COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry
Alessio Cortellini, Alessandra Gennari, Fanny Pommeret, Grisma Patel, Thomas Newsom-Davis, Alexia Bertuzzi, Margarita Viladot, Oriol Mirallas, Eudald Felip, Alvin Lee, Alessia Dalla Pria, Rachel Sharkey, Joan Brunet, M Carmen Carmona-García, John Chester, Uma Mukherjee, Lorenza Scotti, Saoirse Dolly, Ailsa Sita-Lumsden, Daniela Ferrante, Mieke Van Hemelrijck, Charlotte Moss, Beth Russell, Elia Seguí, Federica Biello, Marco Krengli, Javier Marco‐Hernández, Gianluca Gaïdano, Andrea Patriarca, Riccardo Bruna, Elisa Roldán, María Laura Fox, Anna Pous, Frank Griscelli, Ramón Salazar, Clara Martínez-Vila, Anna Sureda, Angela Loizidou, Clara Maluquer, Annabelle Stoclin, María Iglesias, Paolo Pedrazzoli, Gianpiero Rizzo, Armando Santoro, Lorenza Rimassa, Sabrina Rossi, Nadia Harbeck, Ana Sánchez, Bruno Vincenzi, Michela Libertini, Salvatore Provenzano, Daniele Generali, Salvatore Grisanti, Rossana Berardi, Marco Tucci, Francesca Mazzoni, Matteo Lambertini, Marco Tagliamento, Alessandro Parisi, Federica Zoratto, Paola Queirolo, Raffaele Giusti, Annalisa Guida, Alberto Zambelli, Carlo Tondini, Antonio Maconi, Marta Betti, Émeline Colomba, Nikolaos Diamantis, Alasdair Sinclair, Mark Bower, Isabel Ruíz-Camps, David J. Pinato, OnCovid study group, Georgina Hanbury, Chris Chung, Meera Patel, Gino M Dettorre, Christopher C.T. Sng, Tamara Yu, Marianne Shawe‐Taylor, Hamish DC. Bain, Lee Cooper, Lucy Rogers, Katherine Belessiotis, Cian Murphy, Samira Bawany, Saira Khalique, Ramis Andaleeb, Eleanor Apthorp, Roxana Reyes, David García-Illescas, Nadia Saoudi, Ariadna Roqué, Ricard Mesı́a, Andrea Plaja, Marc Cucurull, Federica Grosso, Vittorio Fusco, Alice Baggi
Abstract
BACKGROUND: Fifteen percent of patients with cancer experience symptomatic sequelae, which impair post-COVID-19 outcomes. In this study, we investigated whether a proinflammatory status is associated with the development of COVID-19 sequelae. METHODS: OnCovid recruited 2795 consecutive patients who were diagnosed with Severe Acute Respiratory Syndrome Coronavirus 2 infection between February 27, 2020, and February 14, 2021. This analysis focused on COVID-19 survivors who underwent a clinical reassessment after the exclusion of patients with hematological malignancies. We evaluated the association of inflammatory markers collected at COVID-19 diagnosis with sequelae, considering the impact of previous systemic anticancer therapy. All statistical tests were 2-sided. RESULTS: Of 1339 eligible patients, 203 experienced at least 1 sequela (15.2%). Median baseline C-reactive protein (CRP; 77.5 mg/L vs 22.2 mg/L, P < .001), lactate dehydrogenase (310 UI/L vs 274 UI/L, P = .03), and the neutrophil to lymphocyte ratio (NLR; 6.0 vs 4.3, P = .001) were statistically significantly higher among patients who experienced sequelae, whereas no association was reported for the platelet to lymphocyte ratio and the OnCovid Inflammatory Score, which includes albumin and lymphocytes. The widest area under the ROC curve (AUC) was reported for baseline CRP (AUC = 0.66, 95% confidence interval [CI]: 0.63 to 0.69), followed by the NLR (AUC = 0.58, 95% CI: 0.55 to 0.61) and lactate dehydrogenase (AUC = 0.57, 95% CI: 0.52 to 0.61). Using a fixed categorical multivariable analysis, high CRP (odds ratio [OR] = 2.56, 95% CI: 1.67 to 3.91) and NLR (OR = 1.45, 95% CI: 1.01 to 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 to 0.91), whereas no associations with immune checkpoint inhibitors, endocrine therapy, and other types of systemic anticancer therapy were found. CONCLUSIONS: Although the association between inflammatory status, recent chemotherapy and sequelae warrants further investigation, our findings suggest that a deranged proinflammatory reaction at COVID-19 diagnosis may predict for sequelae development.