Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients
Nicolas Chapuis, Nusaïbah Ibrahimi, Thibaut Belmondo, Claire Goulvestre, Anne‐Emmanuelle Berger, Alice‐Andrée Mariaggi, Muriel Andrieu, Camille Chenevier‐Gobeaux, Arnaud Bayle, Lydia Campos, Chérifa Cheurfa, Richard Chocron, Jean‐Luc Diehl, B. Doumenc, Jérôme Duchemin, Manon Duprat, Fabien François, Nicolas Gendron, T. Mirault, Frédéric Pène, Aurélien Philippe, Fanny Pommeret, Olivier Sanchez, David M. Smadja, Tali‐Anne Szwebel, Aymeric Silvin, Florent Ginhoux, Ludovic Lacroix, Gérôme Jules-Clément, Sarobidy Rapeteramana, Colette Mavier, Laura Steller, Barbara Perniconi, Fabrice André, Damien Drubay, Michaëla Fontenay, Sophie Hüe, Stéphane Paul, Éric Solary
Abstract
BACKGROUND: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. METHODS: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. FINDINGS: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. INTERPRETATION: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. FUNDING: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.