Use of high-dose steroid therapy: addition of anakinra in the treatment of severe COVID-19.

OBJECTIVE: The aim of this study was to compare the clinical effects of the addition of anakinra to high-dose steroid therapy in COVID-19 patients with macrophage activation syndrome. METHODS: This was a single-center retrospective study conducted in Ümraniye Training and Research Hospital between March 11, 2020, and April 28, 2021. Patients receiving only high-dose steroid or anakinra+steroid were enrolled. The first day of anakinra was considered as day 0. Laboratory values and oxygen requirements were followed up for 7 days. Patients were divided into two groups: 66 patients in the high-dose steroid group and 67 patients in the anakinra+steroid group. The primary outcome was 28-day mortality. RESULTS: After treatment, a significant decrease in ferritin levels was detected only in the anakinra+steroid group (p=0.001). In both groups, there were significant changes in lymphocytes, C-reactive protein, lactate dehydrogenase, and fibrinogen levels during the 7-day follow-up. Changes in oxygen status according to the World Health Organization clinical scale on day 3 and day 7 between high-dose steroid and anakinra+steroid groups were similar (p=0.976). Complications were higher in the anakinra+steroid group than in the steroid group (26% vs. 12%, p=0.03). The rates of 28-day mortality were 57% in the anakinra+steroid group and 42% in the high-dose steroid group (p=0.48). In multivariate regression, anakinra did not affect 28-day mortality (p=0.67). CONCLUSION: The addition of anakinra to steroid treatment resulted in a significant decrease in biochemical parameters. However, no significant difference was observed in the oxygen status between the groups. The addition of anakinra to steroid treatment did not decrease mortality. Clinicians should be aware of the complications of anti-inflammatory therapies.

Clinical characteristics and risk factors associated with secondary bacterial pneumonia among COVID-19 patients in ICU.

INTRODUCTION: COVID-19 and secondary infections developing during COVID-19 follow-up are one of the most important causes of morbidity and mortality in intensive care units (ICU). In this study, we aimed to determine the frequency, microbiology, risk factors, and outcomes of secondary bacterial pneumonia in hospitalized patients due to COVID-19. METHODOLOGY: We studied all patients with bacterial pneumonia developed in patients with severe COVID-19 infection in the COVID-19 intensive care unit in a single-center hospital between March 16, 2020 and June 17, 2020. Patients hospitalized and followed up in the ICU for respiratory failure were examined in terms of secondary infection affecting morbidity and mortality. RESULTS: Ninety-six (20%) of 471 patients had secondary bacterial pneumonia, respectively; of the leading pathogens were Acinetobacter baumannii (44.8%) and Klebsiella pneumoniae (39.6%), followed by Pseudomonas aeruginosa (4.2%), Escherichia coli (3.1%), methicillin-resistant Staphylococcus aureus (MRSA) (3.1%), Streptococcus pneumoniae (3.1%), and Methicillin-susceptible Staphylococcus aureus (MSSA) (1%). The mortality rate among infected (75% / 47.5%) was significantly higher than in uninfected patients. Associated with the development of secondary bacterial pneumonia in COVID-19 patients; corticosteroid therapy [odds ratio (OR) 6250, 95% confidence interval (CI) 1.383-28.571, p = 0.017), corticosteroid dose (OR 8.862 CI 2.299-70.258, p= 0.006), duration of mechanical ventilation (OR 1.199 CI) 1.088-1.322, p< 0.001). CONCLUSIONS: Secondary bacterial pneumonia was found to be associated with the severity and survival of the disease in patients admitted to ICU due to COVID-19. Duration of mechanical ventilation and use of corticosteroids and high-dose corticosteroids are risk factors for secondary bacterial pneumonia.

Higher rates of cefiderocol resistance among NDM producing Klebsiella bloodstream isolates applying EUCAST over CLSI breakpoints.

BACKGROUND: Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria. METHODS: A unique collection (n = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes. RESULTS: Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24-26 mm) for all isolates and 18 mm (IQR 15-21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively. CONCLUSIONS: Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing.

Long-Term Results of Immunogenicity of Booster Vaccination against SARS-CoV-2 (Hybrid COV-RAPEL TR Study) in Turkiye: A Double-Blind, Randomized, Controlled, Multicenter Phase 2 Clinical Study.

The immunogenicity of vaccines decreases over time, causing a need for booster doses. This study aimed to present the long-term (Day 84) immunogenicity results of the double-blind, randomized, controlled, phase II Hybrid COV-RAPEL TR Study (NCT04979949), in which the TURKOVAC or CoronaVac vaccines were used as a booster after the second dose of primary vaccination with CoronaVac. A total of 190 participants from the Hybrid COV-RAPEL TR Study, who had both Day 28 and Day 84 immunogenicity results, were included. The immunogenicity on Day 84, regarding the neutralizing antibody positivity (Wuhan and Delta variants) and anti-spike immunoglobulin (Ig) G (IgG) antibody positivity, was compared between TURKOVAC and CoronaVac vaccine arms according to sex and age groups. Overall, antibody positivity showed a slight decrease on Day 84 vs. Day 28, but was not different between TURKOVAC and CoronaVac arms either for sexes or for age groups. However, TURKOVAC produced better antibody response against the Delta variant than CoronaVac, while CoronaVac was superior over TURKOVAC regarding neutralizing antibody positivity in the 50-60 years age group, regardless of the variant. A single booster dose, after the completion of the primary vaccination, increases antibody positivity on Day 28 which persists until Day 84 with a slight decrease. However, an additional booster dose may be required thereafter, since the decrease in antibody titer may be faster over time.

Effects of COVID-19 Disease on DNA Damage, Oxidative Stress and Immune Responses.

Coronavirus disease 2019 (COVID-19) has posed a great threat to public health and has caused concern due to its fatal consequences over the last few years. Most people with COVID-19 show mild-to-moderate symptoms and recover without the need for special treatment, while others become seriously ill and need medical attention. Additionally, some serious outcomes, such as heart attacks and even stroke, have been later reported in patients who had recovered. There are limited studies on how SARS-CoV-2 infection affects some molecular pathways, including oxidative stress and DNA damage. In this study, we aimed to evaluate DNA damage, using the alkaline comet assay, and its relationship with oxidative stress and immune response parameters in COVID-19-positive patients. Our results show that DNA damage, oxidative stress parameters and cytokine levels significantly increased in SARS-CoV-2-positive patients when compared with healthy controls. The effects of SARS-CoV-2 infection on DNA damage, oxidative stress and immune responses may be crucial in the pathophysiology of the disease. It is suggested that the illumination of these pathways will contribute to the development of clinical treatments and to reduce adverse effects in the future.

Prevalence of Polypharmacy and Potential Drug-Drug Interactions Associated with Risk Factors in the Era of HIV Integrase Inhibitors: A Prospective Clinical Study.

People living with human immunodeficiency virus (PLWH), with the availability of modern antiretroviral drugs, have multiple comorbidities, which increase the risk of polypharmacy and potential drug-drug interactions (PDDIs). This is a particularly important issue for the aging population of PLWH. This study aims to review the prevalence and risk factors for PDDIs and polypharmacy in the era of HIV integrase inhibitors. A cross-sectional, two-center, prospective observational study was conducted on Turkish outpatients between October 2021 and April 2022. Polypharmacy was defined as the use of ≥5 non-HIV medications, excluding over-the-counter (OTC) drugs, and PDDIs were classified using the University of Liverpool HIV Drug Interaction Database (harmful/red flagged and potentially clinically relevant/amber flagged). The median age of the 502 PLWH included in the study was 42 ± 12.4 years and 86.1% were males. Most individuals (96.4%) were given integrase-based regimens (unboosted 68.7% and boosted 27.7%). In total, 30.7% of individuals were taking at least one OTC drug. The prevalence of polypharmacy was 6.8% (9.2% when OTC drugs were included). During the study period, the prevalence of PDDIs was 1.2% for red flag PDDIs and 16% for amber flag PDDIs. CD4+ T cell count >500 cells/mm3, number of comorbidities ≥3, comedication with drugs affecting blood and blood-forming organs, cardiovascular drugs, and vitamin/mineral supplements were associated with red flag or amber flag PDDIs. Drug interaction prevention is still important in HIV care. Individuals with multiple comorbidities should be closely monitored for non-HIV medications to prevent PDDIs.

Safety and immunogenicity of inactive vaccines as booster doses for COVID-19 in Türkiye: A randomized trial.

Protective neutralizing antibody titers reduce in time after COVID-19 vaccinations, as in individuals who have had COVID-19. This study aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as a booster dose after CoronaVac primary vaccination. This double-blind, randomized, controlled, phase II, multicenter study included healthy male and female adults (18-60 years) who were vaccinated with two doses of CoronaVac vaccine and did not exceed the duration of at least 90 days and a maximum of 270 days from the second dose of vaccination. Among 236 eligible volunteers, 222 were recruited for randomization between July 12, 2021 and September 10, 2021; 108 and 114 were randomized to the TURKOVAC and CoronaVac arms, respectively. The primary endpoint was adverse events (AEs) (ClinicalTrials.gov; Identifier: NCT04979949). On day 28, at the neutralizing antibody threshold of 1/6, the positivity rate reached 100% from 46.2% to 98.2% from 52.6% in the TURKOVAC and CoronaVac arms, respectively, against the Wuhan variant and the positivity rate reached 80.6% from 8.7% in the TURKOVAC arm vs. 71.9% from 14.0% in the CoronaVac arm against the Delta variant. IgG spike antibody positivity rate increased from 57.3% to 98.1% and from 57.9% to 97.4% in the TURKOVAC and CoronaVac arms, respectively. The TURKOVAC and CoronaVac arms were comparable regarding the frequency of overall AEs. Both vaccines administered as booster yielded higher antibody titers with acceptable safety profiles.

What is the context? The timing of the primary and booster doses for each vaccine differs.We aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as homologous booster dose after CoronaVac primary vaccination.What is new? The neutralizing antibody titers against the Wuhan variant decreased below 1/6- the seropositivity threshold value- in more than 55% of the participants 4 months after administration of two doses of CoronaVac vaccine.Immunogenicity was re-stimulated and the neutralizing antibody titers increased rapidly and markedly with the administration of the CoronaVac or TURKOVAC as a booster dose 4 months after the second dose.While the increase in neutralizing antibodies against the Wuhan variant was similar with both CoronaVac and TURKOVAC, more antibodies developed against the Delta variant with TURKOVAC.What is the impact? With the Hybrid COV-RAPEL TR study, after the primary vaccination consisting of two doses of inactivated vaccine, antibody titers decreased in the long term; however, higher antibody titers are achieved than the primary vaccination after the booster dose administered after 4­6 month interval.Booster application with TURKOVAC provides antibodies at least as much as the CoronaVac booster dose, with an acceptable safety profile.

Comparison of ceftazidime-avibactam susceptibility testing methods against OXA-48-like carrying Klebsiella blood stream isolates.

Ceftazidime-avibactam exhibits good in vitro activity against carbapenem resistant Klebsiella carrying OXA-48-like enzymes. We tested two hundred unique carbapenem resistant Klebsiella blood stream isolates (71% with single OXA-48-like carbapenemases, including OXA-48, n = 62; OXA-232, n = 57; OXA-244, n = 17; OXA-181, n = 5) that were collected as part of a multicentre study against ceftazidime-avibactam using Etest (bioMérieux, Marcyl'Étoile, France), 10/4 µg disc (Thermo Fisher) and Sensititre Gram Negative EURGNCOL Plates (Lyophilized panels, Sensititre, Thermo Fisher) with the aim of comparing the performances of the Etest and disc to that of Sensititre. Ceftazidime-avibactam MIC50/90 was 2/>16 mg/L for the entire collection and was 2/4 mg/L for single OXA-48-like producers. Categorical and essential agreements between the Etest and Sensititre were 100% and 97%, respectively. Categorical agreement between the disc and Sensititre was 100%. Etest and 10/4 µg discs are suitable alternatives to Sensititre for ceftazidime-avibactam sensitivity testing for OXA-48-like producers.

Comparison of the Clinical and Laboratory Findings and Outcomes of Hospitalized COVID-19 Patients Who Were Either Fully Vaccinated with Coronavac or Not: An Analytical, Cross Sectional Study.

COVID-19 vaccines are highly protective against severe disease; however, vaccine breakthrough infections resulting in hospitalization may still occur in a small percentage of vaccinated individuals. We investigated whether the clinical and microbiological features and outcomes were different between hospitalized COVID-19 patients who were either fully vaccinated with Coronovac or not. All hospitalized COVID-19 patients who had at least one dose of Coronavac were included in the study. The oldest unvaccinated patients with comorbidities, who were hospitalized during the same period, were chosen as controls. All epidemiologic, clinical and laboratory data of the patients were recorded and compared between the fully vaccinated and unvaccinated individuals. There were 69 and 217 patients who had been either fully vaccinated with Coronavac or not, respectively. All breakthrough infections occurred in the first 3 months of vaccination. Fully vaccinated patients were older and had more comorbidities than unvaccinated patients. There were minor differences between the groups in symptoms, physical and laboratory findings, anti-spike IgG positivity rate and level, the severity of COVID-19, complications, and clinical improvement rate. The mortality rate of fully vaccinated patients was higher than the mortality rate in unvaccinated patients in univariate analysis, which was attributed to the fact that vaccinated patients were older and had more comorbidities. The severity and clinical outcomes of hospitalized patients with breakthrough COVID-19 after Coronavac vaccination were similar to those of unvaccinated patients. Our findings suggest that the immune response elicited by Coronovac could be insufficient to prevent COVID-19-related severe disease and death within 3 months of vaccination among elderly people with comorbidities.

Clinical characteristics and risk factors associated with severe disease and outcome of patients with COVID-19.

INTRODUCTION: Since the beginning of the pandemic, factors associated with mortality in patients with corona virus infection disease 2019 (COVID-19) have been investigated. Comorbidities and increased age have been frequently reported to be associated with mortality. We aimed to evaluate the factors associated with unfavorable outcome of patients with COVID-19 at an early period of the pandemic. METHODOLOGY: This single center, retrospective, observational study was conducted among laboratory confirmed COVID-19 patients hospitalized between March 11 and May 5, 2020, at Umraniye Training and Research Hospital, Istanbul, Turkey. The effects of the severity of illness, comorbidities, symptoms, and laboratory findings on the clinical outcome were evaluated. Factors associated with unfavorable outcome (necessity of mechanical ventilation or death) were examined using Cox proportional hazards models. RESULTS: Out of a total of 728 patients, 53.8% were men and median age 54 years. The 30-day mortality rate was 4.9% among all hospitalized patients. A logistic regression model identified six predictors of unfavorable clinical outcome: age, severity of illness, the numbers of comorbidities, lymphopenia, high levels of C-reactive protein, and procalcitonin. CONCLUSIONS: The mortality rate was lower among the patients with COVID-19, hospitalized during the early period of the pandemic. Older age, higher severity score on admission, the numbers of comorbidities, higher levels of C-reactive protein, procalcitonin, and lymphopenia were identified to be associated with unfavorable outcome of the hospitalized patients with COVID-19.

Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting.

A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam.

Factors associated with mortality in younger and older (≥75 years) hospitalized patients with community-acquired pneumonia.

BACKGROUND: Pneumonia is among the most serious infections in the elderly. The evaluation of prognosis and predicting the outcome is essential in managing the treatment of patients with pneumonia. OBJECTIVE: Evaluate factors that might affect the mortality of elderly patients hospitalized for community-acquired pneumonia (CAP) in two age groups. DESIGN: Medical record review. SETTINGS: Tertiary care hospital. PATIENTS AND METHODS: The study included CAP patients who were hospitalized during the period from January 2017 and December 2019. The CURB-65 scale was chosen to assess the severity of pneumonia on admission. Multivariate analyses were conducted separately for patients younger than 75 years and 75 years or older. MAIN OUTCOME MEASURES: 30-day mortality, factors associated with mortality. SAMPLE SIZE AND CHARACTERISTICS: 1603 patients with a median age of 74, including 918 women (57%). RESULTS: The 30-day mortality rate was 6.5%. Patients with carbapenem-resistant gram-negative bacteria had lower survival rates (P<.0001). In the multivariate analysis, age, lung cancer, CURB-65, carbapenem resistance, and duration of hospital stay were associated with mortality in patients aged 75 years or older. Lung cancer, malignant disease, carbapenem resistance, duration of hospital stay and procalcitonin level were associated with mortality under the age of 75. Of 640 sputum cultures tested, P aeruginosa (42%) was the most common pathogen. CONCLUSION: The risk factors that affected mortality differed among patients aged 75 years or older versus younger patients. Our findings are important in determining factors associated with mortality in managing the treatment and follow up of hospitalized CAP patients younger or 75 years of age or older. LIMITATIONS: Single-center, retrospective. CONFLICT OF INTEREST: None.

High prevalence of ArmA-16S rRNA methyltransferase among aminoglycoside-resistant Klebsiella pneumoniae bloodstream isolates.

Introduction. Aminoglycosides are used for the treatment of carbapenemase-producing Klebsiella pneumoniae (CPK) infections. 16S rRNA methyltransferases (RMTs) confer resistance to all aminoglycosides and are often cocarried with NDM.Hypothesis/Gap Statement. There is a dart of studies looking at the aminoglycoside resistance mechanisms for invasive CPK isolates, particularly in OXA-48 endemic settings.Aim. We aimed to determine the prevalence of RMTs and their association with beta lactamases and MLSTs amongst aminoglycoside-resistant CPK bloodstream isolates in an OXA-48 endemic setting.Methodology. CPK isolates (n=181), collected as part of a multicentre cohort study, were tested for amikacin, gentamicin and tobramycin susceptibility using custom-made sensititre plates (GN2XF, Thermo Fisher Scientific). All isolates were previously subjected to whole-genome sequencing. Carbapenemases, RMTs, MLSTs and plasmid incompatibility groups were detected on the assembled genomes.Results. Of the 181 isolates, 109(60 %) were resistant to all three aminoglycosides, and 96 of 109(88 %) aminoglycoside-resistant isolates carried an RMT (85 ArmA, 10 RmtC, 4 RmtF1; three isolates cocarried ArmA and RmtC). Main clonal types associated with ArmA were ST2096 (49/85, 58 %) and ST14 (24/85, 28 %), harbouring mainly OXA-232 and OXA-48 +NDM, respectively. RmtC was cocarried with NDM (5/10) on ST395, and NDM +OXA-48 or NDM +KPC (4/10) on ST14, ST15 and ST16. All RMT producers also carried CTX-M-15, and the majority cocarried SHV-106, TEM-150 and multiple other antibiotic resistance genes. The majority of the isolates harboured a combination of IncFIB, IncH and IncL/M type plasmids. Non-NDM producing isolates remained susceptible to ceftazidime-avibactam.Conclusion. Aminoglycoside resistance amongst CPK bloodstream isolates is extremely common and mainly driven by clonal spread of ArmA carried on ST2096 and ST14, associated with OXA-232 and OXA48 +NDM carriage, respectively.

Appropriate Use of Tocilizumab in COVID-19: Early Use is Beneficial.

Objective: Interleukin-6 inhibitor Tocilizumab (TCZ) is effective to prevent the mortality of severe COVID-19 by suppressing the cytokine storm, however, its appropriate use needs to be detailed. We aimed to describe the appropriate use of TCZ in severe to critical cases with COVID-19 pneumonia in the early phase of the pandemic. Materials and Methods: This single-center, retrospective, observational study was conducted in a polymerase chain reaction (PCR) positive COVID-19 patients who received TCZ between April 01, 2020 and June 30, 2020, in Ümraniye Research and Training Hospital Istanbul, Turkey. The factors affecting mortality were compared. Results: A total of 67 patients met the inclusion criteria during the study period. Overall, 76% of those patients were male, with a median age of 61 years. The 28-day mortality rate was 51% among all patients who were hospitalised for COVID-19 pneumonia. A logistic regression model identified the predictors of 28-day fatality; the number of comorbidities, high levels of C-reactive protein (CRP) before initiation of TCZ, initiation of TCZ in the intensive care unit (ICU) and not receiving an additional dose of TCZ. Conclusion: The number of comorbidities, high levels of CRP, initiation of TCZ in the ICU and not receiving the additional dose of TCZ were significant risk factors for fatality among patients with COVID-19 who received TCZ. Early initiation of TCZ when cytokine storm is suspected is appropriate for the prevention of fatality.

Diagnostic performance of thorax CT in mildly symptomatic COVID-19 patients: The importance of atypical CT findings.

OBJECTIVE: Computed tomography of the thorax (Thorax CT) is frequently used to diagnose viral pneumonia in moderate to severe COVID-19 patients, but its diagnostic performance in mildly symptomatic COVID-19 patients is still unclear. Assessing the diagnostic performance of thorax CT in mildly symptomatic COVID-19 patients was the purpose of our study. METHODS: Mildly symptomatic and clinically stable, suspected COVID-19 patients scanned with Thorax CTs between March 11, 2020, and April 13, 2020, were included in this study. The sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, and the respective accuracies were calculated for diagnostic purposes. RESULTS: Among the 1119 patients enrolled in our study, abnormal thorax CT scans were 527 out of which 363/527 (68.9%) had typical CT features for COVID-19. According to analysis of typical COVID findings, sensitivity, specificity, positive predictive values, negative predictive value, and the accuracy of Thorax CTs with were 51.45%, 86.07%, 78.24%, 64.55%, and 68.99%, respectively. When typical CT findings and atypical CT findings were combined for the statistical analysis, the sensitivity, specificity, and accuracy observed 68.84%, 74%, and 71.49%. CONCLUSION: Diagnosing pneumonia can be challenging in mildly symptomatic COVID-19 patients since the Reverse Transcription Polymerase Chain Reaction test results, when compared with symptoms are not always evident. According to our study, thorax CT sensitivity was higher when atypical COVID-19 CT findings were included compared to those with typical COVID-19 CT findings alone. Our study which included the largest number of patients among all other similar studies indicates that not only typical but also atypical CT findings should be considered for an accured diagnosis of COVID-19 pneumonia.

Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19.

COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+ ) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

Evaluation of Modified ATRIA Risk Score in Predicting Mortality in Hospitalized Patients With COVID-19.

BACKGROUND: As the Modified Anticoagulation and Risk Factors in Atrial Fibrillation Risk Score (M-ATRIA-RS) encompasses prognostic risk factors of novel coronavirus-2019 (COVID-19), it may be used to predict in-hospital mortality. We aimed to investigate whether M-ATRIA-RS was an independent predictor of mortality in patients hospitalized for COVID-19 and compare its discrimination capability with CHADS, CHA2DS2-VASc, and modified CHA2DS2-VASc (mCHA2DS2-VASc)-RS. METHODS: A total of 1,001 patients were retrospectively analyzed and classified into three groups based on M-ATRIA-RS, designed by changing sex criteria of ATRIA-RS from female to male: Group 1 for points 0-1 (n = 448), Group 2 for points 2-4 (n = 268), and Group 3 for points ≥5 (n = 285). Clinical outcomes were defined as in-hospital mortality, need for high-flow oxygen and/or intubation, and admission to intensive care unit. RESULTS: As the M-ATRIA-RS increased, adverse clinical outcomes significantly increased (Group 1, 6.5%; Group 2, 15.3%; Group 3, 34.4%; p <0.001 mortality for in-hospital). Multivariate logistic regression analysis showed that M-ATRIA-RS, malignancy, troponin increase, and lactate dehydrogenase were independent predictors of in-hospital mortality (p<0.001, per scale possibility rate for ATRIA-RS 1.2). In receiver operating characteristic (ROC) analysis, the discriminative ability of M-ATRIA-RS was superior to mCHA2DS2-VASc-RS and ATRIA-RS, but similar to that Charlson Comorbidity Index (CCI) score (AUCM-ATRIAvs AUCATRIA Z-test=3.14 p = 0.002, AUCM-ATRIAvs. AUCmCHA2DS2-VASc Z-test=2.14, p = 0.03; AUCM-ATRIAvs. AUCCCI Z-test=1.46 p = 0.14). CONCLUSIONS: M-ATRIA-RS is useful to predict in-hospital mortality among patients hospitalized with COVID-19. In addition, it is superior to the mCHA2DS2-VASc-RS in predicting mortality in patients with COVID-19 and is more easily calculable than the CCI score.

Seroprevalence of coronavirus disease 2019 (COVID-19) among health care workers from three pandemic hospitals of Turkey.

COVID-19 is a global threat with an increasing number of infections. Research on IgG seroprevalence among health care workers (HCWs) is needed to re-evaluate health policies. This study was performed in three pandemic hospitals in Istanbul and Kocaeli. Different clusters of HCWs were screened for SARS-CoV-2 infection. Seropositivity rate among participants was evaluated by chemiluminescent microparticle immunoassay. We recruited 813 non-infected and 119 PCR-confirmed infected HCWs. Of the previously undiagnosed HCWs, 22 (2.7%) were seropositive. Seropositivity rates were highest for cleaning staff (6%), physicians (4%), nurses (2.2%) and radiology technicians (1%). Non-pandemic clinic (6.4%) and ICU (4.3%) had the highest prevalence. HCWs in "high risk" group had similar seropositivity rate with "no risk" group (2.9 vs 3.5 p = 0.7). These findings might lead to the re-evaluation of infection control and transmission dynamics in hospitals.

Changes in antimicrobial resistance and outcomes of health care-associated infections.

To describe the change in the epidemiology of health care-associated infections (HAI), resistance and predictors of fatality we conducted a nationwide study in 24 hospitals between 2015 and 2018. The 30-day fatality rate was 22% in 2015 and increased to 25% in 2018. In BSI, a significant increasing trend was observed for Candida and Enterococcus. The highest rate of 30-day fatality was detected among the patients with pneumonia (32%). In pneumonia, Pseudomonas infections increased in 2018. Colistin resistance increased and significantly associated with 30-day fatality in Pseudomonas infections. Among S. aureus methicillin, resistance increased from 31 to 41%.

The effect of moderate and severe COVID-19 pneumonia on short-term right ventricular functions: a prospective observational single pandemic center analysis.

It has been reported that myocardial damage and heart failure are more common in COVID-19 patients with severe symptoms. The aim of our study was to measure the right ventricular functions of COVID-19 patients 30 days after their discharge, and compare them to the right ventricular functions of healthy volunteers. Fifty one patients with COVID-19 and 32 healthy volunteers who underwent echocardiographic examinations were enrolled in our study. 29 patients were treated for severe and 22 patients were treated for moderate COVID-19 pneumonia. The study was conducted prospectively, in a single center, between 15 May 2020 and 15 July 2020. We analyzed the right ventricular functions of the patients using conventional techniques and two-dimensional speckle-tracking. Right ventricular end-diastolic and end-systolic area were statistically higher than control group. The right ventricular fractional area change (RVFAC) was significantly lesser in the patient group compared to the control group. Tricuspid annular plane systolic motion (TAPSE) was within normal limits in both groups, it was lower in the patient group compared to the control group. Pulmonary artery pressure was found to be significantly higher in the patient group. Right ventricular global longitudinal strain (RV-GLS) was lesser than the control group (- 15.7 [(- 12.6)-(- 18.7)] vs. - 18.1 [(- 14.8)-(- 21)]; p 0.011). Right ventricular free wall strain (RV-FWS) was lesser in the patient group compared to the control group (- 16 [(- 12.7)-(- 19)] vs - 21.6 [(- 17)-(- 25.3)]; p < 0.001). We found subclinical right ventricular dysfunction in the echocardiographies of COVID-19 patients although there were no risk factors.