Can Galectin-3 be a reliable predictive biomarker for post-COVID syndrome development?

BACKGROUND AND OBJECTIVES: Reliable biomarkers able to predict post-COVID syndrome development are still lacking. The aim of the study was to evaluate the relationship between Galectin-3 blood concentrations and the development of post-COVID syndrome. METHODS: We performed a single-center, prospective, observational study, enrolling 437 consecutive patients attending our outpatient clinic for the post-COVID assessment. For each patient, we recorded the main clinical, functional and radiological findings. We also dosed several blood biomarkers which have been related to COVID-19 disease, including Galectin-3. We performed Receiver Operating Characteristic (ROC) and multivariate regression analysis to evaluate the predictive performance of Galectin-3 for post-COVID syndrome development. RESULTS: Among the blood biomarkers tested, Galectin-3 resulted the only one correlated with the outcome, although the insufficient performance of the Cox regression model from a statistical standpoint. Correlation coefficients and ROC curves analysis revealed the close relationship between Galectin-3 levels and the time passed from the acute phase of COVID-19 disease, suggesting a possible predictive role for this biomarker when dosed from 60 to 120 days after the infection. CONCLUSIONS: Galectin-3 could play an important role as predictive biomarker for COVID-19 sequelae, but its evaluation must be carefully planned along the follow up to avoid misinterpretations.

The Predictors of Long COVID in Southeastern Italy.

INTRODUCTION: Long COVID is now recognized as a common consequence of the SARS-CoV-2 infection, but we are still far from fully understanding its pathogenesis and predictive factors. Many pathophysiological factors have been studied, including ethnicity. To our knowledge, the risk factors for Long COVID have not been studied in Southeastern Italy. AIMS: The aim of this study was to evaluate the predictive factors of Long COVID in a cohort of patients from Southeastern Italy. METHODS: We conducted a retrospective longitudinal study, enrolling inpatients and outpatients diagnosed with COVID-19 from June 2021 to March 2022. A total of 436 subjects were evaluated in an outpatient setting 12 weeks after a SARS-CoV-2 infection, recording comorbidities, symptoms, therapy, and clinical information. Univariate and multivariate binomial logistic regression analyses were performed on different risk factors to define the probability of developing Long COVID. RESULTS: A total of 71.8% of patients (313) developed Long COVID, while the remaining 123 (28.3%) had a complete remission of symptoms 3 months after acute infection. During the acute phase of COVID-19, 68.3% of patients experienced respiratory failure and 81.4% received corticosteroid therapy. In a multivariate analysis, the female sex (SEX M ODD 0.513) and corticosteroids (ODD 2.25) were maintained as predictive values. CONCLUSIONS: From our data and in line with other studies, the female sex emerges as a risk factor for Long COVID in the population of Southeastern Italy. Corticosteroid therapy administered in the acute phase also appears to be associated with an increased risk of Long COVID. Although indications for the prescription of corticosteroid therapy in the acute phase were indicated by the presence of pneumonia complicated by respiratory insufficiency, there was an over-prescription of corticosteroid therapy in the real life of our cohort, with 64% of patients having respiratory insufficiency and 81% having corticosteroid therapy. We hypothesize that a synergistic link between viral infection and the side effects of corticosteroid therapy may arise in selected cases.

Asthma and Fixed Airways Obstruction: Real Life Aspects.

We aimed to evaluate asthmatic patients with fixed airways obstruction (FAO) and to verify the impact of follow-up in an asthma-dedicated outpatient clinic on symptoms control and spirometry compared to asthmatics without FAO. We enrolled 20 asthmatic FAO+ patients and 20 FAO- asthmatics at baseline (T0) and at a one-year follow-up visit (T1). FAO+ and FAO- groups were compared for anamnesis, FEV1, asthma control test (ACT) and their ΔT0-T1. FAO+ and FAO- groups did not differ for age, BMI, pack-years, allergy, T0 blood eosinophils, comorbidities or GINA therapy step at T0 and T1, whereas, in the FAO+ group, we found more patients with a delay >5 years between symptoms onset and correct asthma diagnosis (p < 0.05). ACT at T0 and ΔT0-T1, FEV1 at ΔT0-T1 and number of exacerbations at T0 and ΔT0-T1 did not differ between groups. Despite a widespread perception of FAO, per se, as a severity factor for asthma, we found similar severity profiles and amelioration after one year of treatment in the FAO+ and FAO- groups. The only factor linked to FAO development in our population was a delay in asthma diagnosis from respiratory symptoms onset, which may have led to airway remodeling. Physicians should characterize patients with FAO for avoiding misdiagnosis between asthma and other respiratory diseases and for establishing the appropriate therapy.

The impact of healthcare setting on post-COVID mood disorders: a single-centre perspective from Southern Italy Respiratory Intensive Care Unit.

BACKGROUND AND OBJECTIVES: Post-COVID syndrome includes several clinical identities, with both physical and mental alterations lasting several months from the acute phase of COVID-19 disease. However, to date, data concerning the relationship between healthcare settings during COVID-19 disease and post-COVID mood disorders are lacking. METHODS: We performed a prospective study enrolling 440 patients with post-COVID syndrome. Each patient underwent a complete clinical evaluation, along with blood and functional tests. Patients were divided according to the healthcare setting needed during COVID-19 disease. RESULTS: Patients admitted to RICU were more prone to develop mental alterations, even when compared to ICU-admitted patients. Other risk factors for mood disorders included female gender and some post-COVID symptoms. CONCLUSIONS: Healthcare needs during COVID-19 can explain the higher incidence of mood disorders in post-COVID syndrome. RICU arises as an important but underexplored risk factor for post-COVID psychic sequelae.

Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management.

Background: Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. Its efficacy has been demonstrated in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting. Methods: We included 12 patients with severe, uncontrolled asthma and dupilumab was chosen if there was at least one evidence of blood eosinophils> 150 cells/ml and/or FeNO>25 ppb during last year. Recent blood eosinophil count report, assessment through ACT, FeNO test and spirometry were performed at baseline and after 3 months of treatment. We calculated also the number of patients achieving a minimal, yet clinically relevant difference in FEV1 and ACT. Results: After three months of treatment with dupilumab, ACT had a significant improvement (mean ACT pre 13.25±4.65 vs mean ACT post 19.17±4.45; p<0.01), so as FEV1% (mean FEV1% pre 62.58±15.73 vs mean FEV1% post 71.00±13.11; p<0.01). FeNO had a significant reduction (median FeNO 32 pre, IQR 19-48.5 vs median FeNO19 post, IQR 16.5-26), differently from eosinophils blood count (median eosinophils pre 280, IQR 193.8-647.3 vs median eosinophils post 349.5, IQR 103-836.8; p=0.52). Four patients (33%) had a positive MCID for FEV1, and eight patients (67%) had a positive MCID for ACT. Conclusions: In RCTs performed during clinical development program dupilumab showed an early efficacy in increasing FEV1, reducing FeNO and improving asthma control. Our study demonstrates early improvement in asthmatic symptoms, lung function and FeNO in severe type-2 asthma patients after only 3 months of dupilumab biologic therapy. The introduction of FeNO levels evaluation in the selection criteria for dupilumab, further helps the identification of eligible patients among type-2 severe asthma patients and allows a complete outpatient assessment. Further real-life studies with a longer follow up time will be useful to confirm dupilumab efficacy and to promote its use in clinical practice.

Galectin-3 as prognostic biomarker in patients with COVID-19 acute respiratory failure.

OBJECTIVES: Galectin-3 is ß-galactoside-binding lectin with several roles in immune-inflammatory response. To date, there is no evidence of Galectin-3 role as a prognostic biomarker in COVID-19 disease. The aim of this study is to clarify the prognostic role of Galectin-3 in patients with COVID 19 acute respiratory failure. METHODS: We enrolled 156 consecutive patients with COVID-19 disease. Routine laboratory test, arterial blood gas, chest X-ray or Computed Tomography and Galectin-3 dosage were performed. The primary outcome was to assess Galectin-3 predictive power for 30-day mortality. Secondary outcomes were 30-day Intensive Care Unit admission and Acute Respiratory Distress Syndrome stratification according to Galectin-3 dosage. We performed Mann-Whitney U and Kruskal-Wallis tests for continuous variables comparison. Fisher's exact test or Chi-square test were used for categorical variables analysis. Receiver Operating Characteristic curves estimated Galectin-3 predictive power for the endpoints. With a fixed cut-off of 35.3 ng/ml, Kaplan-Meier with Log-Rank test and Cox Regression were performed to assess mortality and Intensive Care Unit admission risk. RESULTS: Galectin-3 correlated with many other prognostic predictors tested in our analysis. Moreover, patients with serum levels of Galectin-3 above 35.3 ng/ml had increased risk for mortality, Intensive Care Unit admission and severe Acute Respiratory Distress Syndrome. CONCLUSIONS: Our study demonstrates the role of Galectin-3 as a predictor of mortality, Intensive Care Unit access and ARDS stratification in patients with COVID 19 acute respiratory failure.

Patient's treatment burden related to care coordination in the field of respiratory diseases.

The management of respiratory diseases requires various levels of care: multidisciplinary teams, educational and behavioural interventions, self-management and home-based technical support are vital to ensure adequate care management. However, it is often difficult to access these networks due to fragmentation of patient care and treatment burden. Care coordination aims to ensure patients have a central role and that there is continuity of care among various levels and professionals involved. Moreover, the coronavirus disease pandemic has caused strain on the global healthcare system, with care coordination becoming increasingly important in increasing the resilience of health systems, supporting healthcare professionals and ensuring the right treatment and adequate level of care for these patients.