The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation. Using ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78). Multiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI [0.03, 0.07], adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI [-0.11, -0.08], adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19. The IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19. This work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.

Postpericardiotomy syndrome (PPS) is worsening or new formation of pericardial and/or pleural effusion mostly 1 to 6 weeks after cardiac surgery, as a result of autoimmune inflammatory reaction within pleural and pericardial space. Its...

Objective: Stratifying patients with paroxysmal or short-term persistent atrial fibrillation (AF) who are at greater risk of developing permanent AF is challenging. Aim of our prospective study was to evaluate association of laboratory parameters (biochemistry and complete blood count (CBC)) together with standard demographic, clinical and echocardiography parameters, with AF progression. Methods: We prospectively recruited 579 patients with AF and divided them into two groups at index hospitalization: paroxysmal or persistent (non-permanent AF), and long-term persistent or permanent AF patients (permanent AF). Clinical, echocardiographic, and relevant CBC parameters were collected. Non-permanent AF patients were selected for follow-up, with a median follow-up time of 21 months. Endpoint was progression to permanent AF. Results: Out of 409 patients with non-permanent AF, 109 (26.6%) progressed within follow-up. In a multivariate Cox regression model only increased left atrium (LA) diameter (HR 2.16, 95% CI 1.20–3.87, p = 0.010), and increased red cell distribution width (RDW; HR 1.19, 95% CI 1.03–1.39, p = 0.022) showed significant independent association with progression. There were 221/409 patients with both LA ≤45 mm and RDW level ≤14.5% who progressed at a rate of only 17.6%, and showed relative risk of AF progression of 0.47 (95% CI 0.34–0.67; p < 0,001). Conclusion: Together with LA size, RDW was independently associated with AF progression. Patients with both LA size ≤45 mm and RDW level ≤14.5% are most probably the best candidates for rhythm control strategies.

Type III transforming growth factor (TGFβ) receptor (TGFβrIII) modulates TGFβ superfamily signaling. Its tumor tissue expression is downregulated in human breast cancer. We determined (indirect ELISA) plasma levels of the soluble receptor (sTGFβrIII) in 47 women with breast cancer (AJCC stages 0-IIB) (cases) pre-surgery and over two months after the surgery, and in 36 healthy women (controls). Plasma sTBFβrIII was lower in cases than in the controls (age-adjusted difference -29.7 ng/mL, p < 0.001), and discriminated between disease and health (sensitivity and specificity 100% at 16.6 ng/mL). With adjustment for age, AJCC stage, lymph node involvement, HER2 and hormone receptor status, higher pre-surgery sTBFβrIII was associated with better progression-free survival (HR = 0.68, 95%CI 0.49-0.89, p = 0.004). An increasing trend in plasma sTBFβrIII was observed over 2 months after the surgery (0.6% increase/day, p < 0.001), consistently across the patient subsets. Data suggest a high potential of plasma sTBFβrIII as a novel diagnostic and prognostic biomarker in breast cancer.