COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry
Authors: Cortellini Alessio , Gennari Alessandra , Pommeret Fanny , Patel Grisma , Newsom-Davis Thomas , Bertuzzi Alexia , Viladot Margarita , Aguilar-Company Juan , Mirallas Oriol , Felip Eudald , Lee Alvin J X , Dalla Pria Alessia , Sharkey Rachel , Brunet Joan , Carmona-García MCarmen , Chester John , Mukherjee Uma , Scotti Lorenza , Dolly Saoirse , Sita-Lumsden Ailsa , Ferrante Daniela , Van Hemelrijck Mieke , Moss Charlotte , Russell Beth , Seguí Elia , Biello Federica , Krengli Marco , Marco-Hernández Javier , Gaidano Gianluca , Patriarca Andrea , Bruna Riccardo , Roldán Elisa , Fox Laura , Pous Anna , Griscelli Franck , Salazar Ramon , Martinez-Vila Clara , Sureda Anna , Loizidou Angela , Maluquer Clara , Stoclin Annabelle , Iglesias Maria , Pedrazzoli Paolo , Rizzo Gianpiero , Santoro Armando , Rimassa Lorenza , Rossi Sabrina , Harbeck Nadia , Sanchez de Torre Ana , Vincenzi Bruno , Libertini Michela , Provenzano Salvatore , Generali Daniele , Grisanti Salvatore , Berardi Rossana , Tucci Marco , Mazzoni Francesca , Lambertini Matteo , Tagliamento Marco , Parisi Alessandro , Zoratto Federica , Queirolo Paola , Giusti Raffaele , Guida Annalisa , Zambelli Alberto , Tondini Carlo , Maconi Antonio , Betti Marta , Colomba Emeline , Diamantis Nikolaos , Sinclair Alasdair , Bower Mark , Ruiz-Camps Isabel , Pinato David J ,   OnCovid study group, Hanbury Georgina , Chung Chris , Patel Meera , Dettorre Gino , Sng Christopher C T , Yu Tamara , Shawe-Taylor Marianne , Bain Hamish D C , Cooper Lee , Rogers Lucy , Belessiotis Katherine , Murphy Cian , Bawany Samira , Khalique Saira , Andaleeb Ramis , Apthorp Eleanor , Reyes Roxana , Garcia-Illescas David , Saoudi Nadia , Lloveras Ariadna Roqué , Mesia Ricard , Plaja Andrea , Cucurull Marc , Grosso Federica , Fusco Vittorio , Baggi Alice , Saponara Maristella , Cantini Luca 
Published: April 2022

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 &lt; .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.