ABSTRACT
Aim: Although most patients with COVID-19 experience respiratory tract infections, severe reactions to the virus may cause coagulation abnormalities that mimic other systemic coagulopathies associated with severe infections, such as disseminated intravascular coagulation and thrombotic microangiopathy. Fluctuations in platelet markers, which are an indicator of the acute phase response for COVID-19, are of clinical importance. The aim of this study is to evaluate the relationship between disease severity and Platelet Mass Index (MPI) parameters in COVID-19 patients. Material(s) and Method(s): This retrospective observational study was conducted with patients who were diagnosed with COVID-19 in a tertiary hospital. The study was continued with the remaining 280 patients. All laboratory data were scanned retrospectively from patient files and hospital information system. Result(s): A very high positive correlation was found between PMI and PLT. The PMI value in women was significantly higher than in men. It was observed that PMI did not differ significantly in terms of mortality, intubation, CPAP and comorbidity. PMI vs. Pneumonia Ct Severity Score, biochemistry parameters (AST, CRP), hemogram parameters (WBC, HGB, HCT, MCV, LYM, MPV EO) and coagulation factors (aPTT and FIB) at various levels of positive/negative, weak and strong, and significant relationship was found. There was no significant relationship between hormone and D-dimer when compared with PMI. Discussion(s): Although platelet count alone does not provide information about the prognosis of the disease, PMI may guide the clinician as an indicator of lung damage in seriously ill patients.Copyright © 2022, Derman Medical Publishing. All rights reserved.
ABSTRACT
Background: The 2019 novel coronavirus disease (COVID-19) has been reported as pandemy and the number of patients continues to rise. Based on recent data, cardiac injury is a prominent feature of the disease, leading to increased morbidity and mortality. In the present study we aimed to evaluate myocardial dysfunction using transthoracic echocardiography (TTE) and tissue Doppler imaging (TDI) in hospitalized COVID-19 patients. Methods and Results: We recruited 30 patients (56.7% male, 55.80 +/- 14.949 years) who were hospitalized with the diagnosis COVID-19 infection. We analyzed left ventricular (LV) and right ventricular (RV) conventional and TDI parameters at the time of hospitalization and during the course of the disease. Patients without any cardiac disease and with preserved LV ejection fraction (EF) were included. TTE examination was performed and all the variables were recorded and analyzed retrospectively. We observed that both LV and RV conventional echocardiographic parameters were similar when the day of admission to the hospital was compared to the 5th day of the disease. Regarding TDI analysis, we demonstrated significant impairment in LV septal and lateral deformation (P < 0.001). In the correlation analysis no marked correlation was observed between impairment in LV deformation and inflammation biomarkers. Conclusion(s): Cardiac involvement is an important feature of the COVID-19 infection but the exact mechanism is still undefined. Echocardiography is an essential technique to describe myocardial injury and provide new concepts for the possible definitions of cardiac dysfunction.Copyright © 2023 The Author(s).
ABSTRACT
Background: COVID-19 has appeared as a pandemic and public health issue at a universal level. First documented as a respiratory disease, COVID-19 has been found to interrelate with and disturb the cardiovascular system causing myocardial injury and also cardiac dysfunction. Initial documentation of cardiac pathology can play a substantial role in dropping the death rate. This study emphasizes on the relationship between the serum levels of cardiac Trop I and prognosis in patients with and without pre-existing CAD in COVID-19 patients. Aims and Objectives: The first objective was to explore the association among the serum levels of cardiac Trop I and bad prognosis in patients with antiquity of CAD and without CAD. The secondary objective was to explore and understand whether increased Trop I is an appreciated prognostic indicator for COVID-19 patient antagonistic prognosis. Material(s) and Method(s): This was conducted as a retrospective observational study in which a whole of 45 patients admitted in COVID Hospital of Malabar Medical College and Research Center category C were studied. The medical record of the patients whose COVID-19 confirmation done by combined conclusions of reverse transcription PCR, symptoms, and chest X-ray was studies by the team. Result(s): Mean age of the study participants was 59.3 +/- 13.7. Every study participants had elevated Trop I levels with a median Trop I in study subjects being 397.9. There was a statistically significant elevation in Trop I levels in patients with CAD linked with non-CAD patients with a median IQR of 641.6 and P = 0.003 and there was a significant increase in Trop I levels in patients who expired related to patients who got discharged with a median IQR of 587.3 and P = 0.003. Conclusion(s): From this study, we accomplish that rise in cardiac troponin-I level is connected with elevated mortality in patients with COVID-19. Hence, it can be used as significant biomarker of disease evolution, hospitalization, and worse prognosis in COVID-19 patients.Copyright © 2023, Mr Bhawani Singh. All rights reserved.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a fatal pandemic viral disease caused by the severe acute respiratory syndrome corona virus type-2 (SARS-CoV-2). The aim of this study is to observe the associations of IL-6, SARS-COV-2 viral load (RNAemia), IL- 6 gene polymorphism and lymphocytes and monocytes in peripheral blood with disease severity in COVID-19 patients. This study was carried out from March 2021 to January 2022. RT-PCR positive 84 COVID-19 patients and 28 healthy subjects were enrolled. Blood was collected to detect SARS-COV-2 viral RNA (RNAemia) by rRT-PCR, serum IL-6 level by chemiluminescence method, SNPs of IL-6 by SSP-PCR, immunophenotyping of lymphocytes and monocyte by flow cytometry. Serum IL-6 level (pg/ml) was considerably high among critical patients (102.02 +/- 149.7) compared to severe (67.20 +/- 129.5) and moderate patients (47.04 +/- 106.5) and healthy controls (3.5 +/- 1.8). Serum SARS-CoV-2 nucleic acid positive cases detected mostly in critical patients (39.28%) and was correlated with extremely high IL-6 level and high mortality (R =.912, P < 0.001). Correlation between IL-6 and monocyte was statistically significant with disease severity (severe group, p < 0.001, and 0.867*** and critical group p < 0.001 and 0.887***). In healthy controls, moderate, severe and critically ill COVID-19 patients, IL-6 174G/C (rs 1800795) GG genotype was 82.14%, 89.20%, 67.85% and 53.57% respectively. CC and GC genotype had strong association with severity of COVID-19 when compared with GG genotype. Significant statistical difference found in genotypes between critical and moderate groups (p < 0.001, OR-10.316, CI-3.22-23.86), where CC genotype was associated with COVID-19 severity and mortality. The absolute count of T cell, B cell, NK cell, CD4+ T cells and CD8+ T cells were significantly decreased in critical group compared to healthy, moderate and severe group (P < 0.001). Exhaustion marker CD94/NKG2A was increased on NK cells and CD8+ cytotoxic T cell among critical and severe group. Absolute count of monocyte was significantly increased in critical group (P < 0.001). Serum IL-6, IL-6 174 G/C gene and SARS-CoV-2 RNAaemia can be used in clinical practice for risk assessment;T cell subsets and monocyte as biomarkers for monitoring COVID-19 severity. Monoclonal antibody targeting IL-6 receptor and NKG2A for therapeutics may prevent disease progression and decrease morbidity and mortality.Copyright © 2023 Elsevier Inc.
ABSTRACT
The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Mortality attributable to COVID-19 remains considerably high, with case fatality rates as high as 8-11%. Early medical intervention in patients who are seriously and critically ill with COVID-19 reduces fatal outcomes. Thus, there is an urgent need to identify biomarkers that could help clinicians determine which patients with SARS-CoV-2 infection are at a higher risk of developing the most adverse outcomes, which include intensive care unit (ICU) admission, invasive ventilation, and death. In COVID-19 patients experiencing the most severe form of the disease, tests of liver function are frequently abnormal and liver enzymes are found to be elevated. For this reason, we examine the most promising liver biomarkers for COVID-19 prognosis in an effort to help clinicians predict the risk of ARDS, ICU admission, and death at hospital admission. In patients meeting hospitalization criteria for COVID-19, serum albumin < 36 g/L is an independent risk factor for ICU admission, with an AUC of 0.989, whereas lactate dehydrogenase (LDH) values > 365 U/L accurately predict death with an AUC of 0.943.The clinical scores COVID-GRAM and SOFA that include measures of liver function such as albumin, LDH, and total bilirubin are also good predictors of pneumonia development, ICU admission, and death, with AUC values ranging from 0.88 to 0.978.Thus, serum albumin and LDH, together with clinical risk scores such as COVID-GRAM and SOFA, are the most accurate biomarkers in the prognosis of COVID-19.Copyright © 2021 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.
ABSTRACT
Background: Sepsis is a life-threatening condition that needs immediate diagnosis and treatment to maximize the chances of survival. Bacterial superinfection is a severe and frequent complication among COVID-19 patients and its diagnosis is challenging. Previous reports suggested that Pancreatic Stone Protein (PSP) may be a predictive biomarker for sepsis in critically ill patients. We report a case series of three COVID- 19 patients admitted to our intensive care unit (ICU) with risk of sepsis. Method(s): We daily monitored PSP, procalcitonin (PCT), and C-reactive protein (CRP) levels in three COVID- 19 patients admitted to our ICU. Microbiological sampling and antibiotic treatment were performed according to the ward organization and in case of clinical suspects for infection. Positive cultures and antibiotic treatment were retrieved from clinical charts and patients were followed from ICU admission up to a maximum of 20 days. Result(s): Patient 1 (male, 55 years-old, overweight, no other comorbidity) was admitted to the ICU in treatment with Ceftriaxone then interrupted on day 7. On day 2 he was intubated and piperacillin/tazobactam was started on day 12 for suspected hospital acquired pneumonia. PSP levels markedly increased on day 10 with no significant changes in CRP and PCT levels. On day 13 a positive bronchospirate for Klebsiella pneumoniae was found. Similarly, patient 2 (male, 70 years-old, mild emphysema and diabetes) was admitted to ICU without antibiotic and with a PSP level of 287 ng/ml. His conditions rapidly worsened in severe septic shock requiring intubation. CRP markedly raised 48-72 hours after PSP with only mild increase of PCT. Patient 3 (male, 78 years-old, no comorbidities) was admitted to ICU with high levels of PSP and piperacillin/tazobactam therapy was started. After 48-72 hours CRP levels increased with no significant changes of PCT. A positive bronchospirate for Ps. aeruginosa was collected on day 3. Conclusion(s): Our findings suggest a potential role of PSP as early biomarker of sepsis in critically ill COVID-19 patients. Daily PSP monitoring may anticipate an appropriate treatment of COVID-19 patients with a septic complication in comparison with the actual laboratory markers. Further studies are needed to confirm our hypothesis.
ABSTRACT
Background/aims: Controlled DCD organ donation (cDCD) is a strategic target for the Italian transplantation network. Italian peculiarities in cDCD donation make published results questionable and raise concern over organ ischemic damage. Consequently, normothermic regional perfusion (NRP) has been strongly recommended in potential cDCD donors. In 2019 the randomized multicenter DONARE study was designed to describe ischemic-reperfusion and inflammatory biomarkers during NRP and to test the potential benefit of apheresis by an adsorbent filter (CytoSorb) included in the NRP circuit. The aim of this report is to describe the modulation of the clinical characteristics and of the NRP in the DONARE study enrolled cases. Method(s): The study protocol was defined by the DCD national working group and proposed to all the Italian DCD donation centers. The coordinating center (CNT) has monitored the evolving cDCD activity to preserve the study capacity of representing the Italian scenario. Samples have been blindly centralized to an independent laboratory for cytokines profiling. The outcomes of transplanted organs have been recorded in the national quality database. Result(s): From September 2020 to June 2022, 27 out of the 40 planned cases have been enrolled in six centers: 4 in 2020, 12 in 2021 and 11 within June 2022. Approval is still pending in other centers. Main causes of exclusion among potential cDCD donors were: age above 65 (in 2020), e-CPR prior- to-death, shortage in personnel and COVID-19 restrictions. The age limit for enrolment (<65yrs) was abolished by amendment due to the national trend: mean age of enrolled cases increased from 57+/-6 in 2020 to 67+/-6 years in 2022. Mean NRP duration decreased from 223,3+/-39,2 in 2020 to 168,9+/-42,6 minutes in 2022;serial samples (4/2 with/without Cytosorb, from T0 to T4) from different points of the NRP circuit have been completed throughout the procedure in all the cases. All the enrolled cases became utilized donors. No study-related adverse event has been reported. Conclusion(s): Coordination of multicenter studies in the rapidly evolving scenario of controlled DCD donation should take advantage of continuous monitoring of real-life procedures and auditing of adherence to operational recommendations. The interim evaluation confirms the feasibility and safety of the study.
ABSTRACT
Background: COVID-19 syndrome is associated with high morbidity and mortality in haemodialyzed patients. Pancreatic Stone Protein (PSP) is an early biomarker of sepsis and a prognostic biomarker of disease severity in critically-ill patients and can be rapidly measured at the patient's bedside with a point-of-care-test from a small drop of whole blood. The aim of our pilot was to investigate PSP in patients requiring haemodialysis with SARS-CoV-2 infection, at different severities of COVID-19 disease. Method(s): Between February and July 2021, 23 patients (6 severe COVID-19 with Acute Kidney Injury, 6 moderate COVID-19 haemodialyzed, 2 haemodialyzed without COVID-19 and 3 healthy controls) were recruited at the University Hospital of Foggia for PSP evaluation. Biomarker's measurements were performed within 48 hours after admission or upon arrival for haemodialysis (pre-treatment). PSP was measured at the patient's bedside with "abioSCOPE", a point-of-care test capable of evaluating PSP levels in five minutes from a small drop (50mul) of whole blood or serum. Result(s): The preliminary results of this pilot study showed a trend for PSP to increase along with the severity of disease. In fact, serum PSP levels were significantly higher in Intensive Care Unit subjects than in COVID-19 negative haemodialysis subjects and controls (ANOVA p=0.032). Furthermore, PSP levels were significantly higher in subjects who died (p<0.017). Whether this increase is due to the kidney injury or COVID-19 disease remains unknown, and more research is needed to understand the relationship. Conclusion(s): Several clinical studies published in literature have shown the predictive value of PSP in the early identification of sepsis and severity of the clinical outcome. In our experience we have seen a trend for PSP to increase with disease severity also in COVID-19 patients. These results are preliminary, but PSP was significantly higher in patients who died, in accordance with the literature. This experience also has demonstrated the feasibility of a point of care system to be easily implemented in the unit and adopted by personnel and its design enables fast results and immediate decisions to be taken, especially in urgent situations.
ABSTRACT
The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
ABSTRACT
In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.
ABSTRACT
Background/Objectives: Genetic factors influence COVID-19 susceptibility and outcomes, including the development of pulmonary fibrosis (i.e. lung scarring). Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease and the most common cause of pulmonary fibrosis in the general population. Genome-wide association studies (GWAS) of COVID-19 and IPF revealed genes associated with both diseases, suggesting these share genetic risk factors. Here we performed a genetic overlap study between COVID-19 and IPF. Method(s): Summary statistics from an IPF 5-way meta-GWAS and from the COVID-19 Host Genetics initiative GWAS metaanalysis (v6) were used. We performed genetic correlation analyses and assessed individual genetic signals to identify those variants shared between both traits. We conducted colocalisation analyses to determine whether the same causal variant was driving both traits. Finally, the association of overlapping variants with gene expression was assessed and a phenome-wide association study was performed. Result(s): There was a positive genetic correlation between severe COVID-19 and IPF. We found four genetic loci with likely shared causal variants between both traits, including one novel risk locus at 7q22.1 that colocalised with decreased ZKSCAN1 and TRIM4 expression in blood. The other three loci colocalised with MUC5B, ATP11A and DPP9 expression. The locus associated with increased ATP11A expression was also associated with higher Hb1AC levels, a biomarker used in diabetes. Conclusion(s): Results suggest there are shared biological processes driving IPF and severe COVID-19 phenotypes.
ABSTRACT
Backgrounds: This study aimed to analyze the applicability of platelet parameters in assessing the severity of COVID-19 disease. Material(s) and Method(s): Patients with RT-PCR confirmed COVID-19 in the Pathology department of a tertiary care hospital in south India from June to December 2020 were included in this study. Clinical details and laboratory parameters of these patients were obtained. The difference between the studied variables in two groups was assessed using independent t-test. The optimum cut-off value of platelet to lymphocyte ratio (PLR) to differentiate between the tested groups was estimated using ROC (receiver operator curve) analysis. Finding(s): This study was conducted on 218 COVID-19 patients, of whom 17.9% showed thrombocytopenia at the time of admission. Among the hematological parameters, PLR, absolute lymphocyte count (ALC), platelet distribution width (PDW), D-dimer, and erythrocyte sedimentation rate (ESR) were significantly different between the ICU (intensive care unit) and non-ICU groups. Increased PLR values were associated with the disease severity. Conclusion(s): PLR could be used as an additional biomarker in assessing the severity of COVID-19 disease, and a cut-off value of 210.27 is optimal to differentiate severe COVID-19 disease from its mild and moderate forms with 79% specificity.Copyright © 2023, TMU Press.
ABSTRACT
Objective: During the COVID-19 pandemic, cancer patients had restricted access to standard of care tissue biopsy. Liquid biopsy assays using next generation sequencing technology provides a less invasive method for determining circulating tumour mutations (ctDNA) associated with targeted treatments or prognosis. As part of deploying technology to help cancer patients obtain molecular testing, a clinical program was initiated to offer liquid biopsy testing for Canadian patients with advanced or metastatic breast cancer. Method(s): Blood was drawn in two 10 mL StreckTM DNA BCTs and sent to the CAP/CLIA/DAP accredited Imagia Canexia Health laboratory for testing using the clinically validated Follow ItTM liquid biopsy assay. Plasma was isolated using a double spin protocol and plasma cell-free DNA (cfDNA) extracted using an optimized Promega Maxwell RSC method. Extracted cfDNA was amplified using the multiplex amplicon-based hotspot 30 or 38 gene panel and sequenced. An inhouse developed bioinformatics pipeline and reporting platform were used to identify pathogenic single nucleotide variants (SNVs), indels (insertions and deletions), and gene amplification. Included in the panel are genes associated with metastatic breast cancer: AKT1, BRAF, ERBB2, ESR1, KRAS, PIK3CA, TP53. Result(s): To identify biomarkers, 1214 metastatic or advanced breast cancer patient cfDNA samples were tested. There were 15 cases sent for repeat testing. We reported 48% of samples harboring pathogenic ctDNA mutations in TP53 (22%), PIK3CA (19%), ESR1 (18%), AKT1 (2%), ERBB2 (1.5%). Co-occurring variants were identified in samples with ESR1/PIK3CA as well as TP53/PIK3CA (both p-values <0.001). Interestingly, 29% of samples with mutated ESR1 harbored >= 2 ESR1 ctDNA mutations. In 56% of cases, previous molecular testing indicated the cancer subtype as hormone receptor (ER, PR) positive with/without HER2 negative status. In this specific subgroup, 49% harbored ctDNA mutations with 63% of those being PIK3CA and/or ESR1 mutations. Conclusion(s): A population of Canadian women with metastatic breast cancer were tested using a liquid biopsy gene panel during the COVID-19 pandemic for identification of biomarkers for targeted therapeutic options. Over 50% of the samples were identified as hormone positive, with greater than 60% harboring PIK3CA and ESR1 ctDNA mutations. Studies have shown that metastatic PIK3CA mutated ER-positive/HER2-negative tumors are predictive to respond to alpelisib therapy and have FDA and Health Canada approval. Additionally, ESR1 mutations are associated with acquired resistance to antiestrogen therapies, and interestingly we identified 29% of ESR1 mutated samples with multiple mutations possibly indicating resistance subclones. In future studies, longitudinal monitoring for presence of multiple targetable and resistance mutations could be utilized to predict or improve clinical management.
ABSTRACT
Background/Objectives: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease (COVID-19) enters the lung tissue through exocytosis, leading to the release of a large amount of pro-inflammatory cytokines called 'cytokine storm'. The aim was to provide more insight into relationship between plasma cytokines profile and fatal outcome of COVID-19. Method(s): Plasma cytokines (IL-17F,GM-CSF,IFNg,IL-10,CCL20/ MIP3a,IL-12P70,IL-13, IL-15,IL-17A,IL-22,IL-9,IL-1b,IL-33,IL-2,IL-21,IL-4,IL-23,IL-5,IL-6,IL-17E/IL-25,IL-27,IL-31,TNFa,TNFb,IL-28A) were detected in 30 patients with severe COVID-19 by a Luminex assay system with Milliplex Human Th17 Magnetic Premix 25 Plex Kit (HT17MG-14K-PX-25, Merk-Millipore, USA) according to the instructions. Patients were followed up for 30 days since admission to intensive care. 18 patients died and 12 patients survived during the period of observation. The control group comprised 10 individuals who had never been diagnosed with COVID-19. Result(s): IL-10 and CCL20/MIP3a plasma levels were elevated in non-survivors patients with COVID-19 compared to controls (p = 0.0027, p = 0.012, respectively). IL-15, IL-6, IL-27 plasma levels were higher in survivors with COVID-19 compared to controls (p = 0.049, p = 0.026, p = 0.00032, respectively). Interestingly, IL-15, IL-27 plasma levels were increased in non-survivors with COVID-19 compared to controls and survivors with severe COVID-19 (IL-15: p = 0.00098, p = 0.00014, respectively;IL-27: p = 0.011, p < 0.0001, respectively). Receiver operating characteristic (ROC) analysis has been conducted for IL-15 and IL-27. Cut-off value was estimated as 25.50 pg/ml for IL-15 and 1.51 pg/ml for IL-27. Conclusion(s): Our study demonstrated a more pronounced immune response in non-surviving patients with severe COVID-19. IL-15, IL-27 could be considered as a sensitive biomarker of the fatal outcome from COVID-19.
ABSTRACT
It is known that inflammatory cytokines exacerbate the persistence and severity of various disease states. Breast cancer is the most frequently detected cancer among women worldwide and our recent studies suggest that the inflammatory state of breast (BrCa) cancer, a byproduct of elevated cytokine expression, induces epigenetic modifications leading to increased recurrence. Ongoing NCI clinical trial data (ClinicalTrials.gov, CCC19, NCT04354701) indicates that among patients with cancer and COVID-19, the mortality is high, and the most prevalent malignancies are of breast [21%] and prostate [16%] origin. Due to the risk of cytokine storm during SARS-CoV-2 infection, it is crucial to identify potential mechanisms of hyperinflammation in BrCa patients. In this study, we have evaluated the level of copy number alteration (CNA) of different inflammatory cytokines including IL-8, IL-1b, IL6, IL-8, GM-CSF, TNF-alpha and many others using cBioportal platform which includes over sixty-nine thousand tumor samples (n>69,000 from 213 different studies) from over 33 different cancers. We found that IL-8 has the highest level of amplification in different breast cancers subtypes. Besides, we also analyzed serum samples from BrCa patients, both recurrent and non-recurrent, by different proteomics methods to identify serum cytokines involved in prognosis and recurrence. Comparative data analysis between non-recurrent BrCa against recurrent BrCa patients identified several proteins with very high significance, mostly proteins associated with epigenetic pathways including HDAC9 (P = 0.0035), HDAC5 (P = 0.013), and HDAC7 (P = 0.020). Besides, we identified differential expression of several pro-inflammatory cytokines and immune regulators (IL-8, IL-4, IL-18, IL-12p70) that were present only in recurrent BrCa patient serum. Our data indicate that inflammatory processes contribute to epigenetic modifications that ultimately play a critical role in breast cancer recurrence. In terms of COVID-19 associated co-morbidity, the already dysregulated inflammatory state of BrCa patients may increase their susceptibility to cytokine-storm, leading to increased severity of COVID-related complications and increased mortality rate. Specifically, we hypothesize that the identified elevated level of IL-8 in BrCa patients may lead to a higher basal level of inflammation and contribute to the risk of attaining cytokine-storm during SARS-CoV-2 infection, making it a valuable target for future studies.
ABSTRACT
Background: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). Material(s) and Method(s): This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. Result(s): Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n = 6951;30.1%) followed by Klebsiella pneumoniae (n = 5801;25.1%) and Pseudomonas aeroginosa (n = 3041;13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. Conclusion(s): This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.Copyright © 2023 Indian Association of Medical Microbiologists
ABSTRACT
The new coronavirus was first reported in China and caused a widespread global outbreak of pneumonia that spread rapidly across this country and many other countries. Acute kidney injury is one of the important complications of COVID-19, which has been shown in some cases. Exploring the diagnostic features of biomarkers of kidney function in COVID-19 patients may lead to better patient management. We collected laboratory data from 206 people with confirmed COVID-19 disease and evaluated their renal biomarkers, Blood Urea Nitrogen (BUN), and creatinine. The age range of the patients was almost 62 years old. The mean age in the dead patients and recovered patients was 71 and 54 years old, respectively. The average LDH value was 755 U/L, and creatine phosphokinase (CPK) was 267 U/L in the patients. The average BUN was 59.1 U/L, and creatinine was 1.5 U/L in COVID-2019 patients. Among all 193 patients, laboratory results revealed that 163 (85.4%) patients had an elevated BUN level. Based on creatinine levels for total patients, laboratory results revealed that 49 (25.4%) patients had an elevated value. The average BUN value in dead patients was 85 mg/dL, while in recovered patients was 40.5 mg/dL (P<0.0001). Also, the average creatinine level in dead patients was 1.86 mg/dL, while in recovered patients was 1.24 mg/dL (P=0.0004). Inflammation following COVID-19 disease causes kidney damage and elevated urea and creatinine levels, which may increase the risk of death in these patients.Copyright © 2023 Tehran University of Medical Sciences.
ABSTRACT
Background: Cardiac arrhythias had a significant association with the increased mortality rate in COVID-19 patients in hospitals. The present study aimed to evaluate the frequency of supraventricular arrhythmias in COVID-19 patients and to assess the echocardiographic parameters and inflammatory biomarkers in COVID-19 patients who developed supraventricular arrhythmias. Method(s): This cross-sectional study enrolled 196 patients, 33 of them developed supraventricular arrhythmias during hospitalization in Zagazig University isolation hospital. Result(s): There was a statistically significant association between the occurrence of atrial fibrillation (AF) and both oxygen saturation and lymphocyte percentage, which was significantly lower in those with AF. There was a statistically significant association between the occurrence of AF and CORADS, C-reactive protein (CRP), and interleukin-6, which were significantly higher in those with AF. Younger age and higher oxygen saturation decreased the risk of supraventricular tachycardia among the studied patients. Increasing oxygen saturation decreased the risk of AF among the studied patients, while higher CRP significantly increased risk by 1.045 folds. Conclusion(s): Atrial arrhythmias, especially with AF considered prevalent in cases with COVID-19. The atrial arrhythmias were correlated with higher cardiac injury and inflammatory markers and elevated severe COVID-19 clinical manifestations. Regarding mortality in-hospital, the association between COVID-19 and atrial arrhythmias was independent. 2023 Journal of Indian College of Cardiology.Copyright © 2023 Intervention, Journal of Mental Health and Psychosocial Support in Conflict Affected Areas.
ABSTRACT
Objectives: Acute respiratory distress syndrome (ARDS) often results in high mortality and morbidity. Hemoadsorption therapy, such as CytoSorb©, is being increasingly used to target the underlying hyperinflammation that occurs with ARDS. This review aims to evaluate the available data on the use of CytoSorb in combination with veno-venous extracorporeal membrane oxygenation (V-V ECMO) in severe ARDS cases, and to assess its effects on inflammatory, laboratory, and clinical parameters, as well as on patient outcomes. Method(s): A systematic literature review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement. Whenever possible, an analysis of changes in relevant biomarkers and clinical parameters was performed. Result(s): CytoSorb© therapy was associated with significant reductions in circulating levels of C-reactive protein and interleukin-6 (p = 0.039 and p = 0.049, respectively), as well as an increase in PaO2/FiO2 levels (p = 0.028). There was also a trend towards reduced norepinephrine dosage (p = 0.067). Mortality rates in patients treated with CytoSorb©tended to be lower than in the control groups, but these studies had high heterogeneity and low power. In an exploratory analysis of 90-day mortality in COVID19 patients receiving V-V ECMO, the therapy was associated with a reduced risk of death. Conclusion(s): Overall, the reviewed data suggests that CytoSorb© therapy can effectively reduce inflammation and potentially improve survival in ARDS patients treated with V-V ECMO. Therefore, early initiation of CytoSorb ©in conjunction with ECMO may offer a promising approach to enhance lung rest and promote recovery in patients with severe ARDS. A randomised trial is warranted to confirm our findings.