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Multicenter Study
. 2021 Mar;9(3):e002277.
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  1 , Saoirse Dolly  2 , Angela Loizidou  3 , John Chester  4   5 , Amanda Jackson  6 , Uma Mukherjee  7 , Alberto Zambelli  8 , Juan Aguilar-Company  9   10 , Mark Bower  11 , Christopher C T Sng  12 , Ramon Salazar  13 , Alexia Bertuzzi  14 , Joan Brunet  15 , Ricard Mesia  16 , Ailsa Sita-Lumsden  2 , Elia Seguí  17 , Federica Biello  18 , Daniele Generali  19   20 , Salvatore Grisanti  21 , Pavetha Seeva  2 , Gianpiero Rizzo  22 , Michela Libertini  23 , Antonio Maconi  24 , Charlotte Moss  25 , Beth Russell  25 , Nadia Harbeck  26 , Bruno Vincenzi  27 , Rossella Bertulli  28 , Diego Ottaviani  12 , Raquel Liñan  15 , Andrea Marrari  14 , M Carmen Carmona-García  15 , Neha Chopra  12 , Carlo Alberto Tondini  8 , Oriol Mirallas  9 , Valeria Tovazzi  21 , Vittoria Fotia  8 , Claudia Andrea Cruz  17 , Nadia Saoudi-Gonzalez  9 , Eudald Felip  16 , Ariadna Roqué  15 , Alvin J X Lee  12 , Tom Newsom-Davis  11 , David García-Illescas  9 , Roxana Reyes  17 , Yien Ning Sophia Wong  12 , Daniela Ferrante  29 , Lorenza Scotti  29 , Javier Marco-Hernández  30 , Isabel Ruiz-Camps  10 , Andrea Patriarca  31 , Lorenza Rimassa  32 , Lorenzo Chiudinelli  8 , Michela Franchi  8 , Armando Santoro  32 , Aleix Prat  33 , Alessandra Gennari  18 , Mieke Van Hemelrijck  2   25 , Josep Tabernero  34 , Nikolaos Diamantis  7 , David J Pinato  35   18 ; OnCovid study group
Affiliations
Multicenter Study

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

Gino M Dettorre et al. J Immunother Cancer. 2021 Mar.

Erratum in

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.

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Conflict of interest statement

Competing interests: DJP received lecture fees from ViiV Healthcare and Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, and Astra Zeneca; research funding (to institution) from MSD and BMS. AP has declared personal honoraria from Pfizer, Novartis, Roche, MSD Oncology, Eli Lilly, and Daiichi Sankyo; travel, accommodations, and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis; and consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb. TND has declared consulting/advisory role for Amgen, Bayer, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Roche, and Takeda; speakers fees from AstraZeneca, MSD, Roche, Takeda; and travel, accommodations and expenses paid by AstraZenca, BMS, Boehringer Ingelheim, Lilly, MSD, Otsuka, Roche, and Takeda. JB has declared consulting/advisory role for MSD and Astra Zeneca. PPS has declared consulting/advisory role for Sanofi and Abbvie. AP has declared consulting/advisory role for Takeda and Sanofi. MP has declared consulting/advisory role for Gilead and Bayer. AG has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: EISAI, Eli Lilly, and Roche. LR reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Sanofi; lectures fees from AbbVie, Amgen, Eisai, Gilead, Incyte, Ipsen, Lilly, Roche, and Sanofi; travel fees from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, and Roche. All remaining authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Patient disposition. mGPS, modified Glasgow Prognostic Score; NLR, neutrophil:lymphocyte ratio; OIS, OnCovid Inflammatory Score; PI, Prognostic Index; PLR, platelet:lymphocyte ratio.
Figure 2
Figure 2
Relationship between inflammatory markers and COVID-19 outcomes and marker values at timepoints. (A) Median inflammatory index values or distributions at COVID-19 diagnosis in living versus deceased patients for the NLR (n=661 alive, n=360 dead; p§amp;lt;0.0001), PLR (n=628 alive, 338 dead; p§amp;lt;0.05), OIS (n=413 alive, n=230 dead; p§amp;lt;0.0001), mGPS (n=430 alive, n=229 dead; p§amp;lt;0.0001), and PI (n=525 alive, n=295 dead; p§amp;lt;0.0001). (B) Median values and distributions across timepoints for the NLR (n=55), PLR (n=50), OIS (n=23), mGPS (n=143 pre-COVID-19, n=672 at diagnosis, n=32 post-COVID-19), and PI (n=163 pre-COVID-19, n=828 at diagnosis, n=36 post-COVID-19). *P§amp;lt;0.05, **P§amp;lt;0.01, ***P§amp;lt;0.001, ****P§amp;lt;0.0001. Error bars represent 95% CIs from the median. mGPS, modified Glasgow Prognostic Score; NLR, neutrophil:lymphocyte ratio; ns, not significant; OIS, OnCovid Inflammatory Score; PI, Prognostic Index; PLR, platelet:lymphocyte ratio.
Figure 3
Figure 3
Relationship between inflammatory markers and unadjusted mortality. Inflammatory marker values at COVID-19 diagnosis divided into good and poor risk groups plotted against unadjusted mortality rates for the (A) training set and (B) validation set. Error bars represent lower and upper limits. ***P<0.001, ****P<0.0001. mGPS, modified Glasgow Prognostic Score; NLR, neutrophil:lymphocyte ratio; ns, not significant; OIS, OnCovid Inflammatory Score; PI, Prognostic Index; PLR, platelet:lymphocyte ratio.
Figure 4
Figure 4
Univariable survival analysis of inflammatory markers (training set). Kaplan-Meier estimates for univariable survival analysis are shown for the NLR (n=447, p§amp;lt;0.001), OIS (n=273, p§amp;lt;0.0001), mGPS (n=278, p§amp;lt;0.0001), and PI (n=361, p§amp;lt;0.0001) at COVID-19 diagnosis with significance calculated following log-rank methodology. ***P§amp;lt;0.001, ****P§amp;lt;0.0001. mGPS, modified Glasgow Prognostic Score; NLR, neutrophil:lymphocyte ratio; OIS, OnCovid Inflammatory Score; PI, Prognostic Index.
Figure 5
Figure 5
Univariable survival analysis of inflammatory markers (validation set). Kaplan-Meier estimates for univariable survival analysis are shown for the NLR (n=452, p§amp;lt;0.0001), OIS (n=272, p§amp;lt;0.0001), mGPS (n=291, p§amp;lt;0.001), and PI (n=384, p§amp;lt;0.01) at COVID-19 diagnosis with significance calculated following log-rank methodology. **P§amp;lt;0.01, ***P§amp;lt;0.001, ****P§amp;lt;0.0001. mGPS, modified Glasgow Prognostic Score; NLR, neutrophil:lymphocyte ratio; OIS, OnCovid Inflammatory Score; PI, Prognostic Index.
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