Investigation of polypharmacy, antimicrobial-related potential drug-drug interactions in patients with hematological malignancies.

PURPOSE: Drug-drug interactions (DDIs) occur when one drug interferes with the pharmacological activity of another and can lead to increased side effects. The purpose of this study was to examine potential interactions between antimicrobials and other drugs in patients with hematological malignancies (HMs). METHOD: The medications used by 233 patients with HMs before and during hospitalization in Ankara City Hospital Hematology Clinic services between January 2021 and July 2021 were examined. Potential DDIs (pDDIs) were identified through UptoDate, Drugs.com, and MedScape databases. The effects of major antimicrobial-related pDDIs on patients were examined. Agreement between the two interaction systems was judged based on the kappa test. SPSS R Version 4.0.2 was used in the statistical analysis of the data, p<.05 was considered significant. RESULTS: The prevalence of polypharmacy before hospitalization was determined as 22.7%. Diagnosed with acute leukemia and multiple myeloma, more antimicrobial-related pDDIs were detected during hospitalization (p<.001). A total of 758 antimicrobial-related pDDIs, which were in the major category in at least one of the three databases, were detected in 72.5% (169/233) of the participants. It was determined that the total hospitalization period of patients with major antimicrobial-related pDDIs was longer (p<.001). There was negligible agreement between UptoDate and Dugs.com and between Drugs.com and MedScape (kappa: 0.008 for both). There was no compatibility between UptoDate and MedScape (kappa<0). CONCLUSION: Interactions between antimicrobials and other drugs are undesirable problems. Further studies are required to evaluate the clinical and economic effects of the interactions on patients with HMs.

Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Development and validation of COVID-19 associated candidemia score (CAC-Score) in ICU patients.

BACKGROUND: The development of candidemia is a highly fatal condition in severe COVID-19 infection. OBJECTIVES: This study aimed to develop a candidemia prediction score in COVID-19 patient based on the patient's clinical characteristics, and healthcare-related factors during intensive care units (ICU) follow-up. PATIENTS/METHODS: Severe COVID-19 patients hospitalised in ICU in Ankara City Hospital during the one-year period (August 15, 2020, and August 15, 2021) were included. After univariate analysis, multivariate analysis was applied using variable selection approach to investigate the effects of variables together and to create a score model for candidemia. Statistically significant factors were included in the development process of candida prediction score. RESULTS: Of 1305 COVID-19 ICU patients, 139 had a candidemia episode. According to the final model, four variables, presence of central venous catheter (CVC) (OR 19.07, CI 8.12-44.8, p < .0001), multifocal colonisation (OR 2.28, CI 1.39-3.72, p 0.001), length of ICU stays ≥14 days (OR 3.62, CI 2.42-5.44, p < .0001) and corticosteroids (OR 0.51, CI 0.34-0.76, p 0.0011) were the only statistically significant independent risk factors for candidemia. Score model was demonstrated by a nomogram, and the risk for candidemia was calculated to be high in patients who scored ≥56 points by using the criteria [CVC = 51, multifocal colonisation = 14, prolonged hospitalisation = 23, no steroid use = 12 points]. The AUC of the score is 0.84 (CI 0.81-0.87). CONCLUSION: We developed and validated an easy-to-use clinical prediction score for candidemia in severe COVID-19 infection. In COVID-19 ICU patients, the risk of candidemia is high if one of the other risk factors is present together with CVC.

Impact of Inflammation-Related Genes on COVID-19: Prospective Study at Turkish Cohort.

The pandemic coronavirus disease 2019 (COVID-19) has caused a high mortality rate and poses a significant threat to the population. The disease may progress with mild symptoms or may cause the need for intensive care, depending on many factors. In this study, it was aimed to determine if there is a tendency due to genetic factors in COVID-19 patients. Ninety-four of 188 patients with mild clinical and 94 with severe clinical symptoms were included in the study. The targeted panel including coagulopathy (F2, F5), viral invasion (ACE2), and inflammation (CXCL8, IFNAR2, IFNL4, IL10, IL2, IL6, IRF7, TLR3, TLR7, TNF) related genes was performed sequenced by the next generation sequencing (NGS). The variants found were classified and univariate analyses were performed to select candidate variables for logistic model. Risk factors and variants were compared. It was revealed that the presence of 2 or more risk factors caused the disease to progress severely (p < 0.001). Heterozygous IRF7:c.1357-23dup variant had a 2.5 times higher risk for mild disease compared to severe disease. Other variants were found to be more significant in mild disease. Since polymorphic variants were not evaluated in the literature, the findings of our study could not be compared with the literature. However, as variants that may be effective in the severity of infections may differ according to ethnicity. This study has the feature of being a guide for subsequent studies to be carried out especially in Turkish population. Clinical course of the COVID-19 is likely to depend on a variety of risk factors, including age, sex, clinical status, immunology and genetic factors.

Pathobiological alterations affecting the distinct clinical courses of pediatric versus adult COVID-19 syndrome.

Background/aim: The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease course of COVID-19 has three clinicobiological phases: initiation, propagation, and complication. This study aimed to assess the pathobiological alterations affecting the distinct clinical courses of COVID-19 in pediatric age groups versus the adult population. We hypothesized that critical biogenomic marker expressions drive the mild clinical presentations of pediatric COVID-19. Materials and methods: Blood samples were obtained from 72 patients with COVID-19 hospitalized at Ankara City Hospital between March and July 2021. Peripheral blood mononuclear cells were isolated using Ficoll-Paque and density-gradient sedimentation. The groups were compared using a t-test and limma analyses. Mean standardized gene expression levels were used to hierarchically cluster genes employing Euclidean Gene Cluster 3.0. The expression levels of identified genes were determined using reverse transcription-polymerase chain reaction. Results: This study found that ANPEP gene expression was significantly downregulated in the pediatric group (p < 0.05, FC: 1.57) and IGF2R gene expression was significantly upregulated in the adult group (p < 0.05, FC: 2.98). The study results indicated that the expression of critical biogenomic markers, such as the first-phase (ACE2 and ANPEP) and second-phase (EGFR and IGF2R) receptor genes, was crucial in the genesis of mild clinical presentations of pediatric COVID-19. ANPEP gene expression was lower in pediatric COVID-19. Conclusion: The interrelationship between the ANPEP and ACE2 genes may prevent the progression of COVID-19 from initiation to the propagating phase in pediatric patients. High IGF2R gene expression could potentially contribute to a protective effect and may be a contributing factor for the mild clinical course observed in pediatric patients.

Increasing rates of extended-spectrum B-lactamase-producing Escherichia coli and Klebsiella pneumoniae in uncomplicated and complicated acute pyelonephritis and evaluation of empirical treatments based on culture results.

Increasing rates of extended-spectrum beta-lactamase (ESBL) producing E. coli and K. pneumoniae over time made empirical treatment complicated. Knowing local antimicrobial resistance patterns of common pathogens can make it easier to decide on empirical antibiotics. We aimed to investigate the prevalence and risk factors of ESBL positivity of E. coli and K. pneumoniae strains in uncomplicated and complicated pyelonephritis acquired in community and healthcare associations and to evaluate the appropriateness of empirical treatment. Adult patients hospitalized with diagnosis of community-acquired or healthcare-associated uncomplicated/complicated pyelonephritis initiated empirical antimicrobial therapy were included in the study. Appropriateness of empirical treatment at 48-72 h based on culture results and treatment modifications were evaluated. A total of 369 uncomplicated (94) and complicated (275) episodes of pyelonephritis were evaluated. The most common agents were E. coli (71.0%) and K. pneumoniae (17.7%), and the ESBL-production rate was 64.4%, and higher in healthcare-associated pyelonephritis (P 0.013). Being of healthcare-associated infection, previous antibiotic use, and presence of urinary catheters were independent risk factors for ESBL-producing E. coli and K. pneumoniae (P 0.009, < 0.001, and 0.024, respectively). The treatment inappropriateness was mostly associated with use of ceftriaxone (56.3%) (P < 0.001). Treatment has escalated in 41.5% of ceftriaxone-initiated patients, in only 8.8% and 9.5% ertapenem and piperacillin-tazobactam-initiated patients, respectively. ESBL-production rates are quite high even in community-acquired infections. The use of broad-spectrum antibiotics covering ESBL-producing pathogens to increase the appropriateness of empirical treatment and then narrowing treatment based on culture results appears a better and life-saving choice.

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study.

BACKGROUND: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. METHODS: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients' characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. RESULTS: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49-2.45). CONCLUSIONS: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245 . Registered 3 May 2019.

Incidence and risk factors for COVID-19 associated candidemia (CAC) in ICU patients.

BACKGROUND: Critically ill COVID-19 patients have a high risk for the development of candidemia due to being exposed to both well-defined classical risk factors and COVID-19-specific risk factors in ICU. OBJECTIVES: In this study, we investigated the incidence of candidemia in critically COVID-19 patients, and the independent risk factors for candidemia. PATIENTS/METHODS: COVID-19 patients hospitalised in ICU during 1-year period (August 2020 to August 2021) were included. Clinical and laboratory characteristics of all COVID-19 patients, applied treatments, and invasive procedures that may predispose to candidemia were recorded. RESULTS: Of 1229 COVID-19 patients, 63 developed candidemia. Candidemia incidence rate was 4.4 episodes per 1000 ICU days. The most common species was Candida albicans (52.3%). Only 37 patients (58.7%) received antifungal therapy. The presence of central venous catheter (OR 4.7, 95% CI 1.8-12.2, p < .005), multifocal candida colonisation (OR 2.7, 95% CI 1.4-5.2, p < .005), a prolonged ICU stay (≥14 days) (OR 1.9, 95% CI 1.08-3-37, p < .05), the absence of chronic lung disease (OR 0.4, 95% CI 0.1-0.9, p < .05) and the absence of corticosteroid use (OR 0.3, 95% CI 0.14-0.52, p < .0001) were significantly associated with candidemia. CONCLUSIONS: Our study filled the knowledge gap in the literature about the impact of COVID-19-associated risk factors for the development of candidemia. The classical risk factors for candidemia had a significant effect on candidemia, and contrary to expectations, corticosteroids had a protective effect against the development of candidemia. The results of these studies showing interesting effects of corticosteroids in critically ill COVID-19 patients should be confirmed by further studies.

Post-COVID syndrome: A single-center questionnaire study on 1007 participants recovered from COVID-19.

Post recovery manifestations have become another concern in patients who have recovered from coronavirus disease 2019 (COVID-19). Numerous reports have shown that COVID-19 has a variety of long-term effects on almost all systems including respiratory, cardiovascular, gastrointestinal, neurological, psychiatric, and dermatological systems. We aimed to investigate the prevalence and characteristics of the post-COVID syndrome among COVID-19 survivors and to determine the factors associated with persistent symptoms. This prospective study enrolled in patients with COVID-19 followed in hospital or outpatient clinics in Ankara City Hospital. We performed a special questionnaire to inquire about the presence of persistent symptoms beyond 12 weeks from the first diagnosis. Demographic data, comorbid diseases, characteristics of acute COVID-19, presence of persistent symptoms by systems, and knowledge about outpatient clinic visits after recovery were assessed. Of a total of 1007 participants, 39.0% had at least one comorbidity, and 47.5% had persistent symptoms. Fatigue/easy fatigability, myalgia, and loss of weight were the most frequent persistent symptoms (overall 29.3%) followed by respiratory symptoms (25.4%). A total of 235 participants had visited outpatient clinics due to several reasons during the post-COVID-19 period, and 17 of them were hospitalized. Severe acute COVID-19, hospitalization, and presence of comorbidity were independent factors for the development of persistent symptoms. Fully understanding the spectrum of the post-COVID syndrome is essential for appropriate management of all its long-term effects. Our study once again underlined the fact that the prevalence of post-COVID syndrome is higher than expected and concerns many systems, and a multidisciplinary follow-up should be provided to COVID-19 survivors in the post recovery period.

Higher viral loads in asymptomatic COVID-19 patients might be the invisible part of the iceberg.

PURPOSE: SARS-CoV-2 virus dynamics in different hosts and different samples and their relationship with disease severity have not been clearly revealed. The aim of this study is to evaluate the viral loads of 6 different sample types (nasopharyngeal/oropharyngeal combined, oral cavity, saliva, rectal, urine, and blood) of patients with different ages and clinics, to reveal the relationship between disease course and SARS-CoV-2 viral load, and differences in viral loads of asymptomatic and symptomatic patients. METHODS: Nasopharyngeal/oropharyngeal, oral cavity, saliva, rectal, urine, and blood samples are collected from patients who were hospitalized with diagnosis of COVID-19 on admission. Laboratory analysis were carried out at Public Health Institute of Turkey Virology Reference and Research Laboratory. RESULTS: A total of 360 samples from 60 patients were obtained on admission. Fifteen (25%) of the patients were asymptomatic while 45 (75%) were symptomatic. A significant difference was found between mean ages of asymptomatic vs symptomatic patients (26.4 and 36.4, respectively, p = 0.0248). No PCR positivity were found in blood. Only one asymptomatic patient had positive PCR result for urine sample. Viral loads of asymptomatic patients were found to be significantly higher (p = 0.0141) when compared with symptomatic patients. Viral load had a significant negative trend with increasing age. A significant decrease in viral load was observed with increasing disease severity. CONCLUSION: In conclusion, this study demonstrates that asymptomatic patients have higher SARSCoV-2 viral loads than symptomatic patients and unlike in the few study in the literature, a significant decrease in viral load of nasopharyngeal/oropharyngeal samples was observed with increasing disease severity. Factors associated with poor prognosis are found to be significantly correlated with low viral load.

Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients.

BACKGROUND AND OBJECTIVES: An effective treatment option is not yet available for SARS-CoV2, which causes the COVID-19 pandemic and whose effects are felt more and more every day. Ivermectin is among the drugs whose effectiveness in treatment has been investigated. In this study; it was aimed to investigate the presence of gene mutations that alter ivermectin metabolism and cause toxic effects in patients with severe COVID-19 pneumonia, and to evaluate the effectiveness and safety of ivermectin use in the treatment of patients without mutation. MATERIALS AND METHODS: Patients with severe COVID19 pneumonia were included in the study, which was planned as a prospective, randomized, controlled, single-blind phase 3 study. Two groups, the study group and the control group, took part in the study. Ivermectin 200 mcg/kg/day for 5 days in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine + favipiravir + azithromycin- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin. The presence of mutations was investigated by performing sequence analysis in the mdr1/abcab1 gene with the Sanger method in patients included in the study group according to randomization. Patients with mutations were excluded from the study and ivermectin treatment was not continued. Patients were followed for 5 days after treatment. At the end of the treatment and follow-up period, clinical response and changes in laboratory parameters were evaluated. RESULTS: A total of 66 patients, 36 in the study group and 30 in the control group were included in the study. Mutations affecting ivermectin metabolism was detected in genetic tests of six (16.7%) patients in the study group and they were excluded from the study. At the end of the 5-day follow-up period, the rate of clinical improvement was 73.3% (22/30) in the study group and was 53.3% (16/30) in the control group (p = 0.10). At the end of the study, mortality developed in 6 patients (20%) in the study group and in 9 (30%) patients in the control group (p = 0.37). At the end of the follow-up period, the average peripheral capillary oxygen saturation (SpO2) values of the study and control groups were found to be 93.5 and 93.0%, respectively. Partial pressure of oxygen (PaO2)/FiO2 ratios were determined as 236.3 ± 85.7 and 220.8 ± 127.3 in the study and control groups, respectively. While the blood lymphocyte count was higher in the study group compared to the control group (1698 ± 1438 and 1256 ± 710, respectively) at the end of the follow-up period (p = 0.24); reduction in serum C-reactive protein (CRP), ferritin and D-dimer levels was more pronounced in the study group (p = 0.02, p = 0.005 and p = 0.03, respectively). CONCLUSIONS: According to the findings obtained, ivermectin can provide an increase in clinical recovery, improvement in prognostic laboratory parameters and a decrease in mortality rates even when used in patients with severe COVID-19. Consequently, ivermectin should be considered as an alternative drug that can be used in the treatment of COVID-19 disease or as an additional option to existing protocols.

Development and validation of nomogram to predict severe illness requiring intensive care follow up in hospitalized COVID-19 cases.

BACKGROUND: Early identification of severe COVID-19 patients who will need intensive care unit (ICU) follow-up and providing rapid, aggressive supportive care may reduce mortality and provide optimal use of medical resources. We aimed to develop and validate a nomogram to predict severe COVID-19 cases that would need ICU follow-up based on available and accessible patient values. METHODS: Patients hospitalized with laboratory-confirmed COVID-19 between March 15, 2020, and June 15, 2020, were enrolled in this retrospective study with 35 variables obtained upon admission considered. Univariate and multivariable logistic regression models were constructed to select potential predictive parameters using 1000 bootstrap samples. Afterward, a nomogram was developed with 5 variables selected from multivariable analysis. The nomogram model was evaluated by Area Under the Curve (AUC) and bias-corrected Harrell's C-index with 95% confidence interval, Hosmer-Lemeshow Goodness-of-fit test, and calibration curve analysis. RESULTS: Out of a total of 1022 patients, 686 cases without missing data were used to construct the nomogram. Of the 686, 104 needed ICU follow-up. The final model includes oxygen saturation, CRP, PCT, LDH, troponin as independent factors for the prediction of need for ICU admission. The model has good predictive power with an AUC of 0.93 (0.902-0.950) and a bias-corrected Harrell's C-index of 0.91 (0.899-0.947). Hosmer-Lemeshow test p-value was 0.826 and the model is well-calibrated (p = 0.1703). CONCLUSION: We developed a simple, accessible, easy-to-use nomogram with good distinctive power for severe illness requiring ICU follow-up. Clinicians can easily predict the course of COVID-19 and decide the procedure and facility of further follow-up by using clinical and laboratory values of patients available upon admission.

Characteristics of candidemia in COVID-19 patients; increased incidence, earlier occurrence and higher mortality rates compared to non-COVID-19 patients.

Severe COVID-19 patients in ICU are at high risk for candidemia due to exposure to multiple risk factors for candidemia. We aimed to compare the incidence of candidemia in ICU patients with and without COVID-19, and to investigate epidemiologic and clinical characteristics of candidemia patients and risk factors for mortality in candidemia patients. This retrospective study was conducted in patients followed in the ICUs of Ankara City Hospital for 2 years, divided into pre-pandemic and pandemic periods. The incidence (event per 1000 patient-days) and epidemiology of candidemia, clinical and laboratory characteristics of patients were compared in COVID-19 and non-COVID-19 groups. Candidemia incidence was higher in the COVID-19 group (2.16, 95% CI 1.77-2.60) than the non-COVID-19 group (1.06, 95% CI 0.89-0.125) (p < .001). A total of 236 candidemia episodes (105 in COVID-19 patients and 131 in non-COVID-19 patients) were detected during the study periods. COVID-19 cases had a higher rate of corticosteroid use (63.8% vs. 9.9%, p < .001). Epidemiology of candidemia and antifungal susceptibility were similar. Candidemia developed 2 weeks earlier in COVID-19 groups and resulted in higher mortality (92.5% vs. 79.4%, p .005). One-third of candidemia patients died before receiving any antifungal treatment, and this rate was higher in the COVID-19 group. In multivariate logistic regression analysis, corticosteroid use, presence of sepsis and age older than 65 years were independent risk factors for mortality in candidemia patients. Candidemia with high mortality is a more serious problem for COVID-19 patients due to its increased incidence, earlier occurrence and a higher rate of mortality.

The Effect of prolonged PCR Positivity on patient Outcomes and Determination of Isolation period in COVID-19 patients.

AIMS: The impact of ongoing PCR positivity on COVID-19 patients and the strategy and period of isolation were not fully understood. We aimed to investigate the factors that cause prolonged PCR positivity and its clinical impact on COVID-19 infection. In addition, we searched for an answer on what length of time would be best for isolation. METHODS: Patients with confirmed COVID-19 infection were included in this retrospective study. Patients with PCR positivity (after symptom onset) longer than 14 days and PCR positivity less than 14 days were compared. The relationship between duration of symptoms and PCR negation time was examined. RESULTS: A total of 339 patients were included in this study. Fifty (14%) patients had prolonged PCR positivity after 14 days. Demographic and clinical features, and clinical outcomes (disease severity and mortality) were similar among the two groups. Age (p 0.035) and symptom duration at admission (P < .001) were found as independent factors for prolonged PCR positivity. Median of total symptom duration was 7 days (IQR: 5-11). The duration of negative conversion of PCR test was median 9 days (IQR: 7-12) after symptom onset and PCR tests became negative 3 days (IQR: 2-5) after symptom improvement. CONCLUSIONS: We found that ongoing PCR positivity has no detrimental effect on the course of the disease and clinical outcomes in COVID-19 patients. In addition, our results showed that isolation may be discontinued 10-14 days after symptom onset and/or after 2-5 days after resolution of symptoms. This results also support WHO and ECDC recommendations on this matter.

Prognostic utility of pulmonary artery and ascending aorta diameters derived from computed tomography in COVID-19 patients.

AIM: Chest computed tomography (CT) imaging plays a diagnostic and prognostic role in Coronavirus disease 2019 (COVID-19) patients. This study aimed to investigate and compare predictive capacity of main pulmonary artery diameter (MPA), ascending aorta diameter (AAo), and MPA-to-AAo ratio to determine in-hospital mortality in COVID-19 patients. MATERIALS AND METHODS: This retrospective study included 255 hospitalized severe or critical COVID-19 patients. MPA was measured at the level of pulmonary artery bifurcation perpendicular to the direction of the vessel through transverse axial images and AAo was measured by using the same CT slice at its maximal diameter. MPA-to-AAo ratio was calculated by division of MPA to AAo. RESULTS: Multivariate logistic regression model yielded MPA ≥29.15 mm (OR: 4.95, 95% CI: 2.01-12.2, p = 0.001), MPA (OR: 1.28, 95% CI: 1.13-1.46, p < 0.001), AAo (OR: .90, 95% CI: .81-.99, p = 0.040), and MPA-to-AAo ratio ≥.82 (OR: 4.67, 95% CI: 1.86-11.7, p = 0.001) as independent predictors of in-hospital mortality. Time-dependent multivariate Cox-proportion regression model demonstrated MPA ≥29.15 mm (HR: 1.96, 95% CI: 1.03-3.90, p = 0.047) and MPA (HR: 1.08, 95% CI: 1.01-1.17, p = 0.048) as independent predictors of in-hospital mortality, whereas AAo and MPA-to-AAo ratio did not reach statistical significance. CONCLUSION: Pulmonary artery enlargement strongly predicts in-hospital mortality in hospitalized COVID-19 patients. MPA, which can be calculated easily from chest CT imaging, can be beneficial in the prognostication of these patients.

COVID-19 and Sepsis

The COVID-19 pandemic has created a major alteration in the medical literature including the sepsis discussion. From the outset of the pandemic, various reports have indicated that although there are some unique features pertinent to COVID-19, many of its acute manifestations are similar to sepsis caused by other pathogens. As a consequence, the old definitions now require consideration of this new etiologic agent, namely SARS-CoV-2. Although the pathogenesis of COVID-19 has not been fully explained, the data obtained so far in hospitalized patients has revealed that serum cytokine and chemokine levels are high in severe COVID-19 patients, similar to those found with sepsis. COVID-19 may involve multiple organ systems. In addition to the lungs, the virus has been isolated from blood, urine, faeces, liver, and gallbladder. Results from autopsy series in COVID-19 patients have demonstrated a wide range of findings, including vascular involvement, congestion, consolidation, and hemorrhage as well as diffuse alveolar damage in lung tissue consistent with acute respiratory distress syndrome (ARDS). The presence of viral cytopathic-like changes, infiltration of inflammatory cells (mononuclear cells and macrophages), and viral particles in histopathological samples are considered a consequence of both direct viral infection and immune hyperactivation. Thromboembolism and hyper-coagulopathy are other components in the pathogenesis of severe COVID-19. Although the pathogenesis of hypercoagulability is not fully understood, it has been pointed out that all three components of Virchow's triad (endothelial injury, stasis, and hypercoagulable state) play a major role in contributing to clot formation in severe COVID-19 infection. In severe COVID-19 cases, laboratory parameters such as hematological findings, coagulation tests, liver function tests, D-dimer, ferritin, and acute phase reactants such as CRP show marked alterations, which are suggestive of a cytokine storm. Another key element of COVID-19 pathogenesis in severe cases is its similarity or association with hemophagocytic lymphohistiocytosis (HLH). SARS-CoV-2 induced cytokine storm has significant clinical and laboratory findings overlapping with HLH. Viral sepsis has some similarities but also some differences when compared to bacterial sepsis. In bacterial sepsis, systemic inflammation affecting multiple organs is more dominant than in COVID-19 sepsis. While bacterial sepsis causes an early and sudden onset clinical deterioration, viral diseases may exhibit a relatively late onset and chronic course. Consideration of severe COVID-19 disease as a sepsis syndrome has relevance and may assist in terms of determining treatments that will modulate the immune response, limit intrinsic damage to tissue and organs, and potentially improve outcome.

Investigation of SARS-CoV-2 in Semen of Patients in the Acute Stage of COVID-19 Infection.

INTRODUCTION: The presence of new coronavirus (SARS-CoV-2) in semen and the possibility of sexual transmission have become new subjects of curiosity. There is a discrepancy regarding this issue in the literature. The presence of SARS-CoV-2 in semen has been investigated in a limited number of studies, and mostly in recovering patients. We aimed to investigate the presence of SARS-CoV-2 RNA in semen of patients with a positive nasopharyngeal swab test for SARS-CoV-2 in the acute stage. METHODS: We enrolled adult male patients who were hospitalized with confirmed SARS-COV-2 infection in the study. In addition to routine laboratory and radiological tests, semen sample was obtained from volunteers and transferred to the Turkish Public Health Institution, National Virology Laboratory. The samples were processed for the detection of SARS-CoV-2 RNA on the day of collection. RESULTS: Sixteen patients were included in the study. The median age was 33.5 years (18-54). All but one had respiratory symptoms. None of the patients had a history or symptoms of urogenital disease. All semen samples were obtained during hospitalization and in the acute stage of the infection. The median time to obtain a semen sample after positive nasopharyngeal test was 1 day (0-7). All semen samples were detected as negative for SARS-CoV-2 PCR. DISCUSSION/CONCLUSION: Although all semen samples were obtained in acute stage of the infection when the nasopharyngeal swab test was positive, we did not detect SARS-CoV-2 in semen. The results of our study support the thought that sexual transmission via semen does not have an important role in the person-to-person transmission of SARS-CoV-2. We think that our study will provide new information to fill the gap in the literature.

Monitoring Crimean-Congo haemorrhagic fever virus RNA shedding in body secretions and serological status in hospitalised patients, Turkey, 2015.

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease in Africa, Asia, the Balkan peninsula, the south-east of Europe and the Middle East, with mortality rates of 3-30%. Transmission can also occur through contact with infected animals or humans.AimThis observational, prospective case series aimed to investigate detectable viral genomic RNA in whole-body fluids and antibody dynamics in consecutive daily samples of patients diagnosed with CCHF until discharge from hospital.MethodsWe tested 18 patients and 824 swabs and sera with RT-PCR and 125 serum samples serologically.ResultsThe longest duration until clearance of viral RNA was 18 days from serum collection and 18, 15, 13, 19 and 17 days, respectively, from nasal, oral, genital (urethral or vaginal) and faecal swab, and urine. In seven patients, viral load decreased in serum at the same time as it increased in urine or persisted at the same logarithmic values. Despite clearance in serum, viral RNA was detected in faeces and genital swabs in two and three patients, respectively. Viral clearance from body fluids occurred earlier than from serum in eight patients on ribavirin treatment. The shortest seroconversion time was 3 days after symptom onset for IgM and IgG. Seroconversion of IgG occurred until Day 14 of symptoms.ConclusionWe report persistence of viral RNA in urine, faeces and genital swabs despite serum clearance. This may indicate a need for extending isolation precautions, re-evaluating discharge criteria and transmission risk after discharge, and considering oral swabs as a less invasive diagnostic alternative.

Crushing the curve, the role of national and international institutions and policy makers in COVID-19 pandemic

Nobody can be fully prepared to a pandemic. Of course there are signs of it, the scientists can predict, alarming speeches can be made. But there are always alarmist people around, maybe that is why sometimes even the most serious warnings may be not considered by the authorities on time. The first patients may be lost without a proper diagnosis. When everybody realizes that there may be a big problem in the horizon, sometimes it is too late. That is why it is very important to monitor contagious diseases and follow the warnings and releases of national and international disease control centers and other related organizations. China celebrated Lunar New Year with more than 40 thousand families on the 18 of January 2020. Nobody seem to be expecting this emerging new viral pneumonia outbreak appeared in Wuhan, in the last days of 2019, will break the chains and turn out to be a pandemic! But maybe this time it was not too late. There were four important pandemics within the last century: Spanish Flu, Hong Kong Flu, Asian Flu and Swine Flu. Each left different story behind. Millions of people had infected, hundreds, thousands of people died. This time, the Modern World had different tools to limit the SARS CoV2 outbreak. The national and international institutions of our globe were all communicating and taking precautions in a very fast manner than ever. However, this time, unexpectedly, the SARS-CoV-2 contagion was also faster. Besides the international organizations like WHO, UNESCO and UNICEF, the roles of local authorities, health ministries, disease control centers, health protection agencies, research centers and universities are all very important in different operational levels to control and survive from the pandemic. This paper will review the immediate response of different national and international institutions and authorities to COVID-19 pandemic.

COVID-19 experience of the major pandemic response center in the capital: results of the pandemic's first month in Turkey

Background/aim: The aim of this study is to evaluate the epidemiological and clinical characteristics and parameters that determined the clinical course and prognosis of the COVID-19 patients admitted to Ankara City Hospital during the first month of the pandemic in Turkey. Materials and methods: SARS-CoV-2 PCR positive patients who were hospitalized between March 10 and April 10, 2020 were included. Results: Among 222 patients, mean age was higher in severe acute respiratory illness (SARI)/critical disease group (P < 0.001). Median time from illness onset to admission and presence of comorbidity, especially coronary artery disease and chronic obstructive pulmonary disease, were significantly higher in the SARI/critical disease group (P < 0.05). Cough and fever were the most common symptoms, while anosmia and loss of taste were observed in 8.6% and 7.7% patients, respectively. The mortality rate was 5.4%. A high neutrophil/lymphocyte ratio; low lymphocyte, monocyte, and platelet count; elevated liver enzymes; low GFR; and high levels of muscle enzymes, ferritin, and IL-6 on admission were found to be associated with SARI/critical disease (P < 0.05). Bilateral ground-glass opacity and patchy infiltration were more frequently seen in the SARI/critical disease group (P < 0.001). Patients older than 65 years had an 8-fold increased risk for development of SARI/critical disease. Conclusion: This cohort study regarding COVID-19 cases in Turkey reveals that older age, presence of comorbidity, bilateral infiltration on CT, high neutrophil/lymphocyte ratio, low monocyte and platelet count, elevated liver enzymes, low GFR, high levels of muscle enzymes, and high levels of ferritin and IL-6 on admission are predictors of SARI and severe disease.