Analysis of peripheral lymphocyte subsets and T-cell exhaustion in SARS-CoV-2 Infection.

Introduction: : Immune responses against Coronavirus (SARS-CoV-2) may be highly complex. It has been suggested that T-cell fatigue develops due to continuous stimulation of T-cells by SARS-CoV-2 in Coronavirus disease-2019 (COVID-19). It was aimed to assess peripheral lymphocyte subsets and T-cell exhaustion in various clinical courses of the disease in patients diagnosed with COVID-19. Materials and Methods: This study included 150 patients who were assigned into the "mild-to-moderate disease" group, or "severe disease" group based on their clinical and laboratory characteristics. Peripheral lymphocyte subsets and T-cell exhaustion markers [programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)] were determined in the peripheral blood using flow cytometry. Result: Mean (±SD) age was 53.3 ± 14.5 years, and female to male ratio was 55/95. In the mild-to-moderate disease (MMD) group, 55 patients had pneumonia and 20 patients had COVID-19 without pneumonia. In the severe disease (SD) group, 43 patients had severe pneumoniae and 32 patients were in critical condition. Lymphocyte counts were less than 1.0 x 109/L in 69.3% of the patients in the SD group, and the difference between the MMD group and SD group was statistically significant (p= 0.001). Total T cells, CD4+ and CD8+ T-cell counts were significantly lower in the SD group vs. MMD group (p< 0.001, p< 0.001, p< 0.001, respectively). PD-1 expression by CD8+ and CD4 T+ cells was higher (p= 0.042, p= 0.029, respectively) and Tim-3 expression from CD4 T+ cells was lower (p= 0.000) in the SD group vs. MMD group. Serum IFN-γ levels were not statistically different in the MMD and SD groups (p= 0.2). Conclusions: T-cell counts may be significantly reduced along with an increased expression of the T-cell exhaustion marker PD-1 in severe COVID-19, but Tim-3 expression was not increased in our study patients.

Expansin gene family database: A comprehensive bioinformatics resource for plant expansin multigene family.

Expansins, which are plant cell wall loosening proteins associated with cell growth, have been identified as a multigene family. Plant expansin proteins are an important family that functions in cell growth and many of developmental processes including wall relaxation, fruit softening, abscission, seed germination, mycorrhiza and root nodule formation, biotic and abiotic stress resistance, invasion of pollen tube stigma and organogenesis. In addition, it is thought that increasing the efficiency of plant expansin genes in plants plays a significant role, especially in the production of secondary bioethanol. When the studies on the expansin genes are examined, it is seen that the expansin genes are a significant gene family in the cell wall expansion mechanism. Therefore, understanding the efficacy of expansin genes is of great importance. Considering the importance of this multigene family, we aimed to create a comprehensively informed database of plant expansin proteins and their properties. The expansin gene family database provides comprehensive online data for the expansin gene family members in the plants. We have designed a new website accessible to the public, including expansin gene family members in 70 plants and their features including gene, coding and peptide sequences, chromosomal location, amino acid length, molecular weight, stability, conserved motif and domain structure and predicted three-dimensional architecture. Furthermore, a deep learning system was developed to detect unknown genes belonging to the expansin gene family. In addition, we provided the blast process within the website by establishing a connection to the NCBI BLAST site in the tools section. Thus, the expansin gene family database becomes a useful database for researchers that enables access to all datasets simultaneously with its user-friendly interface. Our server can be reached freely at the following link (http://www.expansingenefamily.com/).

bHLHDB: A next generation database of basic helix loop helix transcription factors based on deep learning model.

The basic helix loop helix (bHLH) superfamily is a large and diverse protein family that plays a role in various vital functions in nearly all animals and plants. The bHLH proteins form one of the largest families of transcription factors found in plants that act as homo- or heterodimers to regulate the expression of their target genes. The bHLH transcription factor is involved in many aspects of plant development and metabolism, including photomorphogenesis, light signal transduction, secondary metabolism, and stress response. The amount of molecular data has increased dramatically with the development of high-throughput techniques and wide use of bioinformatics techniques. The most efficient way to use this information is to store and analyze the data in a well-organized manner. In this study, all members of the bHLH superfamily in the plant kingdom were used to develop and implement a relational database. We have created a database called bHLHDB (www.bhlhdb.org) for the bHLH family members on which queries can be conducted based on the family or sequences information. The Hidden Markov Model (HMM), which is frequently used by researchers for the analysis of sequences, and the BLAST query were integrated into the database. In addition, the deep learning model was developed to predict the type of TF with only the protein sequence quickly, efficiently, and with 97.54% accuracy and 97.76% precision. We created a unique and next-generation database for bHLH transcription factors and made this database available to the world of science. We believe that the database will be a valuable tool in future studies of the bHLH family.

COVID-19 in patients with severe asthma using biological agents.

As the COVID-19 pandemic continues, case reports have been published where patients with severe asthma using biological agents survived with a mild course of illness and encouraged the continuation of biological therapies in patients with severe asthma. However, contrary to previous information, a more severe course of COVID-19 has recently been reported in severe asthmatics using biological therapy compared to the general population. To evaluate the COVID-19 rate and disease severity in severe asthmatics using biological agents. A retrospective study was conducted in patients with severe asthma treated with biological agents. Data concerning whether the subjects had contracted COVID-19 and the severity of the disease were evaluated. Eihgty-four severe asthmatics using biological agents (omalizumab or mepolizumab) aged 48.3 ± 10.6 years (mean ± standard deviation) with female/male ratio: 53 (63.1%)/31 (36.9%) were included in the study. Among participants 13 (15.5%) had contracted COVID-19. The course of COVID-19 was mild in five (38.5%) and moderate in eight patients (61.5%), while none of the patients had a severe course of COVID-19. Mechanical ventilation or intensive care follow-up was not required in any of the six patients (46.2%) who were treated as inpatients. All participants survived COVID-19 in full recovery and no deaths occurred in the cases. A higher rate of COVID-19 was found in patients with severe asthma using biologics compared to those reported in previous reports. However, all patients with COVID-19 have a mild to moderate disease course.

Real-life adherence to subcutaneous immunotherapy: What has changed in the era of the COVID-19 pandemic.

BACKGROUND: Allergen immunotherapy (AIT) must be continued for 3 years, to achieve a long-term modifying effect. Adherence is a key to ensure effectiveness. The objective of this study was, first of all, to evaluate the adherence with subcutaneous immunotherapy (SCIT) and to identify the main causes of SCIT withdrawal in real-life practice in our clinic. Secondly, we also aimed to investigate to what extent the COVID-19 pandemic altered our SCIT receiving patients' treatment adherence behaviors and the factors that affected their decisions. METHODS: Retrospective analysis of the medical records of patients ages ≥18 years, who had started SCIT in January 2014 or later until September 2020 in our department for the diagnosis of allergic rhinitis, allergic asthma or venom allergy, were included in the study. Adherence was determined as the accomplishment of 3 years of SCIT. RESULTS: A total of 124 patients (72 female [58.1%]; median age, 35 [19-77] years) were included. The adherence rate to SCIT in our tertiary center's real-life setting was 56.25% with a follow-up duration of 3 years before COVID-19 pandemic. Dose modification, defined as reducing patient's planned SCIT dose due to a systemic allergic/large local reaction or missed injection, and its frequency, which is the number of dose adjustments done throughout the SCIT, was found to be the only factor related to nonadherence. But with the pandemic only in 6 months, among 63 patients receiving SCIT, 15 patients (23.81%) dropped out, and the most common reason was fear of being infected with COVID-19 virus during receiving SCIT in hospital (93.33%). The only independent predictor of drop-out during the COVID-19 pandemic was short duration of AIT (p = 0.012). When we compare the dropped-out cases before and after the start of pandemic, AIT duration was significantly shorter in pandemic period (p = 0.005). CONCLUSION: Adherence rate to SCIT in our real-world setting study was 56.25% before the COVID-19 pandemic. Our results indicated that patients requiring dose modification were more prone to be non-adherent. Approximately one quarter of patients dropped-out with the start of pandemic, almost all due to fear of being infected during receiving SCIT in hospital. Since short SCIT follow-up time was found to be the only risk factor for drop-out during the COVID-19 pandemic, we believe that patients who are in the early phases of their treatment should be observed more closely and their concerns should be answered by their doctors.

COVID-19 in a patient with severe asthma using mepolizumab.

Background: There is a lack of information about the course of coronavirus disease 2019 (COVID-19) in patients with severe asthma who were treated with biologics. Some reports indicated that treatment with benralizumab, dupilumab, and omalizumab in patients with severe asthma was not associated with significant adverse effects during COVID-19. Methods: Asthma itself or the biologic agents used to treat asthma can have a positive effect on the course of COVID-19. There seem not to be any cases that specifically reported the use of mepolizumab in a patient who was infected with COVID. Results: We reported of a 55-year-old woman with a diagnosis of severe asthma for; 3 years and who was being treated with mepolizumab, with no evidence of loss of asthma control, at the time of contracting COVID-19 and who had been followed up in the allergy clinic. In addition, there are no data on mepolizumab therapy in patients with elevated liver enzyme levels. Conclusion: With this case, we also reported that no adverse effects were observed during mepolizumab treatment in a patient with elevated liver enzyme levels.

Frailty is associated with poor sleep quality in the oldest old

Background/aim: Sleep disorders and frailty increase with advancing age, along with physical disabilities, cognitive dysfunction, mood disorders, and social vulnerability. Thus, the study objective was to evaluate the relationship between frailty and sleep quality in the oldest old patients. Materials and methods: In this study, 100 patients aged ≥80 years were assessed using comprehensive geriatric assessment (CGA) including basic activities of daily living (ADL), instrumental ADL, handgrip strength, the Geriatric Depression Scale-15, the Mini- Mental State Examination, and the Mini-Nutritional Assessment-Short Form. The sleep quality and frailty status of the patients were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Fried Frailty Index, respectively. Results: The median age of the participants was 84 years (80­92), 55% of them were women, and 41% of them were frail. There was no statistically significant difference between the frail and nonfrail groups in terms of age, sex, and comorbidities (P > 0.050). The frail patients scored poorly according to the CGA tests when compared to the nonfrail ones (P < 0.050). The median score for the PSQI was significantly higher in the frail group, 12 points (3­19) versus 6 points (1­19) in the nonfrail patients (P < 0.001). The PSQI score (odds ratio [OR] of 1.308, 95% confidence interval [CI]: 1.092­1.566, P = 0.004), female sex (OR of 5.489, 95% CI: 1.063­28.337; P = 0.042), and the basic ADL score (OR of 0.383; 95% CI: 0.207­0.706; P = 0.002) were found to be independently associated with frailty using multivariate analysis. Conclusion: Sleep quality was significantly decreased in the oldest old frail patients compared to the nonfrail ones, and poor sleep quality was independently associated with frailty. Evaluating the sleep patterns of the oldest old patients with CGA in daily geriatric practice might help to improve the quality of life of frail patients.

The relationship between procalcitonin and thyroid autoantibodies in patients with autoimmune thyroiditis.

BACKGROUND: The aim of this study is to investigate the serum levels of procalcitonin and its association with autoantibodies in patients with euthyroid Hashimoto's thyroiditis. METHODS: A total of 80 participants were included in the study; 40 of which were newly diagnosed with Hashimoto's thyroiditis, aged over 18, and 40 of which were healthy volunteers. The serum levels of procalcitonin were measured by enzyme-linked immunosorbent assay kit. Thyroid function tests were analyzed in hormone laboratory with Electro-chemiluminescence immunoassay. RESULTS: Hashimoto's thyroiditis patients had higher median procalcitonin levels than those of the control group (34.3 pg/mL vs 27.8 pg/mL respectively; P=.037). Also, male patients had higher median procalcitonin levels as compared to female patients (37 pg/mL vs 27 pg/mL respectively; P=.013). In the Hashimoto's thyroiditis group, procalcitonin level was positively correlated with anti-thyroglobulin and anti-thyroid peroxidase levels (r=.559, P<.001; r=634, P<.001, respectively). The procalcitonin and anti-thyroid peroxidase levels were identified to be an independent predictor in diagnosis of Hashimoto's thyroiditis. CONCLUSIONS: The fact that procalcitonin was found to be correlated with thyroid autoantibodies and found to be an independent risk factor for Hashimoto's thyroiditis in the regression analysis in the framework of this study urges us to think that procalcitonin may be associated with the autoimmunity.