Safety and Tolerability of COVID-19 Vaccine in Mast Cell Disorders Real-Life Data from a Single Centre in Italy.

Background In the past three years, COVID-19 has had a significant impact on the healthcare systems and people's safety worldwide. Mass vaccinations dramatically improved the health and economic damage caused by SARS-CoV-2. However, the safety of COVID-19 vaccines in patients at high risk of allergic reactions still has many unmet needs that should be clarified. Material and methods A retrospective, single-centre study was performed by collecting demographic and clinical data of patients with Mast Cell Disorders (MCDs) to evaluate the safety and tolerability of COVID-19 vaccinations. Moreover, any changes in the natural history of the underlying disease following the vaccine have been evaluated. Results This study included 66 patients affected with MCDs. Out of them, 52 (78.8%) received a COVID-19 vaccination and 41 (78.8%) completed the vaccination course. Premedication came first in 86.6% of our patients. A total of seven (4.5%) patients complained about an immediate reaction and two (1.3%) had a late reaction. Worsening of MCD history was observed in a single patient. Conclusions Despite the overall high risk of allergic reactions, our study did not reveal any increased risk for SARS-CoV-2 allergic reactions in MCD patients, thus supporting the recommendation in favour of the SARS-CoV-2 vaccination. However, due to the potentially increased rate of anaphylactic reactions, MCD patients should receive vaccine premedication and should be treated in a hospital setting after an allergological specialistic evaluation.

MAURIVAX: A Vaccination Campaign Project in a Hospital Environment for Patients Affected by Autoimmune Diseases and Adult Primary Immunodeficiencies.

Background: Patients with autoimmune diseases (ADs) and primary immunodeficiencies (PIDs) are characterized by an increased risk of noninvasive and widespread infections as they are considered frail patients. In addition, many flares of the underlying disease are reported after routine vaccinations. To date, the vaccination rate in these two populations is suboptimal. According to the latest guidelines, targeted interventions are needed, such as strengthening the network of vaccination activities. Our project aimed to propose a pilot network for carrying out the recommended vaccinations in frail patients. Methods: The Allergy and Immunology Center of the Mauriziano Hospital in Turin, Italy started the "Maurivax" project, a facilitated pathway for frail patients to administer the recommended vaccinations in the setting of a dedicated structure where they could be properly followed up. Results: From June 2022 to February 2023, 49 patients underwent a vaccination consultation: 45 of them (91.8%) were subsequently vaccinated. Among these, 36 subjects (80%) were affected by an active AD and were already in treatment with immunosuppressive therapy or about to start it. Seven patients (15.5%) had a confirmed diagnosis of PID or showed a clinical presentation that was highly suggestive of that condition. Overall, twenty-seven patients (60%) showed a high-grade immunosuppression and six (13.3%) had a low-grade immunosuppression. No patients had a disease flare within 30 days from vaccination and no severe reactions after vaccination was observed. Conclusions: Adherence and vaccination safety at our immunology hospital vaccine clinic dedicated to patients with ADs and PIDs were high. We propose an effective model for managing vaccinations in frail patients in a specialist hospital setting.

Biologics in Severe Eosinophilic Asthma: Three-Year Follow-Up in a SANI Single Center.

INTRODUCTION: Biologic drugs have dramatically improved severe eosinophilic asthma (SEA) outcomes. Our aim was to evaluate the long-term efficacy of biological therapy in SEA in a real-life setting and to identify the predictors for switching to another biological drug in patients with poor asthma control. The outcomes for efficacy were decreased annual exacerbations (AE) and improved asthma control test (ACT). METHODS: In 90 SEA patients being treated with a biological drug, clinical examination, ACT, blood eosinophils count and spirometry were assessed before (T0) and after 6 (T1), 12 (T2), 24 (T3) and 36 (T4) months from the start of biological therapy. Patients were considered responders (R) or non-responders (NR) to biologics depending on whether or not they had less than two AE and a 20% increase in the ACT after 12 months of treatment. RESULTS: 75% of the patients were R, 25% NR. In R patients, biological therapy add-on was followed by significant improvement in AE and ACT throughout the whole follow-up period. The percentage of patients on oral corticosteroids (OCS) dropped from 40% to 12%. By contrast, the NR patients were shifted to another biological drug after 12 months of therapy, as they still had high AE and nearly unchanged ACT; 40% of them still needed OCS treatment. The predictors of switching to another biological drug were three or more AE, ACT below 17, nasal polyposis and former smoking (p < 0.05). In NR, the shift to another biological drug was followed by a significant decrease in AE and an increase in the ACT. DISCUSSION: This real-life study confirms the long-term efficacy of biologics in most SEA patients and indicates that even in non-responders to a first biological drug, it is worth trying a second one. It is hoped that the availability of additional biologics with different targets will help improve the personalization of SEA therapy.

COPD, but Not Asthma, Is Associated with Worse Outcomes in COVID-19: Real-Life Data from Four Main Centers in Northwest Italy.

Introduction: Asthma, along with inhaled steroids, was initially considered a risk factor for worse clinical outcomes in COVID-19. This was related to the higher morbidity observed in asthma patients during previous viral outbreaks. This retrospective study aimed at evaluating the prevalence of asthma among patients admitted due to SARS-CoV-2 infection as well as the impact of inhaled therapies on their outcomes. Furthermore, a comparison between patients with asthma, COPD and the general population was made. Methods: All COVID-19 inpatients were recruited between February and July 2020 from four large hospitals in Northwest Italy. Data concerning medical history, the Charlson Comorbidity Index (CCI) and the hospital stay, including length, drugs and COVID-19 complications (respiratory failure, lung involvement, and the need for respiratory support) were collected, as well as the type of discharge. Results: patients with asthma required high-flow oxygen therapy (33.3 vs. 14.3%, p = 0.001) and invasive mechanical ventilation (17.9 vs. 9.5%, p = 0.048) more frequently when compared to the general population, but no other difference was observed. Moreover, asthma patients were generally younger than patients with COPD (59.2 vs. 76.8 years, p < 0.001), they showed both a lower mortality rate (15.4 vs. 39.4%, p < 0.001) and a lower CCI (3.4 vs. 6.2, p < 0.001). Patients with asthma in regular therapy with ICS at home had significantly shorter hospital stay compared to those with no treatments (25.2 vs. 11.3 days, p = 0.024). Discussion: Our study showed that asthma is not associated with worse outcomes of COVID-19, despite the higher need for respiratory support compared with the general population, while the use of ICS allowed for a shorter hospital stay. In addition, the comparison of asthma with COPD patients confirmed the greater frailty of the latter, according to their multiple comorbidities.

IL-17 Promotes Nitric Oxide Production in Non-Small-Cell Lung Cancer.

INTRODUCTION: Lung cancer is the second most frequent malignancy worldwide, but its aetiology is still unclear. Inflammatory cytokines and Th cells, including Th17, are now emerging as being involved in NSCLC pathways, thus postulating a role of IL-17 in tumour angiogenesis by stimulating the vascular endothelial growth factor and the release of nitric oxide. Despite the fact that many biomarkers are used for chest malignancy diagnosis, data on FeNO levels and inflammatory cytokines in NSCLC are still few. Our study aimed to evaluate the relationship between pulmonary nitric oxide production and VEGF and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. METHODS: FeNO measurement and lung function tests were performed in both patients affected by NCSLC and controls; EBC samples were also taken, and Th1 (IL-1, IL-6, IL-12, IFN-g, TNF-a), Th17 (IL-17, IL-23) and Th2 (IL-4, IL-5, IL-13) related cytokines were measured. RESULTS: Th1 and Th17-related cytokines in EBC, except for IFN-gamma and TNF-alpha, were significantly higher in patients than in healthy controls, whereas no differences were seen for Th2-related cytokines. FeNO at the flow rate of 50 mL/s, JawNO and CalvNO levels were significantly higher in patients affected by NSCLC compared to controls. Significant correlations were found between FeNO 50 mL/s and IL-17, IL-1 and VEGF. JawNO levels positively correlated with IL-6, IL-17 and VEGF. No correlations were found between FeNO and Th2-related cytokines. CONCLUSION: This is the first report assessing a relationship between FeNO levels and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. IL-17, which could promote angiogenesis through the VEGF pathway, might be indirectly responsible for the increased lung production of NO in patients with NSCLC.

Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disorder which key feature is a fibrotic process. The role of Endothelin-1 (ET-1) and T-helper (Th)-1 cells in lung and skin fibrosis is well known, although Th17- and Treg-cells were found to be involved. However, no studies analyzed cytokines expression in gastric-juice of SSc patients. Our study aimed to evaluate proinflammatory and profibrotic cytokines in gastric-juice of SSc patients and to investigate their correlations with esophageal dysmotility. METHODS: Patients performed upper-gastrointestinal-endoscopy with gastric-juice collection, esophageal manometry and thoracic CT-scan. GM-CSF, ET-1, Th-1 (IFN-γ, IL-1ß, TNF-α, IL-2, IL-6, IL-9), Th-17 (IL-17, IL-21, IL-22, IL-23) and T-reg (IL-10, TGF-ß) related cytokines were measured in 29 SSc-patients and 20 healthy-controls. RESULTS: Patients showed significant lower levels of IL-6, IL-17, IL-22 and ET-1 (p < 0.005) compared with controls. Patients with atrophic gastritis presented significant lower levels of IL-2, IL-9, IL-6, TGF-ß, GM-CSF, IL-17 and ET-1 (p < 0.005) compared to patients without gastritis. Increased values of IL-2, IL-9, IL-1ß, IL-17, ET-1 and GM-CSF (p < 0.005) were observed in patients with esophageal impairment. This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis.