Transforming growth factor beta 1 (TGF-ß1) in COVID-19 patients: relation to platelets and association with the disease outcome.

Transforming growth factor beta (TGF-ß) is a ubiquitously distributed cytokine known to contribute to the pathogenesis of numerous pathological processes. The aim of this study was to measure serum concentrations of TGF-ß1 in severely ill COVID-19 patients and to analyze its relationship with selected hematological and biochemical parameters and with the disease outcome. The study population included 53 COVID-19 patients with severe clinical expression of the disease and 15 control subjects. TGF-ß1 was determined in serum samples and supernatants from PHA-stimulated whole blood cultures using ELISA assay. Biochemical and hematological parameters were analyzed using standard accepted methods. Our results showed that serum levels of TGF-ß1 in COVID-19 patients and controls correlate with the platelet counts. Also, positive correlations of TGF-ß1 with white blood cell and lymphocyte counts, platelet-to-lymphocyte (PLR) ratio, and fibrinogen level were shown, while negative correlations of this cytokine with platelet distribution width (PDW), D-dimer and activated partial thromboplastin time (a-PTT) values in COVID-19 patients were observed. The lower serum values of TGF-ß1 were associated with the unfavorable outcome of COVID-19. In conclusion, TGF-ß1 levels were strongly associated with platelet counts and unfavorable disease outcome of severely ill COVID-19 patients.

Admission Predictors of Mortality in Hospitalized COVID-19 Patients-A Serbian Cohort Study.

BACKGROUND: Early prediction of COVID-19 patients' mortality risk may be beneficial in adequate triage and risk assessment. Therefore, we aimed to single out the independent morality predictors of hospitalized COVID-19 patients among parameters available on hospital admission. METHODS: An observational, retrospective-prospective cohort study was conducted on 703 consecutive COVID-19 patients hospitalized in the University Clinical Center Kragujevac between September and December 2021. Patients were followed during the hospitalization, and in-hospital mortality was observed as a primary end-point. Within 24 h of admission, patients were sampled for blood gas and laboratory analysis, including complete blood cell count, inflammation biomarkers and other biochemistry, coagulation parameters, and cardiac biomarkers. Socio-demographic and medical history data were obtained using patients' medical records. RESULTS: The overall prevalence of mortality was 28.4% (n = 199). After performing multiple regression analysis on 20 parameters, according to the initial univariate analysis, only four independent variables gave statistically significant contributions to the model: SaO2 < 88.5 % (aOR 3.075), IL-6 > 74.6 pg/mL (aOR 2.389), LDH > 804.5 U/L (aOR 2.069) and age > 69.5 years (aOR 1.786). The C-index of the predicted probability calculated using this multivariate logistic model was 0.740 (p < 0.001). CONCLUSIONS: Parameters available on hospital admission can be beneficial in predicting COVID-19 mortality.

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis.

Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.

The effect of the COVID-19 pandemic on severe asthma care in Europe - will care change for good?

Background The COVID-19 pandemic has put pressure on health-care services forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic, and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

Cytokine producing ability of peripheral blood cells from COVID-19 patients after unspecific in vitro stimulation.

OBJECTIVE AND DESIGN: Perturbations of peripheral T cell homeostasis and dysregulation of the immune response to SARS-CoV-2, especially in severely ill patients, were observed. The aim of this study was to analyze the cytokine producing ability of peripheral blood cells from severely ill COVID-19 patients upon non-specific in vitro stimulation with phytohemagglutinin (PHA). Possible associations of cytokine levels with patients' age and gender, glucocorticosteroid therapy, as well as the trend of the inflammatory process at the time of sampling (increased or decreased) were also analyzed. SUBJECTS AND METHODS: The study included 23 COVID-19 patients and 17 healthy control subjects. The concentrations of selected Th1/Th2/Th9/Th17/Th22 cytokines were determined using a multi-analyte flow assay kit. RESULTS: Our results showed that peripheral blood cells from severely ill COVID-19 patients had a much reduced ability to produce cytokines in comparison to healthy controls. When inflammation was raised, blood cells produced more IL-6 and IL-17, which led to increases of some Th17/Th1 and Th17/Th2 ratios, skewing towards the Th17 type of response. The methylprednisolone used in the treatment of patients with COVID-19 influences the production of several cytokines in dose dependent manner. CONCLUSION: Our results indicate that the stage of the inflammatory process at the time of sampling and the dose of the applied glucocorticosteroid therapy might influence cytokine producing ability upon non-specific stimulation of T cells in vitro.

Cardiopulmonary Exercise Test in the Detection of Unexplained Post-COVID-19 Dyspnea.

There is emerging evidence of prolonged recovery in survivors of coronavirus disease 2019 (COVID-19), even in those with mild COVID-19. In this paper, we report a case of a 39-year-old male with excessive body weight and a history of borderline values of arterial hypertension without therapy, who was mainly complaining of progressive dyspnea after being diagnosed with mild COVID-19. According to the recent guidelines on the holistic assessment and management of patients who had COVID-19, all preferred diagnostic procedures, including multidetector computed tomography (CT), CT pulmonary angiogram, and echocardiography, should be conducted. However, in our patient, no underlying cardiopulmonary disorder has been established. Therefore, considering all additional symptoms our patient had beyond dyspnea, our initial differential diagnosis included anxiety-related dysfunctional breathing. However, psychiatric evaluation revealed that our patient had only a mild anxiety level, which was unlikely to provoke somatic complaints. We decided to perform further investigations considering that cardiopulmonary exercise test (CPET) represents a reliable diagnostic tool for patients with unexplained dyspnea. Finally, the CPET elucidated the diastolic dysfunction of the left ventricle, which was the most probable cause of progressive dyspnea in our patient. We suggested that, based on uncontrolled cardiovascular risk factors our patient had, COVID-19 triggered a subclinical form of heart failure (HF) with preserved ejection fraction (HFpEF) to become clinically manifest. Recently, the new onset, exacerbation, or transition from subclinical to clinical HFpEF has been associated with COVID-19. Therefore, in addition to the present literature, our case should warn physicians on HFpEF among survivors of COVID-19.