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.

Physicians' irrational attitudes on the antibiotic prescribing for the treatment of COVID-19 in Turkey: A multicenter survey.

BACKGROUND: The inappropriate and excessive use of antibiotics during the coronavirus pandemic has become an important issue. OBJECTIVE: Our primary aim is to ascertain the attitudes of physicians toward the antibiotics prescribing for the treatment of COVID-19 in Turkey. Our secondary aim was to identify factors affecting to physicians' decisions regarding antibiotic therapy for the treatment of COVID-19 and risk factors associated with antibiotic overprescribing. METHODS: It was a multicenter cross-sectional survey. Physicians from 63 different cities were invited to survey through social media (Facebook, Instagram, WhatsApp). Data were collected from respondents through an online questionnaires during November-December 2021. RESULTS: The survey was completed by 571 participants from 63 cities. Pulmonologists comprised the majority (35.20%), followed by internal medical specialists (27.85%) and general practitioners (23.29%). The rates of participants who started empirical antibiotics in the outpatient, ward, and ICU (intensive care unit) were 70.2%, 85.5%, and 74.6%, respectively. When the practice of prescribing antibiotics by physicians for the treatment of COVID-19 in outpatients was compared according to the healthcare setting (primary, secondary, tertiary care hospitals) no significant difference was found. Sputum purulence (68.2%) was recognized as the most important factor for the decision of antibiotic therapy, followed by procalcitonin levels (64.9%) and abnormal radiological findings (50.3%). The most prescribed antibiotics were respiratory quinolones. (48%, 65.9%, 62.7% outpatient, ward, ICU respectively) CONCLUSIONS: In this study, we found that physicians frequently had irrational attitudes toward antibiotic prescription to COVID-19 patients, including those with minor diseases. Our findings underline that the necessity of particular, workable interventions to guarantee the prudent use of antibiotics in COVID-19.

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.

Coronavirus Disease 2019 Frequency After CoronaVac Vaccine: Ascovid Study.

OBJECTIVE: It is accepted that the only way to end severe acute respiratory syndrome coronavirus 2 epidemic is through community vaccination. The frequency and clinical features of infection after vaccination are not known clearly. The aim of this study is to determine the frequency and clinical features of coronavirus disease 2019 seen after either the first or second dose of CoronaVac vaccination in healthcare workers and their relatives. MATERIAL AND METHODS: This is a cross-sectional retrospective survey study. The study was carried out in 2013 volunteers, including 1903 (94.5%) healthcare workers and 110 (5.5%) relatives of healthcare workers. The frequency and clinical features of coronavirus disease 2019 before and after the first or second dose of CoronaVac vaccination were retrospectively evaluated using an online questionnaire conducted in July 2021. RESULTS: A total of 2013 people, 1312 women and 701 men, participated in the study. Of these individuals, 245 (12.1%) were polymerase chain reaction positive for coronavirus disease 2019 before vaccination. Of this group, 185 (75.5% of polymerase chain reaction positives and 9.1% of the whole population) received home-based therapy, while 38 (15.5%) received hospital admission. Asymptomatic polymerase chain reaction positivity before vaccination was seen in 22 (9%) individuals. There were 177 (8.8%) participants who developed polymerase chain reaction positivity at any time after vaccination. In 129 (72.8%) of these participants, polymerase chain reaction positivity occurred 21 days after the second dose of vaccine. While the number of patients hospitalized before vaccination was 38 (15.5% of the polymerase chain reaction positivity group and 1.89% of the general population), the number of patients hospitalized after the vaccination was 17 (10.1% of the polymerase chain reaction positivity group and 0.80% of the general population). The decrease in hospitalization proportion was statistically significant (P = .002). CONCLUSION: The frequency of coronavirus disease 2019, severe illness, and hospitalization rates were found to be lower in postvaccination period. The vaccine is effective in preventing coronavirus disease 2019 and severe disease.

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.

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.