Is diagnostic performance of SARS-CoV-2 detection dogs reduced -due to virus variation- over the time?

Medical detection dogs have a high potential for use as alternative diagnostic tools not only for organic diseases, but also for infectious diseases. However, new variants emerging over time may affect the accuracy and sensitivity of diagnostic methods including medical detection dogs in case of viral pandemics. To the best of our knowledge, this is a pioneer study aimed to investigate diagnostic performances and generalization ability of SARS-CoV-2 detection dogs against the new variant after being trained with the original virus. Two SARS-CoV-2 detection dogs were used in this study. In total, 1002 samples including the Omicron variant were introduced to the dogs using a double-blinded design. Two different refresher training sessions were conducted to train the dogs to identify the scent of the Omicron variant. In the first refreshment training, mixed samples (original virus and Omicron variant) were used. The diagnostic performances of the dogs were significantly increased only after the second refreshment training where only the Omicron variant was introduced. This study illustrates that diagnostic performances of SARS-CoV-2 detection dogs were not consistent over time with the emerging new variants. Thus, refreshment training with new variant(s) should be conducted with every new variant which may affect the diagnostic performances of those dogs in such infectious outbreaks.

Erratum: Evaluation of prevalence and risk factors for bloodstream infection in severe coronavirus disease 2019 (COVID-19) patients - CORRIGENDUM.

[This corrects the article DOI: 10.1017/ash.2021.254.].

The Prognostic Value of Lung Injury and Fibrosis Markers, KL-6, TGF-ß1, FGF-2 in COVID-19 Patients.

Background: Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-ß1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19. Methods: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-ß1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed. Results: Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, P = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis. Conclusions: Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-ß1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.

Immunogenicity and safety of the CoronaVac and BNT162b2 Covid-19 vaccine in patients with inflammatory rheumatic diseases and healthy adults: comparison of different vaccines.

OBJECTIVES: To determine the seroconversion (SC) rate after CoronaVac and BNT162b2 vaccines in adults with inflammatory rheumatic disease (IRD). METHODS: Patients who were followed up with IRD and who received two doses of either CoronaVac or BNT162b2 vaccines were included in this prospective observational single-center study. Subjects with two doses of CoronaVac or BNT162b2 without known IRD were included in the healthy controls. The blood samples were taken at a minimum of two and a maximum of 12 weeks after the second dose of vaccine. RESULTS: A total of 81 patients with IRD (61 CoronaVac, 20 BNT162b2) and 100 healthy controls (70 CoronaVac, 30 BNT162b2) were included. The SC rate was slightly lower among patients with IRD versus controls (84 vs 97%, p = 0.002). The SC rate was 100% in all participants who received BNT162b2 both in the patient and control group. The IgG antibody level after CoronaVac in the patient group was significantly lower than both the BNT162b2 (p = 0.031) and the healthy group (p < 0.001). Among patients with IRD, those on rituximab (RTX) (12/81,14.8%) had significantly less SC rate (5/12, 41.7%). The median neutralizing antibody titers were significantly higher in patients with BNT162b2 compared with CoronaVac (1.97 vs. 16.34, p < 0.001). CONCLUSIONS: This study showed that all patients with BNT162b2 vaccine developed immunogenicity in patients with IRD, while there was a decreased antibody response with CoronaVac vaccine compared to that of BNT162b2. In particular, RTX significantly reduces the SC rate.

Distribution and Clinical Features of Viral Respiratory Infections in Children After Face-To-Face Education in 2021-2022 Winter Period: Journal of Pediatric Infection

The incidence in children is similar to that in adults but they generally have a lower risk of exposure and are tested less frequently than adults (3). Besides they are known to have milder diasese than adults. In this study, we evaluated a multiplex real-time PCR panel for the simultaneous detection of 21 types of respiratory viral pathogens (Influenza A, Influenza B, H1N1, human parainfluenza (PIV 1, PIV 2, PIV 3, PIV 4), human rhinovirus, human coronavirus (NL63-229E-OC43-HKU1), human metapneumovirus A/B, human bocavirus, human respiratory syncytial virus A/B, human adenovirus, human parechovirus, enterovirus) using Fast Tract Respiratory Pathogens 21 (Siemens Healthcareb GmbH, Germany) in nasopharyngeal specimens of the patients with respiratory tract infections. The study was conformed with the principles of the Declaration of Helsinki and was approved by the local ethics committee and the Institutional Review Board of Gazi University Clinical Research in 2022/January. The respiratory viral multiplex PCR results of patients were as follows: 32.7% (n= 132) of patients were positive for COVID-19, 15.3% (n= 62) were positive for human respiratory syncytial viruses A/B (RSV), 8.7% (n= 35) were positive for rhinovirus, 6.4% (n= 26) were positive for influenza virus, 3.2% (n= 13) were positive for coronaviruses (HCoV), 3.2% (n= 13) were positive for bocavirus, 2.7% (n= 11) were positive for human parainfluenza virus, 2.2% (n= 9) were positive human-metap- neumovirus and 1.5% (n= 6) were positive for human adenovirus.

Retrospective evaluation of viral respiratory tract infections in a university hospital in Ankara, Turkey (2016-2019).

INTRODUCTION: Viruses are responsible for two-thirds of all acute respiratory tract infections. This study aims to retrospectively detect respiratory tract viruses in patients from all age groups who visited the hospital. METHODOLOGY: A total of 1592 samples from 1416 patients with respiratory tract symptoms were sent from several clinics to the Molecular Microbiology Laboratory at Gazi University Hospital from February 2016 to January 2019. Nucleic acid extraction from nasopharyngeal swabs, throat swabs or bronchoalveolar lavage (BAL) samples sent to our laboratory was done using a commercial automated system. Extracted nucleic acids were amplified by a commercial multiplex-real time Polymerase Chain Reaction (PCR) method, which can detect 18 viral respiratory pathogens. RESULTS: Among 1592 samples, 914 (57.4%) were positive for respiratory viruses. The most prevalent were rhinovirus (25.2%) and influenza A virus (12.1%), the least prevalent was the bocavirus (2.6%). Rhinovirus was the most detected as a single agent (21.2%, 194/914) among all positive cases, followed by coronavirus (9.3%, 85/914). The detection rates of coronavirus, human adenovirus, respiratory syncytial virus A/B, human parainfluenza viruses, human metapneumovirus-A/B, human parechovirus, enterovirus and influenza B virus were 9.9%, 8%, 7.7%, 5%, 3.4%, 3.1%, 3%, and 2.8%, respectively. CONCLUSIONS: The most detected viral agents in our study were influenza A virus and rhinovirus. Laboratory diagnosis of respiratory viruses is helpful to prevent unnecessary antibiotic use and is essential in routine diagnostics for antiviral treatment. Multiplex Real-time PCR method is fast and useful for the diagnosis of viral respiratory infections.

Evaluation of prevalance and risk factors for bloodstream infection in severe coronavirus disease 2019 (COVID-19) patients.

Objectives: In this study, we sought to determine the prevalence of bloodstream infection (BSI) in severe coronavirus disease 2019 (COVID-19) patients and to determine the risk factors of BSI in critical COVID-19 patients. Design: Retrospective, descriptive study between March 2020 and January 2021. Setting: An 1,007-bed university hospital. Participants: Patients who were hospitalized due to severe COVID-19 disease and had an aerobic blood culture taken at least once during hospitalization. Methods: Case definitions were made according to National Institutes of Health clinical definitions. According to the blood culture results, the patients were grouped as with and without BSIs, and compared for BSIs risk factors. Results: In total, 195 patients were included in the study. Blood culture positivity was detected in 76 (39.0%) of 196 patients. Excluding blood culture positivity considered as contamination, the prevalence of BSI in all severe COVID-19 cases was 18.5% (n = 36). In intensive care unit patients the prevalence of BSI was 30.6% (n = 26). In multivariate analyses, central venous catheter (odds ratio [OR], 8.17; 95% confidence interval [CI], 2.46-27.1; P < .01) and hospitalization in the multibed intensive care unit (OR, 4.28; 95% CI, 1.28-14.3; P < .01) were risk factors associated with the acquisition of BSI. Conclusion: The prevalence of BSI in COVID-19 patients is particularly high in critically ill patients. The central venous catheter and multibed intensive care follow-up are risk factors for BSI. BSIs can be reduced by increasing compliance to infection control measures and central venous catheter insertion-care procedures. The use of single-bed intensive care units where compliance can be achieved more effectively is important for the prevention of BSIs.

Genomic characterization of SARS-CoV-2 isolates from patients in Turkey reveals the presence of novel mutations in spike and nsp12 proteins.

Novel mutations have been emerging in the genome of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2); consequently, the evolving of more virulent and treatment resistance strains have the potential to increase transmissibility and mortality rates. The characterization of full-length SARS-CoV-2 genomes is critical for understanding the origin and transmission pathways of the virus, as well as identifying mutations that affect the transmissibility and pathogenicity of the virus. We present an analysis of the mutation pattern and clade distribution of full-length SARS-CoV-2 genome sequences obtained from specimens tested at Gazi University Medical Virology Laboratory. Viral RNA was extracted from nasopharyngeal specimens. Next-generation sequencing libraries were prepared and sequenced on Illumina iSeq 100 platform. Raw sequencing data were processed to obtain full-length genome sequences and variant calling was performed to analyze amino acid changes. Clade distribution was determined to understand the phylogenetic background in relation to global data. A total of 293 distinct mutations were identified, of which 152 missense, 124 synonymous, 12 noncoding, and 5 deletions. The most frequent mutations were P323L (nsp12), D614G (ORF2/S), and 2421C>T (5'-untranslated region) found simultaneously in all sequences. Novel mutations were found in nsp12 (V111A, H133R, Y453C, M626K) and ORF2/S (R995G, V1068L). Nine different Pangolin lineages were detected. The most frequently assigned lineage was B.1.1 (17 sequences), followed by B.1 (7 sequences) and B.1.1.36 (3 sequences). Sequence information is essential for revealing genomic diversity. Mutations might have significant functional implications and analysis of these mutations provides valuable information for therapeutic and vaccine development studies. Our findings point to the introduction of the virus into Turkey through various sources and the subsequent spread of several key variants.

Relationship between chest computed tomography findings and clinical conditions of coronavirus disease (COVID-19): A multicentre experience.

AIMS: This study aimed to investigate the clinical and chest computed tomography (CT) features associated with clinical parameters for coronavirus disease (COVID-19) in the capital of Turkey, Ankara. MATERIALS AND METHODS: Epidemiological, clinical features, laboratory findings and radiological characteristics of 1563 hospitalised patients with COVID-19 in Ankara were collected, reviewed and analysed in this study. The risk factors associated with disease severity were investigated. RESULTS: Non-severe (1214; 77.7%) and severe cases (349; 22.3%) were enrolled in the study. Compared with the non-severe group, the severe group were significantly older and had more comorbidities (ie, hypertension, diabetes mellitus, cardiovascular disease and chronic kidney disease). Smoking was more common in the severe group. Severe patients had higher respiratory rates and higher incidences of cough and dyspnoea compared with non-severe patients. Compared with the non-severe patients, the severe patients had increased C-reactive protein (CRP), procalcitonin, neutrophil to lymphocyte ratio (NLR) and CRP/albumin ratio and decreased albumin. The occurrence rates of consolidation, subpleural sparing, crazy-paving pattern, cavity, halo sign, reversed halo sign, air bronchogram, pleural thickening, micronodule, subpleural curvilinear line and multilobar and bilateral involvement in the CT finding of the severe patients were significantly higher than those of the non-severe patients. CONCLUSIONS: Many factors are related to the severity of COVID-19, which can help clinicians judge the severity of the patient and evaluate the prognosis. This cohort study revealed that male sex, age (≥55 years), patients with any comorbidities, especially those with cardiovascular disease, dyspnoea, increased CRP, D-dimer and NLR, and decreased lymphocyte count and CT findings of consolidation and multilobar involvement were predictors of severe COVID-19.

The prognostic role of neopterin in COVID-19 patients.

In Coronavirus disease-2019 (COVID-19) cases, hyper inflammation is associated with the severity of the disease. High levels of circulating cytokines were reported in severe COVID-19 patients. Neopterin produced by macrophages on stimulation with interferon-gamma, which is an important cytokine in the antiviral immune response, hence it can be used to predict the severity of disease in COVID-19 cases. In this study, it was aimed to determine the prognostic value of the neopterin for the prediction of severe disease in patients with COVID-19. This single-center, prospective study was conducted in hospitalized COVID-19 patients and healthy volunteers. Severe and mild COVID-19 cases were compared in terms of clinical and laboratory findings as well as serum neopterin levels on hospital admission. To assess the prognostic utility of neopterin between the severe and mild COVID-19 groups, a receiver-operating characteristic (ROC) curve was generated, and the area under the curve (AUC) was calculated. The median serum neopterin level was four times higher in COVID-19 patients than the healthy controls (46 vs. 12 nmol/L; p < .001). The AUC value of serum neopterin was 0.914 (95% confidence interval, 0.85-0.97). The sensitivity and specificity of serum neopterin for the cut-off value of 90 nmol/L to identify severe COVID-19 cases were 100% and 76%, respectively. Serum neopterin levels on hospitalization were significantly higher in severe COVID-19 disease than mild COVID-19 patients. Neopterin levels can be used as an early prognostic biomarker for COVID-19 on admission.

Early predictors of acute kidney injury in COVID-19 patients.

AIM: This study aims to determine the frequency of COVID-19 related AKI and to identify the early predictors of AKI. METHODS: This study is a single-center, retrospective, observational study. Hospitalized COVID-19 patients between 24/03/2020 and 31/05/2020 were included in the study. All patients were evaluated for renal dysfunctions with urine dipstick, protein/creatinine ratio, albumin/creatinine ratio in spot urine, serum cystatin C, serum creatinine level on hospital admission, and 28th day of hospital admission. To assess the utility of these parameters to predict AKI, a receiver-operating characteristic curve was generated and the area under the curve (AUC) was calculated. RESULTS: 348 patients were included. The average incidence of AKI was 4.9% (n = 17). The incidence of AKI in mild, moderate and severe COVID-19 cases was 1.3% (n = 4), 9.0% (n = 3) and 76.9% (n = 10), respectively. Proteinuria was detected in 7.8% (n = 27) of patients with a urine dipstick test. In spot urine analysis, proteinuria was found in 20.1% (n = 70) of patients. The frequency of persistent proteinuria was 5.2% (n = 18). The AUC alue of serum cystatin C, D-dimer and albumin/creatinine ratio to predict COVID-19 related AKI were 0.96 (0.90 to 1.0), 0.94 (0.89-0.98), and 0.95 (0.91-0.98). CONCLUSION: In COVID-19 patients with normal serum creatinine levels on hospital admission, albuminuria, serum cystatin C and D-dimer levels may be an early predictor of COVID-19 related AKI and these patients should be monitored closely for AKI. Since the sample size in the AKI group was small, our study results should be confirmed with larger cohort studies.

The factors predicting pneumonia in COVID-19 patients: preliminary results from a university hospital in Turkey

Background/aim: Pneumonia is the most serious clinical presentation of COVID-19. This study aimed to determine the demographic, clinical, and laboratory findings that can properly predict COVID-19 pneumonia. Materials and methods: This study was conducted in the Gazi University hospital. All hospitalized patients with confirmed and suspected SARS-CoV-2 infection between 16 March 2020 and 30 April 2020 were analyzed retrospectively. COVID-19 patients were separated into two groups, pneumonia and nonpneumonia, and then compared to determine predicting factors for COVID-19 pneumonia. Variables that had a P-value of less than 0.20 and were not correlated with each other were included in the logistic regression model. Results: Of the 247 patients included in the study 58% were female, and the median age was 40. COVID-19 was confirmed in 70.9% of these patients. Among the confirmed COVID-19 cases, 21.4% had pneumonia. In the multivariate analysis male sex (P = 0.028), hypertension (P = 0.022), and shortness of breath on hospital admission (P = 0.025) were significant factors predicting COVID-19 pneumonia. Conclusion: Shortness of breath, male sex, and hypertension were significant for predicting COVID-19 pneumonia on admission. Patients with these factors should be evaluated more carefully for diagnostic procedures, such as thorax CT.