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.

Serum Asprosin Level as a New Biomarker in Differentiating Familial Mediterranean Fever Attacks.

Introduction Familial Mediterranean fever (FMF) is a recessively inherited disease characterized by recurrent attacks of fever and sterile polyserositis. Recently, some proteins originating from adipose tissue have been demonstrated to play a critical role in the inflammatory process. Asprosin is a new adipokine secreted by adipose tissue, and proinflammatory cytokines have been determined to increase with the decrease of circulating asprosin. This study was designed to evaluate the level of asprosin in the acute attack and attack-free period in FMF patients. Materials and methods A total of 65 FMF patients were evaluated for this cross-sectional case-control study. Those who were obese and had concomitant diabetes mellitus, hypertension, heart failure, and rheumatological disease were excluded from the study. The patients were divided into two groups: attack-free period and attack period. Fifteen healthy individuals who were not obese and had no additional disease were included as the control group. Demographic data, gene analyses, laboratory findings, and symptoms were recorded at the time of diagnosis. Serum asprosin level was studied by enzyme-linked immunosorbent assay test in the outpatient clinic controls of the patients. Asprosin levels and other laboratory findings were compared between the attack, attack-free, and control groups. Results Of the patients included in the study, 50% were in the attack period, and 50% were in the free-attack period. The mean age of the FMF patients was 34±10 years. Asprosin level in the control [median (interquartile range (IQR))=30.4 (21.5-57.7) ng/mL] group was significantly higher than the attack [median (IQR)=21.5 (17.5-28) ng/mL] and attack-free [median (IQR)=19(18.7-23) ng/mL] groups (p=0.001). C-reactive protein and sedimentation levels were significantly higher in the attack group compared to the other two groups (p<0.001). There was a moderate correlation between C-reactive protein and asprosin levels (Ro=-0.314, p=0.01). The cut-off value of serum asprosin level was determined as 21.6 ng/mL; sensitivity was 78%, and specificity was 77% (p<0.001). Conclusion The study demonstrated that the serum asprosin levels of FMF patients with acute attack were lower than those in the attack-free periods and healthy controls. Asprosin is likely to have a role in the anti-inflammatory cascade.

Correlation of Serum Asprosin Levels With Normalized Protein Catabolic Rate in Patients Receiving Peritoneal Dialysis Treatment.

Background Peritoneal dialysis patients are malnourished due to loss of protein in the dialysate and inadequate dialysis, although they take additional calories every day during treatment. Many parameters are used to assess nutritional status, with normalized protein catabolic rate (nPCR) being one of the most common. Asprosin, a novel adipokine secreted by adipose tissue, peaks during fasting and induces hepatic glucose release through the activation of the G-protein-cAMP-PKA pathway, which has been indicated to have a curative effect on chronic inflammation. In this study, we aimed to investigate the relationship between asprosin levels and nutritional parameters in patients receiving peritoneal dialysis treatment as well as to investigate the applicability of more practical tests. Methodology A total of 70 peritoneal dialysis patients, 35 female (59%) and 24 male (41%), were included in the study. The mean age of the patients was 53 ± 14 years (range = 18-80 years), and the median peritoneal dialysis duration was 31.5 months (range = 20-56.2 months). The most common etiologic cause was hypertension (37%). Patients over 18 years of age who had been receiving peritoneal dialysis treatment for at least 24 months were included in the study. The correlation between patients' nPCR levels and serum asprosin, body mass index, and lipids was evaluated. Results The correlation between the level of nPCR and the serum asprosin level, body mass index, and lipids was evaluated. Patients with nPCR <0.815 were considered malnourished, and factors affecting malnutrition were determined by univariate analysis. Among the factors affecting malnutrition according to univariate analysis, those with p-value <0.05 were analyzed by multivariate analysis. Low asprosin level was one of the independent factors affecting malnutrition in patients (Exp(B) = 0.944, 95% confidence interval (CI) = 0.896-0.994). Other independent factors affecting malnutrition were Kt/V (Exp(B) = 0.018, 95% CI = 0.001-0.550) and residual renal function (Exp(B) = -0.004, 95% CI = 0.993-0.999). Conclusions There is a need for more accessible tests and reliable parameters to evaluate dialysis and nutritional deficiency in peritoneal dialysis patients. One possible hormone that could serve as a guide is asprosin.

The Relationship Between Cytokine Concentrations and Severity Scoring Index for Crimean-Congo Hemorrhagic Fever.

Background This study aimed to investigate the effects of serum high mobility group box-1 (HMGB1), interleukin (IL)-6, IL-8, IL-1ß, IL-10, and tumor necrosis factor alpha (TNF-α) levels on disease severity and mortality in Crimean-Congo hemorrhagic fever (CCHF) patients. Materials and methods This study was performed prospectively in the intensive care unit (ICU) and infection ward of a tertiary hospital in the Republic of Türkiye. Patients aged 18 years and older diagnosed with CCHF were included. Results Our study included 30 patients, of whom 83.3% were male, where the mean age was 51.6±14.35 years. The most common clinical findings in patients were malaise (90%) and myalgia (63.3%). In our study, IL-1ß levels were found to be 1173.6 (783.0-1823.0) pg/mL, IL-6 69.9 (56.8-133.1) pg/mL, IL-8 191.2 (152.8-516.9) pg/mL, TNF-α 129.5 (104.9-270.8), HMGB1 37.01 (29.26-75.18), and IL-10 190.1 (IQR: 147.8-387.8) pg/mL. The patients' median Severity Scoring Index (SSI) score was found to be 2.5 (1.8-5.5). There was a moderate correlation between the patients' SSI score and serum IL-6 (r=0.464, p=0.010), TNF-α (r=0.420, p=0.021), and IL-10 levels (r=0.518, p=0.003), and a weak correlation between serum HMGB1 (r=0.392, p=0.032). The correlation between SSI and creatine phosphokinase (CPK) levels (r=0.499, p=0.036) was observed to be moderate. Conclusion It was seen that IL-10, IL-6, TNF-α, HMBG-1, and CPK levels evaluated at the CCHF patients' time of admission to the clinic and SSI clinical score were found to be significantly related. It is clear that more studies with patients and groups of healthy volunteers are needed on this subject.

Cytokine Levels and Severity of Illness Scoring Systems to Predict Mortality in COVID-19 Infection.

Various scoring systems and cytokines have been cited as predicting disease severity in COVID-19 infection. This study analyzed the link between mortality rate, levels of cytokines, and scoring systems such as the Glasgow Coma Scale (GCS), Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Charlson Comorbidity Index in patients infected with COVID-19. Adult patients infected with COVID-19 were followed up in the intensive care unit (ICU) and analyzed prospectively. We measured serum cytokine levels (Interleukin-10 (IL-10), Interleukin-8 (IL-8), Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and High mobility group box 1 (HMGB-1)) and recorded GCS, APACHE II, SOFA, and Charlson comorbidity index scores on admission to the ICU. Receiver operating curve (ROC) analysis was performed to predict mortality from IL-1ß, IL-6 IL-10, IL-8, TNF-α, and HMGB-1 values. Study participants were grouped as follows: Group A, survivors, and Group B, deceased, during the 28-day follow-up. The mean age was 65.69 (±13.56) in Group A (n = 36) and 70.85 (±10.06) in Group B (n = 27). The female/male ratio was 23/40. Age, sex, body mass index (BMI), comorbid illnesses, GCS, APACHE II, SOFA, and Charlson scores, duration of hospitalization or ICU admission, therapeutic choices, and lymphocyte, PMNL, NLR, platelet, D-dimer, fibrinogen, GGT, CRP, procalcitonin, and lactate levels were similar between the groups. The frequency of acute kidney injury (AKI) was higher in Group B (p = 0.005). Serum IL-10, IL-8, IL-6, IL-1ß, TNF-α, HMGB-1, ferritin, and LDH values were higher, and PaO2/FiO2 was lower in Group B than in Group A. ROC analysis showed that there was an association between serum IL-1ß (>1015.7), serum IL-6 (>116.7), serum IL-8 (>258.4), serum IL-10 (>247.5), serum TNF-α (>280.7), and serum HMGB-1 (>23.5) and mortality. AKI gave rise to a greater risk of mortality (odds ratio: 7.081, p = 0.014). Mortality was associated with serum IL-10, IL-8, IL-6, IL-1ß, TNF-α, and HMGB-1 but not with GCS, APACHE II, SOFA, or Charlson comorbidity index scores. AKI increased the risk of mortality by seven times. Our findings suggest that cytokine levels (serum IL-10, IL-8, IL-6, IL-1ß, TNF-α, and HMGB-1) were predictors of mortality in COVID-19 infection. In addition, our results might give an opinion about the course of COVID-19 infection.

Gastric ultrasound, citrulline, and intestinal fatty acid-binding protein as markers of gastrointestinal dysfunction in critically ill patients: A pilot prospective cohort study.

BACKGROUND: Gastrointestinal (GI) dysfunction is common in the intensive care unit (ICU), although there is no consensus on biomarkers of GI dysfunction. We aimed to evaluate ultrasound-based gastric antrum measurements and serum intestinal fatty acid-binding protein (IFABP) and citrulline levels in relation to GI dysfunction in critically ill patients. METHODS: Adult critically ill patients receiving enteral nutrition and stayed for in the ICU for ≥48 h was included. GI dysfunction was described using Gastrointestinal Dysfunction Score (GIDS). Gastric antrum measurements, including craniocaudal (CC) diameter, anteroposterior diameter, and antral-cross sectional area (CSA), as well as serum levels for IFABP and citrulline, were prospectively recorded at baseline and on day 3 and day 5 of enteral nutrition. The receiver operating characteristic (ROC) analysis was performed to evaluate gastric ultrasound parameters, serum IFABP, and citrulline concentrations in predicting GI dysfunction. RESULTS: Thirty-nine participants with a median age of 60 years were recruited and 46.2% of participants had GI dysfunction. ROC analysis revealed that the cutoff value of CSA score to predict GI dysfunction was 4.48 cm2 , which provided 72.7% sensitivity and 77.2% specificity (area under the curve = 0.768, 95% CI: 0.555-0.980). At baseline, gastric residual volume was highly correlated with CC diameter and CSA (r = 0.764, P < 0.001 and r = 0.675, P < 0.001, respectively). Serum IFABP and citrulline levels had no correlation with GI dysfunction or gastric ultrasound parameters (P > 0.05). CONCLUSION: CSA was associated with GI dysfunction in critically ill patients. Serum IFABP and citrulline concentrations were poor in predicting GI dysfunction.

Importance of Asprosin for Changes of M. Rectus Femoris Area during the Acute Phase of Medical Critical Illness: A Prospective Observational Study.

Asprosin, a new adipokine, is secreted by subcutaneous white adipose tissue and causes rapid glucose release. The skeletal muscle mass gradually diminishes with aging. The combination of decreased skeletal muscle mass and critical illness may cause poor clinical outcomes in critically ill older adults. To determine the relationship between the serum asprosin level, fat-free mass, and nutritional status of critically ill older adult patients, critically ill patients over the age of 65 receiving enteral nutrition via feeding tube were included in the study. The patients' cross-sectional area of the rectus femoris (RF) of the lower extremity quadriceps muscle was evaluated by serial measurements. The mean age of the patients was 72 ± 6 years. The median (IQR) serum asprosin level was 31.8 (27.4-38.1) ng/mL on the first study day and 26.1 (23.4-32.3) ng/mL on the fourth study day. Serum asprosin level was high in 96% of the patients on the first day, and it was high in 74% on the fourth day after initiation of enteral feeding. The patients achieved 65.9 ± 34.1% of the daily energy requirement for four study days. A significant moderate correlation between delta serum asprosin level and delta RF was found (Rho = -0.369, p = 0.013). In critically ill older adult patients, a significant negative correlation was determined between serum asprosin level with energy adequacy and lean muscle mass.

The Evaluation of Different Treatment Approaches in Patients With Earthquake-Related Crush Syndrome.

BACKGROUND: On February 6, 2023, an earthquake occurred in Kahramanmaras, Turkey, resulting in loss of life, injuries, and the displacement of thousands of people. The aim of this study is to determine the factors affecting amputation and fasciotomy decisions in patients with crush syndrome, along with clinical laboratory parameters. MATERIALS AND METHODS: The study included patients over 18 years of age who presented with crush injuries and exhibited systemic symptoms. Inclusion criteria comprised patients with creatine kinase (CK) levels exceeding 1,000 IU/L, oliguria (urine output less than 400 mL per day), elevated blood urea nitrogen (BUN) levels surpassing 40 mg/dL, serum creatinine exceeding 1.5 mg/dL, potassium levels over 6 mEq/L, phosphorus levels surpassing 8 mg/dL, and serum calcium levels below 8 mg/dL. Multiple parameters were evaluated, including blood glucose, serum sodium, potassium, calcium, phosphorus, BUN, creatinine, uric acid, CK, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin, prothrombin time (international normalized ratio (INR)), urinalysis, C-reactive protein (CRP), venous blood gas, ECG, and chest radiography. RESULTS: Following the Maras earthquake, a total of 3,184 patients were admitted to our hospital within the first seven days. Out of these patients, 2,216 received outpatient treatment, 639 were hospitalized in the general ward, and 128 were admitted to the intensive care unit. Among the admitted patients, 237 were diagnosed with crush syndrome, with 126 being male and 111 being female. The average duration of being trapped under debris was eight hours, ranging from four to 36 hours. In the study population, extremity trauma was observed in 84 patients, thoracic trauma in 32 patients, and abdominal trauma in 20 patients. Erythrocyte replacement was administered to 123 patients, while fresh frozen plasma was given to 69 patients, for a total of 1008 units utilized. Mannitol infusions were provided to 58 patients, while bicarbonate infusions were administered to 116 patients. Among the cohort, 71 patients underwent dialysis, with nine of them receiving hemodialysis along with mannitol. Additionally, 67 patients experienced stage 3 acute kidney injury, and 41 patients were deceased. None of the patients required permanent hemodialysis. CONCLUSION: Earthquakes are considered to be one of nature's most significant and inevitable disasters. While it is impossible to prevent them, effective management strategies are crucial in mitigating the ensuing chaos and reducing casualties. In order to achieve this, it is imperative to draw lessons from past seismic events and apply appropriate treatment protocols to the affected individuals.

Lactate dehydrogenase/albumin ratio as a prognostic factor in severe acute respiratory distress syndrome cases associated with COVID-19.

BACKGROUND: Patients with severe acute respiratory distress syndrome (ARDS) have high mortality rates; therefore, new biomarkers are necessary to predict the prognosis in the early stages. Serum lactate dehydrogenase (LDH) level is a specific marker of lung damage, but it is not sensitive because it is affected by several factors. This study aimed to determine whether the LDH/albumin ratio could be used as a prognostic biomarker in patients with severe ARDS due to COVID 19. METHODS: Tertiary intensive care unit (ICU) patients with severe ARDS and confirmed COVID-19 diagnosis between August 1, 2020, and October 31, 2021, were included. The demographic and clinical characteristics of the patients were recorded from the hospital databases, together with laboratory results on the day of admission to the ICU and the length of stay in the ICU and hospital. LDH/albumin, lactate/albumin, C-reactive protein (CRP)/albumin, and BUN/albumin ratios were calculated. Logistic regression analysis was performed to determine independent risk factors affecting mortality. RESULTS: Nine hundred and five patients hospitalized in a tertiary ICU were evaluated. Three hundred fifty-one patients with severe ARDS were included in this study. The mortality rate of the included patients was 61.8% (of 217/351). LDH/albumin, lactate/albumin, and BUN/albumin ratios were higher in the nonsurvivor group (P < .001). The area under the curve (AUC) from the receiver operating characteristic analysis that predicted in-hospital mortality was 0.627 (95% confidence intervals (CI): 0.574-0.678, P < .001) for the LDH/albumin ratio, 0.605 (95% CI: 0.551-0.656, P < .001) for lactate/albumin, and 0.638 (95% CI: 0.585-0.688, P < .001) for BUN/albumin. However, LDH/albumin ratio was independently associated with mortality in multivariate logistic regression analysis. CONCLUSION: LDH/albumin ratio can be used as an independent prognostic factor for mortality in patients with severe ARDS caused by COVID-19.

The Impact of Sequential Organ Failure Assessment (SOFA) Score on Mortality in Geriatric Patients With Sepsis and Septic Shock in the ICU.

Objective One of the most common causes of mortality and morbidity in elderly patients is sepsis. Malnutrition is widespread in elderly patients, affecting mortality and morbidity. The present study aimed to evaluate the clinical features of patients hospitalized in the tertiary intensive care unit with the diagnosis of sepsis, as well as the effects of the Sequential Organ Failure Assessment (SOFA) score, prealbumin, albumin, and other laboratory parameters on hospital mortality. Methods The patients were divided into two groups according to their survival. The demographic and clinical characteristics of the two groups were compared. Independent risk factors affecting mortality were determined by logistic regression. Results A total of 653 patients admitted to the medical ICU were evaluated out of which 254 geriatric patients with sepsis and septic shock were included. There was in-hospital mortality in 122 (48%) patients. There was no difference in age in both groups (76 (71-84) vs. 76 (70-84), p=0.896). BUN (p=0.013), LDH (p=0.014), LDH/albumin (p<0.001), BUN/albumin (p<0.001), lactate/albumin (p= 0.007), and CRP/albumin (p=0.001) was higher in deceased patients compared to surviving patients. Prealbumin and albumin were lower in non-survivors (p=0.001). When the factors affecting mortality were examined by multivariate analysis, it was determined that none of the laboratory parameters alone predicted mortality. SOFA score was the only independent risk factor indicating mortality in the geriatric patient population with sepsis (OR=1.886 (1.410-2.510), p<0.001). Conclusion In conclusion, we demonstrated that high age and parameters of nutrition indicators did not affect mortality in geriatric patients hospitalized in the intensive care unit due to sepsis. In our study, the SOFA score was an independent risk factor affecting mortality in geriatric patients with sepsis, as in all sepsis cases.

Risk factors and lethality associated with Candidemia in severe COVID-19 patients.

Background and Purpose: Candidemia remained important in the intensive care units (ICU) during the COVID-19 pandemic. This study aimed to investigate the clinical and laboratory data on candidemia in COVID-19 patients. Materials and Methods: The baseline characteristics, as well as laboratory and clinical findings of candidemia and non-candidemia patients, were compared. Candidemia was defined as the isolation of Candida spp. from blood cultures. The isolates were identified by VITEK® 2 (bioMérieux, France) commercial method. Antifungal susceptibility was assessed using the E-test method. Univariate and multiple binary logistic regression analyses were performed to compare the variables. Results: In total, 126 patients with the COVID-19 disease were included. Candidemia was diagnosed in 44 (35%) of the patients. The number of patients with diabetes mellitus and chronic renal failure was higher in the candidemia group. In the candidemia group, the duration of ICU stay of patients, the 30-day mortality rate, mechanical ventilation therapy, and systemic corticosteroids (Prednisone) usage were significantly higher in candidemia patients. Moreover, the median white blood cell, neutrophils, and lactate dehydrogenase were higher in the candidemia group.Univariate and multiple binary logistic regression analyses were performed to compare the variables. Isolated species were identified as Candida albicans (n=12, 41%), Candida parapsilosis (n=7, 24%), Candida glabrata (n=6, 21%), Candida tropicalis (n=3, 10%), and Candida dublinensis (n=1, 3%). In total, three isolates of six C. glabrata species had dose-dependent sensitivity to fluconazole, and one C. parapsilosis was determined to be resistant. Conclusion: The COVID-19 patients who are admitted to ICU have many risk factors associated with candidemia. The most common risk factors for the development of candidemia were mechanical ventilation, diabetes mellitus, neutrophilia, and low hemoglobin level. The most frequently isolated species was C. albicans. Moreover, caspofungin was found to be the most effective drug in vitro. No significant resistance pattern was detected against the isolated species. It should be noted that risk-stratified antifungal prophylaxis in the ICU is possible.

Does serum butyrylcholinesterase level determine the severity and mortality of COVID-19 pneumonia?: Prospective study.

Background: The WHO emphasized the importance of knowing the risk factors for the severity of the disease in the COVID-19 pandemic. Our aim in this study was to determine the relationship between serum Butyrylcholinesterase (BChE) level, which is rapidly affected by inflammation, and the severity of COVID-19 pneumonia and mortality. Methods: Patients diagnosed with COVID-19 pneumonia between March and May 2021 were included in the study. The patients were divided into two groups as severe and mild to moderate pneumonia according to the WHO's guidelines. Serum BChE levels were studied by ELISA method from the blood samples taken from the patients on the day of hospitalization. The severity of the disease and other factors affecting hospital mortality were also evaluated. Results: 147 patients with COVID-19 pneumonia were included in this study. Of these patients, 58% had severe pneumonia and 42% had mild to moderate pneumonia. The BChE level was median 13 (IQR: 11.2-21.5)ng/ml in patients with severe COVID-19 pneumonia and median 20 (IQR: 10-35.7)ng/ml in patients with mild to moderate pneumonia (p: 0.001). Hospital with mortality rate was higher in patients with low BChE levels. However, statistically, BChE hasn't associated mortality in COVID-19 pneumonia [OR 1.002 (0.957-1.049) p: 0.490]. CRP, procalcitonin, lactate, and D-dimer levels were associated mortality in COVID-19 pneumonia. Conclusion: Being not statistically significant, the mortality rate was higher in patients with low BChE levels. BChE level is an important marker in determining the severity of COVID-19 pneumonia. Early prediction of the severity of COVID-19 pneumonia will enable early planning of the treatment process.

Enteral nutrition interruptions in critically ill patients: A prospective study on reasons, frequency and duration of interruptions of nutritional support during ICU stay.

BACKGROUND & AIMS: Enteral Nutrition (EN) may be interrupted due to various reasons in the setting of intensive care unit (ICU) care. This study aimed to investigate the reasons, frequency, and duration of EN interruptions in critically ill patients within the first 7 days of ICU stay. METHODS: A total of 122 critically ill patients (median age: 63 years, 57% were males) initiating EN within the first 72 h of ICU admission and continued EN for at least 48 h during ICU stay were included in this observational prospective study conducted at a Medical ICU. Patients were followed for hourly energy intake as well as the frequency, reason, and duration of EN interruptions, for the first seven nutrition days of ICU stay or until death/discharge from ICU. RESULTS: The median APACHE II score was 22 (IQR, 17-27). The per patient EN interruption frequency was 2.74 and the median total EN interruption duration was 960 (IQR, 105-1950) minutes. The most common reason for EN interruption was radiological procedures (91 episodes) and the longest duration of EN interruption was due to tube malfunctions (1230 min). Target energy intake were achieved on the 6th day at a maximum rate of 89.4%. Logistic regression showed that there was relationship between increased mortality and patients with ≥3 EN interruptions (OR: 6.73 (2.15-30.55), p = 0.004) after adjusting for confounding variables (age and APACHE II score). According to Kaplan Meier analysis, patients with ≥3 EN interruptions had significantly lower median survival times than patients with <3 EN interruptions (24.0 (95% CI 8.5-39.5) vs 18.0 (95% CI 13-23) days, p = 0.014). CONCLUSION: During the first week of EN support, the most common reason of EN interruptions was related to radiological procedures and the longest EN interruptions was due to feeding tube malfunctions. There was relationship between ≥3 EN interruptions and increased mortality.