Staging of COVID-19 disease, using selected laboratory profiles for prediction, prevention and management of severe SARS-CoV-2 infection in Africa-review

There are many uncertainties on the future management of the coronavirus disease 19 (COVID-19) in Africa. By July 2021, Africa had lagged behind the rest of the world in Covid-19 vaccines uptake, accounting for just 1.6% of doses administered globally. During that time COVID 19 was causing an average death rate of 2.6% in Africa, surpassing the then global average of 2.2%. There were no clear therapeutic guidelines, yet inappropriate and unnecessary treatments may have led to unwanted adverse events such as worsening of hyperglycemia and precipitating of ketoacidosis in administration of steroid therapy. in order to provide evidence-based policy guidelines, we examined peer-reviewed published articles in PubMed on COVID 19, or up-to date data, we focused our search on publications from 1st May 2020 to 15th July, 2021. For each of the studies, we extracted data on pathophysiology, selected clinical chemistry and immunological tests, clinical staging and treatment. Our review reports a gross unmet need for vaccination, inadequate laboratory capacity for immunological tests and the assess-ment of individual immune status, clinical staging and prediction of disease severity.We recommend selected laboratory tools in the assessment of individual immune status, prediction of disease severity and de-termination of the exact timing for suitable therapy, especially in individuals with co-morbidities.

Staging of COVID-19 disease, using selected laboratory profiles for predictionprevention and management of severe SARS-CoV-2 infection in Africa-review

There are many uncertainties on the future management of the coronavirus disease 19 (COVID-19) in Africa. By July 2021, Africa had lagged behind the rest of the world in Covid-19 vaccines uptake, accounting for just 1.6% of doses administered globally. During that time COVID 19 was causing an average death rate of 2.6% in Africa, surpassing the then global average of 2.2%. There were no clear therapeutic guidelines, yet inappropriate and unnecessary treatments may have led to unwanted adverse events such as worsening of hyperglycemia and precipitating of ketoacidosis in administration of steroid therapy. in order to provide evidence-based policy guidelines, we examined peer-reviewed published articles in PubMed on COVID 19, or up-to date data, we focused our search on publications from 1st May 2020 to 15th July, 2021. For each of the studies, we extracted data on pathophysiology, selected clinical chemistry and immunological tests, clinical staging and treatment. Our review reports a gross unmet need for vaccination, inadequate laboratory capacity for immunological tests and the assessment of individual immune status, clinical staging and prediction of disease severity. We recommend selected laboratory tools in the assessment of individual immune status, prediction of disease severity and determination of the exact timing for suitable therapy, especially in individuals with co-morbidities.Copyright © 2023 Sendagire H et al.

Changes in Diagnosis of Gestational Diabetes Mellitus during the Covid-19 Pandemic at a large Maternity Hospital in Southwest Ireland

Background Targeted screening for Gestational Diabetes Mellitus (GDM) occurs routinely at 24-28 weeks gestation using the oral glucose tolerance test (OGTT). During the COVID-19 pandemic, the Health Service Executive (HSE) and the Royal College of Obstetricians and Gynaecologists recommended discontinuing the OGTT to minimise hospital visits. Fasting plasma glucose (FPG), random plasma glucose (RPG), and glycated haemoglobin (HbA1c) were instead proposed for diagnosing GDM. This study retrospectively compared testing patterns and putative diagnostic rates for GDM in pregnancies using the HSE guidelines pre- and post-pandemic. Methods Pregnancies with complete gestation in the 18 months before (Group1) or 18 months after (Group2) adoption of revised HSE guidance at CUMH (01/05/2020) were included. Women with pre-existing diabetes mellitus were excluded. Results were extracted from databases at the Departments of Clinical Biochemistry and Haematology at CUH. Diagnostic cut-offs for GDM were: OGTT (FPG >=5.1 mmol/L or 2-h plasma glucose >=8.5 mmol/L), FPG (>=5.1 mmol/L), RPG (>=9 mmol/L), and HbA1c (>=39 mmol/mol). Diagnostic rates were compared using Chi-square analysis. The study was approved by the Cork Teaching Hospitals Clinical Research Ethics Committee. Results In Group1, 43.8% of 6,737 pregnancies had an OGTT, compared with 20.5% of 6,743 pregnancies in Group2. After implementing the revised guidelines, OGTT requests were 34.5% and 79.7% lower for primary and secondary care, respectively. Comparing Group1 with Group2, FPG was measured in 46.9 vs 49.8%, RPG in 13.3 vs 11.8%, and HbA1c in 23.7 vs 51.9%. The positive rate for GDM testing was 15.9% in Group1 and 22.0% in Group2 (p<0.00001). Conclusions OGTT use fell significantly with revised HSE guidelines, although only a modest reduction was observed in primary care. HbA1c use in pregnancy doubled during the pandemic. The proportion of pregnancies with biomarkers positive for GDM showed a small but significant increase upon adopting the new diagnostic guidelines.

Investigation of the Formal Pathogenesis of Green Liver Discoloration in Organically Reared Female Bronze Turkeys (Melleagris gallovapo).

Green liver discoloration (GL) in fattening turkeys is suspected to be a multifactorial disease complex with a compromised immune system as the key factor. This study aimed to identify the formal pathogenesis of GL and to investigate possible nutritional influences. A total of 360 Bronze turkey hens out of 10 flocks from 5 fattening farms were necropsied for detection of GL during 2 consecutive trials on 2 examination dates each (70th to 75th and 120th to 127th day of fattening, respectively). At each examination date, hematological and clinical chemistry analyses, as well as determination of vitamin E and selenium concentrations in the liver, were carried out in 6 hens with (if applicable) and 6 hens without GL, representing a total of 130 individuals. Raw nutrient, energy, amino acid, bulk and trace element, and vitamin E and D3 concentrations were analyzed in feed samples for each of the five feeding phases during each trial. The results of the hematological analyses, clinical chemistry analyses, and determination of vitamin E and selenium liver concentrations were statistically evaluated between: (i) individuals with and without GL, and (ii) individuals from flocks with and without turkeys with GL. At both fattening stages, the occurrence of GL was characterized by an inflammatory reaction. A subacute inflammatory reaction was detected in the early fattening stage, indicating a viral cause of the disease. In the late fattening stage, acute inflammation indicated a bacterial cause of the disease. The results of the feed sample analyses of the different flocks were generally quite homogeneous. However, the nutrient and energy content of the feed likely contribute to GL pathogenesis.

Association of Interleukin-6 (IL-6) and High-Density Lipoprotein Cholesterol (HDL-C) with Disease Severity of Coronavirus Disease 2019 (COVID-19)

Introduction: IL-6 is the key molecule of cytokine storm in COVID-19. Dyslipidemia is a common complication in patients with Coronavirus disease 2019 (COVID-19), but the association of dyslipidemia with the severity of COVID-19 is still unclear. In this study, we aimed to investigate the biochemical alterations of High-Density Lipoprotein Cholesterol (HDL-C), and Interleukin-6 (IL-6) in COVID-19 patients and their relationships with the disease severity. Material(s) and Method(s): We conducted a retrospective single-institutional study of 99 consecutive confirmed cases of COVID-19. Serum IL-6 and HDL-C concentrations, demographic and clinical profile were collected during hospital stay. Duration of study was from September 2020 to August 2021. Descriptive statistics were applied to summarize the demographic data. Results are reported as mean with standard deviation. Receiver operating characteristic curve (ROC) analysis was used to compare biochemical markers. Result(s): Serum HDL-C levels had a significant positive correlation with SpO2 with correlation coefficient r = 0.589. Serum IL-6 had a negative correlation with SpO2 with correlation coefficient r =-0.632. The AUC for IL6 and HDL-C in predicting COVID severity is 0.982 and 0.985 respectively. Conclusion(s): HDL-C is decreased and IL-6 is increased with the disease severity.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Lactate and D-Dimer levels in acute pulmonary embolism and COVID-19 Lactate and D-Dimer in COVID-19

Aim: This study aimed to compare clinical data and laboratory results in patients examined for suspected pulmonary embolism (PE) in the emergency department based on three groups: patients with coronavirus disease-2019 (COVID-19), patients with PE and patients with both COVID-19 and PE. Material(s) and Method(s): This retrospective study was approved by the local ethics committee of the university. Patients included in the study were divided into three groups: Group 1, consisting of COVID-19-polymerase chain reaction (PCR) (negative) and PE (positive) patients;Group 2, consisting of COVID-19-PCR (positive) and PE (negative) patients, and Group 3, consisting of COVID-19-PCR (positive) and PE (positive) patients. Result(s): The three patient groups included in the study had no difference in terms of age (p = 0.916) or sex. The laboratory results of the groups were compared using the Kruskal-Wallis test, which showed significant differences in the levels of white blood cells (p = 0.005), lymphocytes (p < 0.001), neutrophils (p = 0.016), D-Dimer (p < 0.001) and lactate (p = 0.001). Receiver operating characteristic curve analysis with a cut-off value of >2590 for D-Dimer showed 71.43% specificity and 78% sensitivity in differentiating Group 1 from Group 2, and with a cut-off value of >3640, it had 80% specificity and 81.82% sensitivity in differentiating Group 3 from Group 2. Discussion(s): COVID-19 leads to increased incidence of PE. In addition to clinical data, D-Dimer and lactate levels can be used in the differentiation of these patients.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Association of immature granulocytes (IG) with prognosis in severe COVID-19 patients Immature granulocytes and COVID-19

Aim: Recent research have shown that immature granulocytes (IG) can be utilized to predict severe infection, inflammation, and sepsis. As a result, the ability of IG levels to predict the severity of severe COVID-19 and its association with prognosis were studied in our study. Material and Mthods: A total of 317 patients diagnosed with severe COVID-19 in the emergency department were analyzed retrospectively. IGC and IG% levels were compared statistically between patient groups (survivors and non-survivors, those who received and did not get mechanical ventilation (MV) assistance, patients who required and did not require vasopressors, and hospital stays >=10 and <10 days). Result(s): When compared to patients who survived but did not get treatment, non-survivors who got MV and vasopressor support had substantially higher IGC and IG% values (for all p<0.001). Additionally, it was shown that the IG% of patients with hospital stays of >=10 days was substantially greater than that of patients with hospital stays of <10 days (p<0.001). While the IG% cut-off value was >0.45, it reached 75.5% sensitivity, 81.9% specificity, 87.6% NPV and 66.4% PPV for predicting mortality (AUC:0.86, p<0.001). Discussion(s): IG levels are a low-cost, easily accessible, and strong marker that may be used to predict mortality and prognosis in COVID-19 patients.Copyright © 2023, Derman Medical Publishing. All rights reserved.

Altered lipid profile in patients with COVID-19 infection

Background: In this study, we aimed to investigate the pathological alterations of LDL-cholesterol, HDL-cholesterol, total cholesterol and triglycerides in COVID-19 patients during the acute phase of infection, and after recovery. Method(s): A retrospective study was performed to examine serum levels of LDL-cholesterol, HDL-cholesterol, total cholesterol and triglycerides on 55 COVID-19 patients who were hospitalized in our center between February and April 2020. The lipid profile and the hematological parameters were analyzed in the same group of patients before (Group before) and after clinical management (Group after). The laboratory tests results were compared between these two groups, as well as with a group of healthy subjects (Healthy controls), matched for age and sex and selected among the blood donors. Result(s): LDL-cholesterol, HDL-cholesterol, total cholesterol levels were significantly lower in COVID-19 patients (Group before) as compared with normal subjects (P<0.0001). Comparing healthy controls and the group after, statistically significant differences were observed for all parameters except for total cholesterol (P=0.9006). Total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride were found to be significantly higher after recovery than during the acute phase of infection (P<0.0001). C-reactive protein levels were found to be inversely correlated with those of LDL-cholesterol (rs =-0573, P<0.0001), total cholesterol (r=-0.732, P<0.0001), and HDL-cholesterol (r=-0.700, P<0.0001). Conclusion(s): The results of our study seemingly attest that lipids, especially cholesterol, may play an important role in viral replication, internalization and immune activation in patients with COVID-19 infection. Moreover, lipid abnormalities observed during and after this infection could be used for assessing indirectly the response to clinical treatment.Copyright © Journal of Laboratory and Precision Medicine. All rights reserved.

Validating a clinical laboratory parameter-based deisolation algorithm for patients with COVID-19 in the intensive care unit using viability PCR: the CoLaIC multicentre cohort study protocol.

INTRODUCTION: To investigate whether biochemical and haematological changes due to the patient's host response (CoLab algorithm) in combination with a SARS-CoV-2 viability PCR (v-PCR) can be used to determine when a patient with COVID-19 is no longer infectious.We hypothesise that the CoLab algorithm in combination with v-PCR can be used to determine whether or not a patient with COVID-19 is infectious to facilitate the safe release of patients with COVID-19 from isolation. METHODS AND ANALYSIS: This study consists of three parts using three different cohorts of patients. All three cohorts contain clinical, vital and laboratory parameters, as well as logistic data related to isolated patients with COVID-19, with a focus on intensive care unit (ICU) stay. The first cohort will be used to develop an algorithm for the course of the biochemical and haematological changes of the host response of the COVID-19 patient. Simultaneously, a second prospective cohort will be used to investigate the algorithm derived in the first cohort, with daily measured laboratory parameters, next to conventional SARS-CoV-2 reverse transcriptase PCRs, as well as v-PCR, to confirm the presence of intact SARS-CoV-2 particles in the patient. Finally, a third multicentre cohort, consisting of retrospectively collected data from patients with COVID-19 admitted to the ICU, will be used to validate the algorithm. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethics Committee from Maastricht University Medical Centre+ (cohort I: 2020-1565/300523) and Zuyderland MC (cohorts II and III: METCZ20200057). All patients will be required to provide informed consent. Results from this study will be disseminated via peer-reviewed journals and congress/consortium presentations.

Central role of laboratory medicine in public health and patient care.

Clinical laboratories play a vital role in the healthcare system. Objective medical data provided by clinical laboratories supports approximately 60-70% of clinical decisions, however, evidence supporting this claim is poorly documented and laboratories still lack visibility, despite their indisputable impact on patient care and public health. The International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Outcome Studies in Laboratory Medicine (TF-OSLM) was recently developed to support directed research evaluating the role of laboratory medicine on clinical outcomes. Establishing and documenting this evidence is key to enhance visibility of the field in the eye of the public and other healthcare professionals together with optimizing patient outcomes and health care system operations. In this review, we discuss four areas that exemplify the contribution of laboratory medicine directly to patient care. This includes high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptides (NT-proBNP/BNP) for the diagnosis and prognosis of myocardial infarction and heart failure, respectively, and procalcitonin for the management of sepsis and antibiotic stewardship. Emerging markers of traumatic brain injury and the role of laboratory medicine in the fight against the COVID-19 pandemic are discussed along with an introduction to plans of IFCC TF-OSLM.

Could tear be an alternative specimen for SARS-CoV-2 detection?

Objectives: For a definitive diagnosis of COVID-19, respiratory tract samples are evaluated by polymerase chain reaction (PCR). In our study, PCR using a tear sample was used to diagnose COVID-19, and it was questioned whether it was a screening method. Unlike the general practice, Schirmer strips were used instead of a swab for tear sample collection in this study. In addition, the diagnostic values of serum procalcitonin (PCT), C-reactive protein (CRP), and Neutrophil (NEU) count in predicting COVID-19 disease from tears were also questioned. Method(s): A total of 94 patients who were positive for COVID-19 by PCR test were included in this study. Tear samples were obtained from patients with Schirmer strips, commonly used in eye examination, and studied with the PCR technique. CRP, PCT value, and NEU count were also compared between the positive and negative groups of the PCR. The obtained data were analyzed using the R Studio software, and the results were considered statistically significant for p<0.05. Result(s): Of these patients, 61 (64.9%) tear PCR was negative, and 33 (35.1%) tear PCR was positive. The mean age was 61.72 +/- 17.62 years. The patients were divided into two groups: tear PCR positive and negative. There was no significant age difference between these groups. As a result of ROC Analysis;When serum PCT, CRP, and NEU % values were examined in predicting COVID-19 disease from tears, it was seen that CRP (p=0.027) and especially PCT (p=0.003) values of patients with PCR-positive were significantly higher. Conclusion(s): PCR study on tears collected with Schirmer strips is a different and non-invasive method, but it was concluded that the proposed method could not be used as a screening test. In addition, significantly higher serum PCT values were found in patients with COVID-19 positivity in tears (p<0.05). Copyright © 2022 the author(s), published by De Gruyter.

The importance of LDH/Albumin, LDH/Lymphocyte, and LDH/Platelet ratios in the evaluation of COVID-19 B.1.1.7 variant

Objectives: The aim is to investigate the usefulness of lactate dehydrogenase (LDH)/Albumin, LDH/Lymphocyte and LDH/Platelet ratios on the prognosis of coronavirus disease (COVID-19) Alpha (B.1.1.7) variant pneumonia. Method(s): A total of 113 patients who were diagnosed with COVID-19 pneumonia and 60 healthy control group were included in this study. The cases were divided into 2 as classic COVID-19 group, and COVID-19 B.1.1.7 variant group. Complete blood count (CBC) and biochemical parameters of the patients were analyzed retrospectively. Patients with COVID-19 B.1.1.7 variant group were also grouped according to the length of stay in the hospital and the days of hospitalization. Result(s): LDH/Albumin, LDH/Platelet, and LDH/Lymphocyte ratios were found to be higher in COVID-19 B.1.1.7 variant group when compared to the control group (p<0.001). The ferritin, neutrophils/lymphocyte (NLR) ratio, procalcitonin (PCT) and LDH/Albumin had the highest area under the curve (AUC) values in the COVID-19 B.1.1.7 variant group (0.950, 0.802, 0.759, and 0.742, respectively). Albumin, Lymphocytes and hemoglobin values were significantly higher in the COVID-19 B.1.1.7 variant group than in the classic COVID-19 group (p<0.05). Conclusion(s): LDH/Albumin and LDH/Lymphocyte ratios may be useful for clinicians in predicting the risk of progression to pneumonia in COVID-19 B.1.1.7 variant patients. Copyright © 2022 the author(s), published by De Gruyter.

Association of Lactate Dehydrogenase and C-reactive Protein Levels as Predictors of Respiratory Failure in Covid-19

Background and Aim: Inflammatory markers reproduce amount of disease development or revival. They are used to assess improvement or worsening of the illness. Hence the aim of the study was to determine the correlation of laboratory markers (LDH and CRP) and oxygen requirement with clinical severity in Covid 19 subjects. Material(s) and Method(s): There were 216 subjects admitted to the emergency department of the hospital. The incorporated subjects were divided into two groups: group I subjects had covid19 pneumonia and in group 2 subjects did not have covid 19 pneumonia. Blood count and serum values of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were quantified in all subjects enrolled in the research. An automated hematology analyzer was utilized to perform blood count according to the manufacturer's protocol. Serum samples were analyzed on a fully automated clinical chemistry Instrument. Result(s): LDH was amplified in 82% of subjects, CRP resulted elevated in 98% of subjects, only 21% of subjects presented pathological values of white blood cell (WBC), but 18% had a neutrophils count above the upper normal range value, while 89% of subjects had lymphocytes count below the lower normal range value, as formerly reported. Conclusion(s): LDH and CRP could be helpful for the premature identification of subjects who are at elevated risk for acute respiratory failure. They should be considered a helpful test for the early recognition of subjects who need closer respiratory monitoring and more aggressive supportive therapies to avoid poor prognosis. These subjects could be benefited from a quick hospitalization, a closer observation and correct treatments. Copyright © 2022, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Correlation between Clinical Features and Immunological Parameters with Viral Load in Hospitalised Covid Positive Patients

Background: COVID has caused a worldwide pandemic and brought the countries to a halt. It is not only a disease of the respiratory system but the entire body. RT-PCR remains the main stay of diagnosis for COVID, limited study has been done in terms of usability of cycle threshold (CT) values for understanding the severity of the disease. This study was done to find association between CT values, clinical features and biomarkers Material(s) and Method(s): this is an observational study done between November 2022 to October 2022. A total of 200 cases were studied. RT-PCR was performed using Quant studio 12K flex system. Biomarker estimation was done on Architect c8000 Results: A total of 200 cases studied. 43.28% cases had low CT value in E gene and 40.79% cases in RdRp gene. The predominant symptom noted in our study is breathlessness. No statistical correlation was made between CT values and clinical symptoms and also no statistical correlation was made between biomarkers. Conclusion(s): COVID RT-PCR is the gold standard diagnostic method but the viral load cannot be used as a prognostic marker because the sample collection technique is not standardised across the board and also the quantity of sample obtained during nasopharyngeal swabbing varies. Further studies and establishment of standardised protocols can bring about a usability for the CT values. Copyright © 2022 Ubiquity Press. All rights reserved.

Quality improvement of outpatient clinical chemistry tests through a novel middleware-laboratory information system solution.

OBJECTIVES: Rapid and accurate laboratory tests are essential to support clinical decision-making. Despite the various efforts to control quality in the laboratory, our outpatient chemistry turnaround time (TAT) has deteriorated since 2018. Moreover, these difficulties have accelerated further due to the COVID-19 pandemic. Therefore, we aimed to improve laboratory work efficiency by identifying and eliminating the causes of reduced laboratory work efficiency. DESIGN & METHODS: We surveyed to identify tasks that reduce work efficiency. Based on our survey, a new-concept of work assistance middleware linked to laboratory information system (LIS) was developed. The middleware supports test end-time prediction, automatic real-time TAT monitoring, and urgent test requests so that medical technologists can focus on their chemistry tests. The developed middleware was used for 6 months in laboratory and outpatient clinics, and its effectiveness was evaluated. RESULTS: The median TAT for outpatient chemistry tests was reduced by 6.6 min, from 72.4 min to 65.8 min. And not only did the maximum TAT for the sample decrease from 353 min to 214 min, but the proportion of samples exceeding the TAT target (120 min) also decreased by 77%; from 2.00% in 2010 (1,905 out of 94,989 samples) to 0.46% in 2021 (453 out of 98,117 samples). 2,199 samples were urgently requested through middleware, and they were processed about 15% faster than other samples, effectively performing urgent tests. The test end-time prediction showed an error of 8.6 min in the evaluation using the MAE (Mean Absolute Error) index. CONCLUSIONS: Through this study, the quality and efficiency of the laboratory were improved, and while reducing the workload of medical staff, it contributed to enhancing patient safety and satisfaction.

PHASE 1b STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI-HEPATITIS B VIRUS (HBV) ACTIVITY OF NCO-48 FUMARATE (NCO48F), A NOVEL LIVER-TARGETED PRODRUG (LTP) OF TENOFOVIR (TFV), IN TREATMENT-NAIVE ADULTS WITH CHRONIC HBV INFECTION

Background: TFV is a nucleotide analogue whose active form, TFV diphosphate (TDP), inhibits reverse transcription of hepatitis B virus (HBV) and is the active metabolite of HBV treatment TFV alafenamide (TAF). NCO-48F is a novel TFV prodrug designed to increase the liver concentration and maximize efficacy and/or potency while reducing drug exposure outside of the liver. NCO-48F is expected to minimize kidney and bone toxicity by reducing systemic exposure of TFV. Method(s): Safety, tolerability, pharmacokinetics (PK), and anti-HBV activity of multiple daily oral doses of 4 and 20 mg of NCO-48F, compared with 25 mg TAF, were evaluated in a randomized, open-label, active-controlled, parallel-assignment study in adult subjects with treatment-naive HBV infection (3 groups of 8 subjects each). Each subject was administered NCO-48F or TAF daily for 28d and followed for 28d after the last dose. Result(s): Preliminary data from 12 subjects (4 subjects/group) were available for analysis. NCO-48F at 4 mg and 20 mg and TAF were safe and well tolerated. No subjects had a serious adverse event (AE) or were discontinued due to an AE. There were no clinically significant or dose-dependent changes in hematology, clinical chemistry, urinalysis, electrocardiograms, or vital signs. One treatment-emergent AE was reported by 1 NCO-48F 4 mg subject (COVID-19 infection) which was not considered drug-related. NCO-48F was orally absorbed with Cmax observed within 30 minutes. NCO-48F was metabolized to TFV and rapidly cleared. Minimal urinary excretion of intact NCO-48F was detected, consistent with conversion to TFV. TFV Cmax was observed within one hour of NCO-48F administration, a faster uptake than observed after TAF administration. TFV elimination kinetics appeared similar after administration of either NCO-48F or TAF. Plasma concentrations of NCO-48F and TFV increased approximately dose proportionately. Over 28d of treatment, declines in serum HBV DNA levels (log10 IU/mL) were observed among all dose groups, and mean changes in HBV DNA at day 28 were -2.12 and -3.29 for NCO48F 4 mg and 20 mg, and -3.27 for TAF. Three subjects treated with NCO48F 20 mg had levels below limit of quantitation during treatment, and recovery of HBV DNA levels was slower during the follow- up period compared to subjects treated with TAF. Conclusion(s): NCO-48F is a promising agent for the treatment of HBV, demonstrating excellent safety and PK properties, and declines in HBV DNA comparable to TAF.

Effect of the Seraph 100 Biomimetic Pathogen Adsorbing Device on Inflammatory Biomarkers in 42 COVID-19 Patients

Background: Lack of pharmacological treatment options in severely ill hospitalized COVID-19 patients prompted explorations of extracorporeal treatments. The Seraph 100 Microbind Affinity filter, remove viruses, including SARS-CoV-2 from the blood. Data from an international registry, from a multicenter evaluation in the US, as well as from several case reports suggest that Seraph 100 can not only be safely used but it may have an impact on patient centered outcome parameters. As it is unknown whether the effect of the Seraph 100 in COVID-19 patients is solely based on the removal of the virus or, as suggest by a recent observation, by additionally modulating inflammation, we set out to perform a biomarker study. Method(s): We performed this prospective multicenter observational trial at three tertiary care hospitals in patients being treated with Seraph 100 for severe COVID-19 between June 2020 and April 2021. Biomarkers were obtained before the tretment as well as 2-4 hours after the treatment. as well as 4 days after the Seraph 100 treatment. Routine clinical chemistry parameters were performed in the respective clinical chemistry labs using certified methods. For the assessment of the inflammatory markers a Bio-Plex Pro Human Cytokine Screening Panel, 48-Plex #12007283 (Bio-Rad) was used. Result(s): From June 1st 2020 to April 1st 2021, 42 patients with COVID-19 treated with the Seraph 100 in our hospitals could be included in the study. Hemoperfusion treatment was initiated in median 3 days after hospital admission. At beginning of the treatment 41/42 (98%) of patients were in the ICU;8/42 (19%) needed mechanical ventilation, 3/42 (7%) were on additional ECMO support;27/42 (64%) needed pressors. Seraph 100 treatment significantly reduced d-dimer comparing pre-treatment data with data obtained 2-4 hours after treatment Four days after treatment hemoglobin, LDH, D-dimer, troponin and ferritin were significant reduced. From the interleukin assay IL-1b, IL8, IL-10, IL-13, IL-15, Eotaxin, G-CSF and IP-10 were significantly reduced 2-4 hours after treatment, but not 4 days later. The median hospital stay was 20 days. After 3 months 20/42 (48%) of patients had died. Conclusion(s): In conclusion, our data show that Seraph 100 leads to a significant reduction of biomarkers that are either predictive of adverse outcome or the severity COVID-19.

A comparative evaluation of six sigma metrics and quality goal index ratio 3 months prior to first lockdown due to COVID-19 pandemic and 3 months during lockdown in a NABL accredited central laboratory

Introduction and Aim: Sigma represents Standard Deviation (SD) which indicates the degree of variation in a process, where the higher sigma value implies that less likely the laboratory reports false test results. Using a newer parameter called Quality Goal Index (QGI) we can find the reason behind the lower sigma value. Our study aimed to compare the six-sigma metric and QGI ratio 3 months prior to first lockdown due to COVID-19 pandemic and 3 months during the first lockdown. Methodology: A retrospective study was used to compare the six-sigma metric and QGI ratio 3 months prior to first lockdown due to COVID-19 pandemic and 3 months during the first lockdown for the selected ten analytes from 1st of January 2020 to 30th of June 2020 from the clinical biochemistry section of Yenepoya Medical College Hospital, Deralakatte, Mangalore. Result(s): The sigma metrics from January to March (level 1) indicated that urea, TSH, beta-HCG fell short of meeting Six Sigma quality performance and from April to June, glucose, creatinine, urea and ALT had metrics less than 3 at both the Internal Quality Control levels. QGI ratio indicated that from January to March, the problem was imprecision for urea, TSH and beta-HCG (QGI < 0.8). From April to June, urea and creatinine showed imprecision, glucose and ALT showed inaccuracy, urea and ALT showed both imprecision and inaccuracy. Conclusion(s): This study highlights the necessity for stringent Internal Quality Control and External Quality Assurance monitoring even during the lockdown period of the pandemic. By implementing six sigma and finding QGI ratio, quality of laboratory services can be improved immensely. Copyright © 2022, Indian Association of Biomedical Scientists. All rights reserved.

Virtual assessment, training, and evaluation of clinical laboratory technologists amidst peak Covid-19 pandemic: An observational study.

Medical technologists are considered a neglected group when it comes to academic interventions. We developed and implemented an educational intervention and assessment for the technologists based on an online questionnaire as a pre-test consisting of questions related to knowledge (n=5), attitude (n=3), and practices (n=4) of daily internal quality control (QC) monitoring via Google Docs survey tool. This study served multiple purposes. It allowed keeping the technologists engaged during the peak of the COVID-19 pandemic while also improving the knowledge, attitude, and practices about the internal quality control using Bio-Rad Unity Real Time (URT) QC software. Subjects were graded based on the scores they received out of 100 (0-60 = poor; 61-79 = good; 80-100 = excellent). Training materials, i.e., a set of 5 videos every week via e-mail, were circulated. A voice-over PowerPoint presentation was also shared for easy comprehension. This activity was repeated after one month. A post-test was administered to assess the improvement. The study results show significant improvement in the technologists' performance after the intervention.

Trajectories of UCR as a measure of biological mechanisms underlying ethnicity associated outcomes in COVID-19

Introduction: Patients with Black and Asian ethnic background have been disproportionately affected by COVID-19 with increased disease severity, organ failure, intensive care admission, and premature mortality. 1-3 The urea-to-creatinine ratio (UCR) has been described as a biochemical signature of persistent critical illness, its hallmark catabolic state and late mortality during prolonged ICU stay.4 Low serum creatinine reflecting reduced muscle mass, which declines rapidly in acute severe illness in combination with net muscle protein breakdown which contribute substrate for increased hepatic urea synthesis, results in markedly elevated UCR. Objectives: To assess UCR as a candidate biological feature driving ethnicity associated outcomes of COVID-19 disease. Methods: Prospective analysis using registry data from all patients aged ≥16 years with an emergency admission to hospitals within Barts Health NHS Trust with SARSCoV-2 infection during 1 January 2020 - 13 May 2020 (wave 1), and 1 September 2020 -17 February 2021 (wave 2). Trajectories of routine haematology and clinical biochemistry blood results during hospital admission were assessed, and distinct phenotypes defined using unsupervised longitudinal clustering techniques using day 0 to 15 results.We determined distribution of identified phenotypes within patients categorised by ethnic group. Multivariable logistic regression accounting for predefined baseline risk factors was used to assess association between ethnicity, phenotypes, and 30-day mortality. All analyses were performed using R software v4.02 and the kml package for clustering. 5 Results are presented as n (%) and adjusted odds ratios (OR) with 95% confidence intervals. Results: We assessed 459 (wave 1) and 1337 (wave 2) patients after excluding those with unknown ethnicity and those with <7 blood results. Three clusters were identified based on trajectories of UCR. In wave 1, 48.1% of patients had persistently low levels of UCR (A), 38.6% had higher but stable levels (B), and 13.3% had the highest levels peaking after day 7 (C). In wave 2, three clusters were identified in similar proportions: 42.8% (a), 45.1% (b), 12.1% (c). In wave 1, patients in cluster C compared to A had the highest risk of death at 30 days (OR 4.59 [2.27-9.26], p<0.001). In wave 2, both clusters b (OR 1.58 [1.18-2.12], p< 0.001) and c (OR 3.96 [2.62-5.99], p<0.001) had higher risk of death compared to a. Distribution of cluster membership varied by ethnic category. In both waves, greater proportions of patients within cluster A/a were observed in patients with Black ethnicity (65.5% wave 1, 61.1% wave 2) compared to Asian (50.0% wave 1, 37.3% wave 2) and White (39.7% wave 1, 39.6% wave 2) ethnicity. Black ethnicity patients also had lowest proportions in cluster C/c (6.9% wave 1, 6.3% wave 2) compared to Asian (17.4% wave 1, 14.2% wave 2) and White (13.2% wave 1, 12.9% wave 2) ethnicity. Inclusion of UCR trajectory attenuated the higher risk of death seen in Asian patients in wave 1. Conclusion: Phenotypes based on UCR trajectories during hospital admission are associated with adverse outcomes following COVID-19 infection. Further work is needed to understand phenotypes of prolonged COVID-19 disease muscle wasting and its association with longerterm outcomes.