Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing.

The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

Gut barrier protein levels in serial blood samples from critically ill trauma patients during and after intensive care unit stay.

PURPOSE: In an effort to better manage critically ill patients hospitalised in the intensive care unit (ICU) after experiencing multiple traumas, the present study aimed to assess whether plasma levels of intestinal epithelial cell barrier proteins, including occludin, claudin-1, junctional adhesion molecule (JAM-1), tricellulin and zonulin, could be used as novel biomarkers. Additional potential markers such as intestinal fatty acid-binding protein (I-FABP), D-lactate, lipopolysaccharide (LPS) and citrulline were also evaluated. We also aimed to determine the possible relationships between the clinical, laboratory, and nutritional status of patients and the measured marker levels. METHODS: Plasma samples from 29 patients (first, second, fifth and tenth days in the ICU and on days 7, 30 and 60 after hospital discharge) and 23 controls were subjected to commercial enzyme-linked immunosorbent assay (ELISA) testing. RESULTS: On first day (admission) and on the second day, plasma I-FABP, D-lactate, citrulline, occludin, claudin-1, tricellulin and zonulin levels were high in trauma patients and positively correlated with lactate, C-reactive protein (CRP), number of days of ICU hospitalisation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score and daily Sequential Organ Failure Assessment (SOFA) scores (P < 0.05-P < 0.01). CONCLUSION: The results of the present study showed that occludin, claudin-1, tricellulin and zonulin proteins, as well as I-FABP, D-lactate and citrulline, may be used as promising biomarkers for the evaluation of disease severity in critically ill trauma patients, despite the complexity of the analysis of various barrier markers. However, our results should be supported by future studies.

Vaccination status of COVID-19 patients followed up in the ICU in a country with heterologous vaccination policy: A multicenter national study in Turkey.

OBJECTIVE: Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-2) prevents the development of serious diseases has been shown in many studies. However, the effect of vaccination on outcomes in COVID-19 patients requiring intensive care is not clear. METHODS: This is a retrospective multicenter study conducted in 17 intensive care unit (ICU) in Turkey between January 1, 2021, and December 31, 2021. Patients aged 18 years and older who were diagnosed with COVID-19 and followed in ICU were included in the study. Patients who have never been vaccinated and patients who have been vaccinated with a single dose were considered unvaccinated. Logistic regression models were fit for the two outcomes (28-day mortality and in-hospital mortality). RESULTS: A total of 2968 patients were included final analysis. The most of patients followed in the ICU during the study period were unvaccinated (58.5%). Vaccinated patients were older, had higher Charlson comorbidity index (CCI), and had higher APACHE-2 scores than unvaccinated patients. Risk for 28-day mortality and in-hospital mortality was similar in across the year both vaccinated and unvaccinated patients. However, risk for in-hospital mortality and 28-day mortality was higher in the unvaccinated patients in quarter 4 adjusted for gender and CCI (OR: 1.45, 95% CI: 1.06-1.99 and OR: 1.42, 95% CI: 1.03-1.96, respectively) compared to the vaccinated group. CONCLUSION: Despite effective vaccination, fully vaccinated patients may be admitted to ICU because of disease severity. Unvaccinated patients were younger and had fewer comorbid conditions. Unvaccinated patients have an increased risk of 28-day mortality when adjusted for gender and CCI.

CD4+ T-Cell Depression is Linked to the Severity of COVID-19 and Predicts Mortality.

Objective: Most patients with coronavirus disease (COVID-19) have abnormalities of lymphocyte subsets. This study aimed to determine the distribution of lymphocytes in patients with various severity levels of COVID-19 and to describe the relationship between the CD4+ T helper and prognosis. Materials and Methods: Adult (>18 years old) patients with COVID-19 who followed up in a tertiary hospital were included in the study prospectively. Demographic and clinical characteristics of the patients were obtained from the hospital records. Peripheral flow cytometry was studied in patients with different severity of COVID-19 and different prognoses. Next, we analyzed the characteristics and predictive values of lymphocyte subsets in COVID-19 patients. Results: Totally 86 patients were included in the study, of which 21 (24.4%) had asymptomatic, 23 (26.7%) had mild/moderate, and 42 (48.8%) had severe/critical COVID-19. Severe/critical patients had lower lymphocyte levels and older age than asymptomatic patients (p<0.001 and p<0.001, respectively). We determined that decreased CD4+ T cell ratio (p<0.001) and CD4+ /CD8+ ratio (p<0.001) were indicative of the severity of the disease. CD4+ T cell ratio on admission (odds ratio [OR]=0.858; p=0.033), day seven CD4+ T cell ratio (OR=0.840; p=0.029), and C-reactive protein (CRP) levels (OR=1.014; p=0.043) were prognostic factors for mortality. According to receiver operating characteristics (ROC) curve analysis, the area under the curve was greater than 0.9 for decreased CD4 + T cell ratio on admission and the seventh day. Conclusion: A low CD4+ T helper ratio predicts a poor prognosis. In combination with CRP, it can be used in clinical follow-up.

Retrospective analysis on efficacy of convalescent plasma in acute respiratory distress syndrome due to COVID-19

ABSTRACT BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing global health threat. However, currently, no standard therapy has been approved for the disease. OBJECTIVES: To evaluate the clinical effectiveness of convalescent plasma (CP) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN AND SETTING: Retrospective study conducted at Kayseri City Education and Research Hospital, Kayseri, Turkey. METHODS: The case group consisted of adult patients (> 18 years) with ARDS due to COVID-19 who received CP in combination with antiviral and supportive treatment. These patients were compared with others who only received antiviral and supportive treatment. RESULTS: During the study period, a total of 30 patients with ARDS due to COVID-19 were included. Eleven patients (36%) received CP in combination with antiviral and supportive treatment, whereas nineteen patients (64%) in the control group only received antiviral and supportive treatment. On admission, the median age, demographic and clinical data and initial laboratory test results were similar between the groups (P > 0.05). On the 14th day of treatment, the laboratory values remained similar between the groups (P > 0.05). The mortality rates were not significantly different between the groups. CONCLUSION: CP treatment did not affect mortality or lead to clinical improvement for COVID-19 patients with ARDS.

Retrospective analysis on efficacy of convalescent plasma in acute respiratory distress syndrome due to COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing global health threat. However, currently, no standard therapy has been approved for the disease. OBJECTIVES: To evaluate the clinical effectiveness of convalescent plasma (CP) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN AND SETTING: Retrospective study conducted at Kayseri City Education and Research Hospital, Kayseri, Turkey. METHODS: The case group consisted of adult patients (> 18 years) with ARDS due to COVID-19 who received CP in combination with antiviral and supportive treatment. These patients were compared with others who only received antiviral and supportive treatment. RESULTS: During the study period, a total of 30 patients with ARDS due to COVID-19 were included. Eleven patients (36%) received CP in combination with antiviral and supportive treatment, whereas nineteen patients (64%) in the control group only received antiviral and supportive treatment. On admission, the median age, demographic and clinical data and initial laboratory test results were similar between the groups (P > 0.05). On the 14th day of treatment, the laboratory values remained similar between the groups (P > 0.05). The mortality rates were not significantly different between the groups. CONCLUSION: CP treatment did not affect mortality or lead to clinical improvement for COVID-19 patients with ARDS.

Measurement of serial serum total and acylated ghrelin levels in critically ill patients: A prospective and observational pilot study.

BACKGROUND: Ghrelin is a hormone that regulates appetite and energy metabolism. The change of serial serum total and acylated ghrelin levels during hospital stays of critical patients are unknown. In addition, the relationship of this change with the clinical results of patients in the intensive care unit (ICU) is also unknown. The aim of this study was to determine serum total and acylated ghrelin levels serially in critically ill patients. METHODS: This prospective study was performed in the ICU. Patients who were >18 years old and stayed in ICU for >48 h were included in the study. Serum total and acylated ghrelin concentrations were measured at baseline in all participants and serially on the 2nd, 5th, and 10th day after entry into the study in those who remained in the ICU. RESULTS: A total of 60 participants were included. The mean age was 56 ± 21 years. (Baseline, 2nd, 5th, and 10th day median serum total ghrelin levels were 3551 (1651-3995), 3485.20 (1379-4071), 3359 (1167-3919), and 3355 pg/ml (2207-3843), respectively. Baseline, 2nd, 5th, and 10th day acylated ghrelin levels were 47 (0-673), 50 (0-730), 73 (0-808), and 125 pg/ml (0-689), respectively. There was no significant difference between total ghrelin/acylated ghrelin levels and mortality (P > .05). ICU mortality was 30%. CONCLUSION: Ghrelin levels were decreased slightly and acylated ghrelin levels increased substantially over time in critically ill patients. There were no differences between serum total ghrelin/acylated ghrelin levels and ICU mortality .

Antiphospholipid antibodies in COVID-19-associated pneumonia patients in intensive care unit.

OBJECTIVES: Antiphospholipid antibodies (APAs) increase the risk of excessive blood clotting, but their role in COVID-19 remains unclear. We aimed to investigate the presence of conventional APAs used in the classification of antiphospholipid antibody syndrome in patients with severe lung infection with SARS-CoV-2 and to compare these results with non-COVID-19 critically ill patients. METHODS: Thirty-one COVID-19 patients (COVID group) and 28 non-COVID-19 critically ill patients (non-COVID group), were included in the study. Anti-cardiolipin (ACA) (IgG, IgM), anti-ß2-glycoprotein 1 (Anti-ß2GPI) (IgG, IgM, and IgA), and if the patient had not received any anti thrombotic agent before blood collection, lupus anticoagulant (LAC) tests were studied from the plasma of the patients. For testing ACA and Anti-ß2GPI, ELISA method was used, while fully automated coagulometer device was used for LAC test. RESULTS: APAs were positive in 25.81% in the COVID group (8/31) and 25% in the non-COVID group (7/28). LAC was the most common APA present in 23.08% of the COVID-19 group, who underwent measurement (6/26), while 3.57% of the non-COVID group was LAC positive (1/28) (p = .047). In the COVID group, ACA IgM, and IgG were positive in 6.45% and 0%, respectively (2/31 vs 0/31). In the non-COVID group, ACA IgM was not positive in any patient, while ACA IgG was positive in 7.14% (2/28). Anti-ß2GPI IgG and IgM tests were not positive in any patient in either the COVID or the non-COVID group. Anti-ß2GPI IgA were positive in 6.45% and 14.29%, respectively (2/31 vs 4/28). CONCLUSION: In this study, APAs were equally positive in critically ill patients among COVID-19 or non-COVID-19 patients. Only LAC was more observed in COVID-19 patients.

Clinical Outcomes and Independent Risk Factors for 90-Day Mortality in Critically Ill Patients with Respiratory Failure Infected with SARS-CoV-2: A Multicenter Study in Turkish Intensive Care Units.

BACKGROUND: There are limited data on the long-term outcomes of COVID-19 from different parts of the world. AIMS: To determine risk factors of 90-day mortality in critically ill patients in Turkish intensive care units (ICUs), with respiratory failure. STUDY DESIGN: Retrospective, observational cohort. METHODS: Patients with laboratory-confirmed COVID-19 and who had been followed up in the ICUs with respiratory failure for more than 24 hours were included in the study. Their demographics, clinical characteristics, laboratory variables, treatment protocols, and survival data were recorded. RESULTS: A total of 421 patients were included. The median age was 67 (IQR: 57-76) years, and 251 patients (59.6%) were men. The 90-day mortality rate was 55.1%. The factors independently associated with 90-day mortality were invasive mechanical ventilation (IMV) (HR 4.09 [95% CI: [2.20-7.63], P < .001), lactate level >2 mmol/L (2.78 [1.93-4.01], P < .001), age ≥60 years (2.45 [1.48-4.06)], P < .001), cardiac arrhythmia during ICU stay (2.01 [1.27-3.20], P = .003), vasopressor treatment (1.94 [1.32-2.84], P = .001), positive fluid balance of ≥600 mL/day (1.68 [1.21-2.34], P = .002), PaO2/FiO2 ratio of ≤150 mmHg (1.66 [1.18-2.32], P = .003), and ECOG score ≥1 (1.42 [1.00-2.02], P = .050). CONCLUSION: Long-term mortality was high in critically ill patients with COVID-19 hospitalized in intensive care units in Turkey. Invasive mechanical ventilation, lactate level, age, cardiac arrhythmia, vasopressor therapy, positive fluid balance, severe hypoxemia and ECOG score were the independent risk factors for 90-day mortality.

The use of high-flow nasal oxygen vs. standard oxygen therapy in hematological malignancy patients with acute respiratory failure in hematology wards

Background/aim: High flow nasal cannula (HFNC) was mostly used in intensive care units (ICUs) with few studies in other departments. We hypothesized that HFNC applied at wards is beneficial for acute respiratory failure in hematological malignancy patients. Materials and methods: The study is a single center, randomized controlled study. Inclusion criteria were hypoxemic respiratory failure and hematological malignancy. Patients were randomized to either venturi mask/nasal cannula oxygen treatment or HFNC. Results: One hundred patients were included in the study. Median age was 58.5 (18­86) years and APACHE II score was 17 (5­29). HFNC group was 51 patients and the oxygen treatment group 49 patients. P/F ratios were similar between the groups throughout the study period. Endotracheal intubation was required in 10 (20.0%) patients in oxygen group and 17 (33.0%) patients in HFNC group (p = 0.14). A total of 17 (35.0%) patients in oxygen group and 17 (33.0%) patients in HFNC group received noninvasive mechanical ventilation (p = 0.97). Median VAS comfort scores at the 2nd and 24th hours were not different between groups. The 28-day mortality rate was 36.7% (18 deaths) in the standard group and 45.0% (23 deaths) in the HFNC group (p = 0.39). Conclusion: HFNC applied in wards is not superior to standard oxygen treatment for acute respiratory failure in hematological malignancy patients.

The Outcome of Fungal Pneumonia with Hematological Cancer.

BACKGROUND: Fungal pneumonia is a common infectious complication of hematological cancer (HC) patients. In this retrospective study, the objective was set to identify the risk factors and outcome of fungal pneumonia in adult HC patients. MATERIALS AND METHODS: This retrospective study was conducted with adult (>16 years) HC patients from January 2017 and December 2018. RESULTS: During the study period, of 181 patients included 76 were diagnosed with fungal pneumonia. The most common HC was identified as acute myeloid leukaemia (40%). Of the participating patients, 52 (29%) were hematopoietic stem cell transplant (HSCT) recipients. The median age of patients with fungal pneumonia was significantly greater: 57 vs. 48 (odds ratio [OR]: 1.08) and they had longer hospitalization durations (OR: 1.14). Overall, 37 patients (20%) died, and 28-day mortality was significantly greater among patients with fungal pneumonia than without fungal pneumonia (33% vs. 11%). The most significant risk factors for mortality in fungal pneumonia were identified as need of intensive care unit (ICU) (OR: 191.2, P <0.001) and the need of vasopressor support (OR:81.6, P <0.012). ICU-mortality was (88%). CONCLUSION: Fungal pneumonia is a lethal complication in HC patients. Intensive care need is the most important predictive factor for mortality.

Value of prognostic scores in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis patients in intensive care unit: a multicenter retrospective cohort study from Turkey

Background/aim: There is a need for a scoring system for predicting ICU prognosis of patients with ANCA-associated vasculitis (AAV), but there are limited data on it in the literature. Therefore, we aimed to determine the scores that can estimate the prognosis of patients with AAV during intensive care follow up. Materials and methods: All adult patients admitted to the medical ICUs of 4 reference university hospitals in Turkey due to AAV activation and/or disease/treatment complications in the last 10 years were included in this study. Demographic data, treatments before ICU, the Birmingham Vasculitis Activity Score (BVAS) score at the time of vasculitis diagnosis, and BVAS, APACHE II, SOFA, and SAPS II scores at the ICU admission, treatments, procedures, and complications during ICU stay were recorded for all AAV patients. Results: Thirty-four patients were included in the study. The median age of the patients was 60 (42­70) years, and 64.7% were male. Twenty-five patients were diagnosed with Granulomatosis with polyangiitis, and 9 were diagnosed with Microscopic polyangiitis. The most common ICU admission causes were hemorrhage (85.3%) and sepsis/septic shock (67.6%). Twenty patients (58.8%) died in the ICU follow up. There were significant differences in APACHE II (P = 0.004) and SAPS II (P = 0.044) scores between survivors and nonsurvivors, while there were no significant differences in BVAS (during diagnosis P = 0.089 and ICU admission P = 0.539) and SOFA (P = 0.097) scores. APACHE II score was found to be an independent risk factor for ICU mortality (OR = 1.231, CI 95% = 1.011­1.498, P = 0.038) according to logistic regression analysis. An APACHE II score of greater than 20.5 predicted ICU mortality with 80% sensitivity and 70% specificity (AUC = 0.8, P = 0.004, Likelihood ratio = 2.6) according to the ROC curve analysis. Conclusion: APACHE II score can be used for the prediction of ICU mortality in AAV patients.