Bradykinin and Galectin-3 in Survived and Deceased Patients with COVID-19 Pneumonia: An Increasingly Promising Biochemical Target

Introduction There are still no definite curative or preventive strategies for COVID-19 disease. It is crucial to fully comprehend the pathogenesis of COVID-19 infection so that we can develop expedient pharmacological protocols. While the impact of cytokine storm on COVID-19 severity has been one of the most tested hypotheses, the role of bradykinin and various other oxidative stress markers has been relatively under-researched. Their levels can be determined immediately after a hospital admission so they could be used as early predictors of the further development of the disease. Aim The study aims at evaluating the possibility of using bradykinin and galectin-3 levels as early predictors that COVID-19 disease will progress into a severe case. Material and methods. The study was conducted as a prospective cross-sectional study. It included 47 consecutive adult patients with confirmed SARS-CoV-2 infection and COVID-19 pneumonia. All study subjects were admitted for a hospital treatment to the tertiary Clinical Hospital Center Bezanijska kosa, Belgrade, Serbia on June 2021. The blood samples were collected at the patients' admission. The analyses of demographic, radiological, and clinical data were later conducted for both groups (the deceased patients and those who survived). In addition, we analyzed the potential relations between the outcome and the levels of bradykinin and galectin-3 measured immediately after the patients were admitted to the hospital. Results The patients who passed away were predominantly older men with comorbidities. We recorded higher CT scores in the deceased patients and the significantly higher levels of urea, creatinine, CK, troponine, CRP, and other laboratory markers. They stayed at the ICU unit longer and required mechanical ventilation more frequently than the patients who survived. On the other hand, no differences were recorded in the time periods passing from the onset of the systems to the hospital admissions. Finally, we can highlight several independent predictors of mortality in patients with COVID-19 pneumonia, including the following: (1) patients who are 50 or more years old, (2) with in-hospital stays are longer that 4 days, (3) bradykinin levels surpass 220000 pg/ml, (4) D-dimer, creatinine, and CRP are elevated, and (5) comorbidities were present (such as hypertension and diabetes). Conclusion The present study strongly supports the bradykinin storm hypothesis. Since elevated bradykinin levels have been found in most COVID-19 cases with fatal outcomes, the future therapeutical strategies for COVID-19 have to be focused on reducing bradykinin serum concentrations.

Point-of-Care Echocardiographic Characteristics of COVID-19 Patients with Pulmonary Embolism.

INTRODUCTION: Thrombotic complications, such as pulmonary embolism, are common in COVID-19 patients. Point-of-care ultrasound is a highly recommended tool for orientation in critically ill patients with suspected or confirmed complications. METHODS: An observational study was conducted on 32 consecutive patients with confirmed pulmonary embolism and COVID-19 infection treated in the Intensive Care Unit of the University Hospital Medical Center "Bezanijska kosa", Belgrade, Serbia, between April 2021 and March 2022. Predictors of the need for oxygen support were determined, while point-of-care echocardiographic parameters and various anamnestic, laboratory, and clinically significant parameters were correlated with the Pulmonary Embolism Severity Index (PESI) score. RESULTS: More than two-thirds of patients in our study had PE symptoms present at hospital admission (68.8%). The majority of patients had segmental pulmonary embolism (48.4%), with high to very high PESI score values in 31.3% of patients. Pneumonia was present in 68.8% of the study population. The PESI score was negatively correlated with diastolic blood pressure and SaO2 at the time of PE diagnosis, LV ejection fraction, and PVAT. A positive correlation was found between the PESI score, maximum CRP, and D-dimer at the time of PTE diagnosis. A larger right ventricular diameter was associated with a greater need for oxygen support. CONCLUSION: Point-of-care echocardiography is a valuable tool for the risk assessment of COVID-19 patients with pulmonary embolism. Right ventricular size stood out as a significant marker of disease severity.

Elevated Transaminases as Predictors of COVID-19 Pneumonia Severity.

BACKGROUND: This study aimed to calculate the frequency of elevated liver enzymes in hospitalized patients with coronavirus disease 2019 (COVID-19) infection and to test if liver enzyme biochemistry levels on admission could predict the computed tomography (CT) scan severity score of bilateral interstitial pneumonia. METHODS: This single-center study comprised of 323 patients including their demographic data, laboratory analyses, and radiological findings. All the information was taken from electronic health records, followed by statistical analysis. RESULTS: Out of 323 patients, 115 of them (35.60%) had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) over 40 U/L on admission. AST was the best predictor of CT scan severity score of bilateral interstitial pneumonia (R2 = 0.313, Adjusted R2 = 0.299). CT scan severity score in the peak of the infection could be predicted with the value of AST, neutrophils, platelets, and monocytes count (R2 = 0.535, Adjusted R2 = 0.495). CONCLUSION: AST, neutrophils, platelets, and monocytes count on admission can account for almost half (49.5%) of the variability in CT scan severity score at peak of the disease, predicting the extensiveness of interstitial pneumonia related to COVID-19 infection. Liver enzymes should be closely monitored in order to stratify COVID-19 patients with a higher risk of developing severe forms of the disease and to plan the beforehand step-up treatment.

COVID-19 Vaccination Willingness and Vaccine Uptake among Healthcare Workers: A Single-Center Experience.

Healthcare workers (HCWs) are at higher risk of developing COVID-19 due to their professional exposition to the SARS-CoV-2 virus. This study assesses the intention of vaccination against COVID-19 before the vaccines were approved, and the rate of vaccine uptake during the first nine months of immunization among HCWs. A cross-sectional seroprevalence study was carried out during July 2020 in University Clinical Hospital Center Bezanijska Kosa in Belgrade, Serbia that included 62.8% of all HCWs. Besides serological testing for IgG antibodies, data about HCWs' intention to accept COVID-19 vaccination if a vaccine became available were collected. This cohort of HCWs was followed up until the end of October 2021 to assess the number of vaccinated and PCR-positive staff. In the cross-sectional study, 18.3% HCWs had positive SARS-CoV-2 IgG antibodies without difference with IgG-negative HCWs regarding age, gender, profession type, and years of service. Before vaccines became available, a significantly higher percentage of IgG-positive HCWs compared to IgG-negative HCWs was unsure whether to be vaccinated (62.5% vs. 49.0%), and significantly fewer stated that they would not be vaccinated (16.7% vs. 25.1%). When the vaccines became available in Serbia, among IgG-negative HCWs, those who stated clear positive (yes) and clear negative (no) attitude toward vaccination before the immunization period had begun were vaccinated at 28% and 20%, respectively, while 51% of unsure HCWs received a vaccine (p = 0.006). Among IgG-positive HCWs, there was no statistical difference in vaccine uptake regarding those with previous negative, positive, and unsure opinions about vaccination (p = 0.498). In multivariate analysis, independent factors associated with uptake were being female (OR = 1.92; 95%CI: 1.04-3.55), age of 30-59 years, previously vaccine-unsure (OR = 1.84; 95%CI: 1.04-3.25), and those with previous positive vaccine attitudes (OR = 2.48; 95%CI:1.23-5.01), while nurses were less likely to become vaccinated (OR = 0.39 95% CI: 0.20-0.75) These findings indicate a positive change in attitudes of HCWs towards COVID-19 vaccination.

COVID-19 Vaccination Willingness and Vaccine Uptake among Healthcare Workers: A Single-Center Experience

Healthcare workers (HCWs) are at higher risk of developing COVID-19 due to their professional exposition to the SARS-CoV-2 virus. This study assesses the intention of vaccination against COVID-19 before the vaccines were approved, and the rate of vaccine uptake during the first nine months of immunization among HCWs. A cross-sectional seroprevalence study was carried out during July 2020 in University Clinical Hospital Center Bezanijska Kosa in Belgrade, Serbia that included 62.8% of all HCWs. Besides serological testing for IgG antibodies, data about HCWs' intention to accept COVID-19 vaccination if a vaccine became available were collected. This cohort of HCWs was followed up until the end of October 2021 to assess the number of vaccinated and PCR-positive staff. In the cross-sectional study, 18.3% HCWs had positive SARS-CoV-2 IgG antibodies without difference with IgG-negative HCWs regarding age, gender, profession type, and years of service. Before vaccines became available, a significantly higher percentage of IgG-positive HCWs compared to IgG-negative HCWs was unsure whether to be vaccinated (62.5% vs. 49.0%), and significantly fewer stated that they would not be vaccinated (16.7% vs. 25.1%). When the vaccines became available in Serbia, among IgG-negative HCWs, those who stated clear positive (yes) and clear negative (no) attitude toward vaccination before the immunization period had begun were vaccinated at 28% and 20%, respectively, while 51% of unsure HCWs received a vaccine (p = 0.006). Among IgG-positive HCWs, there was no statistical difference in vaccine uptake regarding those with previous negative, positive, and unsure opinions about vaccination (p = 0.498). In multivariate analysis, independent factors associated with uptake were being female (OR = 1.92;95%CI: 1.04–3.55), age of 30–59 years, previously vaccine-unsure (OR = 1.84;95%CI: 1.04–3.25), and those with previous positive vaccine attitudes (OR = 2.48;95%CI:1.23–5.01), while nurses were less likely to become vaccinated (OR = 0.39 95% CI: 0.20–0.75) These findings indicate a positive change in attitudes of HCWs towards COVID-19 vaccination.