SARS-CoV-2/COVID-19 and advances in developing potential therapeutics and vaccines to counter this emerging pandemic.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China, which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 210 countries while affecting more than 25 million people and causing more than 843,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia, and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs, and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. To date, August 30, 2020, no effective, proven therapeutic antibodies or specific drugs, and vaccines have turned up. In this review article, we describe the underlying molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

Hepatitis E virus infection in Turkey: a systematic review.

Hepatitis E virus (HEV), a non-enveloped single stranded RNA virus causes sporadic cases of hepatitis or outbreaks. The disease is generally self-limited although it may cause fulminant hepatitis in pregnant women, elderly, those with underlying chronic hepatitis, immunosuppressed, and transplant recipients. It is transmitted through fecal-oral route and zoonotic transmission. Hepatitis is a main health care problem in Turkey; HBV and HCV prevalences are 4 and 1% respectively. Hepatitis D represents another considerable hepatitis etiology with a prevalence of 5-27%. The information about HEV is not clear. In this systematic review, we aimed to analyze HEV studies reported from Turkey, to determine the current situation of the disease in the country, to delineate the limits of the studies and to determine the future study areas. The prevalence of HEV ranged from 0 to 12.4%. Children had lower prevalence than the adults. The prevalence was determined as 7-8% in pregnant women, 13% in chronic HBV patients, 54% in chronic HCV patients, 13.9-20.6% in patients with chronic renal failure, and ≈ 35% in agriculture workers. Among individuals immigrating form Turkey to Europe, HEV seroprevalence was found 10.3% in Italy and 33.4% in the Netherlands. HEV prevalence seems high in certain risk groups. Although previous studies suggest that Turkey is among the endemic countries of HEV, there are some pitfalls for the analysis of data: the studies are not powered enough to represent the whole population; they did not include immunosuppressed patients and solid organ recipients; and the prevalence of non-A non-B hepatitis was not determined.

Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study.

BACKGROUND: Staphylococcus aureus is one of the causes of both community and healthcare-associated bacteremia. The attributable mortality of S. aureus bacteremia (SAB) is still higher and predictors for mortality and clinical outcomes of this condition are need to be clarified. In this prospective observational study, we aimed to examine the predictive factors for mortality in patients with SAB in eight Turkish tertiary care hospitals. METHODS: Adult patients with signs and symptoms of bacteremia with positive blood cultures for S. aureus were included. All data for episodes of SAB including demographics, clinical and laboratory findings, antibiotics, and outcome were recorded for a 3-year (2010-2012) period. Cox proportional hazard model with forward selection was used to assess the independent effect of risk factors on mortality. A 28-day mortality was the dependent variable in the Cox regression analysis. RESULTS: A total of 255 episodes of SAB were enrolled. The median age of the patients was 59 years. Fifty-five percent of the episodes were considered as primary SAB and vascular catheter was the source of 42.1 %. Healthcare associated SAB was defined in 55.7 %. Blood cultures yielded methicillin-resistant S. aureus (MRSA) as a cause of SAB in 39.2 %. Initial empirical therapy was inappropriate in 28.2 %. Although overall mortality was observed in 52 (20.4 %), 28-day mortality rate was 15.3 %. Both the numbers of initial inappropriate empirical antibiotic treatment and the median hours to start an appropriate antibiotic between the cases of fatal outcome and survivors after fever onset were found to be similar (12/39 vs 60/216 and 6 vs 12 h, respectively; p > 0.05). High Charlson comorbidity index (CCI) score (p = 0.002), MRSA (p = 0.017), intensive care unit (ICU) admission (p < 0.001) and prior exposure to antibiotics (p = 0.002) all were significantly associated with mortality. The Cox analysis defined age [Hazard Ratio (HR) 1.03; p = 0.023], ICU admission (HR 6.9; p = 0.002), and high CCI score (HR 1.32; p = 0.002) as the independent predictive factors mortality. CONCLUSIONS: The results of this prospective study showed that age, ICU stay and high CCI score of a patient were the independent predictors of mortality and MRSA was also significantly associated with mortality in SAB.

Ebola virus disease and the veterinary perspective.

Ebola virus disease (EVD) is a potentially fatal haemorrhagic disease of humans. The last and most serious outbreak of Ebola virus (EBOV) started in December 2013 in West Africa and also affected other continents. Animals such as fruit bats and non-human primates are potential sources of EBOV. This review highlights the clinical features of EVD in humans and animals and addresses the public health implications of EVD outbreaks from the veterinary perspective.

Characteristics of leptospirosis with systemic inflammatory response syndrome: a multicenter study.

BACKGROUND: Leptospirosis is a common zoonotic infection in the world. In patients with leptospirosis, in case of presence of Systemic Inflammatory Response Syndrome (SIRS), clinical and laboratory findings can be mistaken for sepsis due to other causes of infection. The purpose of this study is to assess the clinical and laboratory parameters of patients with leptospirosis in terms of the presence of SIRS and to examine the association of these with mortality. METHODS: One hundred fifty-seven patients were included in the study. The patients were classified according to the presence or absence of SIRS and divided into SIRS (+) and SIRS (-). Patient files were retrospectively evaluated. Clinical features and laboratory data were compared, and risk factors associated with mortality were determined. RESULTS: SIRS (+) was found in 70 % (n = 110) of patients who had signs on admission. Comparison of the clinical symptoms and findings of organ systems in the SIRS (+) and SIRS (-) showed that abdominal pain and vomiting were significantly more common in the SIRS (+) than in the SIRS (-) (p = 0.025 and p = 0.046, respectively). BUN and serum creatinine levels were significantly higher in the SIRS (+) than in the SIRS (-) (p = 0.002 and p < 0.001, respectively). In follow-up posterior-anterior chest radiography, pathological findings improved in 58.8 % (n = 40) of patients in the SIRS (+) and 27.3 % (n = 9) of patients in the SIRS (-) (p = 0.003). The mortality rate of the SIRS (+) and SIRS (-) was not significantly different (p = 0.868). CONCLUSION: In patients with positive SIRS findings, while examining the etiology of sepsis, leptospirosis should come to mind especially in endemic areas for differential diagnosis. Early initiation of antibiotic and supportive therapy can be lifesaving in these patients.

Role of migratory birds in spreading Crimean-Congo hemorrhagic fever, Turkey.

We investigated migratory birds' role in spreading Crimean-Congo hemorrhagic fever virus (CCHFV) through attached ticks. We detected CCHFV RNA in ticks on migratory birds in Turkey. Two isolates showed similarity with CCHFV genotype 4, suggesting a role for ticks in CCHFV epidemics in Turkey and spread of CCHFV by birds.

The interrelations of radiologic findings and mechanical ventilation in community acquired pneumonia patients admitted to the intensive care unit: a multicentre retrospective study.

BACKGROUND: We evaluated patients admitted to the intensive care units with the diagnosis of community acquired pneumonia (CAP) regarding initial radiographic findings. METHODS: A multicenter retrospective study was held. Chest x ray (CXR) and computerized tomography (CT) findings and also their associations with the need of ventilator support were evaluated. RESULTS: A total of 388 patients were enrolled. Consolidation was the main finding on CXR (89%) and CT (80%) examinations. Of all, 45% had multi-lobar involvement. Bilateral involvement was found in 40% and 44% on CXR and CT respectively. Abscesses and cavitations were rarely found. The highest correlation between CT and CXR findings was observed for interstitial involvement. More than 80% of patients needed ventilator support. Noninvasive mechanical ventilation (NIV) requirement was seen to be more common in those with multi-lobar involvement on CXR as 2.4-fold and consolidation on CT as 47-fold compared with those who do not have these findings. Invasive mechanical ventilation (IMV) need increased 8-fold in patients with multi-lobar involvement on CT. CONCLUSION: CXR and CT findings correlate up to a limit in terms of interstitial involvement but not in high percentages in other findings. CAP patients who are admitted to the ICU are severe cases frequently requiring ventilator support. Initial CT and CXR findings may indicate the need for ventilator support, but the assumed ongoing real practice is important and the value of radiologic evaluation beyond clinical findings to predict the mechanical ventilation need is subject for further evaluation with large patient series.

International Nosocomial Infection Control Consortium (INICC) national report on device-associated infection rates in 19 cities of Turkey, data summary for 2003-2012.

BACKGROUND: Device-associated healthcare-acquired infections (DA-HAI) pose a threat to patient safety, particularly in the intensive care unit (ICU). We report the results of the International Infection Control Consortium (INICC) study conducted in Turkey from August 2003 through October 2012. METHODS: A DA-HAI surveillance study in 63 adult, paediatric ICUs and neonatal ICUs (NICUs) from 29 hospitals, in 19 cities using the methods and definitions of the U.S. NHSN and INICC methods. RESULTS: We collected prospective data from 94,498 ICU patients for 647,316 bed days. Pooled DA-HAI rates for adult and paediatric ICUs were 11.1 central line-associated bloodstream infections (CLABSIs) per 1000 central line (CL)-days, 21.4 ventilator-associated pneumonias (VAPs) per 1000 mechanical ventilator (MV)-days and 7.5 catheter-associated urinary tract infections (CAUTIs) per 1000 urinary catheter-days. Pooled DA-HAI rates for NICUs were 30 CLABSIs per 1000 CL-days, and 15.8 VAPs per 1000 MV-days. Extra length of stay (LOS) in adult and paediatric ICUs was 19.4 for CLABSI, 8.7 for VAP and 10.1 for CAUTI. Extra LOS in NICUs was 13.1 for patients with CLABSI and 16.2 for patients with VAP. Extra crude mortality was 12% for CLABSI, 19.4% for VAP and 10.5% for CAUTI in ICUs, and 15.4% for CLABSI and 10.5% for VAP in NICUs. Pooled device use (DU) ratios for adult and paediatric ICUs were 0.54 for MV, 0.65 for CL and 0.88 for UC, and 0.12 for MV, and 0.09 for CL in NICUs. The CLABSI rate was 8.5 per 1,000 CL days in the Medical Surgical ICUs included in this study, which is higher than the INICC report rate of 4.9, and more than eight times higher than the NHSN rate of 0.9. Similarly, the VAP and CAUTI rates were higher compared with U.S. NHSN (22.3 vs. 1.1 for VAP; 7.9 vs. 1.2 for CAUTI) and with the INICC report (22.3 vs. 16.5 in VAP; 7.9 vs. 5.3 in CAUTI). CONCLUSIONS: DA-HAI rates and DU ratios in our ICUs were higher than those reported in the INICC global report and in the US NHSN report.

Recovery of complete genome sequences of Crimean-Congo haemorrhagic fever virus (CCHFV) directly from clinical samples: A comparative study between targeted enrichment and metagenomic approaches.

Crimean-Congo haemorrhagic fever (CCHF) is the most prevalent human tick-borne viral disease, endemic to the Balkans, Africa, Middle East and Asia. There are currently no licensed vaccines or effective antivirals against CCHF. CCHF virus (CCHFV) has a negative sense segmented tripartite RNA genome consisting of the small (S), medium (M) and large (L) segments. Depending on the segment utilised for genetic affiliation, there are up to 7 circulating lineages of CCHFV. The current lack of geographical representation of CCHFV sequences in various repositories highlights a requirement for increased CCHFV sequencing capabilities in endemic regions. We have optimised and established a multiplex PCR tiling methodology for the targeted enrichment of complete genomes of Europe 1 CCHFV lineage directly from clinical samples and compared its performance to a non-targeted enrichment approach on both short-read and long-read sequencing platforms. We have found a statistically significant increase in mapped viral sequencing reads produced with our targeted enrichment approach. This has allowed us to recover near complete S segment sequences and above 90% of the M and L segment sequences for samples with Ct values as high as 31.3. This study demonstrates the superiority of a targeted enrichment approach for recovery of CCHFV genomic sequences from samples with low virus titre. CCHFV is an important vector-borne human pathogen with wide geographical distribution. The validated methodology reported here adds value to front-line public health laboratories employing genomic sequencing for CCHFV Europe 1 lineage surveillance, particularly in the Balkan and Middle Eastern territories currently monitoring the spread of the pathogen. Tracking the genomic evolution of the virus across regions improves risk assessment and directly informs the development of diagnostics, therapeutics, and vaccines.

A Comparison of Clinical and Laboratory Features of Crimean-Congo Hemorrhagic Fever in Children and Adults: A Retrospective Single-Center Cohort Study and Literature Review.

Background: Crimean-Congo hemorrhagic fever (CCHF) is a major emerging infectious disease threat, and children are reported to have a milder disease course compared with adults, in contrast to other viral hemorrhagic fevers. The aim of this study was to compare adult and pediatric patients with CCHF to improve understanding of pathogenesis and the natural history of the disease. Materials and Methods: A retrospective analysis of all children and adults admitted with confirmed CCHF between 2011 and 2020. Epidemiological, clinical, and laboratory features were collated on proformas, together with clinical management details. The Severity Grading Score (SGS) system was used to stratify mortality risk. Data from children were compared with adults in the same center and with other published pediatric cohort studies. Results: A total of 47 children with a median (ranges) age of 14 (2-17) years and 176 adults with a median (ranges) age of 52 (18-83) years with confirmed CCHF were included. The most frequent symptoms in adults were fever, muscle-joint pain, headache, nausea, and vomiting; the most frequent in children were fever, anorexia, nausea, vomiting, and abdominal pain. Adults had lower lymphocyte and platelet counts and higher liver transaminase and creatinine levels than children. SGS values were lower in children, but 97.9% children received ribavirin compared with 8.5% of adults (p < 0.001), and they had associated longer median lengths of hospital admission (10 vs. 7 days, p < 0.001). Mortality of 1 out of 47 (2.1%) children was similar to 11 other cohorts reported in Türkiye and lower than 13.1% in adults (23/176) in the same center (p = 0.059). Conclusions: Children have lower CCHF-related mortality, less severe disease, and different clinical syndromes at presentation. The majority of published case definitions for screening for CCHF in the main endemic countries do not differentiate between adults and children and omit four of the five most common presenting features in children.

Tracing the spread of hepatitis C virus in Turkey: a phylogenetic analysis.

BACKGROUND/AIMS: Molecular epidemiology of hepatitis C virus (HCV) shows that HCV genotypes are unique with respect to their nucleotide sequence, geographical distribution and clinical relationship. METHODS: In this study we enrolled 67 HCV-infected individuals with various stages of liver disease from four geographical regions of Turkey. A partial NS5B region of the HCV genome was sequenced and subjected to phylogenetic analysis to determine the circulating HCV genotypes and subtypes. RESULTS: The results showed that HCV genotype 1 (subtype1b) is the main genetic variant of HCV in Turkey but did not reveal any Turkish indigenous phylogenetic cluster. Phylogenetic analysis showed that Turkish strains have their closest matches from both Asia (Japan) and Europe/USA. CONCLUSIONS: In view of Turkey's geographic position, HCV-1b transmission from Europe is not exceptional. This study could not establish a clear role of other HCV genotypes prevalent in neighboring Asian countries in Turkey's HCV transmission, which would need to be confirmed by further regional epidemiological studies.

Specific mutations of basal core promoter are associated with chronic liver disease in hepatitis B virus subgenotype D1 prevalent in Turkey.

The role of hepatitis B virus (HBV) genetics in the clinical manifestations of infection is being increasingly recognized. Genotype D is one of eight currently recognized major HBV genotypes. The virus is ubiquitous worldwide, but shows different features in different regions. One hundred and ninety-eight patients with chronic HBV infection were enrolled in this study, 38 of whom had been diagnosed with cirrhosis of the liver and/or hepatocellular carcinoma. HBV DNA was isolated from the patients' blood samples and the entire genome and/or the basal core promoter/core promoter region sequenced. Phylogenetic analysis of the complete genomes revealed that subgenotype D1 is the most prevalent subgenotype in Turkey, but there was no definite phylogenetic grouping according to geography for isolates from different regions within Turkey, or for isolates in Turkey relative to other parts of the world. Turkish isolates tended to be genetically similar to European and central Asian isolates. Overall, HBV-infection in Turkey appears to be characterized by early HBeAg seroconversion, a high incidence of the A1896 core promoter mutation and a small viral load. Genotype D characteristic mutations A1757 and T1764/G1766 were found in the BCP region. T1773 was associated with T1764/G1766 and a larger viral load. In conclusion, infection with HBV genotype D in Turkey has a similar clinical outcome to that of Europe and central Asia. Genotypic mutations in genotype D may be linked with disease prognosis in Turkey, but further studies with higher sample numbers and balanced clinical groups are needed to confirm this.

Impact of a multidimensional infection control approach on central line-associated bloodstream infections rates in adult intensive care units of 8 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Central line-associated bloodstream infections (CLABs) have long been associated with excess lengths of stay, increased hospital costs and mortality attributable to them. Different studies from developed countries have shown that practice bundles reduce the incidence of CLAB in intensive care units. However, the impact of the bundle strategy has not been systematically analyzed in the adult intensive care unit (ICU) setting in developing countries, such as Turkey. The aim of this study is to analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control approach to reduce the rates of CLAB in 13 ICUs of 13 INICC member hospitals from 8 cities of Turkey. METHODS: We conducted active, prospective surveillance before-after study to determine CLAB rates in a cohort of 4,017 adults hospitalized in ICUs. We applied the definitions of the CDC/NHSN and INICC surveillance methods. The study was divided into baseline and intervention periods. During baseline, active outcome surveillance of CLAB rates was performed. During intervention, the INICC multidimensional approach for CLAB reduction was implemented and included the following measures: 1- bundle of infection control interventions, 2- education, 3- outcome surveillance, 4- process surveillance, 5- feedback of CLAB rates, and 6- performance feedback on infection control practices. CLAB rates obtained in baseline were compared with CLAB rates obtained during intervention. RESULTS: During baseline, 3,129 central line (CL) days were recorded, and during intervention, we recorded 23,463 CL-days. We used random effects Poisson regression to account for clustering of CLAB rates within hospital across time periods. The baseline CLAB rate was 22.7 per 1000 CL days, which was decreased during the intervention period to 12.0 CLABs per 1000 CL days (IRR 0.613; 95% CI 0.43 - 0.87; P 0.007). This amounted to a 39% reduction in the incidence rate of CLAB. CONCLUSIONS: The implementation of multidimensional infection control approach was associated with a significant reduction in the CLAB rates in adult ICUs of Turkey, and thus should be widely implemented.

Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study.

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.