Caused by the new SARS-CoV-2 coronavirus, COVID-19 (coronavirus disease 2019) evolves with clinical symptoms that vary widely in severity, from mild symptoms to critical conditions, which can even result in the patient's death. A critical aspect related to an individual response to SARS-CoV-2 infection is the competence of the immune system, and it is well known that several trace elements are essential for an adequate immune response and have anti-inflammatory and antioxidant properties that are of particular importance in fighting infection. Thus, it is widely accepted that adequate trace element status can reduce the risk of SARS-CoV-2 infection and disease severity. In this study, we evaluated the serum levels of Cu, Zn, Se, Fe, I and Mg in patients (n = 210) with clinical conditions of different severity (“mild”, “moderate”, “severe” and “exitus letalis”, i.e., patients who eventually died). The results showed significant differences between the four groups for Cu, Zn, Se and Fe, in particular a significant trend of Zn and Se serum levels to be decreased and Cu to be increased with the severity of symptoms. For Mg and I, no differences were observed, but I levels were shown to be increased in all groups.

Aim To investigate infl uence of neutrophil-to-lymphocyte ratio (NLR) and proatherogenic risk factors to improve the accuracy of pneumonia severity index (PSI) in the prediction of community acquired pneumonia (CAP) outcome in healthy individuals. Methods A retrospective observational cross-sectional study conducted at the Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi", University Clinical Centre Sarajevo, included 83 patients with the diagnosis of CAP during the period March 2019-March 2021. Once diagnosed with CAP, PSI score was calculated and according to its value the need for hospital treatment was identifi ed. Patients were divided in two groups: low risk of CAP (PSI <90), and high risk of CAP (PSI> 90). Results The overall average hospital stay was 22.76±10.154 days. In the patients diagnosed with CAP, a positive correlation was established between the following parameters PSI score and age (r=0.670; p<0.01), C-reactive protein-CRP (rho=0.287; p<0.01), leukocytes (rho=0.406; p<0.01), NLR (rho=0.313; p<0.01) and platelet to lymphocyte ratio (PLR) (0.296; p<0.05). CRP, leukocytes, NLR and PLR were statistically signifi cantly higher in patients with high risk of CAP compared to patients with low risk of CAP. Diastolic blood pressure, lymphocytes, eosinophils were signifi cantly lower in patients with high risk of CAP (p<0.05;) compared to patients with low risk of CAP (p<0.01). The optimal cut-off value of NLR for CAP patients was 3.089 with an estimated area under curve (AUC) of 0.664. Conclusion Proatherogenic parameters such as age, systolic blood pressure and leukocytes in combination with neutrophil-lymphocyte count ratio could improve accuracy of the pneumonia severity index in community acquired pneumonia outcome.

Caused by the new SARS-CoV-2 coronavirus, COVID-19 (coronavirus disease 2019) evolves with clinical symptoms that vary widely in severity, from mild symptoms to critical conditions, which can even result in the patient's death. A critical aspect related to an individual response to SARS-CoV-2 infection is the competence of the immune system, and it is well known that several trace elements are essential for an adequate immune response and have anti-inflammatory and antioxidant properties that are of particular importance in fighting infection. Thus, it is widely accepted that adequate trace element status can reduce the risk of SARS-CoV-2 infection and disease severity. In this study, we evaluated the serum levels of Cu, Zn, Se, Fe, I and Mg in patients (n = 210) with clinical conditions of different severity (“mild”, “moderate”, “severe” and “exitus letalis”, i.e., patients who eventually died). The results showed significant differences between the four groups for Cu, Zn, Se and Fe, in particular a significant trend of Zn and Se serum levels to be decreased and Cu to be increased with the severity of symptoms. For Mg and I, no differences were observed, but I levels were shown to be increased in all groups.

Summary Background 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. Methods 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). Findings 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. Interpretation 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. Funding 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.

Background 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. Methods 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). Findings 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. Interpretation 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. Funding 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.

Aim To analyse the resolution of chest X-ray findings in relation to laboratory parameters in patients infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a two- month followup. Analysis of chest X-ray findings in the first few months after the disease is the main goal of our work. Methods Out of the total of 343 patients chest X-ray findings were followed in 269 patients. Patients were divided into groups according to the severity of findings. D-dimer, inflammatory markers, blood cell count, neutrophil lymphocyte ratio (NLR) were analysed. Chest X-ray was analysed during the hospitalization on the day of admission, on the third, the seventh and the fourteenth day (scoring method was used). After discharge chest X-ray was performed in a two-week follow-up, then after one and two months, and after three months if necessary. Results Incomplete chest X-ray resolution was identified in 24 (39.34%) patients with severe, 27 (22.31 %) patients with moderate and in three (3.91%) patients with mild findings. Statistical significance was established in overall score by comparison between all groups (p<0.001), and in the moderate compared to the mild group (p=0.0051). The difference of NLR in the severe compared to the moderate group was observed (p=0.0021) and in the severe group compared to the mild group (p=0.00013). Conclusion Chest X-ray findings persisted mostly in the severe group followed by the moderate and mild ones. Long-term followup is necessary for the appropriate treatment and prevention of fibrosis, and reduction of symptoms.

Aim To investigate interleukin 6 (IL-6) values depending on duration of diabetes mellitus (DM) and evaluate possible correlation with diabetic polyneuropathy. Methods The research study included 90 patients with DM divided into three groups (30 patients each) according to the duration of DM: group A - patients who had DM for less than 10 years, group B - duration of DM was 10 to 20 years, and group C - patients with DM over 20 years. Control group (K) included 30 healthy participants. Results IL-6 was significantly higher in the healthy control group, 180.318 pg/mL±94.18, than in group A, 47.23pg/ml±34.8, group B, 43.31pg/ml±33.17, and group C, 70.39 pg/ml±59.26 (p=0.0001). All groups had significantly different values of IL-6 between each other (p=0.0001). Level of IL-6 was in correlation with diabetic polyneuropathy in the group A (the youngest participants) (p=0.0001). In other groups there was no significant correlation between IL-6 and diabetic polyneuropathy. Conclusion The level of IL-6 was in correlation with neuropathy among younger patients. A higher level of IL-6 in the control group than in diabetic groups is a sign of stronger inflammatory response among younger and healthy people than in patients with DM.

Aim To investigate the usage of chest computed tomography (CT) scan score for improvement in diagnostic and treatment efficacy of repetitive pleural effusion. Methods CT scan scoring system was used as a part of diagnostic procedures in patients with repetitive pleural effusion. Patients with at least two pleurocentesis were included in the study. Chest and abdominal ultrasound, chest x-ray, bronchoscopy, biochemical, microbiological and cytological analysis of pleural fluid specimen were performed for all patients. Results In a two-year period (during 2017-2018) 79 patients were analysed, 27 (34.17%) female and 52 (65.82%) male patients. Malignant pleural diseases were confirmed in 32 cases (40.5%), nonmalignant pleural effusions in 38 (48.1 %) cases, and nine (11.4%) patients rested without exact cause of pleural effusion after two pleurocenteses. Binary regression model showed odds ratio of 1.314; CI 95% 1.119-1.543) (p=0.00088). Confirmed malignancies with pleural effusion were in high correlation with the number of points in CT scan score. Conclusion CT scan scoring system was helpful for diagnostic and treatment decision making in patients with repetitive pleural effusion.

Despite multistep efforts many asthma patients remain symptomatic. Anti-inflammatory activities of curcumin were shown. Aim was to analyse the add-on therapy with curcumin on inflammatory parameters, lung function, disease control and quality of life in asthma patients. 150 non-smokers with moderate partially controlled asthma were treated during 3 months with stable moderate dose of inhaled glucocorticoids and divided into three groups (n=50): curcumin group (receiving curcumin 500 mg per os twice daily), placebo and control group. Before study, sputum eosinophils (sEo), blood eosinophils (bEo), high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) were similar between groups. After study, FEV1%, ACT and AQLQ were improved in all groups, but these improvements were more prominent in curcumin group than in placebo and control. Additionally curcumin group only showed improvement in sEo, bEo and hsCRP. Furthermore, curcumin group showed also more frequent clinically significant improvement in ACT score (change>3) and in AQLQ score (change≥0.5) when compared to placebo and control. However, placebo and control showed similar distribution in FEV1%, ACT, AQLQ, hsCRP, sEo and bEo after study. This is the first placebo controlled and single-blind study to suggest that add-on therapy with curcumin could improve lung function, disease control and quality of life in moderate partially controlled asthma. Future studies may benefit from a larger sample size, longer study duration, double blind design, different dose of curcumin and/or improvements in oral bioavailability.

Sputum eosinophils might predict response to inhaled corticosteroids (ICS) in patients with advanced chronic obstructive pulmonary disease (COPD). Induction of sputum requires expertise and may not always be successful. Aim was to investigate correlation and predictive relationship between peripheral blood eosinophils (bEo) and sputum eosinophils (sEo), and impact of peripheral blood eosinophilia on outcome of COPD exacerbation. 120 current smokers with COPD (GOLD group C) (57.4 ± 0.92 years, M/F ratio 1.4), with no blood (≥7% or >0.43x109/L) nor sputum (≥3%) eosinophilia, were treated with moderate dose of ICS and long-acting bronchodilatator during stable disease, but systemic corticosteroids and antibiotics during exacerbation. According to sputum eosinophilia (≥4%) during exacerbation, patients were divided into eosinophilic (n=45) and non-eosinophilic group (n=75). In stable disease, bEo and sEo were similar in both groups (p>0.05). During exacerbation, bEo and sEo were significantly higher in eosinophilic group (eosinophilic vs. non-eosinophilic: blood: 1.42 ± 0.39 x109/l vs. 0.23 ± 0.02 x109/l, p<0.001; sputum: 8% (4, 19) vs. 1% (0, 3), p<0.0001), but bEo correlated with sEo in both groups (eosinophilic: r=0.52, p<0.001; non-eosinophilic: r=0.25, p<0.05). Relative bEo predicted sputum eosinophilia (area under the curve=0.71, standard error=0.05; 95% confidence interval [CI] =0.61-0.81; p<0.001) and enabled identification of the presence or absence of sputum eosinophilia in 82% of the cases at a threshold of ≥4% (specificity=83.56%, sensitivity=93.83%, positive likelihood ratio=3.67). Eosinophilic group during exacerbation showed less frequent hospitalisations and shorter exacerbation (eosinophilic vs. non-eosinophilic: hospitalisations: 26.7% vs. 60.0%, p<0.001; duration of exacerbation (days): 8.1±0.35 vs. 10.13±0.31, p<0.0001). In COPD exacerbation, relative peripheral blood eosinophils ≥4% might identify sputum eosinophilia. Blood eosinophilia indicate better outcome of COPD exacerbation. Further investigations are needed to predict eosinophilic exacerbation in COPD patients, with prior absence of sputum or blood eosinophilia.