Analysis of peripheral lymphocyte subsets and T-cell exhaustion in SARS-CoV-2 Infection.

Introduction: : Immune responses against Coronavirus (SARS-CoV-2) may be highly complex. It has been suggested that T-cell fatigue develops due to continuous stimulation of T-cells by SARS-CoV-2 in Coronavirus disease-2019 (COVID-19). It was aimed to assess peripheral lymphocyte subsets and T-cell exhaustion in various clinical courses of the disease in patients diagnosed with COVID-19. Materials and Methods: This study included 150 patients who were assigned into the "mild-to-moderate disease" group, or "severe disease" group based on their clinical and laboratory characteristics. Peripheral lymphocyte subsets and T-cell exhaustion markers [programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)] were determined in the peripheral blood using flow cytometry. Result: Mean (±SD) age was 53.3 ± 14.5 years, and female to male ratio was 55/95. In the mild-to-moderate disease (MMD) group, 55 patients had pneumonia and 20 patients had COVID-19 without pneumonia. In the severe disease (SD) group, 43 patients had severe pneumoniae and 32 patients were in critical condition. Lymphocyte counts were less than 1.0 x 109/L in 69.3% of the patients in the SD group, and the difference between the MMD group and SD group was statistically significant (p= 0.001). Total T cells, CD4+ and CD8+ T-cell counts were significantly lower in the SD group vs. MMD group (p< 0.001, p< 0.001, p< 0.001, respectively). PD-1 expression by CD8+ and CD4 T+ cells was higher (p= 0.042, p= 0.029, respectively) and Tim-3 expression from CD4 T+ cells was lower (p= 0.000) in the SD group vs. MMD group. Serum IFN-γ levels were not statistically different in the MMD and SD groups (p= 0.2). Conclusions: T-cell counts may be significantly reduced along with an increased expression of the T-cell exhaustion marker PD-1 in severe COVID-19, but Tim-3 expression was not increased in our study patients.

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.

Adverse outcomes and maternal complications in pregnant women with severe-critical COVID-19: a tertiary center experience.

OBJECTIVES: This study aimed to present perinatal outcomes, clinical challenges, and basic ICU management in pregnant women with severe-critical COVID-19 at our tertiary referral center. METHODS: In this prospective cohort study, patients were divided into two groups, whether they survived or not. Clinical characteristics, obstetric and neonatal outcomes, initial laboratory test results and radiologic imaging findings, arterial blood gas parameters at ICU admission, and ICU complications and interventions were compared between groups. RESULTS: 157 of the patients survived, and 34 of the patients died. Asthma was the leading health problem among the non-survivors. Fifty-eight patients were intubated, and 24 of them were weaned off and discharged healthfully. Of the 10 patients who underwent ECMO, only 1 survived (p<0.001). Preterm labor was the most common pregnancy complication. Maternal deterioration was the most common indication for a cesarean section. Higher neutrophil-to-lymphocyte-ratio (NLR) values, the need for prone positioning, and the occurrence of an ICU complication were important parameters that influenced maternal mortality (p<0.05). CONCLUSIONS: Overweight pregnant women and pregnant women with comorbidities, especially asthma, may have a higher risk of mortality related to COVID-19. A worsening maternal health condition can lead to increased rates of cesarean delivery and iatrogenic prematurity.

The Evaluation of Risk Factors for Vancomycin-Resistant Enterococcus Colonization and Infection Among Mixed Adult Intensive Care Unit Patients.

Background and objective Despite the adherence to strict infection control measures, vancomycin-resistant enterococcus (VRE) colonization and VRE infections are still important problems nowadays. However, there are only a limited number of studies examining the factors causing the transformation of VRE colonization to VRE infection in the intensive care unit (ICU). The aim of this study is to delineate the prevalence of VRE colonization and its transformation into infection and the risk factors leading to infection. Methods Patients admitted to the third-level mixed-type ICU from 2012 to 2015 for at least 24 hours and acquired VRE colonization and VRE infection, both during and after their admission, were included in the study, and their medical records were examined retrospectively. VRE rectal swabs were taken weekly from each patient on admission and discharge from the ICU. If the VRE-positive patient was detected negative for VRE on the rectal swap taken three times in total as a surveillance culture successively, this patient was accepted as VRE negative. Demographic data, Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores, invasive procedures, treatments (corticosteroid, antibiotic, etc.), nutrition types, laboratory results, and ICU results were recorded. Results Among 1730 patients admitted to ICU, 101 (5.8%) were found to carry VRE colonization. Twelve (11.8%) out of 101 patients colonized with VRE developed VRE infection. About 56.4% had urinary tract infections, 68.3% had pneumonia, 15.8% had surgical site infections, and 24.8% had catheter-associated infections among these infected patients. The most prevalent factor was Enterococcus faecium in patients with VRE colonization (64.3%) and infection (91%). VRE turned negative in 67% of patients with VRE colonization during their stay in ICU. Renal replacement therapy was statistically significant (p < 0.05) in the group with VRE infection (66.7%) compared to the VRE-colonized group (26.1%). Infection development risk among carriers of VRE for more than one week was again found statistically significant (p = 0.025). Demographic data, APACHE-II scores, treatments, nutrition type, previous antibiotic usage and types, invasive procedures, laboratory results, and ICU results were similar among the patients with VRE colonization and infection. Conclusion A longer duration of ICU stay in patients with colonization and previous renal replacement therapy increases the transformation of VRE colonization to VRE infection. Strategies toward decreasing VRE-colonized patients' period of stay in ICU is the main objective to control the rate of VRE infection.

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.

Comparison of anakinra and tocilizumab in management of severe COVID-19: a retrospective cohort study.

BACKGROUND: Studies regarding effectiveness of anakinra and tocilizumab treatments in coronavirus disease 2019 (COVID-19) have contradictory results. Furthermore, there is scarce comparative data regarding superiority of any agent. To further elucidate any superiority between these two agents, we retrospectively investigated and compared outcomes in hospitalized COVID-19 patients of our inpatient cohort who received anakinra or tocilizumab. METHODS: This study was designed as a single-center, retrospective, cross-sectional cohort study. Hospitalized patients with confirmed diagnosis of COVID-19 who had Brescia-COVID respiratory severity scale score ≥3 and hyperinflammation (defined as elevation of C reactive protein ≥50 g/L or ferritin ≥700 ng/mL) and received anakinra or tocilizumab in addition to standard care were enrolled in the study. Length of hospital stay after initiation of antiinflammatory treatment, need for mechanical ventilation, need for intensive care unit admission, mortality were set as primary outcomes and compared between tocilizumab and anakinra recipients after propensity score matching. RESULTS: One hundred and six patients were placed in each group after propensity score matching. In the anakinra group, relative risk reduction for intensive care unit admission was 50% when compared to the tocilizumab group and the number needed to treat to avert an intensive care unit admission was 3 (95% CI, 2-5). In terms of mortality, a 52% relative risk reduction was observed with anakinra treatment and the number needed to treat to avert an intensive care unit admission was 8 (95% CI, 4-50). Significantly more patients were observed to receive glucocorticoids in the anakinra group. DISCUSSION: Anakinra administration in severe COVID-19 patients was significantly associated with better survival and greater clinical improvement compared to the tocilizumab administration in our study. Increased rate of glucocorticoid use in the anakinra group might have contributed to better outcomes.

Is There Any Correlation between Baseline Serum Cortisol Levels and Disease Severity in PCR-Positive COVID-19 Patients with and without Diabetes Mellitus?

Background: COVID-19 has caused a pandemic and is associated with significant mortality. The pathophysiology of COVID-19, affecting many organs and systems, is still being investigated. The hypothalamus, pituitary gland, and possibly adrenal glands are the targets of SARS-CoV-2 because of its angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors expression. Hypocortisolemia can be seen in the postinfection period. COVID-19 infection tends to be severe in diabetic patients due to immune dysfunction. In this study, our aim was to investigate the relationship between basal cortisol levels and the course of COVID-19 infection in diabetic and non-diabetic patients. Methods: Our retrospective study included 311 PCR-positive COVID-19 patients over the age of 18 who were hospitalized in Ankara City Hospital Infectious Diseases Department or Intensive Care Unit (ICU) between 15 March 2020 and 15 May 2020. Serum basal cortisol, fasting plasma glucose (FPG), HbA1c values, and diabetes history were recorded within the first 24 h of hospitalization. The presence of pulmonary involvement was noted from the patients' imaging records. Pregnant and breastfeeding women, patients with chronic liver disease or chronic kidney disease, and patients who were already using steroids or had started COVID-19 infection treatment within the 72 h before blood collection were excluded from the study. Results: Of the 311 patients, 100 had Type 2 Diabetes Mellitus (T2D), while 211 did not. The age, serum basal cortisol, and glucose levels of the patients with T2D (64.51 ± 12.29, 19.5 ± 13.12, and 143.5 (77−345)) were higher than those of the patients without T2D (46.67 ± 16.38, 15.26 ± 8.75, and 96 (65−202)), and the differences were statistically significant (p = 0.004, p = 0.004, and p < 0.001, respectively). The basal cortisol values of the ICU patients (27.89 (13.91−75)) were significantly higher than those of the ward patients (13.68 (1.48−51.93)) and patients who were transferred to the ICU from the ward due to worsening conditions (19.28 (7.74−55.21)) (p < 0.001 and p = 0.007, respectively). The factors affecting ICU admission were determined to be age, T2D history, basal cortisol, and elevation in FPG using univariate logistic regression analysis. In the multiple logistic regression analysis, age, basal cortisol level, and infiltrative involvement in thorax CT were determined to be the risk factors affecting intensive care admission. Conclusion: High basal cortisol levels in patients with T2D may predict the severity of COVID-19 infection or mortality. Although high basal cortisol levels are among the risk factors affecting ICU admission, patients with COVID-19 should also be evaluated in terms of clinical and laboratory findings and relative adrenal insufficiency.

Comparison of clinical features and perinatal outcomes between pre-variant and post-variant periods in pregnant women with SARS-CoV-2: analysis of 1935 cases.

PURPOSE: To compare the clinical features and perinatal outcomes of pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pre-variant and post-variant periods. METHODS: This prospective cohort study includes pregnant women with SARS-CoV-2 who were followed-up at Ankara City Hospital between 11, March 2020 and 15, September 2021. Demographic features, clinical characteristics and pregnancy outcomes were compared between the pre-variant (n = 1416) and post-variant (n = 519) groups. RESULTS: The rates of severe and critical cases significantly increased in the post-variant group (9.7% vs 2%, p < 0.001). The rates of respiratory support (26.8% vs 7.3%, p < 0.001), ICU admission (12.9% vs 1.8%, p < 0.001) and maternal mortality (2.9% vs 0.4%, p < 0.001) were significantly higher in the post-variant group. A significant increase was observed for pregnancy complications in the post-variant group (45.6% vs 18.8%, p = 0.007). The rates of preterm delivery (26.4% vs 4.4%, p < 0.001) and NICU admission (34% vs 18.8%, p < 0.001) were significantly higher in the post-variant group. Positive, weak, statistically significant correlations were observed between the post-variant period, disease severity and maternal mortality (r = 0.19, r = 0.12 and p < 0.001). CONCLUSION: Post-variant COVID-19 period was associated with a severe course of the disease and increased rates of adverse obstetric outcomes in pregnant patients.

COVID-19-Related Rhino-Orbital-Cerebral Mucormycosis in a Renal Transplant Recipient.

Coronavirus disease 2019 increases transplant recipients' susceptibility to rare opportunistic infections as a consequence of the impairment that COVID-19 can cause in the immune system. Mucormycosis is a rare complication but has a high risk of fatal outcome. A 50-year-old woman who received a kidney transplant 10 years previously was admitted to the hospital with COVID-19. During follow-up by the inpatient service, the patient developed pain, edema, and proptosis in the right eye. She was diagnosed with rhino-orbitalcerebral mucormycosis. This is the first reported case of rhino-orbital-cerebral mucormycosis in a renal transplant recipient with COVID-19 infection.

Brescia-COVID Respiratory Severity Scale (BRCSS) and Quick SOFA (qSOFA) score are most useful in showing severity in COVID-19 patients.

In this study, we compare the predictive value of clinical scoring systems that are already in use in patients with Coronavirus disease 2019 (COVID-19), including the Brescia-COVID Respiratory Severity Scale (BCRSS), Quick SOFA (qSOFA), Sequential Organ Failure Assessment (SOFA), Multilobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension, and Age (MuLBSTA) and scoring system for reactive hemophagocytic syndrome (HScore), for determining the severity of the disease. Our aim in this study is to determine which scoring system is most useful in determining disease severity and to guide clinicians. We classified the patients into two groups according to the stage of the disease (severe and non-severe) and adopted interim guidance of the World Health Organization. Severe cases were divided into a group of surviving patients and a deceased group according to the prognosis. According to admission values, the BCRSS, qSOFA, SOFA, MuLBSTA, and HScore were evaluated at admission using the worst parameters available in the first 24 h. Of the 417 patients included in our study, 46 (11%) were in the severe group, while 371 (89%) were in the non-severe group. Of these 417 patients, 230 (55.2%) were men. The median (IQR) age of all patients was 44 (25) years. In multivariate logistic regression analyses, BRCSS in the highest tertile (HR 6.1, 95% CI 2.105-17.674, p = 0.001) was determined as an independent predictor of severe disease in cases of COVID-19. In multivariate analyses, qSOFA was also found to be an independent predictor of severe COVID-19 (HR 4.757, 95% CI 1.438-15.730, p = 0.011). The area under the curve (AUC) of the BRCSS, qSOFA, SOFA, MuLBSTA, and HScore was 0.977, 0.961, 0.958, 0.860, and 0.698, respectively. Calculation of the BRCSS and qSOFA at the time of hospital admission can predict critical clinical outcomes in patients with COVID-19, and their predictive value is superior to that of HScore, MuLBSTA, and SOFA. Our prediction is that early interventions for high-risk patients, with early identification of high-risk group using BRCSS and qSOFA, may improve clinical outcomes in COVID-19.

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.

20-Year-old female with fever, cough, and dyspnea: Acute lupus pneumonitis during the pandemic of coronavirus disease 2019 (COVID-19).

Acute lupus pneumonitis (ALP) is a rare first-presenting manifestation of systemic lupus erythematosus (SLE). The characteristic symptoms are rapid onset of fever, cough (sometimes with hemoptysis), and dyspnea. ALP may progress to acute respiratory distress syndrome (ARDS), and it is a potentially fatal disease unless treated. Coronavirus disease 19 (COVID-19) has overlaps with ALP in terms of clinical presentation, and laboratory and radiological findings. This report describes a case of a young female patient presenting with ARDS during the pandemic of COVID-19. She had pancytopenia, elevated CRP, ferritin, and liver indices resembling macrophage activation syndrome. She also had hepatosplenomegaly, a small spleen infarct, adenopathy, minimal pleural, and pericardial effusion. After excluding COVID-19 by PCR and antibody tests, and other infections by cultures, with the help of antinuclear antibody and anti-double-stranded DNA, SLE and ALP were diagnosed, and she was treated with high-dose steroid and intravenous immunoglobulin. In conclusion, if patients presenting with pneumonia or ARDS have one or more of the findings of arthritis, serositis, rash, oral/nasopharyngeal ulcerations, cytopenias, and renal or neurologic disorder, SLE and ALP should be considered in differential diagnoses. Because of the high mortality rate of ALP reaching up to 50%, early diagnosis and immunosuppressive therapy are of vital importance.

Compliance to not only prone but also lateral and supine positioning improves outcome in hospitalised COVID-19 patients.

BACKGROUND: Positioning of the patient is a common strategy to increase oxygenation in the management of acute respiratory distress syndrome. The aim of this study is to demonstrate the effects of our positioning approach on disease outcomes in COVID-19 patients with respiratory failure, by comparing patients compliant to positioning and not. METHODS: COVID-19 patients who were admitted to our internal medicine inpatient clinic and developed hypoxaemia and underwent positioning during hospital stay were retrospectively investigated for compliance to positioning. Rates of mortality, intensive care unit admission, intubation, initiation of anti-inflammatory treatment and length of hospital stay were compared between patients with and without compliance to positioning. RESULTS: A total of 144 patients were enrolled in this study (97 compliant with positioning, 47 incompliant with positioning). Rates of ICU admission (7.2% vs 25.5%, p < .001), anti-inflammatory treatment initiation (68% vs 97.9%, p < .001) and length of hospital stay (5 (2-16) days vs 12 (3-20) days, p < .001) were significantly reduced in patients compliant with positioning. CONCLUSION: Prone or other positioning should be considered in patients with noninvasive oxygen support for the potential to reduce rates of intensive care unit admissions, airway interventions, anti-inflammatory treatment initiation and mortality.

A single center experience of intravenous immunoglobulin treatment in Covid-19.

BACKGROUND: Intravenous immunoglobulins (IVIg) have been used in management of severe Covid-19. Here in this study, we report our single-center experience regarding IVIg treatment in management of severe Covid-19. MATERIALS AND METHOD: Among hospitalized adult Covid-19 patients between April 1 and December 31, 2020, patients with confirmed diagnosis of Covid-19 who had Brescia-COVID respiratory severity scale score ≥ 3, hyperinflammation and received IVIg treatment in addition to standard of care were retrospectively investigated. We grouped IVIg recipients into three according to reasons for IVIg administration: Group 1 patients requiring anti-inflammatory treatment but complicated with secondary infection and/or sepsis , group 2 patients with Covid-19 related complications including progressive disease refractory to other anti-inflammatory agents, myocarditis, adult multisystem inflammatory syndrome, hemophagocytic lymphohystiocytosis like syndrome and group 3 patients with other complications non-specific to Covid-19. Mortality and clinical data was compared among groups. RESULTS: A total of 46 IVIg recipients were enrolled. Group 1 comprised 17 (36.9%), group 2 comprised 18 (39.1%) and group 3 comprised 11 (23.9%) patients. No significant differences in means of age, gender and comorbidities were observed among groups. Mortality was significantly lower in group 3 when compared to group 1 (64.7% vs 18.2%, p = 0.016) and close to significance when compared to group 2 (50% vs 18.2% p = 0.087). CONCLUSIONS: IVIg seemed to be used mostly in severe, refractory and complicated cases in our population. As a rescue agent in severe cases refractory to other anti-inflammatory strategies, 33.7% survival rate was observed with IVIg.

Comparing ICU admission rates of mild/moderate COVID-19 patients treated with hydroxychloroquine, favipiravir, and hydroxychloroquine plus favipiravir.

BACKGROUND: In this study, we aimed to compare the intensive care unit (ICU) admission rate of hospitalized mild/moderate COVID-19 patients treated with hydroxychloroquine (HCQ), favipiravir, and HCQ plus favipiravir. METHODS: Single center retrospective designed observational study conducted in Ankara City Hospital. Patients who were hospitalized between March 15, 2020 and June 1, 2020 in COVID-19 inpatient clinics with laboratory confirmed diagnosis of COVID-19 were included in the study. An inverse probability of treatment weighting (IPTW) for multiple treatment groups approach was used to balance the differences in several variables on admission. RESULTS: Among 2441 patients hospitalized with diagnosis of COVID-19 during the study period, 824 were eligible for the analysis. Median age of patients was 42 (18-93 years). Among all, 347 (43.2%) of the patients had mild disease, 470 (56.8%) had pneumonia. Propensity scores ranged from 0.1841 to 0.9381 in the HCQ group, from 0.03643 to 0.29885 in the favipiravir group, and from 0.03542 to 0.56184 in the HCQ plus favipiravir group. After IPTW for multiple treatment groups was applied, all the covariates in the planned propensity score had weighted standardized effect sizes below 10% which were ranged from 0.005 to 0.092. Multivariate analysis of treatment effect (adjusted effect of treatment) was indicated that there is no statistically significant difference between HCQ, favipiravir, and HCQ plus favipiravir treatment. After using combination of SMOTE and Bootstrap resampling approach, we found no statistically significant difference between HCQ and HCQ plus favipiravir groups in terms of ICU admission. However, compared with the HCQ group, ICU admission rate was statistically significantly higher in the favipiravir group. We obtained the similar results after the sensitivity analysis. CONCLUSIONS: HCQ with or without favipiravir treatment is associated with reduced risk of ICU admission compared to favipiravir alone in mild to moderate COVID-19 adult patients.

Intrathecal and Intraventricular Administration of Antibiotics in Gram-Negative Nosocomial Meningitis in a Research Hospital in Turkey.

AIM: To evaluate the gram-negative nosocomial meningitis cases which were treated with intrathecal (IT) / intraventricular (IVT) antibiotics. MATERIAL AND METHODS: Medical records were reviewed for IT/IVT antibiotherapy. Gram-negative nosocomial meningitis cases treated with IT/IVT antibiotherapy additional to systemic antibiotics were included. All patients? sex, age, SOFA scores, surgical history, cerebrospinal fluid (CSF) culture results, CSF cell counts, systemic and IT/IVT antibiotics, their dosages and duration, CSF culture sterility and sterility time, 28-day mortality due to meningitis, and all other causes were recorded and analyzed. RESULTS: Thirteen patients were included between 2014 and 2018. Most common microorganism was Acinetobacter baumannii (A.baumannii) (8/13). IT/IVT antibiotics were chosen according to susceptibility. Colistin was used in eight patients, amikacin was used in four, and one patient used amikacin and colistin consecutively. Culture negativity could not be achieved in two patients. Eight patients clinically improved but five patients had no clinical response. 28-day mortality due to infection occured in 2 of 13 patients (15%). 28-day all-cause mortality occured in 3 of 13 patients (23%). CONCLUSION: In our study, CSF culture negativity rate was high. IT/IVT antibiotic therapy should be considered as an effective and acceptable treatment option, especially in patients who do not respond to standard IV antibiotherapy.

Evaluation of 17 patients with COVID-19 pneumonia treated with anakinra according to HScore, SOFA, MuLBSTA, and Brescia-COVID respiratory severity scale (BCRSS) scoring systems.

COVID-19 pandemic has been affecting the whole world by increasing morbidity and mortality rates day by day. Treatment algorithms have been attempted as parallel to the increasing experience with COVID-19. In the pathogenesis of this virus pro-inflammatory cytokine storm has been called to have the main role. The right timing should be made for treatments. We proposed IL- 1 blocking by anakinra in seventeen COVID-19 patients at high risk of worsening. Patients were assessed according to HScore, SOFA (Sequential Organ Failure Assessment Score = SOFA), MuLBSTA Score (multilobular infiltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hyper-tension, and age), Brescia-COVID respiratory severity scale (BCRSS). In our study, the mortality rate was 17.6%. Consequently, 1 (5.9%) patient was receiving low-flow oxygen supply, 3 (17.6%) patients needed no longer oxygen supply and 10 (58.8%) patients were discharged from the hospital. According to the results of our study in the manner of general evaluation; we found that SOFA, MuLBSTA, and BCRSS scores were one step ahead according to HScore being insufficient to determine early phases of the disease. In our opinion, the prominent factors that emphasize the use of anakinra could be listed as comorbidity, risk, or presence of secondary infection, ongoing malignant disease. However, the other factors that enhance the use of anakinra in the situation of viremia also could be sorted as no response to full dose antivirals, antiviral side effects, or no success to antiviral treatment.