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.

Perceived Need for Mental Health Services Among Healthcare Workers During the Coronavirus Disease-19 Pandemic in Turkey: A Multicenter Cross-sectional Study

Background: The coronavirus disease-2019 pandemic has contributed to work-related psychosocial risks in healthcare workers. Aims: To evaluate the perceived need for mental health services and related factors in Turkish healthcare workers practicing in pandemic hospitals. Study Design: Cross-sectional study. Methods: Data were collected from face-to-face interviews with healthcare workers at 19 pandemic hospitals in 13 provinces between September and November 2021. The study survey included the evaluation of the perceived need for and utilization of mental health services in the previous year, as well as sociodemographic, health-related, and work-related characteristics, the General Health Questionnaire-12, the World Health Organization Quality of Life-BREF (WHOQoL-BREF) questionnaire, and the Fear of coronavirus disease-2019 scale (FCV-19S). Results: Of 1,556 participants, 522 (33.5%) reported a perceived need for mental health services, but only 133 (8.5%) reported receiving these services. Multiple logistic regression analysis of the perceived need for mental health services revealed significant relationships with lower age, female sex, being a current smoker, having a chronic disease, having a mental disorder, coronavirus disease-2019 contact within the last three months in settings other than the home or workplace, a positive coronavirus disease-2019 vaccination history, being a physician, being a non-physician healthcare professional, and coronavirus disease-2019 contact within the last three months at work. After adjustment for these characteristics, higher General Health Questionnaire-12 and FCV-19S scores and lower WHOQoL-BREF domain scores were related to the perceived need for mental health services in logistic regression analyses. Conclusion: The findings indicate a substantial need for mental health services amongst Turkish healthcare workers during the pandemic and outline participants' characteristics regarding high-priority groups for the intervention. Future research may focus on developing actions and evaluating their efficiency.

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 use of social media among high school students and its relationship with the perception of loneliness: A pilot study.

BACKGROUND: Physical, psychological, and social impairments are becoming more common in the world due to internet use and excessive use. PURPOSE: This study was conducted to determine the relationship between social media addiction (SMA) and the perception of loneliness in the high school period when peer influence is important. METHODOLOGY: This cross-sectional study was conducted with a total of 988 students studying at four high schools in Ankara, the capital city of Turkey, in the fall semester of 2019-2020. The research data were collected using Introductory Information Form, Social Media Addiction Scale (SMAS), and UCLA Loneliness Scale. RESULTS: According to the findings, 67.2% of the students had different degrees of SMA. It was found that 7.8% of the students had a high or very high degree of addiction. Loneliness levels of the students were found to be high (UCLA mean 62.78). A strong negative correlation (p < 0.01) was found between loneliness and all the subscales of the SMAS except the busyness subscale. CONCLUSIONS: The findings demonstrate the social media addiction and the perception of loneliness in high school students are related at a level that cannot be ignored. Future research should evaluate social media addiction and loneliness together with other psychological markers.

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.

COVID-19 Treatment at a Glance.

As coronavirus disease 2019 (COVID-19) spreads across the world, the ongoing clinical trials are leading to a big race worldwide to develop a treatment that will help control the pandemic. Unfortunately, COVID-19 does not have any known effective treatment with reliable study results yet. In this pandemic, there is not a lot of time to develop a new specific agent because of the rapid spread of the disease. The process of developing a vaccine is long and requires hard work. Although the pathophysiology of the disease is not fully understood, some of the proposed treatment alternatives are based on old evidence and some have been used with the idea that they might work owing to their mechanism of action. The efficacy, reliability, and safety of the currently available treatment alternatives are therefore a matter of debate. Currently, the main therapies used in the treatment of COVID-19 are antiviral drugs and chloroquine/hydroxychloroquine. Other proposed options include tocilizumab, convalescent plasma, and steroids, but the mainstay of the treatment in intensive care units remains supportive therapies.

Unclear Issues Regarding COVID-19.

Scientists from all over the world have been intensively working to discover different aspects of Coronavirus disease 2019 (COVID-19) since the first cluster of cases was reported in China. Herein, we aimed to investigate unclear issues related to transmission and pathogenesis of disease as well as accuracy of diagnostic tests and treatment modalities. A literature search on PubMed, Ovid, and EMBASE databases was conducted, and articles pertinent to identified search terms were extracted. A snow-ball search strategy was followed in order to retrieve additional relevant articles. It was reported that viral spread may occur during the asymptomatic phase of infection, and viral load was suggested to be a useful marker to assess disease severity. In contrast to immune response against viral infections, cytotoxic T lymphocytes decline in SARS-CoV-2 infection, which can be partially explained by direct invasion of T lymphocytes or apoptosis activated by SARS-CoV-2. Dysregulation of the urokinase pathway, cleavage of the SARS-CoV-2 Spike protein by FXa and FIIa, and consumption coagulopathy were the proposed mechanisms of the coagulation dysfunction in COVID-19. False-negative rates of reverse transcriptase polymerase chain reaction varied between 3% and 41% across studies. The probability of the positive test was proposed to decrease with the number of days past from symptom onset. Safety issues related to infection spread limit the use of high flow nasal oxygen (HFNO) and continuous positive airway pressure (CPAP) in hypoxic patients. Further studies are required to elucidate the challenging issues, thus enhancing the management of COVID-19 patients.