Prevalence of Gastrointestinal Symptoms and Clinical Outcomes in Hospitalized Coronavirus Disease 2019 Patients: A Single-Center Study from Turkey.

BACKGROUND: In patients with coronavirus disease 2019, the gastrointestinal symptoms have been reported increasingly in addition to the respiratory system symptoms. The studies show that the prevalence of gastrointestinal system symptoms and how the gastrointestinal system contributes to the severity and prognosis of the disease is still not clear. This study aims to find the prevalence of gastrointestinal symptoms and the correlation between the gastrointestinal symptoms and the clinical results in hospitalized patients diagnosed with coronavirus disease 2019. METHODS: This study retrospectively analyzes patients diagnosed with coronavirus disease 2019 and hospitalized in the pandemic unit between March 2020 and August 2020 and compares their demographic and clinical characteristics, laboratory and radiologic findings, coronavirus disease 2019 treatments received, the clinical course of the disease, and the gastrointestinal symptoms. RESULTS: In our study, we included 322 patients diagnosed with coronavirus disease 2019 and hospitalized; 39 patients (12.1%) were admitted to the hospital with at least one gastrointestinal symptom (nausea and vomiting, diarrhea, abdominal pain, and the loss of taste). Nausea and vomiting are the most common gastrointestinal symptoms with a prevalence of 7.1%, followed by diarrhea with 2.8%, the loss of taste with 2.2%, and abdominal pain with 1.5%. The mean age and D-dimer levels of the patients showing gastrointestinal symptoms were lower than those who did not have any gastrointestinal symptoms. We did not find a significant correlation between the presence of the gastrointestinal symptoms and the severity of the disease, treatment received, risk of acute respiratory distress syndrome and septic shock, admission to the intensive care unit, the need for mechanical ventilation, the mortality rate or the length of hospitalization in the medical floor or the intensive care unit. CONCLUSION: In this study, we observed that 12.1% of coronavirus disease 2019 patients apply to the hospital due to gastrointestinal symptoms. Furthermore, the gastrointestinal symptoms do not seem to affect the severity and the course of the disease, it is important to identify coronavirus disease 2019 patients showing unusual symptoms such as the gastrointestinal symptoms at an early stage to protect healthcare professionals from infection risk.

An analysis of antibody response following the second dose of CoronaVac and humoral response after booster dose with BNT162b2 or CoronaVac among healthcare workers in Turkey.

Limited data are available on the short- to midterm levels of antibodies to the CoronaVac vaccine and quantitative change in humoral response after homologous or heterologous booster doses. In this prospective cohort study, we evaluated the anti-receptor-binding domain (RBD) immunoglobulin G (IgG) levels after two doses of CoronaVac and heterologous/homologous booster administration among healthcare workers in a university hospital in Turkey. Quantitative anti-RBD IgG antibody levels were measured at first and fourth months in 560 healthcare workers who had completed two doses of CoronaVac vaccine, and within 2 months after the third dose of CoronaVac or BNT162b2. Participants were asked to complete a questionnaire during the first blood draw. The seropositivity rate was 98.9% and 89.1%, and the median antibody level was 469.2 AU/ml and 166.5 AU/ml at first and fourth month, respectively. In the fourth month, a mean reduction of 61.4% ± 20% in antibody levels was observed in 79.8% of the participants. The presence of chronic disease (odds ratio [OR]: 1.76, 95% confidence interval [CI]: 1.15-2.69) and being in the 36-50 age group (OR: 2.11, 95% CI: 1.39-3.19) were identified as independent predictors for low antibody response. The antibody level increased 104.8-fold (median: 17 609.4 vs. 168 AU/ml) and 8.7-fold (median: 1237.9 vs. 141.4 AU/ml) in the participants who received BNT162b2 and CoronaVac, respectively. During the follow-up, 25 healthcare workers (4.5%) were infected with severe acute respiratory syndrome coronavirus 2. Considering the waning immunity and circulating variants, a single booster dose of messenger RNA vaccine seems reasonable after the inactivated vaccine especially in risk groups.

Benchmark of thirteen bioinformatic pipelines for metagenomic virus diagnostics using datasets from clinical samples.

INTRODUCTION: Metagenomic sequencing is increasingly being used in clinical settings for difficult to diagnose cases. The performance of viral metagenomic protocols relies to a large extent on the bioinformatic analysis. In this study, the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS) initiated a benchmark of metagenomic pipelines currently used in clinical virological laboratories. METHODS: Metagenomic datasets from 13 clinical samples from patients with encephalitis or viral respiratory infections characterized by PCR were selected. The datasets were analyzed with 13 different pipelines currently used in virological diagnostic laboratories of participating ENNGS members. The pipelines and classification tools were: Centrifuge, DAMIAN, DIAMOND, DNASTAR, FEVIR, Genome Detective, Jovian, MetaMIC, MetaMix, One Codex, RIEMS, VirMet, and Taxonomer. Performance, characteristics, clinical use, and user-friendliness of these pipelines were analyzed. RESULTS: Overall, viral pathogens with high loads were detected by all the evaluated metagenomic pipelines. In contrast, lower abundance pathogens and mixed infections were only detected by 3/13 pipelines, namely DNASTAR, FEVIR, and MetaMix. Overall sensitivity ranged from 80% (10/13) to 100% (13/13 datasets). Overall positive predictive value ranged from 71-100%. The majority of the pipelines classified sequences based on nucleotide similarity (8/13), only a minority used amino acid similarity, and 6 of the 13 pipelines assembled sequences de novo. No clear differences in performance were detected that correlated with these classification approaches. Read counts of target viruses varied between the pipelines over a range of 2-3 log, indicating differences in limit of detection. CONCLUSION: A wide variety of viral metagenomic pipelines is currently used in the participating clinical diagnostic laboratories. Detection of low abundant viral pathogens and mixed infections remains a challenge, implicating the need for standardization and validation of metagenomic analysis for clinical diagnostic use. Future studies should address the selective effects due to the choice of different reference viral databases.

Investigation of Cytomegalovirus in Intestinal Tissue in a Country With High CMV Seroprevalence.

BACKGROUND: In Turkey, cytomegalovirus (CMV) seropositivity has been reported to be high, between 85 and 100%. CMV has been responsible for disease exacerbation in inflammatory bowel disease (IBD). We aimed to evaluate the presence of CMV in intestinal tissue by immunohistochemical staining in IBD and non-IBD patient groups, in a country with high CMV seroprevalence. METHODS: In this prospective cross-sectional study, the presence of intestinal CMV was investigated with tissue immunohistochemistry (IHC) staining, which is accepted as the gold standard method, and with polymerase chain reaction (PCR) in tissue and blood. Patients (≥18 years old, n = 189) who had a colonoscopic biopsy between January and May 2017 were included in the study at our hospital. Clinical, laboratory, endoscopic, and histopathological data of patients were assessed by dividing them into IBD (n = 34) and non-IBD (n = 155) groups. RESULTS: In this study, 567 colonic biopsy samples from 189 patients were evaluated. Tissue IHC staining was positive for 3 (1.58%) non-IBD patients. One of them was diagnosed as CMV ileitis. CMV DNA was also detected in 14 plasma (7.40%, <80-469 copies/mL) and 20 tissue samples (10.69%, 7-15 289 copies/mL). Tissue IHC staining is accepted as the gold standard for CMV ileitis, and the sensitivity and specificity of tissue PCR was 33% and 89.67%, while the sensitivity and specificity of plasma PCR was 66.66% and 93.54%, respectively. CONCLUSION: Although CMV seroprevalence is high in Turkey, CMV ileitis was diagnosed in only one non-IBD patient (0.53%). Compared to tissue IHC staining, the sensitivity of tissue and blood CMV PCR was low while their specificity was higher.

Recommendations for the introduction of metagenomic next-generation sequencing in clinical virology, part II: bioinformatic analysis and reporting.

Metagenomic next-generation sequencing (mNGS) is an untargeted technique for determination of microbial DNA/RNA sequences in a variety of sample types from patients with infectious syndromes. mNGS is still in its early stages of broader translation into clinical applications. To further support the development, implementation, optimization and standardization of mNGS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mNGS for viral diagnostics to share methodologies and experiences, and to develop application guidelines. Following the ENNGS publication Recommendations for the introduction of mNGS in clinical virology, part I: wet lab procedure in this journal, the current manuscript aims to provide practical recommendations for the bioinformatic analysis of mNGS data and reporting of results to clinicians.

COVID-19 Pandemic Action Plan of a University Hospital.

In December 2019, in Wuhan, China, scientists observed a sudden and sharp increase in the number of cases of pneumonia and acute respiratory distress syndrome of an unknown origin. By the end of January 2020, the outbreak had spread to Asia, Europe, America, and Australia. In this article, we have outlined the pandemic action plan of our university hospital.

Clinical Outcome of PCR-Negative COVID-19 Patients: A Retrospective Study.

OBJECTIVE: To evaluate the clinical features and outcomes of patients who were admitted with a diagnosis of coronavirus disease 2019 (COVID-19) but who were not confirmed with polymerase chain reaction (PCR) positivity. MATERIAL AND METHODS: This is a retrospective analysis of all patients admitted to two tertiary care centers between March 15 and May 15, 2020, with a diagnosis of COVID-19. From a common database prepared for COVID-19, we retrieved the relevant data and compared the clinical findings and outcomes of PCR-positive patients with those of PCR-negative cases who had been diagnosed on the basis of typical clinical and radiographic findings. RESULTS: A total of 349 patients were included in the analysis, of which 126 (36.1%) were PCR-negative. PCR-negative patients were younger (54.6 ± 20.8 vs. 60.8 ± 18.9 years, P = .009) but were similar to PCR-positive patients in terms of demographics, comorbidities, and presenting symptoms. They had higher lymphocyte counts (1519 ± 868 vs. 1331 ± 737/mm3, P = .02) and less frequently presented with bilateral radiographic findings (68.3% vs. 79.4%, P = .046) than PCR-positive patients. Besides, they had less severe disease and better clinical outcomes regarding admission to the intensive care unit (9.6% vs. 20.6%, P = .023), oxygen therapy (21.4% vs. 43.5%, P < .001), ventilatory support (3.2% vs. 11.2%, P = .03) and length of hospital stay (5.0 ± 5.0 vs. 9.7 ± 5.9 days, P < .001). CONCLUSION: This study confirms that about one-third of the COVID-19 patients are PCR-negative and diagnosed based on clinical and radiographic findings. These patients have a more favorable clinical course, shorter hospital stays, and are less frequently admitted to the intensive care unit.

Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure.

Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for implementation of mHTS for virus diagnostics and to give recommendations for development and validation of laboratory methods, including mHTS quality assurance, control and quality assessment protocols.

The Prevalence of Mixed Genotype Infections in Turkish Patients with Hepatitis C: a Multicentered Assessment.

BACKGROUND: HCV virus infections are one of the major health problems in the world that can cause cirrhosis and liver cancer at a higher rate than other hepatitis data. The aim of this study was to determine the prevalence of mixed infections with different HCV genotypes in Turkey and also to evaluate the current HCV genotype and sub-type distributions by a multicentered assessment. METHODS: The HCV genotype data of 17,578 hepatitis C patients collected from 23 centers from different geographic regions covering all Turkey were collected. The data included information about the HCV genotypes in the last 10 years (between 2007 and 2016), demographic properties of the patients and the methods/systems used to determine the genotypes. RESULTS: Two hundred twenty-eight of the patients (1.3%) had mixed genotype. The most common mixed genotype combination was 1b + 4 (0.83%) followed by 1a + 1b (0.26%). Genotype distribution varies according to geographical regions. However, genotype 1 (82.92%) was the most common genotype in all regions and all years. This was followed by genotype 3 (7.07%) and genotype 4 (5.43%). A variety of methods were used by the centers including sequencing, pyrosequencing, real-time PCR, in-house RFLP, reverse hybridization (LIPA), and hybridization. CONCLUSIONS: Infection with mixed HCV genotypes in Turkey is uncommon. Genotype distribution varies according to geographic regions; the most common genotype 1 is encountered all over the country, while genotypes 3 and 4 are only in some of the centers. Since there is limited information about mixed HCV infection, further investigations are needed to determine the clinical importance of mixed HCV infection.

Are cytokines and cortisol important predictors for the severity of pediatric croup: A case control study.

Üzüm Ö, Çaglar A, Küme T, Sayiner A, Er A, Akgül F, Ulusoy E, Yilmaz D, Duman M. Are cytokines and cortisol important predictors for the severity of pediatric croup: A case control study. Turk J Pediatr 2017; 59: 281-287. The aim of this study is to investigate the role of cytokines (TNF-α, IL-6, IL-10, and PAF), cortisol, and IgE in the pathogenesis of croup and the factors determining its clinical severity. Patients diagnosed with croup at the Pediatric Emergency Department were included and thirty healthy children were included as a control group. Patients` demographic characteristics, clinical findings, recurrent croup history, and patient-family atopy history were recorded. Patients were grouped according to the Westley croup scoring system. Blood samples were taken from the control group and the patients for cytokines and cortisol. Respiratory pathogens were studied with PCR. Sixty-nine pediatric cases who were diagnosed as croup were included in the study (34 mild, 31 moderate, 4 severe). Group comparisons were made in terms of mild and moderate/severe groups. In the moderate/severe group, IL-10 and cortisol levels were higher than the mild group. The moderate/severe cortisol levels between 12:00 am-6:00 pm were found to be higher. PAF and TNF-alpha levels were detected to be higher in patients with a history of atopy. Viral agents were isolated in 45 patients; rhinovirus PCR tests were positive in 22 patients. In this study, rhinovirus was the most common etiology for croup. Increased levels of IL-10 and cortisol in the moderate/severe group indicate that different systemic and local mechanisms may play a role in the pathogenesis of croup.

Bronchiolitis in young female smokers.

BACKGROUND: Smoking is a growing concern among young women. However, the pulmonary effects of smoking in young female smokers in their 20's are unknown. OBJECTIVE: The purpose of this study was to determine whether young female smokers demonstrate smoking-related lung abnormalities such as bronchiolitis in their 20's. METHODS: We recruited young females (20-30 yr) from Izmir, Turkey; 29 smokers and 31 lifetime non-smokers. They were all asymptomatic. All subjects performed complete lung function measurements and underwent thoracic computed tomography (CT) scanning at suspended full inspiration using a Toshiba "Aquilion" multi-slice CT scanner. The CT images were analyzed using custom software (Emphylx-J) and published equations to calculate total lung volume, mean lung density, lung mass, and the extent of emphysema. CT images were also read semi-quantitatively for respiratory bronchiolitis and emphysema by 2 experienced chest radiologists. When there was substantial difference in scoring, a 3rd (independent) radiologist read the CT scans. Plasma biomarkers of smoking were also measured in these subjects. RESULTS: Although none of the subjects demonstrated emphysema on CT images, 41% of smokers (compared with only 15% of non-smokers) had evidence for respiratory bronchiolitis (with a score of 2 or more; p = 0.0301). There was a significant relationship between pack-years of smoking and the severity of respiratory bronchiolitis in smokers. Plasma interleukin (IL)-6 levels were also higher in smokers than in non-smokers (p = 0.028). Quantitative analysis for emphysema or airways disease on CT scans did not reveal any significant differences in the two groups with the exception of lung mass, which was higher in the smokers than in non-smokers. Lung function was similar between the two groups. CONCLUSION AND CLINICAL RELEVANCE: Young female smokers in their 20's and 30's demonstrate CT changes consistent with respiratory bronchiolitis and elevated plasma IL-6 levels. They also have "heavier" lungs compared with lifetime non-smokers. These data indicate that pathologic changes of smoking occur early in young female smokers in the absence of demonstrable airflow limitation or symptoms. Public health efforts to curb smoking in young women are clearly needed to reduce the burden of smoking related lung disease in women.

Chlamydial infections in term and preterm neonates.

The aim of this study was to evaluate the incidence and morbidities of Chlamydia trachomatis infections in newborn infants. Tissue culture and direct immunofluorescence (DIF) tests were used to detect the presence of nasopharyngeal C. trachomatis infection in 35 preterm and 21 healthy term neonates. All infants were followed up clinically for 3 months, and enzyme-linked immunosorbent assay analysis for serum antichlamydial IgG and IgM was performed on day 15 and week 6. Tissue culture and/or DIF studies showed that 10 of the preterm infants (28.57%), but none of the term infants, were C. trachomatis-positive. The sensitivities of DIF and tissue culture were 40% and 70%, respectively, demonstrating the diagnostic superiority of tissue culture tests for detecting C. trachomatis. Only one asymptomatic preterm infant was found to be positive for antichlamydial antibodies at the 6th week. All C. trachomatis-positive infants were given macrolide antibiotics for 14 days. The study showed that male infants were more frequently infected, but types of delivery, mean gestational ages, mean birth weights, and the need for mechanical ventilation were similar in C. trachomatis-infected and uninfected preterm infants. However, the duration of oxygen treatment was longer in infected preterm infants. Clinical conjunctivitis was more frequent in C. trachomatis-infected infants (60%) than in uninfected infants (24%). C. trachomatis-positive infants had pneumonia more frequently; however, all patients with pneumonia were negative for antichlamydial IgM and IgG antibodies. Macrolide treatment for 2 weeks for nasopharyngeal C. trachomatis positivity may have prevented C. trachomatis related pneumonia, but it may not have significantly influenced the risk of pneumonia caused by other agents. Chlamydial infections may lead to early and late respiratory problems in preterm infants. Nasopharyngeal screening may help physicians detect C. trachomatis infections and provide a means of early diagnosis in this vulnerable patient group.

Unilateral acute retinal necrosis in a multiple sclerosis patient treated with high-dose systemic steroids.

A 50-year-old man with multiple sclerosis developed unilateral acute retinal necrosis following a long-term systemic corticosteroid administration for treatment of an attack of paraparesis. The patient was treated with systemic acyclovir, aspirin, oral steroids and topical cyclopentolate and prednisolone acetate for almost 3 months. Pars plana vitrectomy and 360° endolaser photocoagulation posterior to necrotic retinal areas were performed a week after the initial diagnosis. Varicella zoster DNA was confirmed by PCR analysis in the vitreous sample. Two months later, pars plana vitrectomy with silicone oil injection was performed successfully to treat complicated retinal detachment. Careful peripheral fundus examination is essential when acute unexplained visual loss is noted in patients receiving systemic corticosteroids to exclude acute retinal necrosis syndrome.

Photodynamic therapy as an adjunct to systemic treatment in a case with unilateral presumed vascularized choroidal tuberculous granuloma.

Intraocular tuberculosis cannot be diagnosed easily in some clinical circumstances. A 29-year-old otherwise healthy woman who was initially misdiagnosed and treated empirically with systemic steroids and sulfamethoxazole-trimethoprim for toxoplasmosis was referred to us for severe visual loss. We instituted quadruple antituberculosis treatment upon chest medicine consultation as all attempts, including consecutive intravitreal antibiotic injections, could not prevent the enlargement of lesion. Systemic antituberculosis treatment halted the fulminant course but the granuloma became vascularized. Because photodynamic therapy (PDT) has very recently been shown to reduce viable mycobacterial cells in animal experiments we performed PDT, and the vascularized tuberculous granuloma was successfully treated. PDT may have an antimycobacterial effect besides its well-known antiangiogenic effect.

PCR and serology were effective for identifying Chlamydophila pneumoniae in a lower respiratory infection outbreak among military recruits.

During endemic infections, the sensitivity of diagnostic tests and rapid diagnosis of the respiratory tract pathogens is particularly important. Utilization of just one diagnostic technique, such as serological tests or polymerase chain reaction (PCR)-based detection methods, during outbreaks of lower respiratory tract infections (LRI) can result in some of the patients being missed. In this study we aimed to investigate the etiology of LRI in military recruits in Izmir, Turkey, among whom several pneumonia cases have been reported and 47 patients have been hospitalized. Nasopharyngeal swabs were used for PCR analysis of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Legionella spp. Serum samples were collected in the acute and convalescent phase of infection for C. pneumoniae and M. pneumoniae. Thirty-nine patients were diagnosed with C. pneumoniae infection by PCR and/or serology. Diagnoses were established by PCR in the acute phase of infection in 40.4% of the group. Based on the results of these studies, PCR is a useful method for early detection and identification of C. pneumoniae-related LRI outbreaks. However, this technique is not sufficient to detect all positive cases per se. After effective therapy and introduction of appropriate infection control measures, the outbreak ceased without mortality. This is the first closed-community C. pneumoniae outbreak report from Turkey.

[Two cases of herpes encephalitis with normal cerebrospinal fluid findings]. / Olgu sunumu: beyin omurilik sivisi bulgulari normal olan iki herpes ensefaliti olgusu.

In this report, characteristics of two cases of Herpes simplex virus (HSV) encephalitis with normal cerebrospinal fluid (CSF) findings at the time of admission have been discussed and the current literature has been reviewed. The diagnosis of the cases (one was 23 years old male, and the other was 75 years old female patient) was made on the magnetic resonance imaging (MRI) findings concordant with HSV encephalitis, together with HSV-1 DNA positivity by polymerase chain reaction (PCR). Both of the patients were treated with acyclovir (3 x 750 mg/day) lasting for 15 days and 21 days, respectively. The first male patient recovered with mild neurological defects, whereas the second female patient died because of nosocomial pneumonia and septicemia. In conclusion, even the CSF findings are normal, in cases considered to be HSV encephalitis, MRI should be the first radiological diagnostic step and the diagnosis should be confirmed by the detection of HSV DNA in CSF by PCR.