Comparative Transcriptomic Analyses of Peripheral Blood Mononuclear Cells of COVID-19 Patients without Pneumonia and with Severe Pneumonia in the First Year of Follow-Up.

The multisystemic effects of COVID-19 may continue for a longer time period following the acute phase, depending on the severity of the disease. However, long-term systemic transcriptomic changes associated with COVID-19 disease and the impact of disease severity are not fully understood. We aimed to investigate the impact of COVID-19 and its severity on transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) following 1 year of the disease. PBMCs were isolated from the peripheral blood of healthy control donors who did not have COVID-19 (C; n = 13), from COVID-19 patients without pneumonia (NP; n = 11), and from COVID-19 patients with severe pneumonia (SP; n = 10) after 1-year of follow-up. Following RNA isolation from PBMCs, high-quality RNAs were sequenced after creating a library. Differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified using Benjamini-Hochberg correction and they were analysed for hierarchical clustering and principal component analysis (PCA). Intergroup comparisons (C vs. NP, C vs. SP, and NP vs. SP) of DEGs and DElncRNAs were performed and hub genes were determined. Functional enrichment analyses of DEGs and DElncRNAs were made using Metascape (v3.5.20240101) and the first version of NCPATH. The RNA sequencing analysis revealed 4843 DEGs and 1056 DElncRNAs in "C vs. NP", 1651 DEGs and 577 DElncRNAs in "C vs. SP", and 954 DEGs and 148 DElncRNAs in "NP vs. SP", with 291 DEGs and 70 DElncRNAs shared across all groups, respectively. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation and downregulated DEGs to viral infections and immune responses. The analysis showed that 291 common and 14 hub genes were associated with pneumonia and that these genes could be regulated by the transcription factors JUN and NFκB1 carrying the NFκB binding site. We also revealed unique immune cell signatures across DEG categories indicating that the upregulated DEGs were associated with neutrophils and monocytes, while downregulated DEGs were associated with CD4 memory effector T cells. The comparative transcriptomic analysis of NP and SP groups with 52 gene signatures suggestive of IPF risk showed a lower risk of IPF in the SP group than the NP patients. Our findings suggest that COVID-19 may cause long term pathologies by modulating the expression of various DEGs, DeLncRNAs, and hub genes at the cellular level.

Elderly and aged asthma have different characteristics: results of a multicenter study.

Background/aim: Characteristics of asthma in the elderly population is not well-known. The aim of the present study was to evaluate asthma in the elderly population, to compare disease characteristics between patients diagnosed <60 (aged asthma) and ≥60 (elderly asthma) years of age. Materials and methods: The study was a prospective, multicenter, cross-sectional type. A questionnaire was filled out to patients 60 years of age and over, that have been followed for asthma for at least 3 months. Asthma Control Test (ACT), eight-item Morisky Medication Adherence Scale (MMAS-8) was filled out, inhaler device technique was assessed. Results: A total of 399 patients were included from 17 tertiary care centers across the country. Mean age was 67.11 years and 331 (83%) were female. The age at asthma diagnosis was ≥60 in 146 (36.6%) patients. Patients diagnosed ≥60 years were older (p < 0.001), had higher education level (p < 0.001), more commonly had first-degree relative with asthma (p = 0.038), asthma related comorbidities (p = 0.009) and accompanying rhinitis/rhinosinusitis (p = 0.005), had better asthma control (p = 0.001), were using less controller medications (p = 0.014). Inhaler technique was correct in 37% of the patients with no difference in between the groups. Treatment compliance was better in elderly asthma patients (p < 0.001). In the multivariate logistic regression analysis, having well-controlled asthma (odds ratio = 1.61, CI = 1.04-2.51), and high medication adherence rate (odds ratio = 2.43, CI = 1.48-4.0) were associated with being in the elderly asthma group. Conclusion: The characteristics of asthma are different among patients aged 60 years and over which seems to be related to onset age of asthma. In our cohort, the elderly asthma patients had higher education level, and treatment adherence and asthma control was better. Patients diagnosed ≥60 years of age did not have more severe disease.

An Alpha-1 Antitrypsin Deficiency Screening Study in Patients with Chronic Obstructive Pulmonary Disease, Bronchiectasis, or Asthma in Turkey.

Purpose: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition characterized by decreased serum alpha-1 antitrypsin (AAT) levels. We aim to identify AATD in patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, or asthma and to report the frequency of AAT variants in Turkey. Patients and Methods: This non-interventional, multicenter, prospective study was conducted between October 2021 and June 2022. Adult patients with COPD, bronchiectasis, asthma, liver symptoms, or family members with AATD were included. Demographic and clinical characteristics, pulmonary diagnosis, respiratory symptoms, and AAT serum levels were assessed. Whole blood samples were collected as dried blood spots, and the most common AATD mutations were simultaneously tested by allele-specific genotyping. Results: A total of 1088 patients, mainly diagnosed with COPD (92.7%) and shortness of breath (78.7%), were assessed. Fifty-one (5%) were found to have AATD mutations. Fifteen (29.4%) patients had Pi*S or Pi*Z mutations, whereas 36 (70.6%) patients carried rare alleles Pi*M malton (n=18, 35.3% of mutations), Pi*I (n=8, 16%), Pi*P lowell (n=7, 14%), Pi*M heerlen (n=2, 4%), and Pi*S iiyama (n=1, 2%). The most common heterozygous combinations were Pi*M/Z (n=12, 24%), and Pi*M/M malton (n=11, 22%). Ten patients with severe AATD due to two deficiency alleles were identified, two with the Pi*Z/Z genotype, four with the genotype Pi*M malton/M malton, three with Pi*Z/M malton, and one with Pi*Z/M heerlen. Conclusion: Our results identified AATD mutations as a genetic-based contributor to lung disease in patients with COPD or bronchiectasis and assessed their frequency in a population of Turkish patients.

Lung cancer from suspicion to treatment: An indicator of healthcare access in Turkey.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Before beginning lung cancer treatment, it is necessary to complete procedures such as suspecting lung cancer, obtaining a pathologic diagnosis, and staging. This study aimed to investigate the processes from suspicion of lung cancer to diagnosis, staging, and treatment initiation. METHODS: The study was designed as a multicenter and cross-sectional study. Patients with lung cancer from various health institutions located in all geographic regions of Turkey were included in the study. The sociodemographic and clinical characteristics of the patients, the characteristics of the health institutions and geographic regions, and other variables of the lung cancer process were recorded. The time from suspicion of lung cancer to pathologic diagnosis, radiologic staging, and treatment initiation, as well as influencing factors, were investigated. RESULTS: The study included 1410 patients from 29 different medical centers. The mean time from the initial suspicion of lung cancer to the pathologic diagnosis was 48.0 ± 52.6 days, 39.0 ± 52.7 days for radiologic staging, and 74.9 ± 65.5 days for treatment initiation. The residential areas with the most suspected lung cancer cases were highly developed socioeconomic zones. Primary healthcare services accounted for only 0.4% of patients with suspected lung cancer. The time to pathologic diagnosis was longer in the Marmara region, and the wait time for staging and treatment initiation was longer in Eastern and Southeastern Anatolia. Patients who presented to chest disease referral hospitals with peripheral lesions, those with early-stage disease, and those who were diagnosed surgically had significantly longer wait times. CONCLUSION: The time between pathologic diagnosis, staging, and treatment initiation in lung cancer was longer than expected. Increasing the role of primary healthcare services and distributing socioeconomic resources more equally will contribute to shortening the time to diagnosis and improve treatment processes for lung cancer.

Occupational Risks of Podologists: A Combined Assessment of VOCs, Vibration, Noise Levels and Health Complaints.

Podologists are exposed to many occupational hazards, including volatile organic compounds (VOCs) from insole manufacturing and noise/vibration during nail or tissue grinding. In this study, VOCs, noise, and vibration were measured in five podiatry clinics and three offices. Questionnaires were administered to 23 podologists and 19 office workers to inquire about their pain, ocular, skin and respiratory complaints. The results showed that the podologists' exposure to the total VOC concentrations was approximately twice as high as that of the office workers. The podologists' complaints regarding pain were found to be correlated with ambient noise and hand-arm vibration levels. Ocular, skin, and respiratory complaints were also found to be correlated with total VOC concentrations. These results suggest that VOCs, noise and vibration in the working environment may impair podologists' health and that they have an intensifying effect on each other, increasing the severity of health issues.

Elderly-onset pulmonary sarcoidosis: A radiological approach to diagnosis.

BACKGROUND AND AIM: The aim was to compare the radiological and clinical characteristics of sarcoidosis between elderly and non-elderly patients. METHODS: This retrospective observational study was carried out in patients with sarcoidosis. Elderly-onset sarcoidosis was defined as sarcoidosis diagnosed in patients ≥65 years-old. Patients were stratified by age (≥65 years versus <65 years) and radiological and clinical data were compared between age groups. RESULTS: Of the 163 patients, 38 (23.3%) were in the elderly group and 125 (76.7%) were in the non-elderly group. Elderly patients more frequently demonstrated arthralgia (50% vs. 12.8%, p<0.001), coronary artery disease  (15.8% vs. 2.4%, p=0.005), congestive heart failure (13.2% vs. 0.8%, p=0.003), pneumonia (7.9% vs. 0.8%, p=0.04), and pleural fluid (18.4% vs. 0.0%, p<0.001). Clinical remission was significantly more likely in younger patients than in the elderly (76.8% vs. 55.3%, p=0.01). The clinical course to chronic-progressive disease was similar in both groups (p=0.635). Radiologically, lymph nodes measuring 10-25 mm in the short axis (89.5% vs. 72.6%, p=0.032), usual interstitial pneumonia pattern (10.5% vs. 0.8%, p=0.011), and main pulmonary artery diameter above 30 mm (34.2% vs. 16.0%, p=0.014) were significantly more frequent in the elderly group. Elderly patients tended to demonstrate Scadding stage I and II sarcoidosis (39.5% and 31.6%). CONCLUSIONS: Presentation of elderly-onset sarcoidosis appears to differ from young-onset sarcoidosis. Radiologically, lymph node enlargement and the pattern of fibrosis may be distinctive.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

Impact of COVID-19 pneumonia on interstitial lung disease: semi-quantitative evaluation with computed tomography.

OBJECTIVES: To evaluate the CT scores and fibrotic pattern changes in interstitial lung disease (ILD) patients, with and without previous COVID-19 pneumonia. METHODS: Patients with ILD (idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated ILD (CTD-ILD)) were retrospectively enrolled in the study which consisted of patients who had COVID-19 pneumonia while the control group had not. All patients had two CT scans, initial and follow-up, which were evaluated semi-quantitatively for severity, extent, and total CT scores, fibrosis patterns, and traction bronchiectasis. RESULTS: A total of 102 patients (pneumonia group n = 48; control group n = 54) were enrolled in the study. For both groups, baseline characteristics were similar and CT scores were increased. While there was a 4.5 ± 4.6 point change in the total CT score of the COVID-19 group, there was a 1.2 ± 2.7 point change in the control group (p < 0.001). In the IPF subgroup, the change in total CT score was 7.0 points (95% CI: 4.1 to 9.9) in the COVID-19 group and 2.1 points (95% CI: 0.8 to 3.4) in the control group. Seven patients (14.6%) in the COVID-19 group progressed to a higher fibrosis pattern, but none in the control group. CONCLUSIONS: Semi-quantitative chest CT scores in ILD patients demonstrated a significant increase after having COVID-19 pneumonia compared to ILD patients who had not had COVID-19 pneumonia. The increase in CT scores was more prominent in the IPF subgroup. There was also a worsening in the fibrosis pattern in the COVID-19 group. KEY POINTS: • The impact of COVID-19 pneumonia on existing interstitial lung diseases and fibrosis is unclear. • COVID-19 pneumonia may worsen existing interstitial lung involvement with direct lung damage and indirect inflammatory effect. • COVID-19 pneumonia may affect existing lung fibrosis by triggering inflammatory pathways.

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort.

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

Charlson Comorbidity Index in Predicting Poor Clinical Outcomes and Mortality in Patients with COVID-19.

OBJECTIVE: As known, older age and comorbidities are associated with poor clinical outcomes in patients with coronavirus disease 19. The aim of this study was to investigate the effect of the Charlson Comorbidity Index in predicting poor clinical outcomes in coronavirus disease 19 patients. MATERIAL AND METHODS: Demographic characteristics and poor clinical outcomes (presence of pneumonia, respiratory failure, intensive care unit admission, and mortality) of the patients were evaluated retrospectively. Classical and modified Charlson Comorbidity Index was calculated and adjusted according to age. RESULTS: In this study, 106 women and 107 men were included. The comorbidity rate was 50.7% and the most common comorbidities were hypertension (21.6%) and diabetes mellitus (15%). The rates of respiratory failure, intensive care unit admission, and mortality were 15%, 2.3%, and 2.8%, respectively. Older age was a high risk for poor outcomes. Pneumonia (odds ratio: 6.6; 95% CI: 3.4-12.7), respiratory failure (odds ratio: 5.2; 95% CI: 2.03-13.2), and intensive care unit admission (odds ratio: 1.1; 95% CI: 1.01-1.1) were significantly higher in patients with comorbid diseases than patients without any comorbidity (P < .05). Both median-modified and classical Charlson Comorbidity Index and their age-adjusted scores were significantly higher in patients with poor outcomes. CONCLUSIONS: It is suggested that evaluation of the Charlson Comorbidity Index might contribute to the management of the patients with coronavirus disease 19 by predicting risk group for poor clinical outcomes and mortality.

Awareness and Knowledge of COVID-19 Among Health Care Workers in Early Phase of COVID-19 Pandemic.

OBJECTIVE: The study aims to evaluate the awareness and knowledge of COVID-19 among healthcare workers. MATERIAL AND METHODS: A questionnaire was applied to healthcare workers working at Kocaeli University Faculty of Medicine and University of Kyrenia, Dr. Suat Günsel Hospital, to evaluate the coronavirus disease 2019 awareness and level of knowledge. RESULTS: A total of 598 healthcare workers participated in the study. Two-thirds of the respondents were from Turkey, while one-third were from the Turkish Republic of Northern Cyprus. The general symptoms of coronavirus disease 2019 were well known in the general population. Awareness of most symptoms was significantly lower in the Turkish Republic of Northern Cyprus group. It was well known that coronavirus disease 2019 can be asymptomatic in some patients and it can be contagious. The necessity of wearing surgical masks on sick individuals was less known in the Turkish Republic of Northern Cyprus group (96.6% vs 61.6%; P = .000). While handwashing was found similar in both groups for protection from coronavirus disease 2019 transmission, social distance and mask recommendations were lower in the Turkish Republic of Northern Cyprus group (P < .05). The concern about transmitting the virus to themselves and their relatives was more significant in the Turkish Republic of Northern Cyprus group than the Turkey group (84.4% vs 96.5%; P = .000). And 92.2% of the healthcare workers thought they should stay in an alternative place instead of their homes. CONCLUSION: The awareness and knowledge level of coronavirus disease 2019 is higher in Turkey than in Turkish Republic of Northern Cyprus related to the increased number of coronavirus disease 2019 cases in Turkey. Continuous education programs can contribute to improving the level of knowledge and reducing anxiety.

COVID-19: vaccination vs. hospitalization.

OBJECTIVE: Vaccination is the most efficient way to control the coronavirus disease 2019 (COVID-19) pandemic, but vaccination rates remain below the target level in most countries. This multicenter study aimed to evaluate the vaccination status of hospitalized patients and compare two different booster vaccine protocols. SETTING: Inoculation in Turkey began in mid-January 2021. Sinovac was the only available vaccine until April 2021, when BioNTech was added. At the beginning of July 2021, the government offered a third booster dose to healthcare workers and people aged > 50 years who had received the two doses of Sinovac. Of the participants who received a booster, most chose BioNTech as the third dose. METHODS: We collected data from 25 hospitals in 16 cities. Patients hospitalized between August 1 and 10, 2021, were included and categorized into eight groups according to their vaccination status. RESULTS: We identified 1401 patients, of which 529 (37.7%) were admitted to intensive care units. Nearly half (47.8%) of the patients were not vaccinated, and those with two doses of Sinovac formed the second largest group (32.9%). Hospitalizations were lower in the group which received 2 doses of Sinovac and a booster dose of BioNTech than in the group which received 3 doses of Sinovac. CONCLUSION: Effective vaccinations decreased COVID-19-related hospitalizations. The efficacy after two doses of Sinovac may decrease over time; however, it may be enhanced by adding a booster dose. Moreover, unvaccinated patients may be persuaded to undergo vaccination.

The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients.

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.

Multidimensional Evaluation of Pulmonary Function and Exercise Capacity by BODE Index in Patients with On-Pump Coronary Artery Bypass Grafting.

Coronary artery bypass grafting (CABG) often causes physiological changes in patients. Although functional changes, such as lung function and exercise capacity changes, are observed in patients, there are no detailed studies examining this. The aim was to compare preoperative and postoperative pulmonary function and exercise capacity in patients undergoing on-pump CABG with a multidimensional index (BODE index). Demographic and surgical characteristics of patients were recorded. Pulmonary function test, six-minute walk test (6MWT), and modified Medical Research Council (mMRC) dyspnea score were assessed and BODE index were calculated in preoperative and at six months postoperatively. A total of 75 patients were included with a mean ± standard deviation age of 59.8±10.0 years. The male to female ratio was 57/18. There was a statistically significant decrease in the forced expiratory flow at 25-75% (FEF25-75%) value after CABG. Other pulmonary function test values were also lower in the postoperative period compared to the preoperative period, but these changes were not significant. The mean distance achieved in the 6MWT (p=0.02) and the mMRC dyspnea score (p=0.001) were significantly better postoperatively. The BODE index, which combines these parameters, had increased in the postoperative period. Age (OR 1.09; 95% CI: 1.008-1.181) and postoperative FEF25-75% (OR -0.96; 95% CI: 0.938-0.988) were the independent predictors of BODE score ≥3 in multivariate analysis. Despite the decrease in pulmonary function in patients undergoing CABG, there was an improvement in exercise capacity and dyspnea score.