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Item Comparison Of Clinical Characteristics Of Second And Third Peaks Of COVID-19 Pandemic: Effects Of Vaccination And Preventive Measures(2022) Ozdemir, Ozer; Arslan, Atakan; Bulbul, Hande M.; Ozdemir, PelinBACKGROUND: Understanding the differences in consequent peaks of COVID-19 may guide us for better predicting future disease characteristics. In this study, we aimed to compare clinical and radiological characteristics as well as out-comes of hospitalized patients with the diagnosis of COVID-19 in second and third peaks of disease.METHODS: We retrospectively included 303 hospitalized patients with COVID-19. The study population was examined in two groups: patients hospitalized between October 2020 and January 2021 during second peak and patients hospital-ized between March and June 2021 during third peak.RESULTS: There were 171 patients in group 1 and 132 patients in group 2. The patients in group 2 were younger (64 +/- 13.27 vs. 56.02 +/- 15.39, respectively; P<0.001) and female proportion was higher (64.9% and 48.5% males; P=0.005). Smoking history and presence of comorbidities were less in group 2 (41.5% vs. 25.7%, P=0.008; and 78.5% vs. 59.1%, P<0.001) and symptom duration was shorter (median 7 days vs. 6 days, P=0.039). CT severity scores, LDH, CRP, D-di-mer, Ferritin, and creatinine levels were lower in group 2 (P=0.003, P=0.008, P<0.001, P<0.001, P<0.001, respectively), and mortality ratio was lower (N.=39 [28%] vs. N.=15 [11.4%], P=0.01). Duration of hospital stay and need for intensive unit care were similar across groups (median 8 days vs. 7 days, P=0.673 and N.=39 [22.8%] vs. N.=33 [25.2%], P=0.683).CONCLUSIONS: Although duration of hospital stay was lower in third peak, clinical severity scores and prognostic markers were lower compared with second peak. These may reflect the increased proportion of immunized people, and the effect of preventive measures.Item Promising Drug Fondaparinux for the Treatment of COVID-19: an In Silico Analysis of Low Molecular Weight Heparin, Direct Oral Anticoagulant, and Antiplatelet Drug Interactions with Host Protease Furin(2022) Ertan-Bolelli, Tugba; Bolelli, Kayhan; Elci, Sitki Doga; Belen-Apak, F. Burcu; 0000-0002-2179-997X; 0000-0002-9278-6703; 36401727; G-5289-2013Purpose As of July 2022, the COVID-19 pandemic has affected over 555 million worldwide confirmed cases and caused more than 6.3 million deaths. The studies showed that the D-dimer levels were increased in non-survivors compared to survivors and heparin treatment has begun to be administered to the patients in severe clinics. As we knew that the entrance of SARS-CoV-2 to the host cell needs to be facilitated by host proteases; we published our hypothesis that heparin as a serine protease inhibitor may block the interaction between spike protein receptor-binding domain and host proteases. In our study, we aimed to investigate the interactions between not only heparins but also other antiplatelet and anticoagulant drugs including fondaparinux. Methods In this study, docking studies were carried out to evaluate the interactions between low molecular weight heparins (LMWHs) (enoxaparin, dalteparin, tinzaparin), direct oral anticoagulant, and antiplatelet drugs with host proteases. Molecular docking studies were performed by using Schrodinger molecular modeling software. 3D structures of the ligands were obtained from the 2D structures by assigning the OPLS-2005 force field using the Maestro 12.7. The 3D crystal structure of the furin complexed with an inhibitor, 2,5-dideoksistreptamin derivative, was extracted from the Protein Data Bank (PDB ID: 5MIM). Docking studies were carried out using the Grid-based Ligand Docking with Energetics module of the Schrodinger Software. Results The docking studies revealed that fondaparinux was the most relevant molecule to interact with furin with a docking score of - 12.74. It showed better interaction than the natural ligand of furin with an increased score compared to the docking score of - 8.155 of the natural ligand. AnaGA*IsA structure representing LMWH structure has shown a docking score of - 11.562 which was also better than the score of the natural ligand of furin. Conclusion Our findings have shown that LMWHs and fondaparinux can be used for their possible antiviral effects in COVID-19 patients. Our results have shown that in accordance with heparin and LMWH, fondaparinux can also be a candidate for "drug repurposing" in COVID-19 therapy, not only because of their anticoagulant but also possible antiviral effects.Item Comparison Of Confirmed And Probable COVID-19 Patients In The Intensive Care Unit During The Normalization Period(2022) Yesiler, Fatma Irem; Capras, Mesher; Kandemir, Emre; Sahinturk, Helin; Gedik, Ender; Zeyneloglu, Pinar; https://orcid.org/0000-0002-0612-8481; https://orcid.org/0000-0003-0159-4771; 34812130; AAJ-4212-2021; AAJ-1419-2021The decrease in social distance together with the normalization period as of June 1, 2020, in our country caused an increase in the number of coronavirus disease 2019 (COVID-19) patients. Our aim was to compare the demographic features, clinical courses, and outcomes of confirmed and probable COVID-19 patients admitted to our intensive care unit (ICU) during the normalization period. Critically ill 128 COVID-19 patients between June 1, 2020, and December 2, 2020, were analyzed retrospectively. The mean age was 69.7 +/- 15.5 y (61.7% male). Sixty-one patients (47.7%) were confirmed. Dyspnea (75.0%) was the most common symptom and hypertension (71.1%) was the most common comorbidity. The mean Acute Physiology and Chronic Health Evaluation System (APACHE II) score; Glasgow Coma Score; Sequential Organ Failure Assessment scores on ICU admission were 17.4 +/- 8.2,12.3 +/- 3.9, and 5.9 +/- 3.4, respectively. One hundred and one patients (78.1%) received low-flow oxygen, 48 had high-flow oxygen therapy (37.5%), and 59 (46.1%) had invasive mechanical ventilation. Fifty-three patients (41.496) had vasopressor therapy and 30 (23.4%) patients had renal replacement therapy due to acute kidney injury (AKI). Confirmed patients were more tachypneic (p= 0.005) and more hypoxemic than probable patients (p < 0.001). Acute respiratory distress syndrome and AKI were more common in confirmed patients than probable (both p < 0.001). Confirmed patients had higher values of hemoglobin, C- reactive protein, fibrinogen, and D-dimer than probables (respectively, p = 0.028. 0.006, 0.000. and 0.019). The overall mortality was higher in confirmed patients (p = 0.209, 52.6% vs. 47.4%). Complications are more common among confirmed COVID-19 patients admitted to ICU. The mortality rate of confirmed COVID-19 patients admitted to the ICU was found to be higher than probable patients. Mortality of confirmed cases was higher than prediction of APACHE-II scoring system.Item SARS-CoV-2 Mutations and their Viral Variants(2022) Cosar, Begum; Karagulleoglu, Zeynep Yagmur; Unal, Sinan; Ince, Ahmet Turan; Uncuoglu, Dilruba Beyza; Tuncer, Gizem; Kilinc, Bugrahan Regaip; Ozkan, Yunus Emre; Ozkoc, Hikmet Ceyda; Demir, Ibrahim Naki; Eker, Ali; Karagoz, Feyzanur; Simsek, Said Yasin; Yasar, Bunyamin; Pala, Mehmetcan; Demir, Aysegul; Atak, Irem Naz; Mendi, Aysegul Hanife; Bengi, Vehdi Umut; Sevel, Guldane Cengiz; Altuntas, Evrim Gunes; Kilic, Pelin; Demir-Dora, Devrim; https://orcid.org/0000-0003-0359-6308; 34580015Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occur spontaneously during replication. Thousands of mutations have accumulated and continue to since the emergence of the virus. As novel mutations continue appearing at the scene, naturally, new variants are increasingly observed.Since the first occurrence of the SARS-CoV-2 infection, a wide variety of drug compounds affecting the binding sites of the virus have begun to be studied. As the drug and vaccine trials are continuing, it is of utmost importance to take into consideration the SARS-CoV-2 mutations and their respective frequencies since these data could lead the way to multi-drug combinations. The lack of effective therapeutic and preventive strategies against human coronaviruses (hCoVs) necessitates research that is of interest to the clinical applications.The reason why the mutations in glycoprotein S lead to vaccine escape is related to the location of the mutation and the affinity of the protein. At the same time, it can be said that variations should occur in areas such as the receptor-binding domain (RBD), and vaccines and antiviral drugs should be formulated by targeting more than one viral protein.Item The Changing Dynamics Of Neutralizing Antibody Response Within 10 Months Of SARS-Cov-2 Infections(2022) Bastug, Aliye; Bodur, Hurrem; Aydos, Omer; Filazi, Nazlican; Oksuz, Ergun; https://orcid.org/0000-0002-5723-5965; 34967013; K-8238-2012There are limited data on how long neutralizing antibody (NAb) response elicited via primary SARS-CoV-2 infection will last. Eighty-four serum samples were obtained from a prospective cohort of 42 laboratory-confirmed COVID-19 inpatients at the time of discharge from the hospital and in the late convalescent phase. A virus neutralization assay was performed to determine the presence and titers of NAbs with authentic SARS-CoV-2. Long-term dynamics of NAbs and factors that may have an impact on humoral immunity were investigated. Mild and moderate/severe patients were compared. The mean sampling time was 11.12 +/- 5.02 days (4-28) for the discharge test and 268.12 +/- 11.65 days (247-296) for the follow-up test. NAb response was present in 83.3% of the patients about 10 months after infection. The detectable long-term NAb rate was significantly higher in mild patients when compared to moderate/severe patients (95.7% vs. 68.4%, p = 0.025). In the follow-up, NAb-positive and -negative patients were compared to determine the predictors of the presence of long-term humoral immunity. The only significant factor was disease severity. Patients with mild infections have more chance to have NAbs for a longer time. Age, gender, and comorbidity did not affect long-term NAb response. NAb titers decreased significantly over time, with an average rank of 24.0 versus 19.1 (p = 0.002). Multivariate generalized estimating equation analysis revealed that no parameter has an impact on the change of NAb titers over time. The majority of the late convalescent patients still had detectable low levels of neutralizing antibodies. The protective effect of these titers of NAbs from re-infections needs further studies.Item Cross-Sectional Analysis Of Tobacco Addiction In Hospitalized COVID-19 Patients(2022) Darilmaz Yuce, Gulbahar; Torun, Serife; Hekimoglu, Koray; Tuna, Derin; Sozbilici, Betul Rana; Cetin, Hikmet Oguz; Narlioglu, Mehmet Emin; Balli, Murat; Ozyesil, Ahmet Suheyl; Yavuz Colak, Meric; Ulubay, Gaye; Akcay, Muserref Sule; https://orcid.org/0000-0002-0805-0841; 36164949; AAD-9097-2021Introduction: The COVID-19 pandemic has become an important health issue with consequences for special populations since 2019. Tobacco use is an important public health issue and tobacco users are a risk group for lung infections.Materials and Methods: The aim of this study is to obtain information about disease prevalence and severity, laboratory parameters, and changes in radio-logical findings between smokers and non-smokers who were hospitalized, followed up, and treated for COVID-19, and to find answers to critical questi-ons regarding the response to antiviral and supportive therapy. Two hundred eighty-six patients who were hospitalized and treated between March 2020-February 2021 in the COVID-19 Isolation Ward of Baskent University Hospital were included in the study. The patients were grouped as current smokers, non-smokers, and ex-smokers. The groups were compared in terms of symptoms, laboratory findings, radiological findings, and treatment respon-se.Results: The median age of the patients included in the study was 59 (IQR= 32). Of the patients, 40.6% were female and 59.4% were male. In our study, we discovered that there were fewer female smokers (p< 0.001). When the current smokers (n= 56), non-smokers (n= 159), and ex-smokers (n= 71) were compared based on their findings, it was found that dyspnea was more common in current smokers (p= 0.009). Lung involvement was found to be more common (p= 0.002) and multifocal in the current smokers group (p= 0.038). The levels of oxygen saturation at the times of admission and discharge were lower in current smokers (p= 0.002 and p= 0.038). The need for nasal oxygen and noninvasive mechanical ventilation was also found to be higher in current smokers (p= 0.008 and p= 0.039). Systemic steroid requirement was higher in current smokers (p= 0.013). There was no statistically significant differen-ce in terms of mortality between current smokers, ex-smokers, and non-smokers (p= 0.662).Conclusion: The analysis of the findings of the patients hospitalized in the COVID-19 isolation ward indicated that COVID-19 leads to a more serious course in patients with a history of smoking.Item A new DoE-MTOPSIS based prediction model suggestion to capture potential SARS-CoV-2 reactivated patients(2021) Tansel, Yusuf I. C.; 0000-0001-9274-7467; AGE-3003-2022Difficulties to use convenient data during the Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV-2) pandemic outbreak and complexities of the problem attitude crucial challenges in infectious disease modelling studies. Motivated by the on-going reach to predict a potential reactivated SARS-CoV-2 (COVID-19), we suggest a prediction model that beyond the clinical characteristics based evaluation approaches. In particular, we developed a possibly available and more efficient prediction model to predict a potential reactivated SARS-CoV-2 (COVID-19) patient. Our paper aims to explore the applicability of a modified Technique for Order Preference by Similarity to Ideal Solutions (MTOPSIS) integrated Design of Experiment (DoE) method to predict a potential reactivated COVID-19 patient in real-time clinical or laboratory applications. The presented novel model may be of interest to the readers studying similar research areas. We illustrate MTOPSIS integrated DoE method by applying it to the COVID-19 pandemic real clinical cases from Wuhan/China-based data. Despite the small sample size, our study provides an encouraging preliminary model framework. Finally, a step by step algorithm is suggested in the study for future research perspectives.Item Detection of COVID-19 by Machine Learning Using Routine Laboratory Tests(2021) Cubukcu, Hikmet Can; Topcu, Deniz Ilhan; Bayraktar, Nilufer; Gulsen, Murat; Sari, Nuran; Arslan, Ayse Hande; 0000-0002-1219-6368; 0000-0002-7886-3688; 34791032; E-3717-2019; Y-8758-2018Objectives The present study aimed to develop a clinical decision support tool to assist coronavirus disease 2019 (COVID-19) diagnoses with machine learning (ML) models using routine laboratory test results. Methods We developed ML models using laboratory data (n = 1,391) composed of six clinical chemistry (CC) results, 14 CBC parameter results, and results of a severe acute respiratory syndrome coronavirus 2 real-time reverse transcription-polymerase chain reaction as a gold standard method. Four ML algorithms, including random forest (RF), gradient boosting (XGBoost), support vector machine (SVM), and logistic regression, were used to build eight ML models using CBC and a combination of CC and CBC parameters. Performance evaluation was conducted on the test data set and external validation data set from Brazil. Results The accuracy values of all models ranged from 74% to 91%. The RF model trained from CC and CBC analytes showed the best performance on the present study's data set (accuracy, 85.3%; sensitivity, 79.6%; specificity, 91.2%). The RF model trained from only CBC parameters detected COVID-19 cases with 82.8% accuracy. The best performance on the external validation data set belonged to the SVM model trained from CC and CBC parameters (accuracy, 91.18%; sensitivity, 100%; specificity, 84.21%). Conclusions ML models presented in this study can be used as clinical decision support tools to contribute to physicians' clinical judgment for COVID-19 diagnoses.Item Conjunctivitis as sole symptom of COVID-19: A case report and review of literature(2020) Ozturker, Zeynep Kayaarasi; 0000-0002-5513-9857; 32703010; AAC-5790-2021Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus causing an ongoing pandemic in 2020. Although the symptomatic patients infected by SARS-CoV-2 generally show respiratory distress, atypical manifestations such as conjunctivitis are also observed. A series of cases is reported in which reverse transcriptase polymerase chain reaction (RT-PCR) testing on tears had demonstrated the presence of the virus. However, the transmission of the virus through ocular fluids remains unknown. Case description: In this case report, the development of conjunctivitis is presented as the sole symptom of a new coronavirus disease 2019 (COVID-19) in an emergency health care worker. The patient's first application was to the ophthalmology clinic due to redness, stinging, tearing, and photophobia for one day in the right eye. The patient had no symptoms of fever, cough, shortness of breath, or fatigue. Two days later, the RT-PCR test, blood analysis, and chest computed tomography (CT) were applied to the patient for being in contact with a COVID positive patient. Conjunctival swabs did not identify SARS-CoV-2 by RT-PCR. However, nasopharyngeal swab and blood test confirmed the diagnosis of COVID-19. Chest CT did not show pneumonia. Conclusion: This phenomenon shows that conjunctivitis may occur as a sole manifestation of COVID-19 which needs to be carefully evaluated by health care workers and eye care professionals during the pandemic.Item Tobacco and COVID-19(2020) Sonmez, Ozlem; Tasdemir, ZeynepAtam; kara, H. Volkan; Akcay, Sule; 0000-0002-8360-6459; AAB-5175-2021Tobacco and its products are the well-known causes of premature deaths associated with cancer, cardiovascular disease, and chronic obstructive pulmonary disease, as well as they constitute a significant risk factor that increases the tendency to respiratory system infection and other systemic infections. Active tobacco use and passive smoking increase the risk of infection. Both increase peribronchial and alveolar inflammation and fibrosis and mucosal permeability, cause inadequate mucociliary cleaning, damage to the respiratory tract epithelium resulting in fibrosis, and they adversely affect cellular and humoral immunity. Smoking has been known to increase the risk for viral infections and influenza. Similar data have been approved found for coronavirus disease-2019 (COVID-19) pandemic. Smoking is reported to be associated with the frequency of the disease and its severity of the clinical course. Severe acute respiratory syndrome-coronavirus-2 penetrates the cell using the angiotensin-converting enzyme 2 receptors. Such receptor proteins had been shown to increase in smoker individuals. Also, smoking facilitates penetration of the virus into the cell. The frequency of smoking and the rates of admission to intensive care, mechanical ventilation, and mortality have been also found to be higher was higher in severe cases. The risk for disease progression was found to be 14-fold higher in smokers. Further, the World Health Organization emphasized similar negative effects of hookah and new tobacco products such as electronic cigarettes and heated tobacco products. It is vital to underline the adverse effects of tobacco and tobacco products and to raise awareness among the public and to make efforts to smoking on every opportunity during the COVID-19 pandemic. Public awareness campaigns during the pandemic must always accompanied by the methods and strategies to avoid active and passive smoking.