ASSOCIATING eNOS GENE VARIANTS WITH COVID-19 SUSCEPTIBILITY IN THE TURKISH POPULATION

Objective: COVID-19 is a serious respiratory and vascular disease that impairs the protective function of the endothelial barrier. Endothelial nitric oxide synthase (eNOS), the most important isoform for nitric oxide (NO) production, is mostly expressed in endothelial cells. Therefore, this study aims to evaluate whether eNOS G894T and variable tandem repeat number (VNTR) functional variants show predisposition to developing COVID-19. Materials and Methods: The study includes a total of 384 subjects (284 COVID-19 patients and 100 healthy controls). Two eNOS gene variants (G894T and VNTR) were genotyped using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, with the results being evaluated using statistical methods. Results: A significant association has been identified between eNOS G894T and COVID-19. For the eNOS G894T variant, the T/T genotype (p=0.035) and T allele carriers (p=0.030) appear to have an increased risk of developing COVID-19. The eNOS G894T G/G genotype (p=0.030) was more common in the control group compared to the patient group. No significant difference was found between groups regarding the eNOS VNTR genotype and allele frequencies (p>0.05). The genotypes of the patient and control groups for these variants were in Hardy-Weinburg equilibrium (HWE). Conclusion: These results provide evidence supporting the hypothesis that the eNOS G894T variant is associated with an increased risk of developing COVID-19 in the Turkish population. These findings may lead to the emergence of new treatment options. Further research is required to understand the molecular mechanisms involved in the pathogenesis of the disease. © 2023 The authors.

Patient Characteristics and Risk Factors for Mortality in 504 Hospitalized Patients Due to Covid-19

Objective: In this study, we aimed to analyze the demographic characteristics, symptoms, and comorbidities of 504 patients hospitalized for COVID-19. We also sought to describe the relationship between these features and intensive care unit (ICU) admission and mortality. Materials and Methods: This study is a descriptive study involving 504 COVID-19 patients hospitalized between 16.03.2020 and 07.05.2020 at Istanbul Universitys' Istanbul Faculty of Medicine Hospital. Information about the patients was obtained from the hospital automation system and evaluated retrospectively. Results: The average age of the 504 patients was 56 +/- 15.14, and 59.1% of them were male. The proportion of the patients admit-ted into ICU 11.9% and for 8.52% of them the disease resulted in death. Real time polymerase chain reaction (RT-PCR) test results were positive for 60.5% of the patients. The median time spent in the hospital was eight days. Fifty six percent of the patients had at least one accompanying comorbid disease, with hyper-tension (39.3%) and diabetes (20.8%) being the most common. Being 65 years old or older (p<0.001), days spent in the hospital (p<0.001), presence of at least one comorbidity (p=0.009), hypertension (p=0.003), coronary artery disease (p=0.004), congestive heart failure (p=0.005) and dyspnea (p<0.001) were all factors found in those admitted to ICU. Conclusion: COVID-19 infection leading to high morbidity-mortality rates and an increased requirement for ICU admission is mainly seen among older patients and those who have dyspnea. During the process of analyzing patients suspected of COVID-19 who are admitted to hospital, it is crucial to consider both the patient's age and any respiratory symptoms. Such a clinical evaluation is crucial for a better understanding of the course of the disease.

Newly Diagnosed Type 1 Diabetes Presenting with Diabetic Ketoacidosis After SARS-CoV-2 Vaccine

The COVID-19 pandemic has deeply affected the whole world in the last 3 years due to the mortality and morbidity it causes. Billions of doses of vaccines have been administered to overcome the pan-demic. The increased incidence of various autoimmune diseases during the pandemic has given rise to the thought that COVID-19 infection or vaccine may be the triggering factor. Recently, new-onset autoimmune phenomena after COVID-19 vaccination have been reported for some autoimmune diseases like Guillain–Barré syndrome and other neurological autoimmune diseases, IgA nephropathy, rheumatoid arthritis and systemic lupus erythematosus, immune thrombotic thrombocytopenia, autoimmune liver diseases, and autoimmune thyroid diseases. Here, we present a case of newly diagnosed type 1 diabetes that developed 1 month after the SARS-CoV-2 vaccine. © Author(s).

The effect of hereditary thrombotic factors and comorbidities on the severity of COVID-19 disease.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and presents critical challenges for public health. Due to its chronic and systemic course, COVID-19 is currently accepted as a multi-systemic infectious disease. Here we explore the possible association between disease course and hereditary thrombotic factors and comorbidities. PATIENTS AND METHODS: The patients admitted to the COVID-19 center in the Istanbul Faculty of Medicine were recruited for the study. The patients were classified according to the clinical course, severe vs. mild. Five polymorphic loci were analyzed by multiplex PCR: Factor V Leiden (FVL), FII G20210A, Beta-fibrinogen G-455A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. RESULTS: FII G20210A and Beta-fibrinogen G-455A genotypes were significantly higher in the study group compared to the literature. Wildtype genotype (GG) in Factor V Leiden locus was significantly associated with low D-Dimer levels (p =0.013). The GA genotype increased the D-Dimer levels 2.55-times compared to the GG genotype (p =0.003). Moreover, the Beta-fibrinogen G-455G genotype was significantly higher in the LDH>250 group (p =0.046). CONCLUSIONS: The presence of solid tumors in patients with COVID-19 was related to the severity of the disease course. No evidence of a correlation between the severity of the disease and all five thrombotic mutations was found, whereas the FII G20210A and Beta-fibrinogen G-455A mutations were significantly high compared to previously reported Turkish population data and global carrier rates. This finding will need to be verified by further studies with larger samples since it may reflect a likelihood of having the COVID-19 disease. The high carrier frequency of FVL mutation was more likely present in the D-dimer high group generating an increase in the D-dimer levels 2.55-times compared to the wildtype.

A Mountain of Debt: Navigating the Legacy of the Pandemic

The COVID-19 pandemic has triggered a massive increase in global debt levels and exacerbated the trade-offs between the benefits and costs of accumulating government debt. This paper examines these trade-offs by putting the recent debt boom into a historical context. It reports three major findings. First, during the 2020 global recession, both global government and private debt levels rose to record highs, and at their fastest single-year pace, in five decades. Second, the debt-financed, massive fiscal support programs implemented during the pandemic supported activity and illustrated the benefits of accumulating debt. However, as the recovery gains traction, the balance of benefits and costs of debt accumulation could increasingly tilt toward costs. Third, more than two-thirds of emerging market and developing economies are currently in government debt booms. On average, the current booms have already lasted three years longer, and are accompanied by a considerably larger fiscal deterioration, than earlier booms. About half of the earlier debt booms were associated with financial crises in emerging market and developing economies. © 2022 Walter de Gruyter GmbH, Berlin/Boston 2022.

POTENTIAL PREDICTORS of OUTCOME for ANAKINRA TREATMENT in COVID-19 PATIENTS with MACROPHAGE ACTIVATION SYNDROME

Background: A hyperinfammatory response compatible with features of macrophage activation syndrome (MAS) contributes to this worse outcome in patients with Coronavirus Disease 2019 (COVID-19). Glucocorticoids have become the standard of care for those requiring oxygen support or mechanical ventilation. More targeted anti-infammatory treatments with tocilizumab and anakinra have also been shown to be effective. Objectives: More studies are being awaited to clarify the features of patients who would beneft more, and we investigated the characteristics of the surviving and dead patients who received anakinra. Methods: The records of hospitalized adult patients between March 2020 and May 2021 in a tertiary referral center were evaluated. Diagnosis of COVID-19-re-lated MAS was based on the expert opinion and preliminary criteria developed by our group that patients with a score of ≥45 were accepted COVID-19-related MAS.1 Patients who received anakinra constituted the study group. Anakinra dose was determined according to the clinical and infammatory parameters;and doses varied between daily 100-300 mg SC to 400-800 mg IV. Laboratory data of surviving and died patients were comparatively analyzed by using the ANCOVA method on the relevant days (baseline, anakinra-onset day, frst response to anakinra treatment, and discharge or death). The temporal variation (drug onset day-frst response day, drug onset day-discharge, or death day) was evaluated using the ANOVA method. A 50% reduction of CRP compared to the anakinra start day was accepted as the frst response to the treatment. Results: Out of 1080 hospitalized patients, 218 (151 male, 67 female, mean age 60.0±14.1) who received anakinra were identifed. Among them, 125 (57.3%) patients were followed in the ward, 21 (9.6%) did not need oxygen treatment during the hospitalization;69 (31.6%) patients were followed at ICU, 40 of them were intubated, 30 (13.7%) died in ICU. Anakinra had been started in a mean of 4.8 days of hospitalization. Twenty had tocilizumab initially and then received anak-inra because of ongoing infammatory parameters. The majority (83.5%) received steroid treatment (79.5% methylprednisolone, 5% of dexamethasone), and 6 received one IV pulse 250 mg of methylprednisolone;36 (16.5%) were followed before September 2020 and received anakinra without steroids because of the standard of care at that period. Only CRP was different between the alive and dead patients for the baseline parameters (p=0.05). On the frst day of drug treatment, CRP and procalcitonin values were signifcantly higher in dead patients (Table 1). A 50% decrease in CRP level was achieved in 3.1 days in survivors and 4.7 days in dead patients. D-dimer (p=0.018), CRP (p=0.006), LDH (p=0.003), procalcitonin (p=0.005), creatinine kinase (p=0.001), and fbrinogen levels (p=0.05) were significantly different between the surviving and dead patients when the measurements between the frst drug administration day and response day were compared. Neu-trophil, lymphocyte count, ferritin, D-dimer, CRP, LDH, AST, procalcitonin, creati-nine kinase, and fbrinogen levels were signifcantly different between the patients when the parameters between the frst drug administration day and discharge/death day were compared. Dead patients had higher CRP values and they did not show a continuing CRP decrease with the steroids and anakinra (Figure 1). Conclusion: Retrospective analysis of 218 patients suggests that starting anakinra earlier in hospitalized patients may provide better results, and a decrease in CRP, ferritin, D-dimer values, as well as an increase in lymphocyte count, are associated with favorable outcomes. Increasing values of D-dimer and troponin during treatment are associated with worse outcomes, possibly indicating cardiovascular and thrombotic pathologies not responding to anakinra. Changes in the CRP values are found to help monitor the response to anakinra. Other infammatory pathways could be targeted in those who are not responding to appropriate doses of anakinra within 5 days.

Dipyridamole does not have any additive effect on the prevention of COVID-19 coagulopathy

Objective: Severe acute respiratory syndrome (SARS) coronavirus 2 (SaRS-Cov-2) associated respiratory disease (COVID-19), announced as a pandemic, is a multisystem syndrome. SARS-CoV-2 directly infects and damages vascular endothelial cells, which leads to microvascular dysfunction and promotes a procoagulant state. Dipyridamole (DP) acts as a reversible phosphodiesterase inhibitor and is used mainly as an antiplatelet agent. It is hypothetised that it has possible activities in COVID-19. Design and Methodology: We report our retrospective, real-world results of DP added to low-molecular weight heparin (LMWH) in the treatment of 462 clinically diagnosed and hospitalized COVID-19 patients. We compared anticoagulation with and without DP addition with no administration of anticoagulation in the same time frame. The primary outcome was proven or highly suspected coagulopathy within 30 days of hospitalization. Results: Definitive coagulopathy has been diagnosed in 3 (3.5%) of 85 LMWH administered patients and 7 (2.13%) of 328 DP + LMWH received patients (P=0.456). Five cases with definitive coagulopathy were not initiated any anticoagulation at the time of the event. The multivariate analysis showed that DP addition to the anticoagulant approach did not have any impact on the risk of demonstrated coagulopathy and highly-suspected coagulopathy. Conclusion: We think that our clinical experience is valuable in showing the real-life results of DP + LMWH treatment in COVID-19. This approach did not affect the coagulopathy rate. Our data did also not document an additive effect of DP in the COVID-19 outcome. Prospective controlled trials would give more convincing results regarding the role of DP in COVID-19 endothelial dysfunction and clinical outcome.

PATIENT CHARACTERISTICS AND RISK FACTORS FOR MORTALITY IN 504 HOSPITALIZED PATIENTS DUE TO COVID-19

Objective: In this study, we aimed to analyze the demographic characteristics, symptoms, and comorbidities of 504 patients hospitalized for COVID-19. We also sought to describe the relationship between these features and intensive care unit (ICU) admission and mortality. Materials and Methods: This study is a descriptive study involving 504 COVID-19 patients hospitalized between 16.03.2020 and 07.05.2020 at Istanbul Universitys’ Istanbul Faculty of Medicine Hospital. Information about the patients was obtained from the hospital automation system and evaluated retrospectively. Results: The average age of the 504 patients was 56±15.14, and 59.1% of them were male. The proportion of the patients admitted into ICU 11.9% and for 8.52% of them the disease resulted in death. Real time polymerase chain reaction (RT-PCR) test results were positive for 60.5% of the patients. The median time spent in the hospital was eight days. Fifty six percent of the patients had at least one accompanying comorbid disease, with hypertension (39.3%) and diabetes (20.8%) being the most common. Being 65 years old or older (p<0.001), days spent in the hospital (p<0.001), presence of at least one comorbidity (p=0.009), hypertension (p=0.003), coronary artery disease (p=0.004), congestive heart failure (p=0.005) and dyspnea (p<0.001) were all factors found in those admitted to ICU. Conclusion: COVID-19 infection leading to high morbidity-mortality rates and an increased requirement for ICU admission is mainly seen among older patients and those who have dyspnea. During the process of analyzing patients suspected of COVID-19 who are admitted to hospital, it is crucial to consider both the patient’s age and any respiratory symptoms. Such a clinical evaluation is crucial for a better understanding of the course of the disease. © 2022 Istanbul University Press. All Rights Reserved.

Atopy and Allergic Diseases Have No Impact on the Severity of COVID-19

Objective: The clinical features of COVID-19 range from asymptomatic disease to severe pneumonia or even death. Therefore, many researchers have investigated the factors that could affect the severity of COVID-19. We aimed to assess the impact of aero-allergen sensitization and allergic diseases on the severity of COVID-19. Materials and Methods: We included 60 adult patients with symptomatic COVID-19 and allocated them into two groups equal in number as having severe and non-severe COVID-19. We evaluated the demographic features and allergic diseases in addition to clinical, laboratory and radiological findings of COVID-19. Skin prick tests (SPTs) with common aero-allergens, serum total IgE levels and blood eosinophil counts were evaluated 3 months after the patient's recovery from COVID-19. Results: The mean age of the patients was 52 ± 11 years and 73.3% of the patients were male. There was no significant difference between the two groups in terms of age, gender, smoking habits, obesity and comorbidities. Although the frequency of sensitization to aeroallergens and the allergic diseases were similar, the history of allergic diseases in the family was higher in the severe group (p<0.001). The polysensitization in SPTs was associated with the presence of a cytokine storm during the infection (p=0.02). Total IgE levels and blood eosinophil counts were not significantly different between the two groups. Conclusion: The presence of atopy or allergic diseases does not seem to be related to the severity of COVID-19. However, polysensitization and a family history of allergic diseases are more prominent in those having a cytokine storm and severe COVID-19, respectively.

PATIENT CHARACTERISTICS AND RISK FACTORS FOR MORTALITY IN 504 HOSPITALIZED PATIENTS DUE TO COVID-19

Objective: In this study, we aimed to analyze the demographic characteristics, symptoms, and comorbidities of 504 patients hospitalized for COVID-19. We also sought to describe the relationship between these features and intensive care unit (ICU) admission and mortality. Material and Methods: This study is a descriptive study involving 504 COVID-19 patients hospitalized between 16.03.2020 and 07.05.2020 at Istanbul University's Faculty of Medicine Hospital. Information about the patients was obtained from the hospital automation system and evaluated retrospectively. Results: The average age of the 504 patients was 56 +/- 15.14, and 59.1% of them were male. The proportion of the patients admitted into ICU 11.9% and for 8.52% of them the disease resulted in death. Real time polymerase chain reaction (RT-PCR) test results were positive for 60.5% of the patients. The median time spent in the hospital was eight days. Fifty six percent of the patients had at least one accompanying comorbid disease, with hypertension (39.3%) and diabetes (20.8%) being the most common. Being 65 years old or older (p<0.001), days spent in the hospital (p<0.001), presence of at least one comorbidity (p=0.009), hypertension (p=0.003), coronary artery disease (p=0.004), congestive heart failure (p=0.005) and dyspnea (p<0.001) were all factors found in those admitted to ICU. Conclusion: COVID-19 infection leading to high morbidity-mortality rates and an increased requirement for ICU admission is mainly seen among older patients and those who have dyspnea. During the process of analyzing patients suspected of COVID-19 who are admitted to hospital, it is crucial to consider both the patient's age and any respiratory symptoms. Such a clinical evaluation is crucial for a better understanding of the course of the disease.

COVID-19 Experience of Higher Education Students in Urban and Rural Areas

According to official statistics, there are approximately eight million higher education students in Turkey. In other words, one-eighth of Turkey's population continues to higher education in Turkey. In this study, the digital divide in distance education in terms of the physical and social environment of higher education students is discussed. When the first COVID-19 cases were recorded in Turkey in the second week of March 2020, formal education was immediately stopped with distance education until finishing 2020-2021 education year and 2021-2022 higher education year started with partly (approximately %40) distance education. This paper focusses on undergraduate (BA) and postgraduate students (both MA and PhD) from Ankara Yildirim Beyazit University (AYBU) in Turkey to compare the function of living in the urban area or rural area during the COVID-19 pandemic. After finishing literature review and getting ethical approval for collecting original data, Phone and Skype interviews between June and September 2020 has done with thirty-four students. Then, the datasets analyzed with the NVivo program with regards to emerged main themes (e.g., location, urban and rural areas, and distance education). In this study, students living in the city center stated that they experienced more psychological, social and economic difficulties in order to overcome this pandemic. Students who live in rural or suburban areas and can access educational materials and facilities with secure internet access have been found to be more independent, safe and productive during the COVID-19 pandemic.