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.].

Prognostic Value of Serial Measurement of Serum Des-Arg(9)-Bradykinin Levels in Severe COVID-19 Patients.

BACKGROUND: Excessive inflammatory immune response during SARS-CoV-2 infection contributes to severe disease in COVID-19 patients. Recently, some researchers hypothesized that dysregulation of the bradykinin (BK) system may also play a role in the pathogenesis of severe disease. Des-Arg(9)-bradykinin (DABK), an active metabolite of BK, is responsible for vasodilatation and increased permeability in the lungs and regulated by angiotensin converting enzyme 2 (ACE-2). Viral inhibition of ACE-2 by SARS-CoV-2 increases DABK levels. Serum levels of this metabolite may be linked to disease severity in COVID-19 patients. In this study, it is aimed to investigate the prognostic value of serial measurement of serum DABK levels in severe COVID-19 patients. METHODS: This prospective cohort study was conducted in hospitalized severe COVID-19 patients. Serum DABK levels of patients were serially measured on day 0, day 3 and day 5. Patients were categorized as cases with poor or good prognosis and critical or non-critical cases. Serum DABK levels of these patient groups were compared with paired sample t-test. Serum DABK levels on different days in the same patients were compared with repeated measures ANOVA tests. RESULTS: There was no statistically significant difference in serum DABK levels measured at day 0, day 3, and day 5 between good and poor prognosis groups. DABK levels in critical and non-critical COVID-19 patients also did not show any significant difference. CONCLUSIONS: According to our results serially measured serum DABK levels did not correlate with outcome of severe COVID-19 and do not have prognostic value in severe COVID-19 patients.

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.

Assessment of olfactory and gustatory functions in COVID-19 patients

Background/aim: This study aims to evaluate of olfactory and gustatory functions of COVID-19 patients and possible risk factors for olfactory and gustatory dysfunctions. Materials and methods: The cross-sectional study included adult patients who were diagnosed with COVID-19 in Gazi University Hospital between April 2020 and June 2020. Volunteered patients participated in a survey in which olfactory and gustatory functions and various clinical information were questioned. Sinonasal Outcome Test-22 was also administrated to all patients. Results: A hundred and seventy-one patients participated in this study. Olfactory and gustatory dysfunctions rates were 10.5% (n: 18) and 10.5% (n: 18), respectively. Patients without any symptom other than smell and taste dysfunctions were clustered as group 1 and patients who are clinically symptomatic were clustered as group 2. Olfactory dysfunction occurred in 8% of group 1 and 17.4% of group 2 (p = 0.072). Gustatory dysfunction rate of smokers was 19.7% and significantly higher than gustatory dysfunction rate of nonsmokers (5.5%) (p = 0.007). Twenty-seven-point-eight percent of the patients with olfactory dysfunction (n = 5) were male and 72.2% (n: 13) were female. Sex did not show significant effect on rate of olfactory dysfunction. Twenty-five patients participated in psychophysical olfactory function test. No participant reported olfactory dysfunction at the time of test. Of the participants, 64% (n: 16) were normosmic and 36% (n: 9) were hyposmic according to Sniffin' Stick test. Conclusion: Olfactory and gustatory dysfunctions are more common in patients who are clinically symptomatic than those diagnosed during contact tracing. Objective tests may show that frequency of olfactory dysfunction is greater than frequency of self-reported olfactory dysfunction.

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.

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 assessment of serum ACE activity in COVID-19 and its association with clinical features and severity of the disease.

Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. This pathway has a major role in the development of acute lung injury and acute respiratory distress syndrome (ARDS), which is a devastating complication of SARS-CoV-2 infection. The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. Patients with confirmed COVID-19 by detecting SARS-CoV-2 nucleic acid RT-PCR were included in the study. Demographic data, clinical features, laboratory and radiologic investigations were recorded. Patients were classified by disease severity; asymptomatic, mild, and severe pneumonia. The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. Fifty-five patients (50.9% female) and 18 healthy subjects (33.3 % female) were enrolled in the study. The median age of patients was 40 years, ranging from 22 to 81 years. Eighteen healthy subjects were served as the control group. The baseline characteristics were comparable between groups. The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. There was no correlation between the serum ACE activity and conventional inflammatory markers. In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity.

Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.

BACKGROUND: The effectual immune response is crucial to defeat viral infections. However, exuberant immune response with features of macrophage activation syndrome (MAS) lead detrimental consequences in COVID-19 patients. Interleukin (IL)-18 is one of the leading cytokines in MAS which has not been studied in COVID-19. OBJECTIVE: To investigate the association of IL-18 with the other inflammatory markers and disease severity in COVID-19 for predicting disease prognosis. METHODS: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled into the study. Data on demographic and clinical characteristics, and laboratory values of CRP, ferritin, d-dimer and procalcitonin were measured on admission. Patients were followed up prospectively with a standardized approach until hospital discharge or death. Individuals were classified as asymptomatic, mild and severe pneumonia according to their clinical, laboratory and radiological characteristics. Worse outcome was defined as requirement of intensive care unit (ICU) admission or death. Blood samples were collected at enrollment and serum levels of IL-6 and IL-18 were determined by ELISA. Association between IL-18 and other inflammatory markers and prognosis were analyzed. RESULTS: There were 58 COVID-19 patients (50% male) with a median age of 43 (min 22-max 81) years. Twenty age and sex matched healthy subjects were served as control group. The study population was divided into three groups according to disease severity: asymptomatic (n = 20), mild pneumonia group (n = 27) and a severe group (n = 11). During follow up nine (15.5%) patients required ICU admission and three of them were died eventually. Serum IL-18 were correlated with other inflammatory markers and biochemical markers of organ injury; creatinine, liver enzymes and troponin. Serum IL-18 levels were remarkably higher in COVID-19 patients compared to healthy subjects with being highest in severe pneumonia group (p < 0.001). IL-18 serum concentrations were almost four-fold higher in patients with worse outcome compared to good outcome (p < 0.001). Serum IL-18 above the cut off value of 576 pg/mL on admission was associated with 11.7 fold increased risk of ICU admission. CONCLUSIONS: The serum concentrations of IL-18 correlate with other inflammatory markers and reflect disease severity. Results of the present study shed light on role of IL-18 on COVID-19 pathogenesis and might provide an evidence for the clinical trials on IL-18 antagonists for the treatment of severe COVID-19 patients.

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.

Clinical features and treatment of COVID-19

In December 2019, a novel coronavirus (SARS-CoV-2) was identified as the cause of clustered pneumonia cases in Wuhan, a city in the Hubei Province of China. The virus rapidly spread to the rest of the world after a huge epidemic in China and WHO has declared a pandemic on March 11, 2020. SARS-CoV-2 is transmitted via respiratory droplets and fomites during close unprotected contact. The airborne spread has not been established as a major route of transmission. The mean incubation period of the illness is 5 days and it mainly presents with fever and respiratory symptoms. Myalgia, loss of taste and smell, diarrhea and dermatological findings are also common during the course of the disease. Laboratory findings are nonspecific. Significant elevations in inflammation markers can be observed in some patients due to cytokine storm. Typical CT findings are bilateral ground glass opacities and consolidation with peripheral and lower lobes distribution. COVID-19 causes mild symptoms in most cases, however it may progress to severe pneumonia leading to ARDS and death, especially in those with advanced age and comorbid diseases. There is no specific effective antiviral treatment for COVID-19. A number of in vitro effective agents have been identified. These agents such as chloroquine phosphate/hydroxychloroquine, favipiravir, remdesivir, lopinavir/ritonavir are widely used in the treatment of the disease. Convalescent plasma therapy and the cytokine inhibitory agents such as tocilizumab, used to treat disease-induced cytokine storm, are particularly preferred in the treatment severe cases.