Immune disturbance leads to pulmonary embolism in COVID-19 more than classical risk factors: a clinical and histological study

• Published in: Internal and emergency medicine Vol. 18; no. 7; pp. 1981 - 1993
• Main Authors: Cicco, Sebastiano, Vacca, Antonio, Albanese, Federica, Susca, Nicola, Desantis, Vanessa, Magistro, Arianna, Cazzato, Gerardo, Cicco, Gerolamo, Sablone, Sara, Cariddi, Christel, Marozzi, Marialuisa Sveva, Catena, Cristiana, Brosolo, Gabriele, Marcante, Stefano, Ingravallo, Giuseppe, Dalfino, Lidia, Lauletta, Gianfranco, Pappagallo, Fabrizio, Solimando, Antonio Giovanni, Grasso, Salvatore, Maiorano, Eugenio, Introna, Francesco, Sechi, Leonardo Alberto, Ria, Roberto
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2023; Springer Nature B.V
• Subjects: Alveoli; Biopsy; Blood gas analysis; Blood pressure; CD3 antigen; CD4 antigen; CD8 antigen; Computed tomography; COVID-19; COVID-19 : diagnosis; Embolism; HMGB1 protein; Im - Original; Internal Medicine; management and prognosis; Medicine; Medicine & Public Health; Oxygen; Pulmonary embolisms; Risk factors; Pulmonary embolism; SARS-CoV-2; NETosis; HMGB1; Immune cells; Embolism risk factor
• ISSN: 1828-0447; 1970-9366; 1970-9366
• DOI: 10.1007/s11739-023-03383-9

COVID-19 induces endotheliitis and one of the main complications is enhanced coagulation. The incidence of pulmonary embolism (PE) in COVID-19 (CPE) has increased and clinical features for a rigorous analysis still need to be determined. Thus, we evaluated the clinical characteristics in CPE and the immune infiltration that occurred. Between January 1 and December 31, 2021, 38 patients were affected by CPE (9 ICU, 19 males/19 females, 70.18 ± 11.24 years) out of 459 COVID-19 cases. Controls were subjects who were evaluated for PE between January 1 2015, and December 31, 2019 (92 patients, 9 ICU, 48 males/45 females, 69.55 ± 16.59 years). All patients underwent complete physical examination, pulmonary computed tomography, laboratory tests, D-dimer, and blood gas analysis. There were no differences in laboratory tests or D-dimer. In patients with CPE, pO2, alveolar–arterial oxygen difference (A-aDO2), oxygen saturation %, and the ratio between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2), P/F, were significantly increased. There were no differences in PaCO2. Platelet count was inversely correlated to P/F ( r  = − 0.389, p  = 0.02) but directly to A-aDO2 ( r  = 0.699, p  = 0.001) only in patients with CPE. Histology of lung biopsies (7 CPE/7 controls) of patients with CPE showed an increase in CD15 + cells, HMGB1, and extracellular MPO as a marker of NETosis, while no significant differences were found in CD3 + , CD4 + , CD8 + , and intracellular MPO. Overall, data suggest that CPE has a different clinical setting. Reduced oxygen content and saturation described in Patients with CPE should not be considered a trustworthy sign of disease. Increased A-aDO2 may indicate that CPE involves the smallest vessels as compared to classical PE. The significant difference in NETosis may suggest the mechanism related to thrombi formation.