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, Mark Bower, Christopher C.T. Sng, Ramón Salazar, Alexia Bertuzzi, Joan Brunet, Ricard Mesı́a, 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 Tondini, Oriol Mirallas, Valeria Tovazzi, Vittoria Fotia, Claudia Andrea Cruz, N. Saoudi Gonzalez, Eudald Felip, Ariadna Roqué, Alvin Lee, Tom Newsom‐Davis, David García-Illescas, Roxana Reyes, Yien Ning Sophia Wong, Daniela Ferrante, Lorenza Scotti, Javier Marco‐Hernández, Isabel Ruíz-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
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.