Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients.

BACKGROUND: The role of autoreactive T cells on the course of Coronavirus disease-19 (COVID-19) remains elusive. Type II pneumocytes represent the main target cells of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autoimmune responses against antigens highly expressed in type II pneumocytes may influence the severity of COVID-19 disease. OBJECTIVE: The aim of this study was to investigate autoreactive T cell responses against self-antigens highly expressed in type II pneumocytes in the blood of COVID-19 patients with severe and non-severe disease. METHODS: We collected blood samples of COVID-19 patients with varying degrees of disease severity and of pre-pandemic controls. T cell stimulation assays with peptide pools of type II pneumocyte antigens were performed in two independent cohorts to analyze the autoimmune T cell responses in patients with non-severe and severe COVID-19 disease. Target cell lysis assays were performed with lung cancer cell lines to determine the extent of cell killing by type II PAA-specific T cells. RESULTS: We identified autoreactive T cell responses against four recently described self-antigens highly expressed in type II pneumocytes, known as surfactant protein A, surfactant protein B, surfactant protein C and napsin A, in the blood of COVID-19 patients. These antigens were termed type II pneumocyte-associated antigens (type II PAAs). We found that patients with non-severe COVID-19 disease showed a significantly higher frequency of type II PAA-specific autoreactive T cells in the blood when compared to severely ill patients. The presence of high frequencies of type II PAA-specific T cells in the blood of non-severe COVID-19 patients was independent of their age. We also found that napsin A-specific T cells from convalescent COVID-19 patients could kill lung cancer cells, demonstrating the functional and cytotoxic role of these T cells. CONCLUSIONS: Our data suggest that autoreactive type II PAA-specific T cells have a protective role in SARS-CoV-2 infections and the presence of high frequencies of these autoreactive T cells indicates effective viral control in COVID-19 patients. Type II-PAA-specific T cells may therefore promote the killing of infected type II pneumocytes and viral clearance.

[COPD : a still neglected condition]. / BPCO : une maladie encore négligée.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disorder with a complex clinical picture. The diagnosis may be difficult at times, as COPD may develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in early detection of disease. Suspected COPD may be confirmed by further investigations in collaboration with a pulmonologist. The most recent GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. General practitioners are crucial for implementing non-pharmacological measures such as smoking cessation, regular exercise, vaccinations, and patient self-management education. However, this also underlines the challenges to implement the GOLD recommendations in daily practice.

La BPCO est une maladie hétérogène avec un tableau clinique complexe. Le diagnostic n'est pas toujours facile à évoquer, car elle peut se développer insidieusement et passer longtemps inaperçue. Les médecins de premier recours (MPR) jouent donc un rôle central dans le diagnostic précoce. La suspicion de BPCO peut être confirmée en collaboration avec un pneumologue par des examens fonctionnels respiratoires avant l'instauration d'un traitement médicamenteux. Les nouvelles recommandations GOLD, publiées en 2022 définissent trois groupes de risques pour la BPCO (A-B-E). Les MPR sont importants pour la mise en œuvre de mesures accompagnant le traitement (arrêt du tabac, activité physique régulière, vaccinations, éducation thérapeutique). Mais cela souligne également les exigences élevées de la mise en œuvre des recommandations GOLD dans la pratique quotidienne.*.

Characteristics of Severe Asthma Patients and Predictors of Asthma Control in the Swiss Severe Asthma Registry.

BACKGROUND: Asthma is a chronic airway disease, affecting over 300 million people worldwide. 5-10% of patients suffer from severe asthma and account for 50% of asthma-related financial burden. Availability of real-life data about the clinical course of severe asthma is insufficient. OBJECTIVES: The aims of this study were to characterize patients with severe asthma in Switzerland, enrolled in the Swiss Severe Asthma Registry (SSAR), and evaluate predictors for asthma control. METHOD: A descriptive characterisation of 278 patients was performed, who were prospectively enrolled in the registry until January 2022. Socio-demographic variables, comorbidities, diagnostic values, asthma treatment, and healthcare utilisation were evaluated. Groups of controlled and uncontrolled asthma according to the asthma control test were compared. RESULTS: Forty-eight percent of patients were female and the mean age was 55.8 years (range 13-87). The mean body mass index (BMI) was 27.4 kg/m2 (±6). 10.8% of patients were current smokers. Allergic comorbidities occurred in 54.3% of patients, followed by chronic rhinosinusitis (46.4%) and nasal polyps (34.1%). According to the ACT score, 54.7% had well controlled, 16.2% partly controlled and 25.9% uncontrolled asthma. The most common inhalation therapy was combined inhaled corticosteroids/long-acting ß2-agonists (78.8%). Biologics were administered to 81.7% of patients and 19.1% received oral steroids. The multivariable analysis indicated that treatment with biologics was positively associated with asthma control whereas higher BMI, oral steroids, exacerbations, and COPD were negative predictors for asthma control. CONCLUSION: Biologics are associated with improved control in severe asthma. Further studies are required to complete the picture of severe asthma in order to provide improved care for those patients.

[COPD - An Underestimated Disease]. / COPD ­ eine unterschätzte Erkrankung.

COPD - An Underestimated Disease Abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition with a complex clinical picture. The diagnosis is not easy to make because COPD can develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in the early detection of the disease. Suspected COPD can be confirmed by special examinations in collaboration with pulmonologists. The new GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. A short- or long-acting bronchodilator (SAMA/SABA or LAMA/LABA) is recommended for group A, and a dual long-acting bronchodilator therapy (LABA+LAMA) is recommended for group B and E. In case of blood eosinophilia (≥300 cells/µl) and/or recent hospitalization for COPD exacerbation, triple therapy (LABA+LAMA+ICS) is recommended. General practitioners are important in implementing non-pharmacological measures (smoking cessation, regular exercise, vaccinations, patient selfmanagement education). However, this also underlines the high demands of the implementation of the GOLD guideline in daily practice.

Remdesivir in Coronavirus Disease 2019 patients treated with anti-CD20 monoclonal antibodies: a case series.

PURPOSE: COVID-19 patients on anti-CD20 treatment can suffer a delayed viral clearance and worse clinical outcome. We aim to present our experience with remdesivir treatment in anti-CD20-treated patients with prolonged symptoms, a patient population for which no data from randomized controlled trials are available. METHODS: From the beginning of the pandemic until February 2021, we included all consecutive patients from our healthcare network on anti-CD20 treatment with prolonged COVID-19 symptoms, who received remdesivir. Patient informed consent was gathered and patients' charts were reviewed to collect baseline data, COVID-19 history including time of symptom onset, diagnosis, data on treatment and disease course. Patients or their next of kin were contacted in March 2022 to assess long-term outcomes. RESULTS: We included 11 patients, who received remdesivir at a median of 33 days after diagnosis. Eight patients showed clinical improvement along with reductions in viral loads, one patient with relapsing infection recovered after administration of convalescent plasma, and two patients died. No clinical relapses were reported (median follow-up 13 months), while follow-up PCRs were not performed. One patient died of underlying malignancy 8 months after recovery from COVID-19. CONCLUSIONS: We observed a benefit of antiviral therapy in a majority of COVID-19 patients on anti-CD20 treatment, without any clinical relapses in the 1-year follow-up. Although these data suggest that remdesivir might be a promising management option in patients with delayed viral clearance, the lack of a control group is an important limitation of the study design. TRIAL REGISTRATION: Ethikkommission Ostschweiz, Scheibenackerstrasse 4, CH-9000 St. Gallen approved this case series. Project-ID 2021-00349 EKOS 21/027.

Bronchodilator Response in Patients with COPD, Asthma-COPD-Overlap (ACO) and Asthma, Evaluated by Plethysmographic and Spirometric z-Score Target Parameters.

BACKGROUND: Airflow reversibility criteria in COPD are still debated - especially in situations of co-existing COPD and asthma. Bronchodilator response (BDR) is usually assessed by spirometric parameters. Changes assessed by plethysmographic parameters such as the effective, specific airway conductance (sGeff), and changes in end-expiratory resting level at functional residual capacity (FRCpleth) are rarely appreciated. We aimed to assess BDR by spirometric and concomitantly measured plethysmographic parameters. Moreover, BDR on the specific aerodynamic work of breathing (sWOB) was evaluated. METHODS: From databases of 3 pulmonary centers, BDR to 200 g salbutamol was retrospectively evaluated by spirometric (∆FEV1 and ∆FEF25-75), and plethysmographic (∆sGeff, ∆FRCpleth, and ∆sWOB) parameters in a total of 843 patients diagnosed as COPD (478 = 57%), asthma-COPD-overlap (ACO) (139 = 17%), or asthma (226 = 27%), encountering 1686 BDR-measurement-sets (COPD n = 958; ACO n = 276; asthma n = 452). RESULTS: Evaluating z-score improvement taking into consideration the whole pre-test z-score range, highest BDR was achieved by combining ∆sGeff and ∆FRC detecting BDR in 62.2% (asthma: 71.4%; ACO: 56.7%; COPD: 59.8%), by ∆sGeff in 53.4% (asthma: 69.1%; ACO: 51.6%; COPD: 47.4%), whereas ∆FEV1 only distinguished in 10.6% (asthma: 21.8%; ACO: 18.6%; COPD: 4.2%). Remarkably, ∆sWOB detected BDR in 49.4% (asthma: 76.2%; ACO: 47.8%; COPD: 46.9%). CONCLUSION: BDR largely depends on the pre-test functional severity and, therefore, should be evaluated in relation to the pre-test conditions expressed as ∆z-scores, considering changes in airway dynamics, changes in static lung volumes and changes in small airway function. Plethysmographic parameters demonstrated BDR at a significant higher rate than spirometric parameters.

Management of parapneumonic effusion and empyema: medical thoracoscopy and surgical approach.

Parapneumonic effusions or empyemas are frequently seen in patients with lower respiratory tract infections. The condition is associated with significant morbidity and mortality. Since Gram stains and bacterial cultures are usually negative, treatment focuses on empiric antibiotic treatment and chest tube drainage. The role of intrapleural fibrinolytics is still a matter of debate. Medical thoracoscopy is a simple and effective therapeutic alternative associated with better outcome and fewer complications than conservative treatment. Furthermore, it can be performed in analgo-sedation in a bronchoscopy suite. Video-assisted thoracic surgery carries the advantage of providing optimal visibility of the pleural cavity, thus allowing better debridement. Thoracotomy is the treatment of choice when thoracoscopic cleaning is not satisfactory.