Showing papers by "Nikoletta Rovina published in 2023"
TL;DR: In this paper , a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 un vaccinated SARS-CoV-2-infected individuals without pneumonia was performed.
Abstract: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10-5).Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
10 citations
TL;DR: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants as mentioned in this paper .
1 citations
TL;DR: In this article , the authors investigated whether adding strength training to a HIIT protocol within a cardiac rehabilitation (CR) program has a cumulative beneficial effect on the functional capacity (FC) and quality of life (QoL) in patients with chronic heart failure.
Abstract: Background: Aerobic exercise, either continuous or high intensity interval training (HIIT), induces important benefits in chronic heart failure (CHF) patients. Resistance training has been also shown to be beneficial in CHF. However, data regarding combined aerobic exercise and muscle strength training is still limited. The aim of this study was to investigate whether adding strength training to a HIIT protocol within a cardiac rehabilitation (CR) program has a cumulative beneficial effect on the functional capacity (FC) and quality of life (QoL) in patients with CHF. Methods: Forty-four consecutive patients [35 males, ejection fraction (EF) <50%] with CHF under medication enrolled in a 36-session CR program and were randomized in two exercise groups; HIIT (HIIT group) or HIIT combined with strength training (high intensity interval training combined with strength training (COM) group). All patients underwent baseline and endpoint outcome measures of a symptom-limited maximal cardiopulmonary exercise testing (CPET), 1 repetition maximum (1RM) test, muscular endurance test, echocardiography, and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Results: Most of the CPET indices, EF, 1RM test, muscular endurance and QoL were improved after the CR program in each exercise training group (p < 0.05). However, COM group demonstrated a further improvement in chest muscle testing and workload at anaerobic threshold (AT) compared to HIIT group. Conclusions: An exercise-based CR program, consisted of either HIIT or HIIT combined with strength training, improves FC and QoL of patients with CHF. However, the addition of strength training to HIIT seems to have further beneficial effects on chest muscle strength and endurance, as well as workload at AT. Clinical Trial Registration: The study was registered in ClinicalTrials.gov with number NCT02387411.
TL;DR: In this paper , the modified Severe COvid Prediction Estimate score (mSCOPE) index was used as a predictor of mortality in patients admitted to the ICU due to severe COVID-19 pneumonia.
Abstract: Introduction: Efficient clinical scores predicting the outcome of severe COVID-19 pneumonia may play a pivotal role in patients’ management. The aim of this study was to assess the modified Severe COvid Prediction Estimate score (mSCOPE) index as a predictor of mortality in patients admitted to the ICU due to severe COVID-19 pneumonia. Materials and methods: In this retrospective observational study, 268 critically ill COVID-19 patients were included. Demographic and laboratory characteristics, comorbidities, disease severity, and outcome were retrieved from the electronical medical files. The mSCOPE was also calculated. Results: An amount of 70 (26.1%) of patients died in the ICU. These patients had higher mSCOPE score compared to patients who survived (p < 0.001). mSCOPE correlated to disease severity (p < 0.001) and to the number and severity of comorbidities (p < 0.001). Furthermore, mSCOPE significantly correlated with days on mechanical ventilation (p < 0.001) and days of ICU stay (p = 0.003). mSCOPE was found to be an independent predictor of mortality (HR:1.219, 95% CI: 1.010–1.471, p = 0.039), with a value ≥ 6 predicting poor outcome with a sensitivity (95%CI) 88.6%, specificity 29.7%, a positive predictive value of 31.5%, and a negative predictive value of 87.7%. Conclusion: mSCOPE score could be proved useful in patients’ risk stratification, guiding clinical interventions in patients with severe COVID-19.
TL;DR: In this paper , the authors investigated the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age with confirmed SARS-CoV-2 infection.
Abstract: Abstract Background Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age. Methods This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan–Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality. Results This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% ( n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06–1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis. Conclusion Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19. Study registration NCT04321265, registered March 19th, 2020.
TL;DR: In this paper , the clinical characteristics and outcomes of critically ill COPD patients with obstructive pulmonary disease were described and compared to patients without obstructive disease, the patients with COPD were younger, suffered from less severe disease on admission, and experienced similar adverse events and outcomes.
Abstract: other hand, it is known that COPD patients are at high risk of mortality from respiratory infections, such as influenza and community acquired pneumonia (CAP) 9,10 . However, the prevalence of COPD among COVID-19 patients was lower than expected 11 . This paradox can be explained by the fact that COPD patients, similarly to patients with other respiratory or smoking-associated conditions, have ABSTRACT INTRODUCTION Asthma and chronic obstructive pulmonary disease (COPD) are the commonest respiratory diseases. The aim of the present study is to describe the clinical characteristics and outcomes of critically ill COVID-19 patients with obstructive pulmonary disease. METHODS We conducted an observational study of severe COVID-19 patients admitted to the intensive care unit of the 1st Respiratory Medicine Department of the University of Athens at Sotiria Hospital, Greece, from 27 August 2020 to 10 November 2021. RESULTS Among 297 patients, 24 (8.1%) had a previous diagnosis of asthma and 18 (6.1%) of COPD. Compared to patients without obstructive disease, asthmatics were younger, suffered from less severe disease on admission, and experienced similar adverse events and outcomes. None of the asthmatics had symptoms suggestive of exacerbation during their hospitalization. In contrast, COPD patients were older, with more severe disease, had more comorbidities, required more frequently mechanical ventilation, and continuous renal replacement therapy. Finally, mortality in COPD patients was greater. CONCLUSIONS Although asthmatic patients with severe COVID-19 do not seem to differ from the non-asthmatics regarding disease course and outcomes, COVID-19 patients with COPD are at increased risk of poor outcomes.
TL;DR: In this article , a population-based, random-digit dialing, telephone nation-wide survey was conducted to estimate the prevalence of asthma in adults, by gender and age, in urban and rural areas of Cyprus.
Abstract: Purpose To estimate the prevalence of asthma in adults, by gender and age, in urban and rural areas of Cyprus. Patients and Methods This was a population-based, random-digit dialing, telephone nation-wide survey to recruit patients with asthma. Among 8996 random landline-telephone contacted from the five major urban and rural regions of Cyprus, 1914 were finally met the age criterion of ≥18 years old and 572 completed valid screening for prevalence estimation. The participants filled a short screening questionnaire in order for asthma cases to be recognized. Then, asthma cases filled the main ECRHS II questionnaire and were evaluated by a pulmonary physician. All underwent spirometry. Data on demographic characteristics, educational level, profession, smoking status, Body Mass Index (BMI), Total IgE and Eosinophil Cationic Protein levels were measured. Results The overall prevalence of bronchial asthma in adults in Cyprus was 5.57% (61.1% men and 38.9% women). Among the participants with self-reported bronchial asthma 36.1% were current smokers, while 12.3% were obese (BMI >30). A total value of IgE >115 IU and Eosinophil Cationic Protein (ECP) >20 IU was found in 40% of the participants with established bronchial asthma. Wheezing and chest tightness were the most frequently reported symptoms in asthma patients (36.1% and 34.5%, respectively), while 36.5% experienced at least one exacerbation during the last year. Interestingly, most of the patients were under-treated (14.2% were on maintenance asthma treatment, and 18% used solely reliever medication). Conclusion This was the first study estimating asthma prevalence in Cyprus. Asthma affects almost 6% of the adult population, with higher prevalence in urban areas and in men compared to women. Interestingly, one-third of the patients were uncontrolled and under-treated. This study revealed that in Cyprus there is space for improvement in the management of asthma.
TL;DR: In this article , the authors present the road trip of the definition of therapeutic response to biologics in severe asthmatics by presenting the current relevant medical literature and also present the suggested predictors of response, with an emphasis on the so-called superresponders.
Abstract: ABSTRACT Introduction In recent years, monoclonal antibodies targeting Type-2 inflammatory pathways have been developed for severe asthma treatment. However, even when patients are carefully selected, the response to treatment varies. Areas covered Different studies have evaluated response to therapy with biologics such as exacerbation reduction, symptom improvement, pulmonary function increase, improvement in QoL, or decrease of oral corticosteroids, showing that all patients do not respond to all disease aspects and leading to an extensive debate regarding the definition of response. Expert opinion Assessing response to therapy is of great importance, but since there is no uniform definition of treatment response, the recognition of patients who really benefit from these therapies remains an unmet need. In the same context, identifying non-responding patients in which biologic therapy should be switched or substituted by alternative treatment options is of paramount importance. In this review, we present the road trip of the definition of therapeutic response to biologics in severe asthmatics by presenting the current relevant medical literature. We also present the suggested predictors of response, with an emphasis on the so-called super-responders. Finally, we discuss the recent insights regarding asthma remission as a feasible treatment goal and provide a simple algorithm for the evaluation of response.