within 14 days of hospitalization for COVID-19 pneumonia in the discovery cohort The comparison includes patients enrolled in the SAVE-MORE trial and randomized to treatment with standard of care (SoC) and placebo (n = 128) and patients who were screened for enrollment in the SAVE-MORE trial and who were not enrolled because suPAR was less than 6 ng/mL (n = 174); all patients with suPAR less than 6 ng/mL received SoC treatment. (A) Time to progression into SRF or death within the first 14 days when suPAR was 6 ng/mL or more and when suPAR was less than 6 ng/mL. (B) Time to progression into SRF or death within the first 14 days when the SCORE score was 6 or more and when the SCOPE score was less than 6. (C) Univariate and multivariate forward stepwise Cox regression analysis of variables associated with progression to SRF or death within 14 days. BMI, body mass index; CI, confidence intervals; HFO, high-flow oxygen; HR, hazard ratio; MV, mechanical ventilation; n, number of patients; NIV, non-invasive ventilation; P/F, respiratory failure; SCOPE, Severe COvid Prediction Estimate; suPAR, soluble urokinase plasminogen activator receptor.
Figure 4
Figure 4
Response to anakinra treatment of patients enrolled in the SAVE-MORE trial with SCOPE score of 6 or more in the discovery cohort (A) Distribution of the World Health Organization (WHO) Clinical Progression Scale (CPS) at day 28 for patients allocated to treatment with SoC and placebo and to treatment with SoC and anakinra. The OR of the unadjusted ordinal regression analysis and the 95% CIs are shown. (B) Univariate and multivariate ordinal regression analysis of the WHO-CPS at day 28. BMI, body mass index; CI, confidence interval; ECMO, extracorporeal membrane oxygenation; HFO, high-flow oxygen; MV, mechanical ventilation; NIV, non-invasive ventilation; OR, odds ratio; PCR, polymerase chain reaction; P/F, respiratory failure; SoC, standard of care.
Figure 5
Figure 5
Comparative performance of the SCOPE score and suPAR to predict progression into severe respiratory failure (SRF) or death within the first 14 days in validation cohort I (A) ROC curves of the SCOPE score and suPAR to predict progression into SRF or death within the first 14 days. (B) Prognostic performance of SCOPE score values of 6 or more to predict progression into SRF or death within the first 14 days. The odds for patients with a score of 6 or more to progress into SRF or death are provided (calculation by Mantel Haenszel statistics). (C) Prognostic performance of suPAR values of 6 ng/mL or more to predict progression into SRF or death within the first 14 days. The odds for patients with suPAR of 6 ng/mL or more to progress into SRF or death are provided (calculation by Mantel Haenszel statistics). (D) The p values of comparisons of the AUC of ROC, of sensitivity, of specificity, of PPV, and of NPV of SCOPE score and of suPAR to predict progression into SRF or death within the first 14 days. AUC, area under the curve; CI, confidence interval; NPV, negative predictive value; n, number of patients; OR, odds ratio; PPV, positive predictive value; suPAR, soluble urokinase plasminogen activator receptor.
Figure 6
Figure 6
Comparative performance of the SCOPE score and suPAR to predict progression into severe respiratory failure (SRF) or death within the first 14 days in validation cohort II (A) ROC curves of the SCOPE score and suPAR to predict progression into SRF or death within the first 14 days. (B) Prognostic performance of SCOPE score values of 6 or more to predict progression into SRF or death within the first 14 days. The odds for patients with a score of 6 or more to progress into SRF or death are provided (calculation by Mantel Haenszel statistics). (C) Prognostic performance of suPAR values of 6 ng/mL or more to predict progression into SRF or death within the first 14 days. The odds for patients with suPAR of 6 ng/mL or more to progress into SRF or death are provided (calculation by Mantel Haenszel statistics). (D) The p values for comparisons of the AUC of ROC, of sensitivity, of specificity, of PPV, and of NPV of SCOPE score and suPAR to predict progression into SRF or death within the first 14 days. AUC, area under the curve; CI, confidence interval; NPV, negative predictive value; n, number of patients; OR, odds ratio; PPV, positive predictive value; suPAR, soluble urokinase plasminogen activator receptor.
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