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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.

Objective: To determine post-discharge mortality and associated factors of the first-wave multicenter Turkish Thoracic Society (TTD)-TURCOVID study. Methods: In this retrospective cohort study, we analyzed the data of 18 of 26 centers included in the first TTD-TURCOVID study, and 1 112 cases diagnosed with COVID-19 between 11 March and 31 July 2020 participated in the study. All causes of death after COVID-19 discharge were recorded. Results: The mean age of the patients was (51.07±16.93) years, with 57.6% male patients. In the cohort group, 89.1% of COVID-19 treatment locations were hospital wards, 3.6% were intensive care units (ICUs), and 7.2% were community outpatients. In the longterm follow-up, the in-hospital mortality rate was 3.6% (95% CI 2.64.8), the post-discharge mortality rate was 2.8% (95% CI 1.9-3.9), and the total mortality was 6.3% (95% CI 5.0-7.8). After discharge, 63.3% of mortality overall occurred during the first six months. Mortality rates in post-discharge follow-ups were 12.7% (95% CI 8.0-30.6) in cancer patients, 10.8% (95% CI 6.3-22.9) in chronic obstructive pulmonary disease patients, 11.1% (95% CI 4.4-22.7) in heart failure patients, 7.8 (95% CI 3.8-14.3) in atherosclerotic heart disease patients, and 2.3% (95% CI 0.8-5.6) in diabetes mellitus patients. In smokers/ex-smokers, the all-mortality rates were higher than in non-smokers. Conclusions: This multicenter study showed that patients over 65 years of age, males, former/active smoker, ICU stay, lung, heart disease, and malignancy should be followed up for at least the first six months after discharge due to COVID-19.

Objective: To evaluate long-term effects of COVID-19, and to determine the risk factors in long-COVID in a cohort of the Turkish Thoracic Society (TTS)-TURCOVID multicenter registry. Methods: Thirteen centers participated with 831 patients; 504 patients were enrolled after exclusions. The study was designed in three-steps: (1) Phone questionnaire; (2) retrospective evaluation of the medical records; (3) face-to-face visit. Results: In the first step, 93.5% of the patients were hospitalized; 61.7% had a history of pneumonia at the time of diagnosis. A total of 27.1% reported clinical symptoms at the end of the first year. Dyspnea (17.00%), fatigue (6.30%), and weakness (5.00%) were the most prevalent long-term symptoms. The incidence of long-term symptoms was increased by 2.91 fold (95% CI 1.04-8.13, P=0.041) in the presence of chronic obstructive pulmonary disease and by 1.84 fold (95% CI 1.10-3.10, P=0.021) in the presence of pneumonia at initial diagnosis, 3.92 fold (95% Cl 2.29-6.72, P=0.001) of dyspnea and 1.69 fold (95% Cl 1.02-2.80, P=0.040) fatigue persists in the early-post-treatment period and 2.88 fold (95% Cl 1.52- 5.46, P=0.001) in the presence of emergency service admission in the post COVID period. In step 2, retrospective analysis of 231 patients revealed that 1.4% of the chest X-rays had not significantly improved at the end of the first year, while computed tomography (CT) scan detected fibrosis in 3.4%. In step 3, 138 (27.4%) patients admitted to face-to-face visit at the end of first year; at least one symptom persisted in 49.27% patients. The most common symptoms were dyspnea (27.60%), psychiatric symptoms (18.10%), and fatigue (17.40%). Thorax CT revealed fibrosis in 2.4% patients. Conclusions: COVID-19 symptoms can last for extended lengths of time, and severity of the disease as well as the presence of comorbidities might contribute to increased risk. Long-term clinical issues should be regularly evaluated after COVID-19.

Background and objectivesAlthough 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.MethodsPatients 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.ResultsWe 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 (β [95% CI]: 4.71 [2.31–7.11]; p = 0.001), favipiravir (β [95% CI]: 3.55 [2.56–4.55]; p = 0.001) and HCQ (β [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).ConclusionOur 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.

OBJECTIVE: The purpose of this study is to detect the prevalence and the factors associated with influenza and pneumococcal vaccination and outcomes of vaccination during 2013–2014 season in patients with chronic obstructive pulmonary disease (COPD) in Turkey. METHODS: This was a multicenter retrospective cohort study performed in 53 different centers in Turkey. RESULTS: During the study period, 4968 patients were included. COPD was staged as GOLD 1-2-3-4 in 9.0%, 42.8%, 35.0%, and 13.2% of the patients, respectively. Influenza vaccination rate in the previous year was 37.9%; and pneumococcus vaccination rate, at least once during in a life time, was 13.3%. Patients with older age, higher level of education, more severe COPD, and comorbidities, ex-smokers, and patients residing in urban areas had higher rates of influenza vaccination. Multivariate logistic regression analysis showed that advanced age, higher education levels, presence of comorbidities, higher COPD stages, and exacerbation rates were associated with both influenza and pneumococcal vaccination. The number of annual physician/outpatient visits and hospitalizations due to COPD exacerbation was 2.73 ± 2.85 and 0.92 ± 1.58 per year, respectively. Patients with older age, lower education levels, more severe COPD, comorbid diseases, and lower body mass index and patients who are male and are residing in rural areas and vaccinated for influenza had significantly higher rates of COPD exacerbation. CONCLUSIONS: The rates of influenza and pneumococcal vaccination in COPD patients were quite low, and the number of annual physician/outpatient visits and hospitalizations due to COPD exacerbation was high in Turkey. Advanced age, higher education levels, comorbidities, and higher COPD stages were associated with both influenza and pneumococcal vaccination.

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.

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 (β [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (β [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (β [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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BH declared a shared affiliation with the authors, II and AK to the handling editor at the time of review., (Copyright © 2022 Babayigit, Kokturk, Kul, Cetinkaya, Atis Nayci, Argun Baris, Karcioglu, Aysert, Irmak, Akbas Yuksel, Sekibag, Baydar Toprak, Azak, Mulamahmutoglu, Cuhadaroglu, Demirel, Kerget, Baran Ketencioglu, Ozger, Ozkan, Ture, Ergan, Avkan Oguz, Kilinc, Ercelik, Ulukavak Ciftci, Alici, Nurlu Temel, Ataoglu, Aydin, Cetiner Bahcetepe, Gullu, Fakili, Deveci, Kose, Tor, Gunluoglu, Altin, Turgut, Tuna, Ozturk, Dikensoy, Yildiz Gulhan, Basyigit, Boyaci, Oguzulgen, Borekci, Gemicioglu, Bayraktar, Elbek, Hanta, Kuzu Okur, Sagcan, Uzun, Akgun, Altinisik, Dursun, Cakir Edis, Gulhan, Oner Eyuboglu, Gultekin, Havlucu, Ozkan, Sakar Coskun, Sayiner, Kalyoncu, Itil and Bayram.)

To evaluate the effects of Caspase-3 (CASP3) gene expression and serum levels on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 41 individuals (male: 21; female: 20) with SARS-CoV-2 infection were included in the current study. Hemograms were examined from patient blood samples, and CASP3 gene expression levels were detected. Also, human CASP3 levels were determined from the serum samples of patients. The mean age of patients was 56.220 ± 18.937 years. Significant differences were detected among all groups for CASP3  2 - ΔΔ C t (p = 0.014) and CASP3 concentration (p = 0.024). The relationship between CASP3 2 - ΔΔ C t levels and hemoglobin (p = 0.023), between CASP3 2 - ΔΔ C t levels and C-reactive protein (CRP) (p = 0.001), between CASP3 2 - ΔΔ C t levels and ferritin (p = 0.003), between CASP3 2 - ΔΔ C t levels and lactate dehydrogenase (p =  0.001), and between CASP3 2 - ΔΔ C t levels and SpO 2 (p = 0.006) were statistically significant. Also, the relationship between CASP3 concentration levels and SpO 2 was statistically significant (p < 0.046). The CASP3 gene and/or its products have an important function to prevent injury caused by SARS-CoV-2 infection. They play crucial roles in maintaining cellular homeostasis and viability. Perhaps CASP3 levels may provide information about the severity of the disease., (© 2021 Wiley Periodicals LLC.)

Aim: We aimed to investigate the effect of short-term pirfenidone treatment on prolonged COVID-19 pneumonia., Method: Hospital files of patients hospitalised with a diagnosis of critical COVID-19 pneumonia from November 2020 to March 2021 were retrospectively reviewed. Chest computed tomography images taken both before treatment and 2 months after treatment, demographic characteristics and laboratory parameters of patients receiving pirfenidone + methylprednisolone (n = 13) and only methylprednisolones (n = 9) were recorded. Pulmonary function tests were performed after the second month of the treatment. CT involvement rates were determined by machine learning., Results: A total of 22 patients, 13 of whom (59.1%) were using methylprednisolone + pirfenidone and 9 of whom (40.9%) were using only methylprednisolone were included. When the blood gas parameters and pulmonary function tests of the patients were compared at the end of the second month, it was found that the FEV1, FEV1%, FVC and FVC% values were statistically significantly higher in the methylprednisolone + pirfenidone group compared with the methylprednisolone group (P = .025, P = .012, P = .026 and P = .017, respectively). When the rates of change in CT scans at diagnosis and second month of treatment were examined, it was found that the involvement rates in the methylprednisolone + pirfenidone group were statistically significantly decreased (P < .001)., Conclusion: Antifibrotic agents can reduce fibrosis that may develop in the future. These can also help dose reduction and/or non-use strategy for methylprednisolone therapy, which has many side effects. Further large series and randomised controlled studies are needed on this subject., (© 2021 John Wiley & Sons Ltd.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) outbreak has caused great difficulties in providing healthcare services worldwide. Accurate and useful indicators are needed for the effective use of resources. Carbon monoxide (CO) is also produced endogenously without exogenous exposure. Studies confirm that endogenous CO increases in conditions such as pneumonia, sepsis, and trauma. This study aimed to compare patients diagnosed with COVID-19 pneumonia and healthy people to reveal whether endogenous carboxyhemoglobin (COHb) levels differ. It was also to determine whether it could be a helpful indicator for the clinician in predicting disease severity in combating the COVID-19 pandemic., Methods: The study included 72 patients admitted to the hospital during the COVID-19 pandemic and diagnosed with COVID-19 pneumonia and a control group of 75 healthy people. The research data was collected retrospectively in a tertiary emergency department. The patients' demographic data, pneumonia severity index (PSI) score, CURB-65 score, 30-day mortality, hospitalization, need for mechanical ventilation (MV), and COHb levels were recorded., Results: While the COHb level was 0.9% (min-max, 0.1 - 4.0) in patients with COVID-19 pneumonia, it was 1% (min-max, 0.1 - 2.6) in the control group. No significant difference was found between the patients and the control group in terms of COHb levels (p = 0.341). Also, there was no correlation between COHb levels and PSI and CURB-65 scores. No significant difference was detected between COHb levels and patients diagnosed with COVID-19 pneumonia in terms of mortality, need for MV, or hospitalization (p > 0.05)., Conclusions: We concluded that COHb levels alone could not be used to diagnose COVID-19 pneumonia or predict disease severity. Besides, in COVID-19 pneumonia, the COHb level was not a useful indicator of mortality, need for MV, or hospitalization decision. Further studies are needed to find useful indicators to assist clinicians in their decision-making process in tackling the COVID-19 pandemic.

Background: Chronic obstructive pulmonary disease (COPD) is not fully reversible disease that is characterized by progressive restricting airflow. Non-invasive mechanical ventilation (NIMV) treatment can be used in COPD patients who had type 2 respiratory failure. This study aimed to determine the effect of BPAP S/T and AVAPS modes on intraocular pressure (IOP), central corneal thickness (CCT) in 40 type 2 respiratory failure patients with COPD., Methods: Forty patients with type 2 respiratory failure who were hospitalized between June and December 2018 with the diagnosis of COPD exacerbations were included to the study. Patients followed up without NIMV for 12 hours after the end of exacerbations treatments end. After IOP, visual acuity and CCT were measured in all patients at the same time (11.00 am), same NIMV treatment was applied to the patients for 4 hours (AVAPS-BPAP S/T). Then the measurements were repeated. The effects of these NIMV modes on IOP were evaluated., Results: After NIMV treatment, it was observed that the mean IOP increased statistically significantly (13.3 vs 12.3 mm Hg; P = 0.001). After treatment with NIMV, there was a decrease for CCT close to statistical significance (P = 0.057) CONCLUSION: As a result; increased IOP and thinning of CCT after NIMV treatment has been shown. The type of NIMV and the level of inspiratory pressure needed in hypercapnic respiratory failure seem to affect IOP and it should be cautiously used to increase IOP., (© 2019 John Wiley & Sons Ltd.)