C-C motive chemokine ligand 2 and thromboinflammation in COVID-19-associated pneumonia: A retrospective study

Nieri, Dario; Neri, Tommaso; Barbieri, Greta; Moneta, Sara; Morelli, Giovanna; Mingardi, Desirè; Spinelli, Stefano; Ghiadoni, Lorenzo; Falcone, Marco; Tiseo, Giusy; Menichetti, Francesco; Franzini, Maria; Caponi, Laura; Paolicchi, Aldo; Pancani, Roberta; Pistelli, Francesco; Carrozzi, Laura; Celi, Alessandro; Degl'Innocenti, Sabrina AgostiniO.; Biancalana, Martina; Borselli, Matteo; Nencini, Elia; Antognoli, Rachele; Calsolaro, Valeria; Monzani, Fabio; Paterni, Simone; Baldassarri, Rubia; Bertini, Pietro; Brizzi, Giulia; Rocca, Alessandra Della; Malacarne, Paolo; Monfroni, Marco; Piagnani, Chiara; Carpenè, Nicoletta; Desideri, Massimiliano; Gherardi, Marco; Serradori, Massimiliano; Cinotti, Francesco; Cipriano, Alessandro; Park, Naria; Forotti, Giovanna; Mengozzi, Alessandro; Masi, Stefano; Ruberti, Francesca; Sciuto, Maria; Virdis, Agostino; Maggi, Fabrizio; Galfo, Valentina

PURPOSE: A derangement of the coagulation process and thromboinflammatory events have emerged as pathologic characteristics of severe COVID-19, characterized by severe respiratory failure. C—C motive chemokine ligand 2 (CCL2), a chemokine originally described as a chemotactic agent for monocytes, is involved in inflammation, coagulation activation and neoangiogenesis. We investigated the association of CCL2 levels with coagulation derangement and respiratory impairment in patients with COVID-19. METHODS: We retrospectively evaluated 281 patients admitted to two hospitals in Italy with COVID-19. Among them, CCL2 values were compared in different groups (identified according to D-dimer levels and the lowest PaO(2)/FiO(2) recorded during hospital stay, P/F(nadir)) by Jonckheere-Terpstra tests; linear regression analysis was used to analyse the relationship between CCL2 and P/F(nadir). We performed Mann-Whitney test and Kaplan-Meier curves to investigate the role of CCL2 according to different clinical outcomes (survival and endotracheal intubation [ETI]). RESULTS: CCL2 levels were progressively higher in patients with increasing D-dimer levels and with worse gas exchange impairment; there was a statistically significant linear correlation between log CCL2 and log P/F(nadir). CCL2 levels were significantly higher in patients with unfavourable clinical outcomes; Kaplan-Meier curves for the composite outcome death and/or need for ETI showed a significantly worse prognosis for patients with higher (> median) CCL2 levels. CONCLUSIONS: CCL2 correlates with both indices of activation of the coagulation cascade and respiratory impairment severity, which are likely closely related in COVID-19 pathology, thus suggesting that CCL2 could be involved in the thromboinflammatory events characterizing this disease.