Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: The OnCovid Inflammatory Score

Gino M. Dettorre; Saoirse Dolly; Angela Loizidou; John Chester; Amanda Jackson; Uma Mukherjee; Alberto Zambelli; Juan Aguilar-Company; Mark Bower; Christopher C.T. Sng; Ramon Salazar; Alexia Bertuzzi; Joan Brunet; Ricard Mesia; Ailsa Sita-Lumsden; Elia Seguí; Federica Biello; Daniele Generali; Salvatore Grisanti; Pavetha Seeva; Gianpiero Rizzo; Michela Libertini; Antonio MacOni; Charlotte Moss; Beth Russell; Nadia Harbeck; Bruno Vincenzi; Rossella Bertulli; Diego Ottaviani; Raquel Liñan; Andrea Marrari; M. Carmen Carmona-García; Neha Chopra; Carlo Alberto Tondini; Oriol Mirallas; Valeria Tovazzi; Vittoria Fotia; Claudia Andrea Cruz; Nadia Saoudi-Gonzalez; Eudald Felip; Ariadna Roqué; Alvin J.X. Lee; Tom Newsom-Davis; David García-Illescas; Roxana Reyes; Yien Ning Sophia Wong; Daniela Ferrante; Lorenza Scotti; Javier Marco-Hernández; Isabel Ruiz-Camps; Andrea Patriarca; Lorenza Rimassa; Lorenzo Chiudinelli; Michela Franchi; Armando Santoro; Aleix Prat; Alessandra Gennari; Mieke Van Hemelrijck; Josep Tabernero; Nikolaos Diamantis; David J. Pinato

doi:10.1136/jitc-2020-002277

Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: The OnCovid Inflammatory Score

Gino M. Dettorre
, Saoirse Dolly
, Angela Loizidou
, John Chester
, Amanda Jackson
, Uma Mukherjee
, Alberto Zambelli
, Juan Aguilar-Company
, Mark Bower
, Christopher C.T. Sng
, Ramon Salazar
, Alexia Bertuzzi
, Joan Brunet
, Ricard Mesia
, Ailsa Sita-Lumsden
, Elia Seguí
, Federica Biello
, Daniele Generali
, Salvatore Grisanti
, Pavetha Seeva

Gianpiero Rizzo, Michela Libertini, Antonio MacOni, Charlotte Moss, Beth Russell, Nadia Harbeck, Bruno Vincenzi, Rossella Bertulli, Diego Ottaviani, Raquel Liñan, Andrea Marrari, M. Carmen Carmona-García, Neha Chopra, Carlo Alberto Tondini, Oriol Mirallas, Valeria Tovazzi, Vittoria Fotia, Claudia Andrea Cruz, Nadia Saoudi-Gonzalez, Eudald Felip, Ariadna Roqué, Alvin J.X. Lee, Tom Newsom-Davis, David García-Illescas, Roxana Reyes, Yien Ning Sophia Wong, Daniela Ferrante, Lorenza Scotti, Javier Marco-Hernández, Isabel Ruiz-Camps, Andrea Patriarca, Lorenza Rimassa, Lorenzo Chiudinelli, Michela Franchi, Armando Santoro, Aleix Prat, Alessandra Gennari, Mieke Van Hemelrijck, Josep Tabernero, Nikolaos Diamantis, David J. Pinato

Dipartimento di Medicina Traslazionale

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Background Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p<0.01), recovering in survivors to pre-COVID-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (p<0.001) and shorter median overall survival in the training and validation sets (p<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 to 4.20, p=0.001; adjusted concordance index score 0.611). Conclusions Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected patients with cancer and can be used as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe COVID-19, supporting their use for risk stratification. Reversal of the COVID-19-induced proinflammatory state is a putative therapeutic strategy in patients with cancer.

Lingua originale	Inglese
Numero di articolo	e002277
Rivista	Journal for ImmunoTherapy of Cancer
Volume	9
Numero di pubblicazione	3
DOI	https://doi.org/10.1136/jitc-2020-002277
Stato di pubblicazione	Pubblicato - 22 mar 2021

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10.1136/jitc-2020-002277

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Dettorre, G. M., Dolly, S., Loizidou, A., Chester, J., Jackson, A., Mukherjee, U., Zambelli, A., Aguilar-Company, J., Bower, M., Sng, C. C. T., Salazar, R., Bertuzzi, A., Brunet, J., Mesia, R., Sita-Lumsden, A., Seguí, E., Biello, F., Generali, D., Grisanti, S., ... Pinato, D. J. (2021). Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: The OnCovid Inflammatory Score. Journal for ImmunoTherapy of Cancer, 9(3), Articolo e002277. https://doi.org/10.1136/jitc-2020-002277

@article{ce9d851a65d747bf8727b46bffb83c41,

title = "Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: The OnCovid Inflammatory Score",

abstract = "Background Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results We evaluated 1071 eligible patients, of which 625 (58.3\%) were men, and 420 were patients with malignancy in advanced stage (39.2\%), most commonly genitourinary (n=216, 20.2\%). 844 (78.8\%) had ≥1 comorbidity and 754 (70.4\%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p<0.01), recovering in survivors to pre-COVID-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (p<0.001) and shorter median overall survival in the training and validation sets (p<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95\% CI 1.47 to 4.20, p=0.001; adjusted concordance index score 0.611). Conclusions Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected patients with cancer and can be used as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe COVID-19, supporting their use for risk stratification. Reversal of the COVID-19-induced proinflammatory state is a putative therapeutic strategy in patients with cancer.",

keywords = "COVID-19, inflammation, inflammation mediators",

author = "Dettorre, \{Gino M.\} and Saoirse Dolly and Angela Loizidou and John Chester and Amanda Jackson and Uma Mukherjee and Alberto Zambelli and Juan Aguilar-Company and Mark Bower and Sng, \{Christopher C.T.\} and Ramon Salazar and Alexia Bertuzzi and Joan Brunet and Ricard Mesia and Ailsa Sita-Lumsden and Elia Segu{\'i} and Federica Biello and Daniele Generali and Salvatore Grisanti and Pavetha Seeva and Gianpiero Rizzo and Michela Libertini and Antonio MacOni and Charlotte Moss and Beth Russell and Nadia Harbeck and Bruno Vincenzi and Rossella Bertulli and Diego Ottaviani and Raquel Li{\~n}an and Andrea Marrari and \{Carmen Carmona-Garc{\'i}a\}, M. and Neha Chopra and Tondini, \{Carlo Alberto\} and Oriol Mirallas and Valeria Tovazzi and Vittoria Fotia and Cruz, \{Claudia Andrea\} and Nadia Saoudi-Gonzalez and Eudald Felip and Ariadna Roqu{\'e} and Lee, \{Alvin J.X.\} and Tom Newsom-Davis and David Garc{\'i}a-Illescas and Roxana Reyes and Wong, \{Yien Ning Sophia\} and Daniela Ferrante and Lorenza Scotti and Javier Marco-Hern{\'a}ndez and Isabel Ruiz-Camps and Andrea Patriarca and Lorenza Rimassa and Lorenzo Chiudinelli and Michela Franchi and Armando Santoro and Aleix Prat and Alessandra Gennari and \{Van Hemelrijck\}, Mieke and Josep Tabernero and Nikolaos Diamantis and Pinato, \{David J.\}",

note = "Publisher Copyright: {\textcopyright} ",

year = "2021",

month = mar,

day = "22",

doi = "10.1136/jitc-2020-002277",

language = "English",

volume = "9",

journal = "Journal for ImmunoTherapy of Cancer",

issn = "2051-1426",

publisher = "BMJ Publishing Group",

number = "3",

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Dettorre, GM, Dolly, S, Loizidou, A, Chester, J, Jackson, A, Mukherjee, U, Zambelli, A, Aguilar-Company, J, Bower, M, Sng, CCT, Salazar, R, Bertuzzi, A, Brunet, J, Mesia, R, Sita-Lumsden, A, Seguí, E, Biello, F, Generali, D, Grisanti, S, Seeva, P, Rizzo, G, Libertini, M, MacOni, A, Moss, C, Russell, B, Harbeck, N, Vincenzi, B, Bertulli, R, Ottaviani, D, Liñan, R, Marrari, A, Carmen Carmona-García, M, Chopra, N, Tondini, CA, Mirallas, O, Tovazzi, V, Fotia, V, Cruz, CA, Saoudi-Gonzalez, N, Felip, E, Roqué, A, Lee, AJX, Newsom-Davis, T, García-Illescas, D, Reyes, R, Wong, YNS, Ferrante, D , Scotti, L, Marco-Hernández, J, Ruiz-Camps, I, Patriarca, A, Rimassa, L, Chiudinelli, L, Franchi, M, Santoro, A, Prat, A, Gennari, A, Van Hemelrijck, M, Tabernero, J, Diamantis, N & Pinato, DJ 2021, 'Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: The OnCovid Inflammatory Score', Journal for ImmunoTherapy of Cancer, vol. 9, n. 3, e002277. https://doi.org/10.1136/jitc-2020-002277

Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: The OnCovid Inflammatory Score. / Dettorre, Gino M.; Dolly, Saoirse; Loizidou, Angela et al.
In: Journal for ImmunoTherapy of Cancer, Vol. 9, N. 3, e002277, 22.03.2021.

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

TY - JOUR

T1 - Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection

T2 - The OnCovid Inflammatory Score

AU - Dettorre, Gino M.

AU - Dolly, Saoirse

AU - Loizidou, Angela

AU - Chester, John

AU - Jackson, Amanda

AU - Mukherjee, Uma

AU - Zambelli, Alberto

AU - Aguilar-Company, Juan

AU - Bower, Mark

AU - Sng, Christopher C.T.

AU - Salazar, Ramon

AU - Bertuzzi, Alexia

AU - Brunet, Joan

AU - Mesia, Ricard

AU - Sita-Lumsden, Ailsa

AU - Seguí, Elia

AU - Biello, Federica

AU - Generali, Daniele

AU - Grisanti, Salvatore

AU - Seeva, Pavetha

AU - Rizzo, Gianpiero

AU - Libertini, Michela

AU - MacOni, Antonio

AU - Moss, Charlotte

AU - Russell, Beth

AU - Harbeck, Nadia

AU - Vincenzi, Bruno

AU - Bertulli, Rossella

AU - Ottaviani, Diego

AU - Liñan, Raquel

AU - Marrari, Andrea

AU - Carmen Carmona-García, M.

AU - Chopra, Neha

AU - Tondini, Carlo Alberto

AU - Mirallas, Oriol

AU - Tovazzi, Valeria

AU - Fotia, Vittoria

AU - Cruz, Claudia Andrea

AU - Saoudi-Gonzalez, Nadia

AU - Felip, Eudald

AU - Roqué, Ariadna

AU - Lee, Alvin J.X.

AU - Newsom-Davis, Tom

AU - García-Illescas, David

AU - Reyes, Roxana

AU - Wong, Yien Ning Sophia

AU - Ferrante, Daniela

AU - Scotti, Lorenza

AU - Marco-Hernández, Javier

AU - Ruiz-Camps, Isabel

AU - Patriarca, Andrea

AU - Rimassa, Lorenza

AU - Chiudinelli, Lorenzo

AU - Franchi, Michela

AU - Santoro, Armando

AU - Prat, Aleix

AU - Gennari, Alessandra

AU - Van Hemelrijck, Mieke

AU - Tabernero, Josep

AU - Diamantis, Nikolaos

AU - Pinato, David J.

PY - 2021/3/22

Y1 - 2021/3/22

N2 - Background Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p<0.01), recovering in survivors to pre-COVID-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (p<0.001) and shorter median overall survival in the training and validation sets (p<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 to 4.20, p=0.001; adjusted concordance index score 0.611). Conclusions Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected patients with cancer and can be used as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe COVID-19, supporting their use for risk stratification. Reversal of the COVID-19-induced proinflammatory state is a putative therapeutic strategy in patients with cancer.

AB - Background Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p<0.01), recovering in survivors to pre-COVID-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (p<0.001) and shorter median overall survival in the training and validation sets (p<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 to 4.20, p=0.001; adjusted concordance index score 0.611). Conclusions Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected patients with cancer and can be used as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe COVID-19, supporting their use for risk stratification. Reversal of the COVID-19-induced proinflammatory state is a putative therapeutic strategy in patients with cancer.

KW - COVID-19

KW - inflammation

KW - inflammation mediators

UR - https://www.scopus.com/pages/publications/85103323662

U2 - 10.1136/jitc-2020-002277

DO - 10.1136/jitc-2020-002277

M3 - Article

SN - 2051-1426

VL - 9

JO - Journal for ImmunoTherapy of Cancer

JF - Journal for ImmunoTherapy of Cancer

IS - 3

M1 - e002277

ER -

Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: The OnCovid Inflammatory Score

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