Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis.

BACKGROUND AND OBJECTIVE: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. RESULTS: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). CONCLUSION: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.

Severe Asthma Remissions Induced by Biologics Targeting IL5/IL5r: Results from a Multicenter Real-Life Study.

Add-on biological therapy has proven to be effective in many patients with severe eosinophilic asthma. In this observational multicenter retrospective study, we report the results obtained with mepolizumab and benralizumab in severe asthmatics treated for 12 months in a real-life setting. In these patients, peripheral eosinophil levels, pulmonary function trends, exacerbation rates, systemic corticosteroid use, and symptom control were evaluated during the observation period, to understand which patients met all the criteria in order to be considered in disease remission. The percentage of remittent patients was 30.12% in the mepolizumab-treated subgroup, while in the benralizumab-treated subgroup, patients in complete disease remission were 40%, after 12 months. The results of this study confirm the efficacy of anti-IL-5 biologic drugs in the treatment of severe eosinophilic asthma in a real-life setting.

Real-Life Clinical and Functional Effects of Fluticasone Furoate/Umeclidinium/Vilanterol-Combined Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Triple therapy consisting of a drug association including an inhaled corticosteroid, a long-acting muscarinic receptor antagonist and a long-acting ß2-adrenergic agonist, delivered via a single device, can be a valuable treatment for chronic obstructive pulmonary disease (COPD) patients experiencing frequent disease exacerbations. OBJECTIVES: The aim of this real-life, single-center, observational study was to evaluate, in 44 COPD patients with recurrent exacerbations, the effects of the triple inhaled therapy combining fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI). METHODS: Within such a therapeutic context, several clinical and lung functional parameters were considered at baseline and after 24 weeks of treatment with combined inhaled triple therapy. RESULTS: With respect to baseline, after 24 weeks of treatment with FF/UMEC/VI, significant changes were recorded with regard to Modified British Medical Research Council (p < 0.0001) and COPD Assessment Test (p < 0.0001) scores, COPD exacerbations (p < 0.001), forced expiratory volume in the first second (p < 0.001), residual volume (p < 0.01), forced mid-expiratory flow between 25 and 75% of FVC (p < 0.0001), inspiratory capacity (p < 0.01), forced vital capacity (p < 0.05), and peak expiratory flow (p < 0.0001). Moreover, in a subgroup of 28 patients, a significant increase of diffusion lung capacity (p < 0.01) was also detected. CONCLUSIONS: In conclusion, our real-life results suggest that triple inhaled therapy with FF/UMEC/VI, when given to COPD patients with frequent exacerbations, is able to positively impact on dyspnea and global health status as well as to significantly decrease COPD exacerbations and improve airflow limitation and lung hyperinflation.

Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma.

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.

Effects of inhaled beclomethasone dipropionate/formoterol fumarate/glycopyrronium on diaphragmatic workload and lung function in uncontrolled asthma: a case report.

Beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) single inhaler extrafine triple therapy is effective for the treatment of uncontrolled asthma. Nevertheless, there is a lack of data about the use of diaphragmatic ultrasonography to monitor adult asthmatics while they are receiving inhaled treatment. We took into consideration a 78-year-old woman complaining of asthma, treated with inhaled corticosteroid/long-acting ß2-adrenergic agonist (ICS/LABA), characterized by an asthma control questionnaire-5 (ACQ-5) score and a lung function test suggestive of uncontrolled asthma. Moreover, a diaphragmatic ultrasound showed signs of high diaphragm workload. Because of these findings, we proposed to our patient a shift toward triple inhaled therapy with BDP/FF/G, and she underwent a second evaluation after 7 days of treatment. Improvements in the diaphragmatic ultrasound parameters, lung function test, and ACQ-5 score were found. In particular, we detected a reduction of thickening fraction (TF), and a normalization of the other diaphragmatic measures, indicative of a decrease in diaphragmatic workload. To our knowledge, this is the first literature report showing concomitant improvements of both lung function tests and diaphragmatic ultrasonography parameters, observed in an adult patient with uncontrolled asthma after short-term treatment with the single inhaler triple therapy BDP/FF/G.

Difficult-To-Treat and Severe Asthma: Can Real-World Studies On Effectiveness of Biological Treatments Change the Lives of Patients?

Many different phenotypes that characterize severe asthma are supported by intricate pathomechanisms called endotypes. The latter are driven by molecular interactions, mediated by intercellular networks. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, real-world studies have confirmed the positive effects of currently available antibodies directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, as well as the receptors of interleukins-4 (IL-4) and 13 (IL-13). The best way to treat severe asthma should be chosen based on the peculiar phenotypic and endotypic traits of each patient. This will lead to relevant improvements in both clinical and functional outcomes. In particular, biological therapies can change the lives of asthma patients with a strong impact on quality of life. Unfortunately, patients with severe non-type-2 asthma, who continue to have pertinent unmet needs, are not receiving satisfactory advances within the context of biological treatments. It is also hopeful that in the next future new therapeutic strategies will be specifically implemented for these people, perhaps offering them the opportunity to improve their current, mostly inadequate asthma management.

Pathobiology of Type 2 Inflammation in Asthma and Nasal Polyposis.

Asthma and nasal polyposis often coexist and are frequently intertwined by tight pathogenic links, mainly consisting of the cellular and molecular pathways underpinning type 2 airway inflammation. The latter is characterized by a structural and functional impairment of the epithelial barrier, associated with the eosinophilic infiltration of both the lower and upper airways, which can be driven by either allergic or non-allergic mechanisms. Type 2 inflammatory changes are predominantly due to the biological actions exerted by interleukins 4 (IL-4), 13 (IL-13), and 5 (IL-5), produced by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2). In addition to the above cytokines, other proinflammatory mediators involved in the pathobiology of asthma and nasal polyposis include prostaglandin D2 and cysteinyl leukotrienes. Within this context of 'united airway diseases', nasal polyposis encompasses several nosological entities such as chronic rhinosinusitis with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD). Because of the common pathogenic origins of asthma and nasal polyposis, it is not surprising that the more severe forms of both these disorders can be successfully treated by the same biologic drugs, targeting many molecular components (IgE, IL-5 and its receptor, IL-4/IL-13 receptors) of the type 2 inflammatory trait.

Effectiveness of Benralizumab in OCS-Dependent Severe Asthma: The Impact of 2 Years of Therapy in a Real-Life Setting.

Patients with severe OCS-dependent asthma can be considered a subgroup of asthma patients with severe disease and great risk of complications, related to chronic OCS use. The introduction of biological drugs has represented a turning point in the therapeutic strategy for severe asthma, offering a valid alternative to OCS. Benralizumab, like other anti-IL-5 agents, has been shown to reduce exacerbations and OCS intake/dosage and improve symptom control and lung function. While these findings have also been confirmed in real-life studies, data on long-term efficacy are still limited. METHODS: In this retrospective study, we evaluated the effects of 2 years of treatment with benralizumab on 44 patients with OCS-dependent severe asthma by analyzing clinical, biological and functional data. RESULTS: After 2 years of benralizumab, 59.4% discontinued OCS and patients who continued to use OCS had their mean dose reduced by approximately 85% from baseline. Meanwhile, 85% of patients had their asthma well-controlled (ACT score > 20) and had no exacerbations, and 41.6% had normal lung function. CONCLUSIONS: Our findings support the long-term effectiveness of benralizumab in severe OCS-dependent asthma in a real-life setting, suggesting potential reductive effects on costs and complications such as adverse pharmacological events.

Clinical and Functional Effects of Inhaled Dual Therapy Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease: A Real-Life Study.

Background: The pharmacological association umeclidinium/vilanterol (UMEC/VI) allows to implement a very effective dual bronchodilation in chronic obstructive pulmonary disease (COPD), thus optimizing bronchodilating therapy. Methods: The main purpose of our real-world observational study was to evaluate in COPD patients the effects of UMEC/VI on lung function and respiratory symptoms. Functional and clinical parameters were assessed at baseline, and after 52 weeks of treatment with this combined double inhaled therapy. Results: We enrolled 110 subjects suffering from COPD. A 12-month UMEC/VI treatment induced significant improvements in total lung capacity (TLC) (p < 0.05), and residual volume (RV) (p < 0.0001). Pulmonary deflation was paralleled by significant increases of forced expiratory volume in one second (FEV1) (p < 0.0001), forced vital capacity (FVC) (p < 0.01), forced expiratory flow between 25% and 75% of FVC (FEF25-75) (p < 0.0001) and diffusion capacity of the lung (DLCOcSB) (p < 0.05). In addition, in the same period, we also observed significant reductions of airway resistance including total resistance (Rtot) (p < 0.0001) and specific effective resistance (sReff) (p < 0.0001). Other improvements were detected with regard to modified British Medical Research Council (mMRC) questionnaire score (p < 0.0001), COPD Assessment Test (CAT) score (p < 0.0001), and COPD exacerbation rate (p < 0.0001). In particular, the reported changes of mMRC/CAT scores and COPD exacerbation numbers were significantly correlated with UMEC/VI-induced modifications of TLC, RV, FVC and FEV1. Conclusion: In conclusion, our study corroborates in a real-life context the effectiveness of UMEC/VI in COPD treatment. Indeed, our broad investigational strategy has allowed to better characterize the functional mechanisms underpinning the therapeutic properties of UMEC/VI association.

Benralizumab in Patients with Severe Eosinophilic Asthma: A Multicentre Real-Life Experience.

BACKGROUND: Mepolizumab and benralizumab are monoclonal antibodies directed against anti-IL-5 and anti-IL5R, respectively, and their use reduces the exacerbation rate and maintains oral corticosteroid requirements in severe eosinophilic asthma. Previous studies have tested the therapeutic switch between two biologics with excellent results, further demonstrating the heterogeneity of asthmatic disease and the complexity of the therapeutic choice. It remains unclear if such patients may improve following a switch from mepolizumab to benralizumab. AIMS: Within a multicentre real-life setting, we decided to evaluate the potential effectiveness of a therapeutic switch to benralizumab in patients with severe eosinophilic asthma initially treated with mepolizumab, who experienced sub-optimal responses. The secondary aim was to identify the clinical factors associated with a better response to benralizumab. METHODS: We retrospectively assessed patients with severe eosinophilic asthma treated at six Italian specialist centres, who were switched from mepolizumab to benralizumab following a sub-optimal response, defined as a partial or total lack of clinical remission (i.e., frequent severe exacerbations and/or poorly controlled symptoms and/or higher OCS daily use in patients with a poor or moderate response in the global evaluation of treatment effectiveness scale), after at least 12 months of treatment. RESULTS: Twenty-five patients were included in the analysis (mean age 56.76 ± 11.97 years, 65% female). At 6 months of treatment with benralizumab, the ACT score was significantly higher than the ACT score with mepolizumab (20.24 ± 3.38 vs. 16.77 ± 3.48, p < 0.0001); the mean number of daily SABA inhalations was significantly lower after 6 months and 12 months of treatment with benralizumab than that after treatment with mepolizumab; OCS intake and the prednisone median dosage at 6 months of treatment with benralizumab were significantly lower than those with mepolizumab. Benralizumab treatment resulted in a marked improvement in asthma control, suppressed blood eosinophil levels and reduction in the number of exacerbations in the subgroup of patients with severe eosinophilic asthma and nasal polyposis. CONCLUSIONS: Patients diagnosed with severe eosinophilic asthma who experience a partial response to mepolizumab could benefit from switching to benralizumab, and even more those who have nasal polyposis.

Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps.

Background: The efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation. Objective: To assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence. Methods: Clinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP. Results: Among the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01). Conclusion: Our results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation.

Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets.

Interleukins (IL)-4 and -13 play a pivotal role in the pathobiology of type-2 asthma. Indeed, IL-4 is crucially involved in Th2 cell differentiation, immunoglobulin (Ig) class switching and eosinophil trafficking. IL-13 cooperates with IL-4 in promoting IgE synthesis, and also induces nitric oxide (NO) production, goblet cell metaplasia and fibroblast proliferation, as well as elicits contractile responses and hyperplasia of airway smooth muscle cells. IL-4 and IL-13 share common signaling pathways, activated by the binding of both cytokines to receptor complexes including the α-subunit of the IL-4 receptor (IL-4Rα). Therefore, the subsequent receptor dimerization is responsible for the pathophysiologic effects of IL-4 and IL-13. By selectively blocking IL-4Rα, the fully human IgG4 monoclonal antibody dupilumab behaves as a dual receptor antagonist of both IL-4 and IL-13. Through this mechanism of action, dupilumab exerts effective therapeutic actions in type-2 inflammation, thus decreasing asthma exacerbations, FeNO (fractional exhaled NO) levels, and the intake of oral corticosteroids (OCS). In addition to being approved for the add-on biological therapy of severe asthma, dupilumab has also been licensed for the treatment of nasal polyposis and atopic dermatitis.

Eosinophilic inflammation: An Appealing Target for Pharmacologic Treatments in Severe Asthma.

Severe asthma is characterized by different endotypes driven by complex pathologic mechanisms. In most patients with both allergic and non-allergic asthma, predominant eosinophilic airway inflammation is present. Given the central role of eosinophilic inflammation in the pathophysiology of most cases of severe asthma and considering that severe eosinophilic asthmatic patients respond partially or poorly to corticosteroids, in recent years, research has focused on the development of targeted anti-eosinophil biological therapies; this review will focus on the unique and particular biology of the eosinophil, as well as on the current knowledge about the pathobiology of eosinophilic inflammation in asthmatic airways. Finally, current and prospective anti-eosinophil therapeutic strategies will be discussed, examining the reason why eosinophilic inflammation represents an appealing target for the pharmacological treatment of patients with severe asthma.

Novel Biological Therapies for Severe Asthma Endotypes.

Severe asthma comprises several heterogeneous phenotypes, underpinned by complex pathomechanisms known as endotypes. The latter are driven by intercellular networks mediated by molecular components which can be targeted by specific monoclonal antibodies. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, currently available antibodies are directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, the receptors of interleukins-4 (IL-4) and 13 (IL-13), as well as thymic stromal lymphopoietin (TSLP) and other alarmins. Among these therapeutic strategies, the best choice should be made according to the phenotypic/endotypic features of each patient with severe asthma, who can thus respond with significant clinical and functional improvements. Conversely, very poor options so far characterize the experimental pipelines referring to the perspective biological management of non-type 2 severe asthma, which thereby needs to be the focus of future thorough research.

Biological Therapy of Severe Asthma with Dupilumab, a Dual Receptor Antagonist of Interleukins 4 and 13.

Interleukin-4 (IL-4) and interleukin-13 (IL-13) are key cytokines involved in the pathophysiology of both immune-inflammatory and structural changes underlying type 2 asthma. IL-4 plays a pivotal role in Th2 cell polarization, immunoglobulin E (IgE) synthesis and eosinophil recruitment into the airways. IL-13 synergizes with IL-4 in inducing IgE production and also promotes nitric oxide (NO) synthesis, eosinophil chemotaxis, bronchial hyperresponsiveness and mucus secretion, as well as the proliferation of airway resident cells such as fibroblasts and smooth muscle cells. The biological effects of IL-4 and IL-13 are mediated by complex signaling mechanisms activated by receptor dimerization triggered by cytokine binding to the α-subunit of the IL-4 receptor (IL-4Rα). The fully human IgG4 monoclonal antibody dupilumab binds to IL-4Rα, thereby preventing its interactions with both IL-4 and IL-13. This mechanism of action makes it possible for dupilumab to effectively inhibit type 2 inflammation, thus significantly reducing the exacerbation of severe asthma, the consumption of oral corticosteroids (OCS) and the levels of fractional exhaled NO (FeNO). Dupilumab has been approved not only for the add-on therapy of severe asthma, but also for the biological treatment of atopic dermatitis and nasal polyposis.

Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-ß.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in PC-associated lung fibrosis-like changes revealed by chest CT scans. Peripheral blood mononuclear cells (PBMCs) obtained from PC patients who did not develop signs of lung fibrosis were not responsive to AIM2 activation by Poly dA:dT. In sharp contrast, PBMCs from PC patients with signs of lung fibrosis were highly responsive to AIM2 activation, which induced the release of IL-1α, IFN-α and TGF-ß. The recognition of Poly dA:dT was not due to the activation of cyclic GMP-AMP (cGAMP) synthase, a stimulator of interferon response (cGAS-STING) pathways, implying a role for AIM2 in PC conditions. The release of IFN-α was caspase-1- and caspase-4-dependent when AIM2 was triggered. Instead, the release of pro-inflammatory IL-1α and pro-fibrogenic TGF-ß were inflammasome independent because the inhibition of caspase-1 and caspase-4 did not alter the levels of the two cytokines. Moreover, the responsiveness of AIM2 correlated with higher expression of the receptor in circulating CD14+ cells in PBMCs from patients with signs of lung fibrosis.

Post-COVID-19 Syndrome: Involvement and Interactions between Respiratory, Cardiovascular and Nervous Systems.

Though the acute effects of SARS-CoV-2 infection have been extensively reported, the long-term effects are less well described. Specifically, while clinicians endure to battle COVID-19, we also need to develop broad strategies to manage post-COVID-19 symptoms and encourage those affected to seek suitable care. This review addresses the possible involvement of the lung, heart and brain in post-viral syndromes and describes suggested management of post-COVID-19 syndrome. Post-COVID-19 respiratory manifestations comprise coughing and shortness of breath. Furthermore, arrhythmias, palpitations, hypotension, increased heart rate, venous thromboembolic diseases, myocarditis and acute heart failure are usual cardiovascular events. Among neurological manifestations, headache, peripheral neuropathy symptoms, memory issues, lack of concentration and sleep disorders are most commonly observed with varying frequencies. Finally, mental health issues affecting mental abilities and mood fluctuations, namely anxiety and depression, are frequently seen. Finally, long COVID is a complex syndrome with protracted heterogeneous symptoms, and patients who experience post-COVID-19 sequelae require personalized treatment as well as ongoing support.

Acute Coronary Syndrome in Patients with SARS-CoV-2 Infection: Pathophysiology and Translational Perspectives.

Acute coronary syndromes (ACS) may complicate the clinical course of patients with Coronavirus Disease 2019 (COVID-19). It is still unclear whether this condition is a direct consequence of the primary disease. However, several mechanisms including direct cellular damage, endothelial dysfunction, in-situ thrombosis, systemic inflammatory response, and oxygen supply-demand imbalance have been described in patients with COVID-19. The onset of a prothrombotic state may also be facilitated by the endothelial dysfunction secondary to the systemic inflammatory response and to the direct viral cell damage. Moreover, dysfunctional endothelial cells may enhance vasospasm and platelet aggregation. The combination of these factors promotes atherosclerotic plaque instability, thrombosis and, consequently, type 1 myocardial infarction. Furthermore, severe hypoxia due to extensive pulmonary involvement, in association with other conditions described in COVID-19 such as sepsis, tachyarrhythmias, anemia, hypotension, and shock, may lead to mismatch between oxygen supply and demand, and cause type 2 myocardial infarction. A deeper understanding of the potential pathophysiological mechanisms underlying ACS in patients with COVID-19 could help the therapeutic management of these very high-risk patients.

Prevalence of Persistent Olfactory Disorders in Patients With COVID-19: A Psychophysical Case-Control Study With 1-Year Follow-up.

The purpose of this multicenter case-control study was to evaluate a group of patients at least 1 year after coronavirus disease 2019 (COVID-19) with Sniffin' Sticks tests and to compare the results with a control population to quantify the potential bias introduced by the underlying prevalence of olfactory dysfunction (OD) in the general population. The study included 170 cases and 170 controls. In the COVID-19 group, 26.5% of cases had OD (anosmia in 4.7%, hyposmia in 21.8%) versus 3.5% in the control group (6 cases of hyposmia). The TDI score (threshold, discrimination, and identification) in the COVID-19 group was significantly lower than in the control group (32.5 [interquartile range, 29-36.5] vs 36.75 [34-39.5], P < .001). The prevalence of OD was significantly higher in the COVID-19 group, confirming that this result is not due to the underlying prevalence of OD in the general population.

Post-COVID-19 Patients Who Develop Lung Fibrotic-like Changes Have Lower Circulating Levels of IFN-ß but Higher Levels of IL-1α and TGF-ß.

PURPOSE: SARS-CoV-2 infection induces in some patients a condition called long-COVID-19, herein post-COVID-19 (PC), which persists for longer than the negative oral-pharyngeal swab. One of the complications of PC is pulmonary fibrosis. The purpose of this study was to identify blood biomarkers to predict PC patients undergoing pulmonary fibrosis. PATIENTS AND METHODS: We analyzed blood samples of healthy, anti-SARS-CoV-2 vaccinated (VAX) subjects and PC patients who were stratified according to the severity of the disease and chest computed tomography (CT) scan data. RESULTS: The inflammatory C reactive protein (CRP), complement complex C5b-9, LDH, but not IL-6, were higher in PC patients, independent of the severity of the disease and lung fibrotic areas. Interestingly, PC patients with ground-glass opacities (as revealed by chest CT scan) were characterized by higher plasma levels of IL-1α, CXCL-10, TGF-ß, but not of IFN-ß, compared to healthy and VAX subjects. In particular, 19 out of 23 (82.6%) severe PC and 8 out of 29 (27.6%) moderate PC patients presented signs of lung fibrosis, associated to lower levels of IFN-ß, but higher IL-1α and TGF-ß. CONCLUSIONS: We found that higher IL-1α and TGF-ß and lower plasma levels of IFN-ß could predict an increased relative risk (RR = 2.8) of lung fibrosis-like changes in PC patients.