Enhanced eosinophilic inflammation associated with antibody and complement-mediated pneumonic insults in severe COVID-19

Abstract

Despite the worldwide effect of the Coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we conducted kinetic profiling of respiratory leukocytes and associated inflammatory mediators to show that severe COVID-19 is associated with delayed but enhanced eosinophilic inflammation when compared to mild cases. In addition, we confirmed increased Th2-biased adaptive immune responses, accompanying overt complement activation, in the severe group. Moreover, enhanced antibody responses and complement activation was associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from a fatal case, as well as by enhanced hallmark gene set signatures of FcgR signaling and complement activation in myeloid cells of respiratory specimens from severe COVID-19 patients. We also observed expression of viral antigen in lung epithelial and endothelial cells without producing viruses during late stage of COVID-19, indicating abortive viral infection which may further fuel antibody responses and aggravate immune-complex-mediated inflammation. These results suggest that SARS-CoV-2 infection may drive scripted specific innate immune responses, including eosinophilic inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of severe pneumonia in COVID-19 patients.

Ultracellular Imaging of Bronchoalveolar Lavage from Young COVID-19 Patients with Comorbidities Showed Greater SARS-COV-2 Infection but Lesser Ultrastructural Damage Than the Older Patients

“…due to the presence of a crystalloid body containing cytotoxic proteins, such as eosinophil cationic protein (ECP) and eosinophil peroxidase, and eosinophil-derived neurotoxin (EDN) (Lindsley et al, 2020). In severe COVID-19, higher EDN and lesser ECP levels were reported in the younger patient than in elderly patients (Kim et al, 2021). In this study, cytolysis and release of the granules, apoptotic changes were observed.…”

Πληθυσμιακή Φαρμακοκινητική Μοντελοποίηση Της Μπεβασιζουμάμπης Σε Ασθενείς Με Μεταστατικό Καρκίνο Του Παχέος Εντέρου

“…Η απομάκρυνσή της από τον ανθρώπινο οργανισμό είναι παρόμοια με της ενδογενούς ανοσοσφαιρίνης IgG. Πραγματοποιείται μέσω ενός αργού πρωτεολυτικού καταβο-1154GG και VEGF-634CC σχετίζονται με μεγαλύτερη παραγωγή VEGF έναντι των υπολοίπων γονοτύπων για τους VEGF-2578C/A, VEGF-1154G/A και VEGF-634G/C πολυμορφισμούς[122,124]. Συνεπώς, τα επίπεδα του μη συνδεδεμένου με την ΙΙ.…”