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BackgroundPatients 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.MethodsIn 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.ResultsWe 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).ConclusionsSystemic 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.

Background 15% of patients with cancer experience symptomatic sequelae, which impair post COVID-19 outcomes. In this study we investigated whether a pro-inflammatory status is associated with the development of COVID-19 sequelae. Methods OnCovid recruited 2795 consecutive patients, diagnosed with SARS-CoV-2 infection between 27/02/2020-14/02/2021. This analysis focused on COVID-19 survivors who underwent a clinical re-assessment after the exclusion of patients with haematological malignancies. We evaluated the association of inflammatory markers collected at COVID-19 diagnosis with sequelae, considering the impact of prior systemic anticancer therapy (SACT). Results Out of 1339 patients eligible, 203 experienced at least one sequela (15.2%). Median baseline C-reactive protein (CRP, 77.5 mg/L vs 22.2 mg/L, p&lt;.001), lactate dehydrogenase (LDH, 310 UI/L vs 274 UI/L, p=.028) and neutrophil-to-lymphocyte ratio (NLR, 6.0 vs 4.3, p=.001) were statistically significantly higher among patients who experienced sequelae, while no association were reported for platelet-to-lymphocyte ratio (PLR) and the OnCovid Inflammatory Score (OIS), which includes albumin and lymphocytes. The widest Area under the ROC curve was reported for baseline CRP (AUC 0.66,95%CI:0.63-0.69), followed by the NLR (AUC0.58,95%CI:0.55-0.61) and LDH (AUC=0.57,95%CI:0.52-0.61). Using a fixed categorical multivariable analysis high CRP (OR 2.56,95%CI:1.67-3.91) and NLR (OR 1.45,95%CI:1.01-2.10) were confirmed to be statistically significantly associated with an increased risk of sequelae. Exposure to chemotherapy was associated with a decreased risk of sequelae (OR 0.57,95%CI:0.36-0.91), while no associations with immune checkpoint inhibitors, endocrine therapy, and other types of SACT were found. Conclusions Although the association between inflammatory status, recent chemotherapy and sequelae warrants further investigations, our findings suggest that a deranged pro-inflammatory reaction at COVID-19 diagnosis may predict for sequelae development.