Clinical Outcomes Of Coronavirus Disease 2019 Research Articles

Impact of Human IFITM3 Polymorphism rs12252 on COVID-19 Severity and Mortality in an Egyptian Cohort

Abstract Background Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease with a high mortality rate, caused by infection with severe acute respiratory syndrome coronavirus 2. Variants of the gene encoding the interferon-induced membrane protein IFITM3 have been linked to severe viral illnesses. We investigated whether the COVID-19 clinical outcomes caused by SARS-CoV-2 infection in a cohort of COVID-19 Egyptian patients were inconsistent and could have been caused by the IFITM3-SNP rs12252 polymorphism. Aim of the Work The purpose of this study is to determine the frequency of the IFITM3 rs12252 SNP in a cohort of COVID-19 Egyptian patients, and its impact on illness severity and outcome, as well as its influence on IL-6 serum levels. Patients and Methods This cross-sectional study included 100 patients diagnosed as positive for COVID-19. They were enrolled in AL-Obour Quarantine Hospital. They were categorized into three groups, mild cases, who attended AL-Obour outpatient clinic, moderate and severe cases who were admitted to the hospital ward and ICU, respectively. All subjects of this study were subjected to full medical history, clinical evaluation, laboratory investigations, serum IL-6 levels by ELISA and IFITM3 gene polymorphism by real-time PCR. Results The results of the current study demonstrated a significant difference between mortality and the minor G allele of rs12252 within IFITM3 in COVID-19 patients (OR = 4.5 [95% CI; 1.4–14.30], P = 0.006). IL-6 showed no association either to disease severity or IFITM3 rs12252 genotype frequency. Conclusion The present study has shown a significant association between G allele variant of IFITM3 rs12252 and COVID-19 mortality. However, results failed to demonstrate any significant association between rs12252 polymorphism and disease severity, ICU admission or serum IL-6 levels. Therefore, understanding the interaction between SARS-CoV-2 and the IFITM3-rs12252 allele could help identify novel therapeutic targets, leading to precise biological and immune therapy for SARS-CoV-2 infection.

The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies.

Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19. We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications. 56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58-0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59-0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69-0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26-1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50-0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76-0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62-0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81-0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79-0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12-1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography. Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies.

Obesity, Inflammation, and Clinical Outcomes in COVID-19: A Multicenter Prospective Cohort Study.

Obesity is a risk factor for coronavirus disease 2019 (COVID-19)-related outcomes; however, the mechanism remains unclear. The objective of this analysis was to determine whether inflammation mediates the association between obesity and COVID-19 outcomes. The International Study of Inflammation in Covid-19 (ISIC): A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients. Ten hospitals in the United States and Europe. Adults hospitalized specifically for COVID-19 between February 1, 2020, through October 19, 2022. Inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), were measured at admission. Associations were examined between body-mass index (BMI, kg/m2) and a composite of death, need for mechanical ventilation, and renal replacement therapy, stratified by pre- and post-Omicron variants. The contribution of inflammation to the relationship between obesity and outcomes was assessed. Among 4644 participants (mean age 59.3, 45.6% male, 21.8% BMI≥35), those with BMI>40 (n=485) had 55% higher odds of the composite outcome (95% CI[1.21 to 1.98]) compared to non-obese individuals (BMI<30, n=2358) in multivariable analysis. In multiple mediation analysis, only suPAR remained a significant mediator between BMI and composite outcome. Associations were amplified for participants younger than 65 years and with pre-Omicron variants. Obesity is associated with worse outcomes in COVID-19, notably in younger participants and in the pre-Omicron era. Inflammation, as measured by suPAR, is a significant mediator of the association between obesity and COVID-19 outcomes.

Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony-stimulating factor following chemotherapy: Triangulation of evidence using population-based cohort and Mendelian randomization analyses.

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study

BackgroundCadmium and nickel exposure can cause oxidative stress, induce inflammation, inhibit immune function, and therefore has significant impacts on the pathogenesis and severity of many diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also provoke oxidative stress and the dysregulation of inflammatory and immune responses. This study aimed to assess the potential associations of cadmium and nickel exposure with the severity and clinical outcomes of patients with coronavirus disease 2019 (COVID-19).MethodsWe performed a retrospective, observational, bicenter cohort analysis of patients with SARS-CoV-2 infection in Taiwan between June 2022 and July 2023. Cadmium and nickel concentrations in blood and urine were measured within 3 days of the diagnosis of acute SARS-CoV-2 infection, and the severity and clinical outcomes of patients with COVID-19 were analyzed.ResultsA total of 574 patients were analyzed and divided into a severe COVID-19 group (hospitalized patients) (n = 252; 43.9%), and non-severe COVID-19 group (n = 322; 56.1%). The overall in-hospital mortality rate was 11.8% (n = 68). The severe COVID-19 patients were older, had significantly more comorbidities, and significantly higher neutrophil/lymphocyte ratio, C-reactive protein, and interleukin-6 than the non-severe COVID-19 patients (all p < 0.05). Blood and urine cadmium and urine nickel concentrations were significantly higher in the severe COVID-19 patients than in the non-severe COVID-19 patients. Among the severe COVID-19 patients, those in higher urine cadmium/creatinine quartiles had a significantly higher risk of organ failure (i.e., higher APACHE II and SOFA scores), higher neutrophil/lymphocyte ratio, lower PaO2/FiO2 requiring higher invasive mechanical ventilation support, higher risk of acute respiratory distress syndrome, and higher 60-, 90-day, and all-cause hospital mortality (all p < 0.05). Multivariable logistic regression models revealed that urine cadmium/creatinine was independently associated with severe COVID-19 (adjusted OR 1.643 [95% CI 1.060–2.547], p = 0.026), and that a urine cadmium/creatinine value > 2.05 μg/g had the highest predictive value (adjusted OR 5.349, [95% CI 1.118–25.580], p = 0.036).ConclusionsUrine cadmium concentration in the early course of COVID-19 could predict the severity and clinical outcomes of patients and was independently associated with the risk of severe COVID-19.

Impacts of Inflammatory Cytokines Variants on Systemic Inflammatory Profile and COVID-19 Severity

BackgroundCytokine storm is known to impact the prognosis of coronavirus disease 2019 (COVID-19), since pro-inflammatory cytokine variants are associated with cytokine storm. It is tempting to speculate that pro-inflammatory cytokines variants may impact COVID-19 outcomes by modulating cytokine storm. Here, we verified this hypothesis via a comprehensive analysis.MethodsPubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 15, 2023. Case–control or cohort studies that investigated the impacts of rs1800795 or rs1800629 on COVID-19 susceptibility, severity, mortality, IL-6, TNF-α, or CRP levels were included after an anonymous review by two independent reviewers and consultations of disagreement by a third independent reviewer.Results47 studies (8305 COVID-19 individuals and 17,846 non-COVID-19 individuals) were analyzed. The rs1800629 A allele (adenine at the −308 position of the promoter was encoded by the A allele) was associated with higher levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). In contrast, the rs1800795 C allele (cytosine at the −174 position of the promoter was encoded by the C allele) was linked to higher levels of interleukin-6 (IL-6) and CRP. In addition, the A allele of rs1800629 increased the severity and mortality of COVID-19. However, the C allele of rs1800795 only increased COVID-19 susceptibility.Conclusionsrs1800629 and rs1800795 variants of pro-inflammatory cytokines have significant impacts on systemic inflammatory profile and COVID-19 clinical outcomes. rs1800629 may serve as a genetic marker for severe COVID-19.

Impact of Antidiabetic Drugs on Clinical Outcomes of COVID-19: A Nationwide Population-Based Study.

Inconsistent results have been reported regarding the association between the use of antidiabetic drugs and the clinical outcomes of coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of antidiabetic drugs on COVID-19 outcomes in patients with diabetes using data from the National Health Insurance Service (NHIS) in South Korea. We analyzed the NHIS data of patients aged ≥20 years who tested positive for COVID-19 and were taking antidiabetic drugs between December 2019 and June 2020. Multiple logistic regression analysis was performed to analyze the clinical outcomes of COVID-19 based on the use of antidiabetic drugs. A total of 556 patients taking antidiabetic drugs tested positive for COVID-19, including 271 male (48.7%), most of whom were in their sixties. Of all patients, 433 (77.9%) were hospitalized, 119 (21.4%) received oxygen treatment, 87 (15.6%) were admitted to the intensive care unit, 31 (5.6%) required mechanical ventilation, and 61 (11.0%) died. Metformin was significantly associated with the lower risks of mechanical ventilation (odds ratio [OR], 0.281; 95% confidence interval [CI], 0.109 to 0.720; P=0.008), and death (OR, 0.395; 95% CI, 0.182 to 0.854; P=0.018). Dipeptidylpeptidase-4 inhibitor (DPP-4i) were significantly associated with the lower risks of oxygen treatment (OR, 0.565; 95% CI, 0.356 to 0.895; P=0.015) and death (OR, 0.454; 95% CI, 0.217 to 0.949; P=0.036). Sulfonylurea was significantly associated with the higher risk of mechanical ventilation (OR, 2.579; 95% CI, 1.004 to 6.626; P=0.049). In patients with diabetes and COVID-19, metformin exhibited reduced risks of mechanical ventilation and death, DPP- 4i was linked with lower risks of oxygen treatment and death, while sulfonylurea was related to the increased risk of mechanical ventilation.

Sex-specific differences in systemic immune responses in MIS-C children

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C. This study is an observational and cross-sectional study and we wanted to examine immune parameters such as cytokines, chemokines, acute phase proteins (APPs), growth factors, microbial translocation markers (MTMs), complement components and matrix metalloproteinases (MMPs) in MIS-C children, based on sex. Male children were associated with heightened levels of pro-inflammatory cytokines—IFNγ, IL-2, TNFα, IL-1α, IL-1β, IL-6, IL-12, G-CSF and GM-CSF, chemokines-CCL2, CCL11, CXCL1, CXCL8 and CXCL10, acute phase proteins-α-2M, CRP, growth factors VEGF and TGFα, microbial translocation markers- iFABP, LBP, EndoCAb, complement components—C1q, MBL and C3 and matrix metalloproteinases MMP-8 and MMP-9 compared to female children with MIS-C. These results indicate that the heightened immune response in males is a characteristic feature of MIS-C. These findings might explain the differential disease pathogenesis in males compared to females with MIS-C and facilitate a deeper understanding of this disease.

Intubation Time, Lung Mechanics and Outcome in COVID-19 Patients Suffering Acute Respiratory Distress Syndrome: A Single-Center Study.

We examined the effect of intubation time and the lung mechanics on clinical outcomes in coronavirus disease 2019 (COVID-19) patients. Based on the patient's hospital admission, intubation time was defined as early (≤ 2 days) or late (> 2 days). Patients were further divided into three groups; early (≤ 3 days), late (4 - 6 days), and very late (> 6 days) intubated. A total of 194 patients were included; 66.5% male, median age 65 years. Fifty-eight patients (29.9%) were intubated early and 136 (70.1%) late. Early intubated patients revealed lower mortality (44.8% vs. 72%, P < 0.001), were younger (60 vs. 67, P = 0.002), had lower sequential organ failure assessment (SOFA) scores (6 vs. 8, P = 0.002) and higher lung compliance on admission days 1, 6 and 12 (42 vs. 36, P = 0.006; 40 vs. 33, P < 0.001; and 37.5 vs. 32, P < 0.001, respectively). Older age (adjusted odds ratio (aOR) = 1.15, P < 0.001), intubation time (aOR = 1.15, P = 0.004), high SOFA scores (aOR = 1.81, P < 0.001), low partial pressure of oxygen (PaO2)/fractional inspired oxygen tension (FiO2) ratio (aOR = 0.96, P = 0.001), and low lung compliance on admission days 1 and 12 (aOR = 1.12, P = 0.012 and aOR = 1.14, P < 0.001, respectively) were associated with higher mortality. Very late and late intubated patients had higher mortality rates than patients intubated early (78.4% vs. 63.4% vs. 44.6%, respectively, P < 0.001). Among COVID-19 intubated patients, age, late intubation, high SOFA scores, low PaO2/FiO2 ratio, and low lung compliance are associated with higher intensive care unit (ICU) mortality.

Quantity of antibiotic use and its association with clinical outcomes in COVID-19 patients: A snapshot from a provincial referral hospital in Indonesia.

Irrational antibiotic use in Indonesia is considered high, yet there are still lacks reliable information regarding the issue. The quantity of antibiotic use studies, in particular during coronavirus disease 2019 (COVID-19) pandemic, was not well reported. The aim of this study was to evaluate antibiotic use in COVID-19 patients at a province referral hospital in Aceh, Indonesia, Dr Zainoel Abidin Hospital, and to assess the association between antibiotic use and COVID-19 clinical outcomes. The defined daily dose (DDD) method was used and expressed in DDDs per 100 patient-days as in hospital setting. The data were obtained from inpatient confirmed COVID-19 patients between March 2020 and December 2021. A logistic regression was used to determine the association between patients' characteristics and antibiotic usage with clinical outcomes. A total of 361 treated COVID-19 patients were included using a random sampling technique and analyzed. Out of 361 patients, 89.2% of them were treated with antibiotic(s). All the antibiotics were given empirically except for cefazoline (5.5%) that was used as prophylaxis to obstetric patients who underwent the c-section. Azithromycin was the most prescribed antibiotic and levofloxacin had the highest DDD. Our data suggested that there was no association between antibiotic use and clinical outcomes of COVID-19 patients (p=0.128). Having sepsis and another pulmonary disease however were associated with mortality of COVID-19 patients with adjusted odds ratio (aOR) 14.14; 95%CI 2.94-67.90, p=0.001 and aOR 8.64; 95%CI 3.30-22.63, p<0.001, respectively. In addition, patients older than 60-year-old had a higher chance to an unfavorable outcome compared to those younger than 30-year-old, aOR: 7.61; 95%CI: 1.07-53.94. In conclusion, the use of antibiotics is prevalent among COVID-19 and it is not directly associated with clinical outcomes.

Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases

The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID‐19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.

Clinical outcomes of COVID-19 in hemodialysis patients.

The coronavirus disease 2019 (COVID-19) is known for its effects on the respiratory system. Three years after the pandemic morbid and mortal consequences, growing evidence is showing that the disease also has adverse outcomes and complications on additional organs including the kidneys. This study aims at investigating the effects of COVID-19 on hemodialysis patients receiving services at Palestine Medical Complex (PMC) kidney dialysis department, and to identify mortality related risk factors. In April 2022, data was collected using the electronic medical records system for the dialysis department at PMC. The study included all PMC hemodialysis patients that were infected with COVID-19 between January 2020-April 2022. The collected data included patient demographics, clinical features, laboratory tests, dialysis frequency and the disease outcome. The results showed that the patients' outcomes and dialysis frequency were impacted by their blood urea nitrogen (BUN), serum creatinine (SCr) and calcium levels. About one third of the study population died after being infected with COVID-19. The frequency of dialysis was also affected by the presence of comorbidities like hypertension, diabetes mellitus (DM) and myocardial infarction (MI). This study found that there was a high mortality rate within the hemodialysis patients infected with COVID-19. Having comorbidities affected the frequency of dialysis following COVID-19 infection. Dialysis patients should be protected from infections such as COVID-19 and their comorbidities should be monitored and kept under control as much as possible.

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) is linked to severe neurological manifestations. Senescent cells contribute to brain aging, but the impact of virus-induced senescence on neuropathologies is unknown. Here we show that senescent cells accumulate in aged human brain organoids and that senolytics reduce age-related inflammation and rejuvenate transcriptomic aging clocks. In postmortem brains of patients with severe COVID-19 we observed increased senescent cell accumulation compared with age-matched controls. Exposure of human brain organoids to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced cellular senescence, and transcriptomic analysis revealed a unique SARS-CoV-2 inflammatory signature. Senolytic treatment of infected brain organoids blocked viral replication and prevented senescence in distinct neuronal populations. In human-ACE2-overexpressing mice, senolytics improved COVID-19 clinical outcomes, promoted dopaminergic neuron survival and alleviated viral and proinflammatory gene expression. Collectively our results demonstrate an important role for cellular senescence in driving brain aging and SARS-CoV-2-induced neuropathology, and a therapeutic benefit of senolytic treatments.

Outbreaks of COVID-19 in a tuberculosis treatment sanatorium on the Thailand-Myanmar border: a retrospective cohort analysis

Background Tuberculosis (TB) is a chronic condition, with overlapping symptoms to those of coronavirus disease 2019 (COVID-19). There has been inconsistent evidence on whether TB is a predisposing factor for developing severe COVID-19. The aim of this report is to explore whether TB influences the severity of COVID-19. Methods COVID-19 cases at two TB sanatoria on the Thailand-Myanmar border were reviewed. Demographic, clinical and laboratory data including TB treatment and co-morbidities, were analyzed. Characteristics and COVID-19 clinical outcomes were compared between two groups of patients: TB and those without TB (the caretakers and the medical personnel). Multivariable ordered logistic regression was conducted to compare the risk of severe COVID-19 between the two groups. Results Between September 2021 and March 2022, 161 COVID-19 cases were diagnosed. Over half of the COVID-19 patients were infected with TB (n= 104, 64.6%), and the rest were not (n=57, 35.4%). The median (interquartile range) age was 48 (33.5-57.0) and 27 (23-33) years in the TB and in the non-TB COVID-19 patients, respectively. Before COVID-19 infection, 67.1% (106/158) of patients had received at least one dose of COVID-19 vaccine. The median cycle threshold value at diagnosis was not different between TB (18.5, IQR 16.1-32.3) and non-TB patients (18.8, 15.1-30.0). Fever, gastrointestinal symptoms and ageusia were more common in non-TB patients. Six patients (3.8%, 6/156) all from the TB group became severe of which five (3.2%, 5/156) required oxygen therapy. One TB patient died (1/104, 0.96%) of lung cancer. After adjustment for potential confounders, the final clinical severity was not different between the two groups (adjusted odds ratio 1.40, 95% confidence interval 0.16–12.39). Conclusions TB was not associated with severe outcomes in the two TB sanatoria. The high uptake of COVID-19 vaccination and active screening could have impacted on disease progression and prevented unfavorable outcomes.

Prognostic values of urea/lymphocyte and LDH/lymphocyte ratios for predicting mortality in COVID-19 patients

Objective: Serum biomarkers are important for accurately predicting clinical outcomes in coronavirus disease 2019 (COVID-19) patients. Although previous studies showed that lymphopenia in patients is related to disease severity, it is unclear how other serum biomarkers improve the prognostic accuracy of lymphopenia. Changes in urea, and lactate dehydrogenase (LDH) were noted to have considerable predictive value in determining the severity of disease in COVID-19 patients. Therefore, the purpose of this study is to determine whether increases in urea, and LDH are linked to worse outcomes in COVID-19 patients and whether the urea/lymphocyte and LDH/lymphocyte ratios improve the prognostic accuracy of lymphopenia.&#x0D; Methods: The data of confirmed COVID-19 patients in our emergency department (ED) between March 2020, and January 2021, were analyzed retrospectively. The area under the curve (AUC) and logistic regression analysis were used to evaluate the discriminative power of the urea/lymphocyte and LDH/lymphocyte ratios in estimating 30-day mortality.&#x0D; Results: The study included 795 confirmed COVID-19 patients admitted to the ED. Twenty-three patients (2.9%) died, and 772 (97.1%) survived in 30 days. The median age of the patients was 51. The number of males (n: 447, 56.2%) was higher than females (n: 348, 43.8%). The ratios of urea/lymphocyte and LDH/lymphocyte were significantly higher in non-survivors (median: 71.21 and 754.1, respectively) compared to survivors (median: 19.51 and 297.42, respectively) (P&lt;0.001). The AUC for 30-day mortality for the urea/lymphocyte and LDH/lymphocyte ratios was 0.864 and 0.840, respectively. Multivariate logistic regression adjustment found the urea/lymphocyte ratio to be an independent and significant predictor of mortality (P=0.007). The optimum cut-off point for the urea/lymphocyte ratio was 28.07, which had a 91.3% sensitivity and a 68.6% specificity.&#x0D; Conclusion: The urea/lymphocyte and LDH/lymphocyte ratios are useful markers that can be evaluated independently to identify high-risk patients and predict the prognosis of COVID-19.&#x0D;

The significance of IFITM3 polymorphism in COVID-19 asymptomatic and ICU admission Kurdish patients

BackgroundThe Coronavirus Disease 2019 (COVID-19) is a global pandemic that exhibits a wide range of clinical symptoms, from asymptomatic to critically ill infections that require admission to an intensive care unit (ICU). Interferon-induced transmembrane protein 3 (IFITM3) prevents the viral envelope fusion with the cell membrane, hence playing a crucial role in the immune response. The association between single nucleotide polymorphisms (SNPs) in the IFITM3 gene and the severity of COVID-19 is controversial among various ethnic groups. MethodsSeven IFITM3 SNPs were genotyped based on DNA sequencing to investigate the association between these variants and asymptomatic and ICU-admitted COVID-19 patients of the Kurdish nation. ResultsThe present study found a significant association between rs12252 and the clinical outcome of COVID-19 (chi2 = 14.83, P = 0.00). The dominant, AA genotype model was significantly associated with a 5.212-fold increased risk of asymptomatic disease (P = 0.000, OR = 5.212). Patients with the GTA haplotypes rs12252, rs34481144, rs7478728 were shown to have a 3.9-fold increased risk of being admitted to the ICU (P = 0.003, OR = 3.9). ConclusionThis study demonstrated that the rs12252 AA genotype is probably associated with asymptomatic COVID-19. In addition, the patients having haplotypes of minor alleles rs12252, rs34481144, and rs7478728 may be associated to COVID-19 ICU admission.

Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports.

Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below 200 mg/dL. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can induce eu-DKA in diabetic patients. Notably, coronavirus disease 2019 (COVID-19) -infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets. This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis. Additionally, we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors, providing indispensable insights for healthcare professionals managing this specific patient population. To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports. We conducted an exhaustive search across prominent electronic databases, including PubMed, SCOPUS, Web of Science, and Google Scholar. This search encompassed the period from December 2019 to May 2022, incorporating published studies and pre-prints. The search terms employed encompassed "SGLT2 inhibitors", "euglycemic DKA", "COVID-19", and related variations. By incorporating these diverse sources, our objective was to ensure a thorough exploration of the existing literature on this subject, thereby augmenting the validity and robustness of our findings. Our search yielded a total of seven case reports and one case series, collectively comprising a cohort of twelve patients. These reports detailed instances of eu-DKA in individuals with COVID-19. Crucially, all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication. Upon admission, all oral medications were promptly discontinued, and the patients were initiated on intravenous insulin therapy to effectively manage the DKA. Encouragingly, eleven patients demonstrated a favorable outcome, while regrettably, one patient succumbed to the condition. Subsequently, SGLT2 were discontinued for all patients upon their discharge from the hospital. These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2, underscoring the critical importance of prompt intervention and vigilant medication adjustments. Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA, as well as encountering adverse outcomes in the context of COVID-19, despite maintaining satisfactory glycemic control. The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous. Consequently, this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.

Exploring the role of tryptophanyl-tRNA synthetase and associations with inflammatory markers and clinical outcomes in COVID-19 patients: A case-control study

Tryptophanyl-tRNA synthetase (WRS) is a critical enzyme involved in protein synthesis, responsible for charging tRNA with the essential amino acid tryptophan. Recent studies have highlighted its novel role in stimulating innate immunity against bacterial and viral infections. However, the significance of WRS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains elusive. In this study, we aimed to investigate the complex interplay between WRS, inflammatory markers, Toll-like receptor-4 (TLR-4), and clinical outcomes in coronavirus disease 19 (COVID-19) patients. A case-control investigation comprised 127 COVID-19 patients, carefully classified as severe or moderate upon admission, and 112 healthy individuals as a comparative group. Blood samples were meticulously collected before treatment initiation, and WRS, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were quantified using a well-established commercial ELISA kit. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples, and RNA was extracted for cDNA synthesis. Semi-quantitative real-time polymerase chain reaction (PCR) was employed to assess the relative expression of TLR-4. COVID-19 patients exhibited elevated levels of WRS, IL-6, CRP, and TLR-4 expression compared to healthy individuals, with the severe group displaying significantly higher levels than the moderate group. Notably, severe patients demonstrated substantial fluctuations in CRP, IL-6, and WRS levels over time, a pattern not observed in their moderate counterparts. Although no significant distinctions were observed in the dynamic alterations of WRS, IL-6, CRP, and TLR-4 expression between deceased and surviving patients, a trend emerged indicating higher IL-6_1 levels in deceased patients and elevated lactate dehydrogenase (LDH) levels in severe patients who succumbed to the disease. This pioneering research highlights the dynamic alterations of WRS in COVID-19 patients, providing valuable insights into the correlation between WRS, inflammatory markers, and disease severity within this population. Understanding the role of WRS in SARS-CoV-2 infection may open new avenues for therapeutic interventions targeting innate immunity to combat COVID-19.

The role of N-acetylcysteine in decreasing neutrophil-lymphocyte ratio in COVID-19 patients: A double-blind, randomized controlled trial.

N-acetylcysteine has antioxidant and anti-inflammatory activities that could potentially improve the clinical outcomes of coronavirus disease 2019 (COVID-19) patients. N-acetylcysteine potentially inhibits NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and results in control oxidative stress and cytokine release in COVID-19 patients. The aim of this study was to assess the effect of N-acetylcysteine in reducing the neutrophil-lymphocyte ratio (NLR) in COVID-19 patients. A randomized controlled clinical trial was conducted among severe and moderate COVID-19 patients. The treatment group received oral 1200 mg daily of N-acetylcysteine (three times a day) and the standard care for COVID-19, while the control group received standard care for COVID-19 and a placebo. The NLR was determined on the first day of admission and after the seventh day of treatment. A paired Student t-test was used to compare the NLR before and after treatment while independent Student t-test was used to compare the NLR between treatment and control groups. A total of 40 severe and moderate COVID-19 were enrolled, 20 people in each group, with a mean age was 44.68±13.24 years old. The mean NLR on the first day was 9.44 in the treatment group and 8.84 in the control group. After the seventh day, the mean NLR was 4.27 and 11.54 in the treatment group and control group, respectively. The mean changes of NLR (the pre-treatment compared to post-treatment) in the treatment and control group were reduced 4.05 and increased 3.34, respectively. The NLR in treatment group significantly decreased compared to the control group (p<0.001). In conclusion, N-acetylcysteine 1200 mg daily could reduce the NLR in severe and moderate COVID-19 patients.

Association of IL-17F Gene Polymorphism and Its Serum Level with SARS-CoV-2 Infection.

Although multiple studies have addressed the clinical outcomes of coronavirus disease, little data exist regarding the defi- nition of immune and inflammatory profiles associated with this infection. Its clinical manifestations often worsen in association with hypercytokinemia (elevated interleukin 8 and interleukin 17). We conducted this research to elucidate the effect of interleukin 17 levels and interleukin 17F gene polymorphism on the severity and outcomes of coronavirus disease. Ninety patients with confirmed coronavirus disease and 30 healthy controls were enrolled. Coronavirus disease cases were classified into nonsevere, severe, and critical according to the World Health Organization definition. Approximately 10 mL peripheral blood sample was collected from all patients and controls by venipuncture in-plane and ethylenediaminetetraacetic acid tube. Enzyme-linked immunosorbent assay kits were used for calculating serum interleukin 17 levels, whereas real-time polymerase chain reaction was used for genotyping using the 5'-nuclease allelic discrimination assay for single nucleotide polymorphisms genotyping. As regards interleukin 17 levels, there was a significant elevation of interleukin 17 in coronavirus disease cases compared to control healthy persons (P < .001). Moreover, serum interleukin 17 levels tended to be significantly higher with increased disease sever- ity (P = .004). Patients with critical diseases expressed a significant rise of interleukin 17 compared to severe (P = .03) and nonsevere cases (P = .02). We noted no significant difference between the critical, severe, and nonsevere cases regarding different interleukin 17F genotypes. Coronavirus disease is associated with elevated levels of interleukin 17, which tended to be considerably higher with disease severity. However, different interleukin 17F genotypes do not affect either the predisposition or the severity of coronavirus disease.