Effects of COVID-19 pandemic on healthcare-associated infections, antibiotic resistance and consumption rates in intensive care units.

Purpose: This paper aimed to evaluate the effects of the COVID-19 pandemic on healthcare-associated infections (HAIs), antibiotic resistance and consumption rates in intensive care units (ICUs) of a tertiary care university hospital. Patients and Methods: Between 1 January 2018 and 31 December 2021, adult patients diagnosed with HAIs in ICUs were investigated retrospectively. Patients were divided into pre-pandemic (2018-2019) and pandemic periods (2020-2021). Antibiotic consumption index was calculated via using the formula of (total dose (grams)/defined daily dose (DDD) x total patient days) x1000. A p value below 0.05 was accepted as statistically significant. Results: The incidence of HAIs (per 1000 patient days) in the ICU of COVID-19 patients was 16.59, while it was 13.42 in the other ICUs during the pandemic period (p=0.107). The bloodstream infection (BSI) incidence was 3.32 in the pre-pandemic period and 5.41 in the pandemic period in ICUs other than the ICU of COVID-19 patients (p<0.001). In the pandemic period, the BSI incidence rate was significantly higher in the ICU of COVID-19 patients than in the other ICUs (14.26 vs 5.41, p<0.001). Central venous catheter bloodstream infections incidence rate was 4.72 in the pre-pandemic and 7.52 in the pandemic period in ICUs other than the ICU of COVID-19 patients (p=0.0019). During the pandemic period, the bacteraemia episode rates of Acinetobacter baumannii (5.375 vs 0.984, p<0.001), Enterococcus spp. (1.635 vs 0.268, p<0.001) and Stenotrophomonas maltophilia (3.038 vs 1.297, p=0.0086) in the ICU of COVID-19 patients were significantly found higher than others. The extended-spectrum beta-lactamase (ESBL) positivity rates for Klebsiella pneumoniae and Escherichia coli were 61% and 42% in the pre-pandemic period; 73% and 69% in the pandemic period in ICUs other than the ICU of COVID-19 patients (p>0.05). In the pandemic period, the ESBL positivity rates for K. pneumoniae and E. coli were 83% and 100% in the ICU of COVID-19 patients, respectively. Meropenem (p<0.001), teicoplanin (p<0.001) and ceftriaxone (p<0.001) consumptions were increased while ciprofloxacin (p=0.003) consumption was decreased in all ICUs after the pre-pandemic period. Conclusions: BSI and CVCBSI incidence rates were significantly increased in all ICUs after the COVID-19 pandemic in our hospital. Bacteraemia episode rates of A. baumannii, Enterococcus spp. and S. maltophilia in ICU of COVID-19 patients were significantly found higher than others. In addition, meropenem, teicoplanin and ceftriaxone consumptions were increased in all ICUs after the COVID-19 pandemic.

An outbreak of Ralstonia insidiosa bloodstream infections caused by contaminated heparinized syringes.

INTRODUCTION: Ralstonia insidiosa, a gram-negative waterborne bacteria able to survive and grow in any type of water source, can cause nosocomial infections, and are considered emerging pathogens of infectious diseases in hospital settings. In this study, we report an outbreak of R. insidiosa at our center related to contaminated heparinized syringes. MATERIAL AND METHODS: The present study was conducted in a tertiary care university hospital in Turkey. An outbreak analysis was performed between September 2021 and December 2021. Microbiological samples were obtained from environmental sources and from patient blood cultures. Species identification was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). To investigate the clonality of strains, all confirmed isolates were sent to the National Reference Laboratory and pulsed-field gel electrophoresis (PFGE) was used to perform molecular typing. RESULTS: Seventeen R. insidiosa isolates were identified from the blood cultures of 13 patients from various wards and intensive care units. Isolates from seven patient blood cultures and two heparinized blood gas syringes were characterized by PFGE. All isolates were found to belong to the same clone of R. insidiosa. CONCLUSION: R. insidiosa was identified as the cause of a nosocomial infection outbreak in our hospital, which was then rapidly controlled by the infection-control team. When rare waterborne microorganisms grow in blood or other body fluid cultures, clinicians and the infection-control team should be made aware of a possible outbreak.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

Tocilizumab treatment in COVID-19: A prognostic study using propensity score matching.

BACKGROUND: The potential role of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) pneumonia provides the rationale for investigating IL-6 signaling inhibitors. OBJECTIVES: To evaluate and report treatment responses to tocilizumab (TCZ) in COVID-19 patients and compare mortality outcomes with those of standard care. MATERIAL AND METHODS: Patients hospitalized with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, diagnosed with reverse transcription polymerase chain reaction (RT-PCR) between March 2020 and April 2021, were enrolled in this single-center retrospective cohort study. Propensity score matching was performed in order to reduce confounding effects secondary to imbalances in receiving TCZ treatment. RESULTS: A total of 364 patients were included in this study. Two hundred thirty-six patients received standard care, while 128 patients were treated with TCZ in addition to standard care (26 (20.3%) patients received a dose of 400 mg intravenously once, while 102 (79.7%) patients received a total dose of 800 mg intravenously). In the propensity score-matched population, less noninvasive mechanical ventilation (p = 0.041) and mechanical ventilation support (p = 0.015), and fewer deaths (p = 0.008) were observed among the TCZ-treated patients. The multivariate adjusted Cox regression model showed a significantly higher survival rate among TCZ patients compared to controls (hazard ratio (HR): 0.157, 95% confidence interval (95% CI): 0.026-0.951; p = 0.044). The hazard ratio for mortality in the TCZ group was 0.098 (95% CI: 0.030-0.318; p = 0.0001 using log-rank test). CONCLUSIONS: This study determined that TCZ treatment in COVID-19 patients was associated with better survival, reduced need for mechanical ventilation and reduced hospital-associated mortality.

Prognostic factors for COVID-19 patients.

INTRODUCTION: Determining prognostic factors in patients with coronavirus disease (COVID-19) can have great impact on treatment planning and follow-up strategies. Herein, we aimed to evaluate prognostic factors and clinical scores for confirmed COVID-19 patients in a tertiary-care hospital in the Bursa region of Turkey. METHODOLOGY: Patients who had been diagnosed with COVID-19 microbiologically and/or radiologically between March and October 2020 in a tertiary-care university hospital were enrolled retrospectively. Adult patients (≥ 18 years) with a clinical spectrum of moderate, severe, or critical illness were included. The dependent variable was 30-day mortality and logistic regression analysis was used to evaluate any variables with a significant p value (< 0.05) in univariate analysis. RESULTS: A total of 257 patients were included in the study. The mortality rate (30-day) was 14.4%. In logistic regression analysis, higher scores on sequential organ failure assessment (SOFA) (p < 0.001, odds ratio (OR) = 1.86, 95% CI = 1.42-2.45) and CURB-65 pneumonia severity criteria (p = 0.001, OR = 2.60, 95% CI = 1.47-4.57) were found to be significant in predicting mortality at admission. In deceased patients, there were also significant differences between the baseline, day-3, day-7, and day-14 results of D-dimer (p = 0.01), ferritin (p = 0.042), leukocyte (p = 0.019), and neutrophil (p = 0.007) counts. CONCLUSIONS: In our study of COVID-19 patients, we found that high SOFA and CURB-65 scores on admission were associated with increased mortality. In addition, D-dimer, ferritin, leukocyte and neutrophil counts significantly increased after admission in patients who died.

The Age-Dependent Role of Th22, Tc22, and Tc17 Cells in the Severity of Pneumonia in COVID-19 Immunopathogenesis.

Coronavirus disease 2019 (COVID-19) has clinical manifestations ranging from mild symptoms to respiratory failure, septic shock, and multi-organ failure. Lymphocytes are divided into different subtypes based on their cytokine production pattern. In this study, we investigated the role of cytokine expressions of CD4+ T (T helper [Th]1, Th2, Th17, Th22) and CD8+ T cell subtypes (T cytotoxic [Tc]1, Tc2, Tc17, Tc22) in the pathogenesis of COVID-19. Peripheral blood mononuclear cells (PBMCs) were extracted with Ficoll by density gradient centrifugation from blood samples of 180 COVID-19 patients (children and adults) and 30 healthy controls. PBMCs were stimulated with PMA and Ionomycin and treated with Brefeldin A in the fourth hour, and a 10-colored monoclonal antibody panel was evaluated at the end of the sixth hour using flow cytometry. According to our findings, the numbers of Th22 (CD3+, CD4+, and interleukin [IL]-22+) and Tc22 (CD3+, CD8+, IL-22+) cells increased in adult patients regardless of the level of pneumonia (mild, severe, or symptom-free) as compared with healthy controls (p < 0.05). In addition, the number of Tc17 (CD3+, CD8+, and IL-17A+) cells increased in low pneumonia and severe pneumonia groups compared with the healthy controls (p < 0.05). Both IL-22 and IL-17A production decreased during a follow-up within 6 weeks of discharge. Our findings suggest that the increase in only IL-22 expressed Tc22 cells in the 0-12 age group with a general symptom-free course and higher levels of Th22 and Tc22 in uncomplicated adult cases may indicate the protective effect of IL-22. On the contrary, the association between the severity of pneumonia and the elevation of Tc17 cells in adults may reveal the damaging effect of IL-22 when it is co-expressed with IL-17.

Association of SARS-CoV-2 cycle threshold (Ct) values with clinical course and serum biomarkers in COVID-19 patients.

INTRODUCTION: Our knowledge has gaps regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication levels and its association to severity of Coronavirus disease 2019 (COVID-19). The aim of this study was to investigate the association of SARS-CoV-2 viral load with disease severity and serum biomarkers in COVID-19 patients. METHODOLOGY: Viral load was determined via cycle threshold (Ct) values of SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 214 adult patients. Ct values were compared with clinical severity, biochemical and hematological biomarkers. RESULTS: Clinical course of the disease was mild (49.1%), moderate (40.2%), and severe (10.7%). Median Ct value was 28.2 (IQR: 22.2-33.8) during the first week of the disease. Ct values were lower within five days after symptom onset [lowest Ct value on the third day (median: 24, IQR: 20.6-32.3)], but they increased significantly during the second and third weeks. No association was detected between admission Ct values and disease severity. Gender, age, co-morbidity, and mortality did not differ significantly in patients with low (≤ 25) and high (> 25) Ct values. White blood cell, neutrophil, platelet, and especially lymphocyte counts, were significantly lower in patients with low Ct values. CONCLUSIONS: No definitive/clear correlation between SARS-CoV-2 viral load and severity and mortality was found in the studied COVID-19 patients. However, neutrophil, platelet, and especially lymphocyte count were significantly lower in patients with a high viral load.

Comparison of SARS-CoV-2 Antibodies and Six Immunoassays in Pediatric and Adult Patients 12 Weeks After COVID-19.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral immune persistence has been proposed to be affected by patients' characteristics. Moreover, available conflicting assay results are needed to be settled through comparative research with defined clinical specimens. Methods This prospective study investigated SARS-CoV-2-specific antibodies among 43 adults and 34 children at a mean of 12 weeks after the onset of COVID-19 symptoms using six serological assays and compared their performance. We used two Euroimmun (Euroimmun, Luebeck, Germany), two automated Roche Elecsys (Basel, Switzerland), and two rapid immuno-chromatographic Ecotest (Matrix Diagnostics, Assure Tech. (Hangzhou) Co., L, China) assays to investigate SARS-CoV-2 antibodies. Results The findings showed that the Roche Elecsys anti-S total test yielded the best positivity/sensitivity (children 94.1% and adults 93.0%; p = 0.877) while five immunoglobulin IgG targeting assays had similar positivity/sensitivity between children (88.2% to 94.1%) and adults (88.4% to 93.0%) (p > 0.05). Although IgM positivity was relatively low (p < 0.001), it was found in the majority of our pediatric and adult patients (67.6% and 86.0%, respectively; p = 0.098). SARS-CoV-2 S IgG titers were found to be higher among males in pediatric and adult groups compared to females (p = 0.027 and p = 0.041, respectively). Furthermore, we observed significantly higher antibody titers among pneumonia patients (p = 0.001). Conclusion Overall, we concluded SARS-CoV-2 antibody persistence over an average of 12 weeks after the onset of COVID-19 symptoms. While automated Roche Elecsys total antibody assays yielded the best sensitivity (> 90%) and five assays targeting IgG had acceptable performance. Patients with pneumonia and males have higher antibody titers. The effect of antibody persistence on re-infections should be monitored in longitudinal studies.

Assessment of CD39 expression in regulatory T-cell subsets by disease severity in adult and juvenile COVID-19 cases.

COVID-19 is a disease characterized by acute respiratory failure and is a major health problem worldwide. Here, we aimed to investigate the role of CD39 expression in Treg cell subsets in COVID-19 immunopathogenesis and its relationship to disease severity. One hundred and ninety COVID-19 patients (juveniles, adults) and 43 volunteers as healthy controls were enrolled in our study. Flow cytometric analysis was performed using a 10-color monoclonal antibody panel from peripheral blood samples. In adult patients, CD39+ Tregs increased with disease severity. In contrast, CD39+ Tregs were decreased in juvenile patients in an age-dependent manner. Overall, our study reveals an interesting profile of CD39-expressing Tregs in adult and juvenile cases of COVID-19. Our results provide a better understanding of the possible role of Tregs in the mechanism of immune response in COVID-19 cases.