Alexandra Nagy

Introduction: Pulmonary manifestations are one of the most frequently observed extra-articular complications in rheumatoid arthritis (RA). Aims: To detect the connection between patient-reported outcome (PRO) and early lung involvement in RA patients. Methods: Our prospective study included a comprehensive assessment of exposure, pulmonary function tests (PFT), and the completion of patient-based questionnaires (EQ-5D-3L, Visual Analogue Scale for health (VAS) and Pittsburgh Sleep Quality Index (PSQI)) for 370 consecutive RA patients. Each patient underwent a low-dose chest CT scan. Results: RA patients (64.7 ± 10.3 years, predominantly female (80%)) were categorized into two groups based on the presence (Group 1, N=148, age 66.1 ± 9.6 years) or absence (Group 2, N=222, age 63.8 ± 10.6 years, p=0.03) of respiratory symptoms such as cough, chest pain or dyspnea. PFT and CO diffusion were significantly lower within the normal range in Group 1, including FVC% (91.5±14.7 vs. 96.4±14.7, p=0.005.), FEV1% (92.0±16.6 vs. 96.4±17.5, p=0.015), and DLCO (125.5±20.9 vs. 117.3±23.0, p < 0.001), compared to Group 2. PRO was found notably inferior in Group 1 compared to Group 2 (EQ-5D-3L index value: 0.89±0.6 vs. 0.92±0.6, p=0.002, VAS 67.2±17.5 vs. 73.9± 19.0, p=0.001, PSQI: 16.2±6.8 vs.11.3±6.18, p<0.001). RA associated lung involvement was observed on chest CT more often in Group 1 vs. Group 2. Conclusion: Respiratory symptoms, decreased quality of life and sleep are valuable indicators of early lung involvement in RA, also associated with PFT functional decline in the normal range. Pulmonary screening in RA is important especially in symptomatic patients.

ILD is a serious manifestation of connective tissue diseases (CTD) often exhausting the definition of progressive pulmonary fibrosis (PPF). Our study aimed to evaluate CTD-ILD cases discussed by the multidisciplinary ILD team (MDT) for functional progression. Our MDT discussed cases (N=217) between 07/01/2019 and 10/30/2020: CTD-ILD 17.5%, hypersensitivity pneumonitis 9.7%, idiopathic interstitial pneumonias 34.6%, granulomatous ILDs 11.5%, others 26.7%. Baseline pulmonary symptoms, BMI, lung function, were processed in all cases. Out of 38 confirmed CTD-ILD, functional follow-up data were available in 29 cases. CTD-ILD patients were mainly women (73.7%) and non-smokers (60.5%). Most common symptoms were cough (68.4%), dyspnea (60.5%) and joint pain (60.5%). Lung function test showed a mild restrictive ventilatory disorder and a decrease in diffusion (FVC %: 81.9 ± 23.9, DLCO 73.3 ± 22.6 %). In 10 cases, the adjusted rate of decline in FVC% and DLCO% reached the functional progression defined in the new ATS/ERS guideline. No differences were observed between the functional (f) PPF (Group1, N=10) and stable (Group2, N=19) groups at baseline. During follow-up, Group1 was characterized by a median 17.14% (range: 5.22-19.85%) decline in FVC and 17.82 (range:13.71-39.69%) in DLCO. Weight loss was more prominent in Group1 (Δbody mass index 2.4 vs. 1.3 kg/m2, p=0.02) compared to Group2. In CTD-ILD, 26.3% of patients met criteria of functional progression. Weight loss is an important predictor for functional worsening. Regular body weight monitoring and lung allow timely recognition of progression.

Acute infections with SARS-CoV-2 variants of concerns (VOCs) differ in clinical presentation. Discrepancies in their long-term sequelae, commonly referred to as long COVID, however, remain to be explored. We retrospectively analyzed data of 287 patients presented at the post-COVID care of the Pulmonology Department, Semmelweis University, Budapest, Hungary, and infected with SARS-CoV-2 during a period of 3 major epidemic waves in Hungary (February–July 2021, VOC: B.1.1.7, Alpha, N = 135; August–December 2021, VOC: B.1.617.2, Delta, N = 89; and January–June 2022, VOC: B.1.1.529, Omicron; N = 63), > 4 weeks after acute COVID-19. Overall, the ratio of long COVID symptomatic (LC) and asymptomatic (NS) patients was 2:1. Self-reported questionnaires on fatigue (Fatigue Severity Scale, FSS), sleepiness (Epworth Sleepiness Scale, ESS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) showed higher scores for LC (4.79 ± 0.12, 7.45 ± 0.33 and 7.46 ± 0.27, respectively) than NS patients (2.85 ± 0.16, 5.23 ± 0.32 and 4.26 ± 0.29, respectively; p < 0.05 for all vs. LC). By comparing data of the three waves, mean FSS and PSQI scores of LC patients, but not ESS scores, exceeded the normal range in all, with no significant inter-wave differences. Considering FSS ≥ 4 and PSQI > 5 cutoff values, LC patients commonly exhibited problematic fatigue (≥ 70%) and poor sleep quality (> 60%) in all three waves. Comparative analysis of PSQI component scores of LC patients identified no significant differences between the three waves. Our findings highlight the importance of concerted efforts to manage both fatigue and sleep disturbances in long COVID patient care. This multifaceted approach should be followed in all cases infected with either VOCs of SARS-CoV-2.

Introduction: Lung transplant recipients (LuTX) represent a vulnerable population for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Even though many vaccines are already developed, more clinical data need to support effective immunological response in immunocompromised patients.Methods: Stable LuTX recipients with no medical history of coronavirus disease (COVID‐19) were enrolled. Currently available messenger RNA (mRNA) (BNT162b2‐mRNA, mRNA‐1273) and non‐mRNA (ChAdOx1, BBIBP‐CorV) vaccines were given according to availability, boosters were all mRNA‐based. SARS‐CoV‐2 Spike1 immunoglobulin G (IgG) antibody titer was evaluated before and 2 weeks after second and third dose. Difference between mRNA versus non‐mRNA vaccines was assessed.RESULTS: Forty‐one patients (49% men, age 48.4 ± 13.8 years) received two doses of SARS‐CoV‐2 vaccines: 23 of mRNA, 18 of non‐mRNA, and 24/41 (58%) received a third dose. Median 92 months passed since transplantation, and serum level of tacrolimus was median 5.5 ng/ml. Positive serology was found in 37% of all patients after the second dose, 86% had mRNA vaccine. After the third dose, 29% became positive who had no antibody before. Significantly higher level of antibody was found after the second mRNA than non‐mRNA vaccines (2.2 vs. 1568.8 U/ml, respectively, p = .002). 6/23 (26%) patients received two doses of mRNA vaccine developed COVID‐19 after the second injection in an average of 178 days, half of them recovered, half of them died in intensive care unit (ICU). 3/6 (50%) patients with two doses mRNA and recovered from COVID‐19 had significantly higher level of antibody (average 20847.3 U/ml) than without infection. After the booster vaccine, 1/24 (4%) developed infection.Conclusion: Immunosuppression therapy may induce a weaker SARS‐CoV‐2 response in LuTX recipients; therefore, third dose is a priority in transplanted patients. The highest antibody level was measured recovering from COVID after two doses. Our data confirm that booster mRNA vaccine could increase antibody levels, even if immunization was started with non‐mRNA vaccine.

(1) Background: SARS-CoV-2 infections are associated with an increased risk of hospital admissions especially in the elderly (age ≥ 65 years) and people with multiple comorbid conditions. (2) Methods: We investigated the effect of additional booster vaccinations following the primary vaccination series of mRNA, inactivated whole virus, or vector vaccines on infections with the SARS-CoV-2 delta variant in the total Hungarian elderly population. The infection, hospital admission, and 28-day all-cause mortality of elderly population was assessed. (3) Results: A total of 1,984,176 people fulfilled the criteria of elderly including 299,216 unvaccinated individuals, while 1,037,069 had completed primary vaccination and 587,150 had obtained an additional booster. The primary vaccination series reduced the risk of infection by 48.88%, the risk of hospital admission by 71.55%, and mortality by 79.87%. The booster vaccination had an additional benefit, as the risk of infection, hospital admission, and all-cause mortality were even lower (82.95%; 92.71%; and 94.24%, respectively). Vaccinated patients needing hospitalization suffered significantly more comorbid conditions, indicating a more vulnerable population. (4) Conclusions: Our data confirmed that the primary vaccination series and especially the booster vaccination significantly reduced the risk of the SARS-CoV-2 delta-variant-associated hospital admission and 28-day all-cause mortality in the elderly despite significantly more severe comorbid conditions.

(1) Background: Systemic sclerosis (SSc) is frequently associated with interstitial lung diseases (ILDs). The progressive form of SSc-ILD often limits patient survival. The aim of our study is to evaluate the clinical characteristics and predictors of lung function changes in SSc-ILD patients treated in a real-world setting. (2) Methods: All SSc-ILD cases previously confirmed by rheumatologists and a multidisciplinary ILD team between January 2017 and June 2019 were included (n = 54). The detailed medical history, clinical parameters and HRCT were analyzed. The longitudinal follow-up for pulmonary symptoms, functional parameters and treatment were performed for at least 2 years in no treatment, immunosuppression and biological treatment subgroups. (3) Results: In SSc-ILD patients (age 58.7 ± 13.3 years, 87.0% women), the main symptoms included dyspnea, cough, crackles and the Raynaud’s phenomenon. The functional decline was most prominent in untreated patients, and a normal body mass index (BMI < 25 kg/m²) was associated with a significant risk of deterioration. The majority of patients improved or were stable during follow-up. The progressive fibrosing-ILD criteria were met by 15 patients, the highest proportion being in the untreated subgroup. (4) Conclusions: SSc-ILD patients who are overweight are at a lower risk of the functional decline and progressive phenotype especially affecting untreated patients. The close monitoring of lung involvement and a regular BMI measurement are advised and early treatment interventions are encouraged.

Rationale: IPAF (interstitial pneumonia with autoimmune features) includes patients with interstitial lung disease (ILD) who have a clinical features of connective tissue disease not fulfilling criteria of systemic autoimmune disorder. Aim of this study was to evaluate real-world clinical characteristics and lung functional changes in IPAF patients. Methods: We identified 44 (8,6%) IPAF patients out if 512 ILD-team discussed cases during the period of January 2017 and June 2019. Twenty patients (45%) had baseline lung function and CO diffusion with at least one additional functional evaluation at minimum interval of 6 months. Pulmonary symptoms, lung function and response to therapy were analyzed. Results: IPAF patients (age 69.9±11.5 years, 25% men) had baseline lung function of FVC: 82.9 ± 18.9 %pred, FEV1: 84.4 ± 22.4 %pred, DLCO 71.4 ± 22.4 %pred. Main symptoms included exercise induced dyspnea (77%), cough (66%), 73% presented with basal crackles and 48% with joint pain. Most common HRCT pattern was pUIP (n=19; 43%). Majority of patients were on immunosuppressive therapy (n=20; 45%), while 14 (32%) received antifibrotic treatment. Lung functional decline was present in 14 patients (average 427 ml and 10 % over 1 year period), while stable lung function was observed in 6 patients mainly receiving antifibrotic treatment. Conclusion: IPAF is associated with FVC decline in a high proportion of patients in real life setting. Patients on antifibrotic therapies show slower decline, while combination with different anti-inflammatory drugs need further investigation to determine safety and effectivity of optimal treatment.