LabMedica International July 2020

WORLD’S CLINICAL LABORATORY NEWS LEADER ISSN 1068-1760

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Blood Test for Earlier GI Cancer Detection

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astrointestinal cancer refers to malignant conditions of the gastrointestinal (GI) tract and accessory organs of digestion, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. Cancers of the esophagus,

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Modular Targeted Capture Assay Detects Clinically Significant Oncology Alterations

he rapid discovery of clinically significant genetic variants has translated to next-generation sequencing assays becoming out-ofdate by the time they are designed, validated, and implemented.

The need to comprehensively assess clinical cancer specimens

for an expanding list of alterations critical to therapeutic decision making led to the adoption of large “fixed-content” genetic panels that utilized massively parallel sequencing, more commonly referred to as next-generation sequencing (NGS).

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COVID-19: Six Months into Pandemic Widespread Testing Remains Global Priority

See article on page 4

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wo newly introduced ELISA kits provide cost-effective solutions to SARS-CoV-2 testing.

ErbaLisa IgG and ErbaLisa IgM antibody kits have been developed and manufactured in California by Calbiotech (El Cajon, CA; www.calbiotech.com) the imunoassay focused affiliate of the Erba Mannheim group (London UK; www.erbamannheim.com).

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Genetic Biomarkers Detect Incipient Tuberculosis, Predict Progression of the Disease

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panel of genetic biomarkers in samples of whole blood has been confirmed as a useful biomarker for the detection of incipient tuberculosis (TB).

Incipient TB is an infection with viable Mycobacterium tuberculosis bacteria, which is like-

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Blood Test Predicts Parkinson's Progression

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t is well established that the cumulative incidence of dementia associated with Parkinson’s disease (PD) is approaching 80% and individuals with PD are five to six times more likely to develop cognitive impairment than agematched controls.

The causes for dementia in PD (PDD) are heterogeneous, complex and not fully understood.

The development of biological

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Clinical lab team from India appearing in IFCC Young Scientists video on COVID-19 testing across the world (see story on Page 37).

Affordable COVID-19 Panel Aims to Serve Emerging Countries

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Diagnostic Assay for leukemic Stem Cells

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ased on the two key disciplines at the foundation of SARS-CoV-2 testing – Molecular Diagnostics (primarily PCR) and Serology (ELISA, rapid tests, IFA) – on the half-year mark of the pandemic, the industry rush to develop, produce and distribute effective diagnostic solutions continues unabated. Our LabMedica Special Report provides a comprehensive update on latest developments.

DAIly ClINICAl lAB NEWS

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A LabMedica Special Report

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ly to progress to active disease in the absence of further intervention but has not yet induced clinical symptoms. Investigators at University College London (UK; www.ucl.ac.uk) sought to identify which, if any, gene expression signatures in blood could be used Cont’d on page 33

cute myeloid leukemia (AML) is the most common type of leukemia in adults. It is characterized by the pathological expansion of immature cells (myeloblasts) that invade the bone marrow and expand into the blood, affecting the production of the rest of the healthy cells.

Although AML patients usually respond well to chemotherapybased treatments, large proportion of them eventually relapse or Cont’d on page 25

INSIDE

Covid-19 Update . . . . . . 4 Clinical News . . . . . . . . . 8 IFCC News . . . . . . . . . . 37 Product News . . . . . 6-26 Events Calendar . . 42-43 PUBLISHED IN COOPERATION WITH

International Federation of Clinical Chemistry and Laboratory Medicine

GlOBETECH >>> MEDIA <<<

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Multiplex Nested Polymerase Chain Reaction Developed for Congenital Infections

To view this issue in interactive digital magazine format visit www.LinkXpress.com

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nfections are the leading cause of perinatal mortality in low- and middle-income countries, which have a higher prevalence of infections, and are responsible for 50% of infant deaths in the first year of life. Definitive diagnosis of congenital and perinatal infections is largely dependent upon the results of laboratory tests.

The finding of positive maternal immunoglobulin M (IgM) antibodies raised to a certain pathogen in the prenatal serologic screening raises the suspicion of a congenital infection, but the pathogen may not cross the placenta. On the other hand, a positive polymerase chain reaction (PCR) result on amniotic fluid (AF) samples confirms the diagnosis.

Scientists at the University of SĂŁo Paulo (SĂŁo Paulo, Brazil; www.fmrp.usp.br) developed a multiplex nested PCR technique for the simultaneous detection of seven pathogens containing DNA in their genomes in suspected cases of congenital infection. Eligible participants were pregnant women with positive IgM antibodies raised to one of the pathogens in the prenatal serologic screening, associated or not with fetal ultrasound abnormalities or positive fetal serology. Neonates whose mothers did not attend prenatal care were included when they presented with symptomatology and laboratory parameters suggestive of infection. The detection rate of the multiplex nested PCR was compared with maternal, fetal, and neonatal serology, as well as placental immunohistochemistry and noncommercial amplifications.

Laboratory examinations included blood count showing leukocytosis or leukopenia, neutropenia, thrombocytopenia, or increased serum C-reactive protein (CRP ultrasensitive kit, Turbitest AA, Wiener Lab, Rosario, Argentina; www.wiener-lab.com.ar). Maternal and neonatal serum samples were tested by the AxSYM (Abbott Laboratories, Abbott Park, IL, USA; www.abbott.com) assay based on microparticle enzyme immunoassay technology to assess Toxoplasma gondii IgM and IgG. Herpes simplex, varicella-zoster virus (VZV), and parvovirus B19 (PV) IgM and IgG antibodies were evaluated by the Liaison chemiluminescent assays (DiaSorin Ltd, Saluggia, Italy; www.diasorin.com). The second-round PCR product was submitted to DNA sequencing on the ABI PRISM 3500 Genetic Analyzer Platform, (Applied Biosystems, Foster City, CA, USA; www.thermofisher.com) to confirm that the multiplex nested PCR amplified products actually belonged to the detected pathogens.

The scientists reported that of 161

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suspected cases, the multiplex nested PCR detected 60 (37.3%), whereas the tests available in hospital laboratories detected 13 of 60 (21.7%) of the cases detected by the multiplex nested PCR, demonstrating a 4.6 times higher detection rate for the multiplex nested PCR. Positive amplifications were to T. gondii (32 cases), cytomegalovirus (14 cases), parvovirus B19 (five cases), and adenovirus (five cases). In four cases, two pathogens were simultaneously detected.

All types of biological matrices were suitable for amplification. Sequencing of multiplex nested PCR products confirmed the molecular findings.

The authors concluded that the multiplex nested PCR significantly increased the number of diagnosed congenital infections. Given the scarcity of DNA recovered from amniotic fluid

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LabMedica International

and some neonatal samples, this multiplex nested PCR allows the simultaneous detection of seven pathogens associated with congenital infections in a reliable, faster, cost-effective, and more sensitive way. The study was published in the January 2020 issue of the journal Archives of Pathology and Laboratory Medicine.

Image: The ABI PRISM 3500 Genetic Analyzer Platform (Photo courtesy of Applied Biosystems)

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COVID-19 Special Report: Six Months into Pandemic Widespread Testing Remains a Global Priority

LabMedica International

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s clinical laboratories and healthcare institutions around the world rush to order large volumes of COVID-19 diagnostic products, the IVD industry appears to have entered a phase of unprecedented expansion in a race to meet exploding global demand.

The LabMedica Special Report that follows, provides a survey of major developments from mid-May until the end of June in 2020. For a recap of earlier developments, the reader is invited to refer to previous issues of LabMedica.

Roche’s New Blood Gas Digital Solution for COVID-19 Patients

Roche (Basel, Switzerland; www.roche. com) has launched Roche v-TAC, a digital diagnostic solution that allows clinicians to obtain results for arterial blood gas values from patients with respiratory or metabolic abnormalities via a simpler, less invasive venous puncture through the use of a digital algorithm. Roche v-TAC is available in markets accepting the CE mark and could help simplify the screening, diagnosis and monitoring of patients with respiratory compromise in the current COVID-19 pandemic. Separately, Roche has acquired Stratos Genomics (Seattle, WA, USA; www.stratosgenomics.com), an early-stage sequencing technology company to advance the development of Roche’s nanopore sequencer. The acquisition provides Roche access to Stratos Genomics unique chemistry, Sequencing by Expansion (SBX).

Meanwhile, Roche’s Elecsys Anti-SARSCoV-2 antibody test is currently live at more than 20 commercial and hospital lab sites throughout the US, with plans in the next several weeks to increase to more than 200 commercial and hospital lab sites with the ability to perform millions of tests per week.

The Elecsys Anti-SARS-CoV-2 antibody test, which received Emergency Use Authorization (EUA) from the FDA, is based on an insolution double-antigen sandwich format, can detect antibodies to the new coronavirus causing COVID-19, indicating whether a person has already been infected and potentially developed immunity to the virus.

Additionally, Roche has secured EUA from FDA for its new Elecsys IL-6 test which measures levels of the biomarker interleukin 6 (IL-6). The test can be used to help identify patients with confirmed COVID-19 disease who could be at high risk of intubation with mechanical ventilation and can support physicians, in combination with other examinations and vital signs, to decide early on if a patient with confirmed COVID-19 illness requires mechanical ventilation.

Also, Roche has announced the CE-IVD launch of its automated digital pathology al-

gorithm, the uPath PD-L1 (SP263) image analysis for non-small cell lung cancer (NSCLC). Roche’s uPath image analysis algorithm suite for pathology decision support offers ready-to-use image analysis tools, providing fast, consistent and automated analysis so that pathologists can quickly, accurately and confidently assess immunohistochemistry/in situ hybridization and hematoxylin and eosin-stained slides.

Hologic’s New COVID-19 Molecular Test

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EDITORIAL BOARD

Graham Beastall United Kingdom Claus Christiansen Denmark Hernán Fares Taie Argentina Bernard Gouget France Maurizio Ferrari Italy Jocelyn M. Hicks United States Anders Kallner Sweden Tahir S. Pillay South Africa Andreas Rothstein Colombia Dmitry B. Saprygin Russia Praveen Sharma India Rosa I. Sierra-Amor Mexico Peter Wilding United States Andrew Wootton United Kingdom

A GLOBETECH PUBLICATION

Hologic, Inc. (Marlborough, MA, USA; www.hologic.com) has received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for its Aptima SARS-CoV-2 assay to detect the novel coronavirus. The newly authorized test runs on Hologic’s fully automated Panther system that can provide initial results in approximately three hours and process more than 1,000 coronavirus tests in 24 hours.

SARS-CoV-2 Serology Test without Use of Containment Facility or Specimen

GenScript Biotech Corporation (Piscataway, NJ, USA; www.genscript.com), DukeNUS Medical School, and the Diagnostics Development Hub (DxD) at Singapore's Agency for Science, Technology and Research (A*STAR) have developed the world’s first serological coronavirus detection system that allows for rapid detection of neutralizing antibodies (NAbs) present in the serum of COVID-19 patients without the need for live biological materials and biocontainment facility. The companies have entered into an exclusive agreement to co-develop and manufacture the unique serological COVID-19 detection system known as the surrogate virus neutralization test (sVNT) or cPass.

Beckman Coulter Expands Partnership with BARDA Beckman Coulter (Brea, CA, USA; www. beckmancoulter.com) has been awarded an expanded partnership with BARDA as part of their rapidly expanding COVID-19 medical countermeasure portfolio. The partnership was awarded to Beckman Coulter, in collaboration with Dascena, Inc. (Oakland, CA, USA; www.dascena.com) for additional advanced research and development toward optimization of a machine-learning based sepsis diagnostic and prediction algorithm to include assessing its use with coronavirus (COVID-19) patients.

Separately, Beckman Coulter has announced that its Access SARS-CoV-2 IgG assay is now available in markets accepting the CE Mark. The Beckman Coulter Access SARSCont’d on page 5

Published in cooperation with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

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ISSN 1068-1760

Vol.38 No.4. Published, under license, by Globetech Media LLC; Copyright © 2020. All rights reserved. Reproduction in any form is forbidden without express permission. Opinions expressed are solely those of the authors, and do not represent an endorsement, or lack thereof, by the Publisher of any products or services.

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LabMedica International June-July/2020

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COVID-19 Special Report: Six Months into Pandemic Widespread Testing Remains Global Priority To view this issue in interactive digital magazine format visit www.LinkXpress.com

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CoV-2 IgG assay detects immunoglobulin G (IgG), and targets antibodies that recognize the receptor-binding domain (RBD) of the spike protein which SARS-CoV-2 uses to bind to a human cell receptor. This is significant as antibodies that target the RBD have the potential to be neutralizing and thus prevent future infection by blocking the virus from entering the cell.

Additionally, Beckman Coulter has also received Emergency Use Authorization (EUA) from the US Food & Drug Administration (FDA) for its Access SARS-CoV-2 IgG assay. Beckman Coulter has already shipped tests to more than 400 hospitals, clinics and diagnostics laboratories in the US, and has begun distribution of the new antibody test globally to countries that accept the FDA EUA and CE Mark. The company is able to deliver more than 30 million tests a month.

fast, scalable and reliable mouth swab test for COVID-19 that is completed on-premises in on average 13-25 minutes with no laboratory involvement. FRANKD requires less time to produce a result than the gold-standard RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) reference test recommended by the World Health Organization and uses a patented enzyme rather than the currently scarce reagents used in RT-PCR tests to rapidly produce a definitive and reliable result.

COVID-19 Platform Combines Antibody Testing and Blockchain Technology

The ADIONA COVID-19 antibody testing platform developed jointly by Kahala Biosciences LLC (Irvine, CA, USA; www.kashiv

biosciences.com) and Rymedi, Inc. (Greenville, SC, USA; www.rymedi.com) is the first system available in the US that integrates antibody testing with a blockchain-based smartphone software application to bring predictability and traceability to COVID-19 antibody testing.

Bio-Rad’s CFX96 Dx Real-Time PCR System

Bio-Rad Laboratories, Inc.’s (Hercules, CA, USA; www.bio-rad.com) CFX96 Dx Real-Time PCR System has been listed with the US Food and Drug Administration (FDA) for IVD testing and may be used to help in the diagnosis of COVID-19. The system has also met the CE mark requirements for IVD use in Europe and

Technopath’s Multichem ID-COVID-19 Quality Control Solutions

Technopath Clinical Diagnostics (Tipperary, Ireland; www.technopathclinicaldiagnostics.com) has launched its Multichem ID-COVID-19 Quality Control Solutions which offer laboratories third-party quality control products, enabling an independent, unbiased assessment of a diagnostic device or method for COVID-19 antibody testing. The third-party quality control products help provide an independent assessment of a diagnostic device or method for COVID-19 antibody testing and are manufactured based on a human base matrix that helps provide a product analogous to a patient sample.

DxGen’s '2 minutes' COVID-19 Antibody Testing System

A newly-launched '2 minutes' detection system for COVID-19 IgM / IgG antibodies offers reliable testing with several attractive features for medical professionals and has also received CE Mark. The newly-developed Epithod 616 analyzer and COVID-19 IgM/IgG test kit from DxGen Corp.

(South Korea; www.dxgen.vbweb.kr) is the fastest system that not only provides positive (+, ++, +++) or negative (–) results, but also shows the results through a relative numerical value in COI (Cut-Off Index), enabling the user to diagnose the levels of IgM and IgG antibodies present and manage their quantitative results more specifically.

New POC COVID-19 Mouth Swab Test without Lab Involvement

GeneMe (Gdańsk, Poland; www. geneme.eu) has developed FRANKD, a

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PRODUCT NEWS

To receive prompt and free information on products, log on to www.LinkXpress.com or fill out reader service form located on last page, or scan the QR code on your mobile device

MULTIPLEX CARBAPENEMASE RAPID TEST NG BIOTECH

BIOFIRE DIAGNOSTICS

ALCOR SCIENTIFIC

The NG-Test Carba 5 allows rapid detection of NDM, OXA-48-, KPC-, VIM- and IMP- like producers on bacterial colony within 15 minutes. All results were correlated with the genotype of the strains determined

by PCR analysis.

The FilmArray Torch is a fully integrated, random access system designed to meet a lab’s syndromic infectious disease testing needs, compatible with all existing FilmArray Panels, providing quick and accurate results.

The miniiSED™ is a single position, fully automated ESR analyzer that works directly from primary EDTA tubes or BD Microtainer® MAP Microtubes, requiring 100 microliters of sample and producing stat results in 15 seconds.

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RANDOM ACCESS SYSTEM

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ESR ANALYZER

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COVID-19 Special Report: Six Months into Pandemic Widespread Testing Remains Global Priority

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is registered with regulatory bodies for IVD use in many other countries. The FDA listing now extends access to the instrument to assay developers and testing laboratories in the US. Ortho and BARDA Collaborate On SARS-CoV-2 Antibody Tests

Ortho Clinical Diagnostics (Raritan, NJ, USA; www.orthoclinicaldiagnostics.com) is collaborating with Biomedical Advanced Research and Development Authority (BARDA) to further advance the development of the company's SARS-CoV-2 total and IgG antibody tests.

BARDA has awarded Ortho USD 678,000 in support of the company's COVID-19 antibody testing program. Ortho's total antibody test detects all COVID-19 related antibodies (IgA, IgM and IgG) and Ortho's COVID-19 IgG antibody test detects the IgG antibody, which appears in a patient's blood in the later phase of the infection and remains elevated even after recovery. The tests offer greater choice in tracking, surveillance and patient management.

Additionally, Ortho Clinical Diagnostics (Raritan, NJ, USA; www.orthoclinicaldiag nostics.com) has received CE Mark for its second COVID-19 antibody test—the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Test (COVID-19 IgG antibody test which offers 100% specificity. It closely follows the introduction of Ortho's COVID-19 Total test and the two tests offer greater choice in tracking and surveillance, patient management, and screening convalescent plasma.

Quidel’s Lyra Direct SARS-CoV-2 Assay

Quidel Corporation (San Diego, CA, USA; www.quidel.com) has received Emergency Use Authorization (EUA) for the Lyra Direct SARS-CoV-2 Assay from the Food and Drug Administration (FDA) to allow direct sample

processing. Under the new EUA, the Lyra Direct SARS-CoV-2 Assay no longer requires an up-front sample extraction.

Thermo Fisher to Distribute Chembio’s DPP COVID-19 System

Chembio Diagnostics, Inc. (Medford, NY, USA; www.chembio.com) has signed a multiyear, non‑exclusive agreement with Thermo Fisher Scientific Inc. (Waltham, MA, USA; www.thermofisher.com) to distribute Chembio’s DPP COVID-19 System in the US. The DPP COVID-19 System is a rapid serological test and analyzer that provides numerical readings for both IgM and IgG antibody levels within 15 minutes from a finger stick drop of blood.

CDC’s Massive COVID-19 Antibody Study

In order to learn more about how many people have been infected with SARS-CoV-2 and how it is spreading through the US population, the US Centers for Disease Control and Prevention (CDC Atlanta, GA, USA; www. cdc.gov) plans to conduct a huge national serology test. The CDC’s SARS-CoV-2 antibody study will test about 325,000 people across 25 US cities. The CDC will test 1,000 blood donors in each of the 25 selected cities every month for 12 months. After 18 months, it plans to also test the blood of an additional 25,000 volunteers.

Enzo Biochem’s Coronavirus SARS-CoV-2 IgG Antibody Test

Enzo Biochem (New York, NY, USA; www. enzo.com) has launched a SARS-CoV-2 IgG ELISA assay kit for serological detection of IgG antibodies against the novel coronavirus under the FDA’s Emergency Use Authorization (EUA) authority as both products and services.

The assay permits the qualitative detection of Immunoglobulin G (IgG) antibodies to SARS-

CoV-2 in human serum and is designed to provide accurate results in a clinical laboratory setting with low- to high-throughput processing of specimens.

GSK and Mammoth Biosciences Develop CRISPR-based COVID-19 Test

GSK Consumer Healthcare (Brentford, UK; www.gsk.com) and Mammoth Biosciences (San Francisco, CA, USA; www.mammoth. bio) have entered into a collaboration to develop a fully disposable, rapid and handheld COVID-19 test using a CRISPR-based platform. The accurate, easy-to-use, fully disposable, rapid and handheld test can be used by consumers and healthcare providers in clinics to detect active SARS-CoV-2.

Abbott’s UK Contract for IgG Antibody Tests

Abbott (Lake Forest, IL, USA: www. abbott.com) has been awarded a government contract to supply millions of its laboratorybased IgG antibody tests to National Health Service (NHS) laboratories across the UK over the coming months. Abbott's IgG antibody test will be available at NHS laboratories across the UK, using its ARCHITECT i1000SR and i2000SR and Alinity i laboratory instruments.

Mount Sinai Venture for COVID-19 Antibody Test Kits

Mount Sinai Health System (New York, NY, USA; www.mountsinai.org), along with Renalytix AI (New York, NY, USA; www.renalytixai. com), has formed a new venture named Kantaro Biosciences, LLC to develop and scale production and distribution of its SARS-CoV-2 antibody test. Kantaro has partnered with Bio-Techne Corporation (Minneapolis, MN, USA; www. bio-techne.com) to develop and launch the new kit, with the goal of producing more than

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Blood Test for Earlier GI Cancer Detection

To view this issue in interactive digital magazine format visit www.LinkXpress.com

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stomach, pancreas, gallbladder, liver, bile duct, colon and rectum will account for 17% of incident cancer diagnoses and 26% of cancer-related deaths in the USA in 2019. An investigational blood-based assay demonstrated efficacy in detecting multiple types of cancer, including gastrointestinal cancers, at various stages and can also predict the tissue of origin (TOO) of these and other cancers types.

A team of scientists led by the Dana-Farber Cancer Institute (Boston, MA, USA; www.dana-farber.org) carried out a prospective, multicenter, observational, casecontrol study that included 273 cancer-free participants and 654 patients with more than 20 tumor types at all stages, including 67 esophageal/stomach, 95 pancreatic/gallbladder/extrahepatic bile duct, 29 liver/intrahepatic bile duct and 121 colon/rectal cancers. Plasma cellfree DNA (cfDNA) was subjected to a cross-validated targeted methylation (TM) sequencing assay (Grail Inc., Menlo Park, CA, USA; https://grail.com) Methylation fragments were combined across targeted genomic regions and assigned a probability of cancer and a predicted TOO. The team reported that with a specificity of greater than 99%, the blood-based assay demonstrated overall sensitivity of 82% for all gastrointestinal cancer types. They reported sensitivity of 72% for stage I to III disease and 96% for stage IV disease. The test showed accuracy for predicted TOO of 92% for all gastrointestinal cancers. Specifically, the assay demonstrated predicted TOO accuracy of 87% for esophageal/stomach cancers (86% stage I to stage III; 89% stage IV), 92% for pancreatic/gallbladder /extrahepatic bile duct cancers (94% stage I-III; 91% stage IV), 78% for liver/intrahepatic bile duct cancers (85% stage I-III 70% stage IV); and 98% for colon/rectal cancers (96% stage I-III; 100% stage IV).

Brian M. Wolpin, MD, MPH, an Oncologist and lead author of the study, said, “The potential of this test is to diagnose cancer earlier, when it is more treatable. The ability to do that across cancer types could be quite valuable. Many of the cancer types that this test detects do not currently have screening tests that allow earlier cancer detection before the cancers cause symptoms.” The study was presented at the Gastrointestinal Cancers Symposium on January 23, 2020 in San Francisco, CA, USA. Image: Histopathology of early gastric cancer, an intramucosal adenocarcinoma. A blood test used in a targeted methylation (TM) sequencing assay may help detect hard-to-detect gastrointestinal cancers in asymptomatic individuals (Photo courtesy of Andrey Bychkov, MD, PhD).

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PRODUCT NEWS

CHEMILUMINESCENCE ANALYZER

To receive prompt and free information on products, log on to www.LinkXpress.com or fill out reader service form located on last page, or scan the QR code on your mobile device

HEMATOLOGY ANALYZER

IMMUNOASSAY ANALYZER

SHENZHEN YHLO BIOTECH

ERBA MANNHEIM

MINDRAY

The iFlash 3000 is an automatic floor-standing chemiluminescence immunoassay analyzer with a four-step magnetic separation system combined with vortex type resuspension of magnetic particles to ensure cleaning efficiency.

The H 560 5-part differential hematology analyzer can run up to 60 samples/hour and requires only 15 microliters of blood. The interpretation of results is aided by the use of an advanced 3D scattergram.

The CL-900i, one of the world’s smallest, fully automated chemiluminescence immunoassay analyzers, with a throughput of up to 180 tests/hour, 50 sample positions, and 15 reagent positions.

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COVID-19 Special Report: Six Months into Pandemic Widespread Testing Remains Global Priority

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10 million patient tests per month by July.

Seasun Biomaterials’ COVID-19 Kit Secures FDA EUA

Seasun Biomaterials, Inc. (Daejeon, Korea; www.seasunbio.com) has received Emergency Use Authorization (EUA) from the US Food and Drug Administration for its second COVID-19 assay AQ-TOP COVID-19 Rapid Detection Kit following the completion of FDA EUA (April-27) of its U-TOP COVID-19 RealTime Detection Kit. The company now plans to provide the kit globally and hopes that its advantage of rapid COVID-19 diagnosis will contribute to quick follow up.

Randox Whole Pathogen Molecular Controls for SARS-CoV-2

Randox Laboratories (Crumlin, UK; www. randox.com) has been granted CE marking for its whole pathogen quality controls for SARS-CoV-2 (COVID-19). Available under the brand name Qnostics, the new SARS-CoV-2 controls are manufactured using whole pathogens and, therefore mimic the patient sample, providing the best sample matrix for laboratories.

Separately, Randox has selected SCIENION AG (Berlin, Germany; www.sci enion.com) as its technology provider and science partner for scaling-up biochip manufacturing in order to transform rapid diagnostic testing. The companies have entered into a multiyear alliance wherein SCIENION will integrate its precision dispensing technology to enable Randox to scale-up biochip manufacturing across the business. Their joint activities will include co-working at Randox and at SCIENION headquarters, including massive scaling-up of SARS CoV2 test manufacturing.

Additionally, Randox has unveiled cytokine testing for COVID-19 risk stratification and treatment monitoring. The test, which looks

for the presence of cytokines (a type of small protein) is performed on the company’s patented Biochip Technology, which can simultaneously detect multiple analytes from a single patient sample. Randox’s comprehensive cytokine testing menu comprises 26 different cytokines across four different biochip panels.

Fulgent SARS-CoV-2 RT-PCR Test

Fulgent Genetics, Inc. (Temple City, CA, USA: www.fulgentgenetics.com) has received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for its RT-PCR test for the detection of SARS-CoV2 using upper respiratory specimens (nasal, nasopharyngeal, and oropharyngeal swabs). The SARS-CoV-2 primer and probe sets are designed to detect RNA from 2019-nCoV in specimens from patients who meet CDC 2019-nCoV clinical criteria. Primer and probe set sequences are based on CDC recommended guidelines that identify two known distinct regions within the SARS-CoV-2 genome.

Aalto Bio Launches Recombinant SARS-CoV-2 Spike (S) Proteins

Aalto Bio Reagents Ltd. (Dublin, Ireland; www. aaltobioreagents.com) has launched its new range of recombinant SARS-CoV-2 spike (S) proteins for diagnostic test manufacturers, vaccine developers and researchers globally.

When used solely or in combination with the company’s new insect-derived Nucleocapsid protein (N) (code BM 6424), its S1-S2 chimeric glycoprotein (code BM 6422) has demonstrated excellent reactivity in ELISA for detection of IgA, IgG and IgM antibodies against SARS-CoV-2.

Siemens Shipping COVID-19 Total Antibody and Molecular Tests

Siemens Healthineers (Erlangen, Germany; www.siemens-healthineers.com) has begun

worldwide shipping of its laboratory-based total antibody test to detect the presence of SARS-CoV-2 IgM and IgG antibodies in blood.

The total antibody test allows for identification of patients who have developed an adaptive immune response, which indicates recent infection or prior exposure.

Separately, Siemens and the Biomedical Advanced Research and Development Authority (BARDA Washington, DC, USA; www.phe. gov) are partnering for an automated SARSCoV-2 total antibody test being developed by the company. The laboratory-based total antibody test is meant to detect the presence of SARS-CoV-2 antibodies, including IgM and IgG in blood, allowing for identification of patients who have developed an adaptive immune response, which indicates recent infection or prior exposure.

Additionally, Siemens has been granted Emergency Use Authorizations (EUAs) by the US Food and Drug Administration (FDA) for its total antibody test to detect the presence of SARS-CoV-2 antibodies running on the company’s Dimension Vista and Dimension EXL analyzers. The FDA has granted EUA to Siemens’ Dimension Vista SARS-CoV-2 total antibody assay and Dimension EXL SARS-CoV-2 total antibody assay in order to identify people with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. Both the products are sandwich-based chemiluminescent immunoassays.

Bio-Rad Collaborates with Biodesix

Bio-Rad Laboratories, Inc. (Hercules, CA, USA; www.bio-rad.com) has entered into a collaboration with Biodesix, Inc. (Boulder, CO, USA; www.biodesix.com) to launch a blood-based immunoassay-based test that identifies antibodies to SARS-CoV-2. The Platelia SARS-CoV-2 Total Ab test identifies if a patient has produced those antibodies and can Cont’d on page 10

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PRODUCT NEWS

SLIDE STAINER

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CLINICAL CHEMISTRY ANALYZER

HEMATOLOGY ANALYZER

ELITECH GROUP

INSTRUMENTATION LAB

MINDRAY

The Aerospray Hematology Pro Series 2 automated slide stainer can be adjusted to meet a wide range of staining requirements of any hematology lab and has a short run time with slides ready for the microscope in five minutes.

The ILab Taurus Twin system connects two ILabTaurus clinical chemistry analyzers and is capable of up to 1,000 photometric tests per hour (+ 375 ISE) with continuous sample and reagent loading.

The BC-6200 is a 5-part differential automatic hematology analyzer featuring SF Cube technology with newly-designed optical and reagent systems that can help doctors to better differentiate the clusters of cells.

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be utilized in combination with the SARS-CoV2 Droplet Digital PCR (ddPCR) test to diagnose symptomatic patients and assess immunity in the population.

NIH COVID-19 Digital Pathology Repository

The National Institutes of Health (NIH Bethesda, MD, USA; www.nih.gov) has launched the online COVID Digital Pathology Repository (COVID-DPR), a virtual collection of high resolution microscopic COVID-related human tissue images. . The whole slide images, annotations and metadata in the repository will be used as a reference data set for education, research and future clinical trials aimed at limiting further infection, disease, and death.

Swift Biosciences’ SNAP SARS-CoV-2 Kit

Swift Biosciences, Inc. (Ann Arbor, MI, USA; www.swiftbiosci.com), which focuses on commercialization of DNA and RNA library preparation kits for Next-Generation Sequencing (NGS), has released its Swift Normalase Amplicon Panel (SNAP) SARS-CoV-2 kit. Targeting the full viral genome in a single tube reaction with a rapid two-hour workflow, Swift's assay enables research and surveillance activities by accommodating the low viral copy titers found in clinical specimens.

New One-Minute COVID-19 Test

A one-minute test for antibodies to SARSCoV-2 is currently being developed based on an innovative testing technology that detects antibodies within one minute from a single drop of blood. The test is being developed on bioLytical Laboratories Inc.’s (Richmond, BC, Canada; www.biolytical.com) proprietary INSTI platform. By detecting antibodies to COVID-19 in a single drop of blood, INSTI does not require additional materials such as swabs. Along with the test device, all materi-

als required to perform the test are provided together in one small pouch; leading this testing platform to become known as “a lab in a pouch.”

Supply Chain Issues Impact Labs Testing for SARS-CoV-2

The Association for Molecular Pathology (AMP Rockville, MD, USA; www.amp.org), a global, molecular diagnostic professional society, surveyed more than 100 clinical laboratory professionals across the US to gather their feedback on COVID-19 diagnostic testing environment and recommendations to improve future pandemic responses. The preliminary results of the SARS-CoV-2 testing survey for clinical laboratories have revealed that more than 70% have experienced supply chain interruptions that have resulted in significant delays.

Global Market Report Published on COVID-19 Detection Kits

The growth of the global COVID-19 detection kits market will be driven by the responsiveness of countries to contain the spread of the coronavirus and advancements in healthcare facilities, according to the Transparency Market Research Pvt. Ltd. (Albany, NY, USA; www.transparencymarketresearch.com). The presence of a seamless industry for COVID-19 testing will play a vital role in driving sales across the global market. The development of test kits that can deliver results in less than six hours will play a defining role in the growth of the global COVID-19 detection kits market.

EKF Diagnostics Secures Contracts

EKF Diagnostics (Cardiff, UK; www.ekf diagnostics.com) has secured new contracts for the manufacture and supply of its novel, patented sample collection device, PrimeStore MTM. The new sample collection device allows COVID-19 samples to be rapidly inactivated in

the collection tube, avoiding contamination and preserving RNA without need for refrigeration.

Mobidiag PCR and Antibody Tests

Mobidiag Ltd. (Espoo, Finland; www.mo bidiag.com) has received CE-IVD markings for its Novodiag COVID-19 and Amplidiag COVID-19 molecular diagnostic tests for the early detection of the SARS-CoV-2 virus. These tests complement the company’s already available antibody test, Anti-SARS-CoV-2 Rapid Test that Mobidiag is distributing from its joint venture partner, Autobio Diagnostics Co., Ltd. (Zhengzhou, Henan, China; www.autobio. com.cn). With this, Mobidiag is now able to commercially offer a comprehensive diagnostic solution for novel coronavirus infections for hospital and lab based settings.

Longhorn Vaccines, Cenetron Diagnostics and Coca-Cola Bottlers to Produce COVID-19 Test Kits

Longhorn Vaccines and Diagnostics LLC (Bethesda, MD, USA; www.lhnvd.com) and Cenetron Diagnostics (Austin, TX, USA; www.cenetron.com) have collaborated with Southeastern Container (SEC) to expand production of COVID-19 testing kits. Cenetron and other medical product manufacturers will begin producing COVID-19 testing kits using Longhorn’s proprietary PrimeStore Molecular Transport Medium (MTM) and preform Coca-Cola bottles, sourced from SEC, as test tubes. The goal is to manufacture 1-2 million preform test tubes per week to help meet the broader US testing goal of performing 10 million COVID-19 tests per week.

Biomolecule Detection Chip to Aid COVID-19 Testing

Researchers have developed a patented method for single biomolecule detection that

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overcomes limitations of current technologies and could help in the fight against COVID-19.

Purdue University (West Lafayette, Ind., USA; www.purdue.edu) innovators have created a method that uses a special sensor similar to a computer chip. The application-specific integrated circuit chip is designed for the early detection of a number of pathogens and viruses.

Healgen’s COVID-19 IgG/IgM Rapid Test Kit

Healgen Scientific, LLC’s (Houston, TX, USA; www.healgen.com) COVID-19 IgG/IgM Rapid Test Kit has been granted Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA). An easy-to-use test kit that provides results in just 10 minutes, COVID-19 IgG/IgM Rapid Test kits are designed for use with whole blood, serum or plasma samples. With a high degree of accuracy, the kits detect IgM that may appear in blood within three-five days following incubation and IgG that appears as soon as 1-2 weeks.

MA, USA; www.sherlock.bio) and Integrated DNA Technologies (IDT Coralville, Iowa, USA; www.idtdna.com) have entered into a strategic collaboration to enable large-scale manufacturing of the Sherlock CRISPR SARS-CoV-2 kit for the detection of the novel coronavirus. The test kit, for which Sherlock Biosciences recently received Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA), works by programming a CRISPR molecule to detect the presence of the genetic signature for SARS-CoV-2 in a nasal swab, nasopharyngeal swab, oropharyngeal swab or bronchoalveolar lavage (BAL) specimen.

Omega Bio-Ttek’s Viral RNA Extraction Kit for COVID-19

Omega Bio-Tek, Inc. (Norcross, GA, USA; www.omegabiotek.com) has launched the MagBind Viral RNA Xpress Kit for the rapid and re-

liable isolation of Viral RNA from nasopharyngeal (NP) swab specimens that are dry or in viral transport media (VTM). The new magnetic bead-based extraction kit is adaptable to most liquid handling platforms for scalable, highthroughput purification and aims to combat the shortage of RNA purification kits, which is used in the first steps of COVID-19 testing.

Genetron’s SARS-CoV-2 RNA Test Receives FDA EUA

Genetron Health (Beijing, China; www.gen etronhealth.com) has secured Emergency Use Authorization (EUA) from the US Food and Drug Administration for the company’s independently developed detection kit for the novel coronavirus. The company’s new Genetron SARS-CoV-2 RNA Test kit has also received approval for export from the relevant authorities

New High-Throughput Testing Approach for COVID-19

A new high-throughput and costeffective testing approach for COVID19 combines digital PCR technology with the group testing method to significantly reduce costs and increase testing capacity, while offering a diagnostic sensitivity greater than the current standard of individual RT-PCR tests. Stilla Technologies (Paris, France; www.stillatechnologies.com) which is offering the new COVID-19 testing approach has also published the largest comparative study to date for group testing of SARS-CoV-2 that demonstrates the new approach of group testing by digital PCR appears to have a diagnostic sensitivity "similar to better" compared to current tests in individual RT-PCR. New COVID-19 Testing Method from Takara Bio and bioSyntagma

Takara Bio USA, Inc. (TBUSA, Mountain View, CA, USA; www. takarabio.com) is collaborating with bioSyntagma, Inc. (Phoenix, AZ, USA; www.biosyntagma.com) and their partners to develop and validate a new high-throughput method for detecting SARS-CoV-2. The method employs automation technology and reagents from TBUSA to detect viral RNA via real-time PCR and will enable rapid, large-scale testing of thousands of patient samples per day.

First-ever FDA-authorized CRISPR-based Rapid Diagnostic Test

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PRODUCT NEWS

LACTOSE INTOLERANCE TEST

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ELECTROLYTE ANALYZER

DNA/RNA EXTRACTOR

BIOHIT HEALTHCARE

ERBA MANNHEIM

BIOVENDOR

The Lactose Intolerance Quick Test for detecting lactose intolerance (hypolactasia of the small intestine) is based on activity of the lactase enzyme in a biopsy specimen taken from the mucosa of the upper part of small intestine.

The EC 90 is an electrolyte analyzer with maintenance-free electrodes in an all-in-one sensor cartridge that directly measures Na+, CI-, K+ and Ca2+ from whole blood, plasma, serum and pre-diluted urine.

The LabTurbo 48 Compact System uses membrane column vacuum technology to fully automate DNA/RNA extraction up to 48 samples in 90 minutes from raw sample (auto-sampling) to nucleic acid elution in unibody.

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in China as well as obtained CE marking.

Cepheid Develops Four-in-One Combination Test

Cepheid (Sunnyvale, CA, USA; www. cepheid.com) has announced the development of a four-in-one test that is expected to deliver qualitative detection of SARS-CoV-2, Flu A, Flu B and RSV from a single patient sample. The test is designed for use on any of the company’s more than 25,000 GeneXpert Systems placed worldwide, with results expected in as little as 35 minutes, and is built for simple, reference lab quality PCR testing – on location at medical centers and hospitals or closer to patient in health clinics and nursing homes.

Quidel’s Rapid Antigen COVID-19 Diagnostic Assay

Quidel Corporation (San Diego, CA, USA; www.quidel.com) has received an amended Emergency Use Authorization (EUA) from the US FDA, allowing the company to run its Sofia SARS Antigen FIA on its first generation Sofia Fluorescent Immunoassay Analyzer (Sofia 1).

The Sofia SARS Antigen FIA is to be used as an aid in the rapid detection of SARS-CoV-2 in nasal or nasopharyngeal specimens from patients meeting the Centers for Disease Control and Prevention’s (CDC) criteria for suspected COVID-19 infection.

Pittsfield, ME. The new top-of-the-line medical device manufacturing space will include a Class 7 cleanroom where the swabs will be made.

US FDA’s Performance Data of COVID-19 Tests

The US Food and Drug Administration (FDA Silver Spring, MD, USA; www.fda.gov) has publicly posted test performance data from four more antibody, or serology, test kits from its independent performance validation study effort. Data from an antibody test kit were first posted in early May and the FDA has now shared data from four additional tests. Additional performance data will be made available as the FDA reviews and determines if any further actions are appropriate for those test kits prior to publication.

PerkinElmer's Euroimmun SARS-CoV-2 Test Secures FDA EUA

PerkinElmer, Inc. (Waltham, MA; USA; www.perkinelmer.com) has secured Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for EUROIMMUN’s (a PerkinElmer company) EuroRealTime SARS-CoV-2 molecular assay COVID-19. The CE-marked PCR-based test is designed for the specific detection of SARSCoV-2 in a quick and simple manner using reverse transcription and real-time PCR in a single step.

Puritan Medical’s New COVID-19 Swab Facility

Sekisui’s New OSOM Ultra Plus Flu A&B Test

Puritan Medical Products (Guilford, ME, USA; www.puritanmedproducts.com) is opening a new facility that will allow the company to produce an additional 20 to 40 million swabs per month in order to fulfill the need for COVID-19 testing swabs in the US. Puritan’s new production facility will be located in the company’s 95,000 square foot building in

Sekisui Diagnostics (Burlington, MA, USA; www.sekisuidiagnostics.com) has received US Food and Drug Administration (FDA) 510(k) clearance and CLIA Waiver for its OSOM Ultra Plus Flu A&B Test. The test is expected to help healthcare professionals accurately diagnose influenza, which is important given the shortage of SARS-CoV-2 tests due to the

COVID-19 pandemic.

US-HHS Issues New Lab Data Guidelines for COVID-19 Testing The US Department of Health and Human Services (US-HHS Washington, D.C., USA; www.hhs.gov) has announced new guidance that specifies what additional data must be reported to HHS by laboratories along with Coronavirus Disease 2019 (COVID-19) test results. The new guidance from HHS standardizes reporting to ensure that public health officials have access to comprehensive and nearly real-time data to inform decision making in their response to COVID-19.

Llumina’s Sequencing-Based COVID-19 Test Granted FDA EUA

Illumina, Inc. (San Diego, CA, USA; www. illumina.com) has received an Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA) for its COVIDSeq Test, a high-throughput, sequencing-based, in vitro diagnostic (IVD) workflow enabling the detection of SARS-CoV-2. COVIDSeq uses upper respiratory specimens, including a nasopharyngeal or oropharyngeal swab, and delivers sample receipt to result in 24 hours using the NovaSeq 6000 Sequencing System.

ChromaCode's HDPCR SARS-CoV-2 Assay Granted FDA EUA

ChromaCode, Inc. (Carlsbad, CA, USA; www.chromacode.com) has been granted an Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA) for its HDPCR SARS-CoV-2 Real-Time PCR Assay which had been launched in April. The HDPCR SARS-CoV-2 Real-Time PCR Assay is intended to detect severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swab specimens from patients suspected by their healthcare

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provider of having contracted COVID-19.

Awareness Technology Launches Two-Plate ELISA and Chemiluminescent Analyzer Awareness Technology, Inc. (Palm City, Florida, USA; www.awaretech.com) has announced the availability of ChemWell 2, its two-probe, two-plate automatic combo analyzer for ELISA and chemiluminescent (CLIA).

With laboratories expanding serology requirements, the two-plate system is expected to be a more suitable primary instrument for lower throughput labs, and ideal for off-line assays in higher throughput settings.

New Extraction-Free Saliva-Based SARS‑CoV‑2 Test

Cordova, CA, USA; www.thermogenesis.com) which has filed patent applications for the device.

First True POC COVID-19 Antibody Tests

Two newly-launched rapid COVID-19 antibody tests are awaiting Emergency Use Authorization (EUA) approval from the US FDA and once authorized, would become the first true point-of-care (POC) tests designed for convenience and ease of use, allowing providers to triage their patients as efficiently as possible. Vivera Pharmaceuticals, Inc. (Newport Beach, CA, USA; www.viverapharma ceuticals.com) has launched the POC ready rapid serology tests which are designed to serve where patients most critically require

screening testing. One test is optimized for use in mass-screening settings, such as drive through testing centers, and the other test is more suitable for use in doctor's offices and health clinics.

BAMS Diagnostic Test for COVID-19 Reaches Prototype Stage

A Bead-Assisted Mass Spectrometry (BAMS) diagnostic test for COVID-19 infection that is currently under development has reached prototype stage and can detect the coronavirus spike protein in model samples in the concentration range appropriate for a clinical diagnostic test. Avacta Group plc (Wetherby, England; www.avacta.com) has entered into a collaboration with Adeptrix (Beverly, MA, USA;

A new extraction-free saliva-based test to detect the SARS‑CoV‑2 virus provides an easy-to-administer protocol that does not require collection via invasive nasopharyngeal swab. The Advanta Dx SARS-CoV-2 RT-PCR Assay, developed by Fluidigm Corporation (South South San Francisco, CA, USA; www.fluidigm.com) in collaboration with scientists at the McDonnell Genome Institute and the Department of Genetics at Washington University School of Medicine (St. Louis, MO, USA; www.genome.wustl.edu), would enable health care providers to conduct testing through collection of saliva, which is significantly easier than invasive nasopharyngeal swab collection and could enhance testing coverage in critical populations.

Cue Health POC COVID-19 Test Receives FDA EUA

Cue Health Inc. (San Diego, CA, USA; www.cuehealth.com) has received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for the company’s rapid, portable, point-of-care COVID19 test. The Cue COVID-19 Test is a molecular test that detects the RNA of SARS-CoV-2 in 25 minutes using a nasal swab sample taken from the lower part of the nose and runs on the compact and portable Cue Health Monitoring System.

New POC Device Improves Detection of COVID-19 IgM/IgG Antibodies

A new point-of-care device improves the speed and accuracy of lateral flow immunoassays (LFIA) to detect COVID-19 IgM and IgG antibodies from a single drop of blood. The COVID-19 LFIA reader has been developed by ThermoGenesis Holdings, Inc. (Rancho

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PRODUCT NEWS

STOOL EXTRACTION DEVICE

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HEMATOLOGY ANALYZER

COVID-19 PCR AND ELISAS

BÜHLMANN LABS

CAROLINA LIQUID CHEMISTRIES

EUROIMMUN

The CALEX Cap is the first and only stool extraction device suitable for safe air and land transportation, offering an efficient, convenient and hygienic extraction of stool samples.

The Mindray BC-3600 is a compact 3-part differential automatic hematology analyzer with a throughput of 60 samples per hour, an intuitive operation system and convenient data communication interface.

EUROIMMUN’s portfolio for COVID-19 diagnostics includes the EURORealTime SARS-CoV-2 for sensitive direct virus detection, as well as ELISAs based on spike protein domain S1 (IgG, IgA) or modified nucleocapsid protein (NCP, IgG).

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www.adeptrix.com) to develop a high throughput COVID-19 antigen test using Adeptrix’s proprietary BAMS platform.

World’s First Quantitative Surrogate Viral Neutralization Test for COVID-19

The world’s first quantitative surrogate Viral Neutralization Test (sVNT) to evaluate COVID-19 protective immunity in the US will measure and quantify the neutralizing capacity of antibodies against the SARS-CoV-2 virus. The test, marketed as Tru-Immune, is being offered

by Ethos Laboratories (Newport, KY, USA; www.ethos-labs.com) in partnership with GenScript (Piscataway, NJ, USA; www.genscript. com). Unlike other tests currently on the market, Tru-Immune detects the presence and magnitude of neutralizing antibodies that prevent infectivity of the COVID-19 virus.

New COVID-19 Test Pinpoints Antibodies Specific to Spike Protein

Scientists at the University of North Carolina at Chapel Hill School of Medicine (Chapel Hill, NC, USA; www.unchealthcare.org) have developed a COVID-19 test that pinpoints human antibodies specific to a particular part of the SARSCoV-2 spike protein. The new kind of antibody test is a simplified experimental assay that could be ramped up to test thousands of blood samples at labs that do not have the resources of commercial labs and large academic medical centers.

Smartphone-Powered, Saliva-Based COVID-19 Test

A portable, saliva-based COVID-19 diagnostic test will be able to detect COVID-19 infection in less than 20 minutes, with an easyto-use device that can be employed in a variety of settings. The COVID-19 diagnostic test called Atlas is being developed by Nicoya (Ontario, Canada; www.nicoyalife.com) and will be powered with smartphone technology so

that it can deliver lab-quality results to an app in less than 20 minutes. The test will be performed with a saliva sample, rather than the more common nasopharyngeal swab samples.

PCR Biosystems’ 4x RT-qPCR SARS-CoV-2 Kit

PCR Biosystems Ltd. (London UK; www. pcrbio.com) has launched qPCRBIO Probe 1Step Virus Detect, a high-concentration 4x RTqPCR kit designed specifically for ultra-sensitive, high-throughput detection of viral RNA sequences, including SARS-CoV-2. The new kit, which marks the latest addition to PCR Biosystems’ specialized RT-qPCR offering, enables users to add more samples to their reactions to boost analytical sensitivity, even when working with small volume reactions.

CDC Consolidated Recommendations for COVID-19 Testing

The Centers for Disease Control and Prevention (CDC Atlanta, GA, USA; www.cdc. gov) has released consolidated recommendations for COVID-19 testing, including interim testing guidelines for nursing home residents and healthcare personnel. These recommendations which compile and update previous testing guidance also include testing strategy options for high-density critical infrastructure workplaces after a COVID-19 case is identified.

SpectronRx’s SARS-CoV-2 Test Kit Secures FDA EUA

SpectronRx (Indianapolis, IN., USA; www. spectronrx.com) has secured Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for its Hymon SARS-CoV-2 Test Kit. The real-time RT-PCR test is intended for the qualitative detection of nucleic acid from the SARS-CoV-2 in upper respiratory specimens (such as nasal, midturbinate, nasopharyngeal, and oropharyngeal swab specimens) and bronchoalveolar lavage

specimens from individuals suspected of COVID-19 by their healthcare provider.

iPLEX Pro SARS-CoV-2 Panel Granted FDA EUA

Agena Bioscience (San Diego, CA, USA; www.agenabio.com), a global provider of low cost and high-throughput molecular testing solutions, has launched the iPLEX Pro SARS-CoV2 Panel for qualitative detection of the novel coronavirus that causes COVID-19. The singlereaction panel targets five regions of the viral genome, providing the accuracy and sensitivity required in the evolving landscape of SARSCoV-2 testing. Clinical laboratories can process more than 6,000 samples each day running the assay on a single MassARRAY instrument, making it one of the highest throughput SARS-CoV2 tests available under the US FDA's Emergency Use Authorization program.

Applied BioCode SARS-CoV-2 Assay Secures FDA EUA

Applied BioCode, Inc. (Santa Fe Springs, CA, USA; www.apbiocode.com) has secured Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for its BioCode SARS-CoV-2 Assay. The CLIA high-complexity multiplex nucleic acid assay is meant for the qualitative detection of SARSCoV-2 nucleic acids in respiratory samples, including nasopharyngeal swabs, nasal swabs, oropharyngeal swabs and bronchoalveolar lavage, from individuals who are suspected of COVID-19 by their healthcare provider. It is designed to detect two different regions of the SARS-CoV-2 virus N gene which are also utilized by the CDC EUA assay.

FDA Joins COVID-19 Diagnostics Evidence Accelerator Project

The US Food and Drug Administration (FDA, Silver Spring, MD, USA; www.fda.gov)

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has announced its participation in the COVID-19 Diagnostics Evidence Accelerator, a multi-stakeholder collaborative project to advance the development of diagnostics. The Diagnostics Evidence Accelerator is the companion project to the previously announced Therapeutic Evidence, which brings together leading experts in health data aggregation and analytics in a unified, collaborative effort to share insights, compare results and answer key questions to inform the collective COVID-19 response.

New Pipetting Robot Automates COVID-19 Testing

A new pipetting robot is automating COVID-19 testing processes in European hospitals, thereby significantly reducing the time taken by laboratories to generate results. The liquid handling robot named flowbot ONE developed by Flow Robotics (Copenhagen, Denmark; www.flow-robot ics.com) makes automating pipetting simple with an intuitive user interface that can be mastered in just one hour.

The company has termed flowbot ONE as a liquid handling cobot as it collaborates with the user in the lab, assisting in workflows and adapting to the lab.

evaluate how new diagnostic tests perform in hospitals, general practices and care homes.

The COVID-19 National DiagnOstic Research and Evaluation Platform (CONDOR) will create a single national route for evaluating new diagnostic tests in hospitals and in community healthcare settings. The research program will bringing together experts who are highly experienced in evaluating diagnostic tests and generating the robust evidence required for a test to be used in the NHS. Steps to Expand and Improve COVID-19 Antibody Tests

More than 300 scientists and clinicians from the federal government, industry and academia have published a report of their conclusions and

recommendations on COVID-19 serology studies. The scientists and clinicians have recommended that additional research is needed to determine if and to what extent a positive antibody test means a person may be protected from re-infection with SARS-CoV-2. They have emphasized that until such data is available, serology tests should not be used as a standalone tool to make decisions about personal safety related to SARS-CoV-2 exposure.

New One-Piece Injection-Molded COVID-19 Swab An innovative one-piece injection molded design for a COVID-19 swab could help close the gap in US and global COVID-19 testing supplies. The Hoowaki NP Collection

World’s First High-Throughput, Multi-Antigen COVID-19 Biochip Test

Sengenics (Singapore; www.sen genics.com), a functional proteomics company, has launched ImmuSAFE COVID+, the world’s first high-throughput, multi-antigen COVID-19 biochip test. A multi-antigen, multi-domain, fully quantitative serology test, ImmuSAFE enables the determination of the target epitopes, titres and Ig class/sub-class (IgG, IgA, IgM; IgG1-4) of antibodies produced across all stages of COVID19 infection, from initial exposure, disease development, post-recovery or post-vaccination. These results will provide critical insights on whether individuals have high titres of potentially neutralizing antibodies against SARS-CoV-2 that may protect against re-infection or whether booster vaccinations are required.

New Platform to Accelerate COVID-19 Tests

Testing for coronavirus infection could become quicker, more convenient and more accurate, following the launch of a multi-centre national program of research in the UK that will

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PRODUCT NEWS

To receive prompt and free information on products, log on to www.LinkXpress.com or fill out reader service form located on last page, or scan the QR code on your mobile device

HEMATOLOGY ANALYZER DIASYS DIAGNOSTIC SYSTEMS

COVID-19 HOME TESTING KIT GENE SCIENCE

SARS-COV-2 IGM & IGG CLIA ASSAYS SHENZHEN YHLO BIOTECH

The respons®5H is a 5 part differential hematology analyzer with a throughput of 60 tests/hour and requires only one drop of blood sample. Its reagent consumption is approximately 70% less than most other analyzers.

The Novel Coronavirus (2019-nCoV) IgM/IgG Antibodies Detection Kit (Latex Chromatography) is intended for the qualitative detection of Coronavirus SARS-CoV-2 to enable preliminary screening of early infected patients.

YHLO’s IgG and IgM combined detection is a good supplementary diagnostic tool to PCR, identifying immunity to COVID-19 after infection in mass population. Its titer change is used to monitor treatment of COVID-19 patients.

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Technology Discriminates Parkinson’s Disease from Multiple System Atrophy

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t is challenging to distinguish between Parkinson’s Disease and Multiple System Atrophy (MSA) because the early signs are similar, disturbances in movement, tremors, uncontrollable movements during sleep, impaired speech, but the diseases progress differently and can require distinct treatment plans.

Parkinson’s Disease (PD) leads to shaking, stiffness, and difficulty with balance and movement as well as a host of nonmotor symptoms. MSA leads to similar motor impairment, and also earlier and more severe dysfunction of the autonomic nervous system, which controls involuntary actions such as blood pressure, digestion, and urination. MSA progresses quicker and is often mistaken for PD at first. Both diseases are characterized by deposits of a protein known as alpha-synuclein (aSyn) in the nervous system.

A team of scientists from different institutions and led by those at the University of

COVID-19 Special Report: Six Months into Pandemic Widespread Testing Remains Global Priority

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Swab has been developed by Hoowaki LLC (Greenville, SC, USA; www.hoowaki. com) using its proprietary HOOWAKI MICROGRIP surface technology to create micropillars. The swab met existing industry-standard products for flexibility and performance in clinical user testing and has also proven to be equivalent to the industry-standard flocked filament swabs in the collection of patient RNA that is critical for COVID-19 testing in independent laboratory testing (qPCR Assay).

Texas McGovern Medical School at Houston (Houston, TX, USA; https://med.uth. edu) used Protein Misfolding Cyclic Amplification (PMCA) technology that was shown in previous studies to detect misfolded proteins associated with diseases such as Creutzfeldt-Jakob and Alzheimer's disease. The investigators targeted misfolded aSyn aggregates as a way of developing a sensitive biochemical diagnosis for PD. The team put a small amount of the proteins in question from the patient's cerebrospinal fluid together with normal proteins and watched to see if and how they converted the normal proteins.

The scientists used a combination of biochemical, biophysical and biological methods to analyze the product of α-synucleinPMCA, and found that the characteristics of the α-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson’s disease and multiple system atrophy. They also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain.

These findings suggest that α-synuclein aggregates that are associated with Parkinson’s disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA. The aSyn-PMCA can successfully discrimi-

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nate between PD and MSA with an overall sensitivity of 95.4%, which could allow doctors a look into the future to see which disease they need to address. The study also helps to understand the basis of these diseases at the molecular basis.

Claudio Soto, PhD, a Professor of Neurology and senior author of the study, said “Our latest study shows that the aSyn aggregates of PD and MSA have different properties, so by amplifying the abnormal aggregates we can detect with high efficiency which disease the patient has. This has huge implications both for accurate diagnosis and clinical care of the patient, and the development of new specific treatments for both diseases.” The study was published on February 5, 2020 in the journal Nature.

Image: Immunohistochemistry for alphasynuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease (Photo courtesy of Marvin101).

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PRODUCT NEWS

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Molecular Characteristics of leptomeningeal Melanoma Metastases Identified

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atients with advanced melanoma who develop metastases in the leptomeninges, the fluid filled membranes surrounding the brain and spinal cord, have an extremely poor prognosis. Most patients only survive for eight to 10 weeks after diagnosis.

Cancer development and progression are highly regulated by intricate interactions between cancer cells and the surrounding environment. Melanoma cells that invade and metastasize into the leptomeninges interact with the surrounding cerebrospinal fluid. One reason for the poor prognosis is that very little information is known about the molecular development of leptomeningeal melanoma metastases (LMM), making it difficult to develop effective therapies.

Molecular oncologists and their colleagues at the Moffitt Cancer Center (Tampa, FL, USA; www.moffitt.org) collected a total of 45 serial cerebrospinal fluid (CSF) samples from 16 patients, eight of these with confirmed LMM. Of those with LMM, seven had poor survival (<4 months) and one was an extraordinary responder (still alive with survival >35 months). CSF samples were analyzed by mass spectrometry and incubated with melanoma cells that were subjected to RNA-Seq analysis. Functional assays were performed to validate the pathways identified.

The scientists reported that mass spectrometry analyses showed the CSF of most LMM patients to be enriched for pathways involved in innate immunity, protease-mediated damage, and insulin-like growth factor (IGF)-related signaling. All of these were anti-correlated in the extraordinary responder. The most commonly altered protein was Transforming growth factor beta 1 (TGF-β1). Interestingly, the one patient who had an extraordinary response to treatment displayed high levels of these proteins at baseline, but expression levels decreased as the patient responded to treatment.

RNA-Seq analysis showed CSF to induce PI3K/AKT, integrin, B-cell activation, S-phase entry, TNFR2, TGF-band oxidative stress responses in the melanoma cells. ELISA assays confirmed that TGF-β expression increased in the CSF of patients progressing with LMM. CSF from poorly responding patients conferred tolerance to BRAF inhibitor therapy in apoptosis assays. However, the protein expression patterns in the remaining LMM patients who had poor responses to treatment were high at baseline and remained high throughout treatment and disease progression.

The findings demonstrate that the CSF from LMM patients who did not respond to treatment promoted survival of melanoma cells,

epsis due to antimicrobial resistant pathogens is a major health problem worldwide. The inability to rapidly detect and thus treat bacteria with appropriate agents in the early stages of infections leads to excess morbidity, mortality, and healthcare costs.

Sepsis can be caused by a very low abundance of pathogens in the bloodstream, and most diagnostic technologies require pathogen

concentration, a days-long culture step, and pathogen extraction steps that have the potential to reduce sensitivity. Time to diagnosis is also critical in cases of suspected sepsis, as mortality increases 4% for every hour delay until treatment.

Scientists at the University of California, Irvine (Irvine, CA, USA; www.uci.edu) and their associates have developed a rapid diagnostic platform that integrates a novel one-step

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while the cerebrospinal fluid from the extraordinary responder did not promote survival. These observations suggest that molecules exist within the cerebrospinal fluid that can stimulate melanoma cell survival and prevent cell death.

The authors concluded that their analyses identified proteomic/transcriptional signatures in the CSF of patients who succumbed to LMM. They further showed that the CSF from LMM patients has the potential to modulate BRAF inhibitor responses and may contribute to drug resistance. The study was published on January 10, 2020 in the journal Clinical Cancer Research.

Image: Histopathology of Leptomeningeal Melanoma Metastases: tumor cell clusters in the subarachnoid space in a brain biopsy (Photo courtesy of selbst).

Rapid UTI, Sepsis Tests Use Digital PCR

blood droplet digital polymerase chain reaction (PCR) assay and a high throughput 3D particle counter system with potential to perform bacterial identification and antibiotic susceptibility profiling directly from whole blood specimens, without requiring culture and sample processing steps.

The team used the cefotaximase-M-9 (CTXM-9) family extended-spectrum β-lactamases Cont’d on page 20

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21-Gene Recurrence Score Helps Radiation Decision-Making

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new study shows that a test that physicians commonly used to guide chemotherapy treatment for postbreast cancer surgery patients may also help them decide whether radiation therapy may be of benefit.

Known as the 21-gene recurrence score, the test is a personalized analysis of the activity of 21 genes found in a patient's breast tumor tissue. The score can be used to predict whether, after undergoing surgery, that patient's breast cancer is likely to return in another part of their body, like the bones or lungs, and whether that patient will likely benefit from chemotherapy treatment.

A large team of scientists led by those at the University of Texas MD Anderson Cancer Center (Houston, TX, USA; www.mdanderson.org) carried out a retrospective analysis of, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy.

Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, nine who received breastconserving surgery without documented radiotherapy, and five with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019. The team examined the association between recurrence score and locoregional recurrence (LRR) in the treated postmenopausal patient population.

The 21-gene recurrence score test was the Oncotype DX Breast Recurrence Score (Genomic

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clinical variables, to assess the risk of LRR during radiotherapy decision-making. The study was published on January 9, 2020 in the journal JAMA Oncology .

Image: The Oncotype DX specimen and collection kit for the Breast Cancer Recurrence Score Assay (Photo courtesy of Genomic Health).

Bone Marrow Donors May Transfer Pathogenic Mutations to Patients

lonal hematopoiesis of indeterminate potential, or CHIP, is characterized by the presence of mutant hematopoietic stem cell clones in the bone marrow without overt signs of disease.

However, emerging evidence suggests that this CHIP condition, which is more common in older patients, may not be as innocuous as previously thought, with recent studies connecting CHIP to a variety of medical problems.

A team of hematology and oncology experts led by the Washington University School of Medicine (St. Louis, MO, USA; www.wustl. edu) demonstrated in a new sequencing study that even young bone marrow donors may have pathogenic mutations that can take hold in those receiving stem cell transplants for acute myeloid leukemia (AML) or other blood cancers. They used deep, error-corrected sequencing, a method designed to detect mutations at levels as low as one in 10,000 cells, to search for somatic mutations in 80 AML-related genes in multiple bone marrow and blood samples from 25 matched bone marrow donors and recipients.

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Health, Inc, Redwood City, CA, USA; www.genomichealth.com).

The investigators reported that median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score. Among 252 patients who had a mastectomy without radiotherapy, the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group versus 16.8% for the intermediate or high recurrence score group.

In a subset analysis of patients with a mastectomy and one to three involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had an 11.1% LRR. Wendy A. Woodward, MD, PhD, a professor and the lead investigator, said, â&#x20AC;&#x153;We believe these data support using recurrence scores along with standard clinical factors like age or tumor size - to determine risk of recurrence and radiotherapy decisions for patients.â&#x20AC;?

The authors concluded that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted

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LabMedica International June-July/2020

In the process, the team tracked down somatic mutations in 11 of the donors between the ages of 20 and 58 years. The vast majority of those mutations were predicted to be pathogenic, and all of those risk mutations subsequently turned up in corresponding bone marrow samples from stem cell transplant recipients. Clonal mutations, with a median variant allele frequency of 0.00247, were found in 11 donors (44%; median, 36 years old). Of the mutated clones, 84.2% of mutations were predicted to be molecularly pathogenic and 100% engrafted in recipients.

Perhaps most concerning, the team noted that graft-versus-host disease eventually occurred in three quarters of the AML patients who received mutation-containing bone marrow and had those mutations in their own marrow later on. In contrast, graft-versus-host disease turned up in around half of the patients who received seemingly mutation-free bone marrow.

Todd Druley, MD, PhD, an associate professor of pediatrics and senior author of the study, Contâ&#x20AC;&#x2122;d on page 25

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HEMATOLOGY ANALYZER

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The HumaStar 600 clinical chemistry analyzer with a throughput of 900 to 2250 tests per day is designed to run daily photometric and immunoturbidimetric routine as well as optional direct ISE measurement.

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Resilient Bacteria May Be Treatable With Currently-Available Therapies

acteria develop defenses against hostile elements in their environment. One common tactic is "tolerance," that is, lying dormant during antibiotic treatment. In this way, bacteria evade antibiotic treatment because antibiotics can only spot and kill growing targets.

However, this intermediary stage called "antibiotic tolerance" lasts only a few days and cannot be detected in standard medical laboratories.

Therefore, doctors miss the tolerance window and with it the opportunity to treat a serious infection before it becomes altogether resistant.

This short window does not affect most healthy adults, but for those patients fighting off a blood infection with a weakened immune system, this window is critical and could mean the difference between life and death.

Scientists at The Hebrew University of Jerusalem (Jerusalem, Israel; www.huji.ac.il) and their colleagues developed a mathematical model that successfully described, measured and predicted when bacteria would develop tolerance to a particular antibiotic. Further, they observed that when bacteria developed tolerance to one antibiotic, they were more likely to develop tolerance to other antibiotics in the cocktail. They have analyzed daily bacterial samples from hos-

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pitalized patients with life-threatening, persistent methicillin-resistant Staphylococcus aureus (MRSA) infections.

The investigators detected the rapid emergence of tolerance mutations, followed by the emergence of resistance, despite the combination treatment. Evolution investigations on the clinical strains in vitro revealed a new way by which tolerance promotes the evolution of resistance under combination treatments. Further, in the study, under different antibiotic classes reveal the generality of the effect. The team believes that the same evolutionary processes involved in the development of antibiotic tolerance and resistance are likely at play in cancer and might be used to inform treatment. For example, tumor cells might first become tolerant of chemotherapy, develop resistance to it, and then develop resistance to other cancer drugs, as well.

Nathalie Q. Balaban, PhD, a professor and the senior author of the study, said, “We ob-

served that bacteria acquired tolerance within a few days. These tolerance mutations then acted as a stepping stone to acquire resistance and, ultimately, treatment failure. Using the right combination of available antibiotic drugs at the outset could dramatically increase a patients' survival rate before their infection becomes tolerant to all the antibiotics in our arsenal.” The study was published on January 10, 2020 in the journal Science.

Image: Methicillin-resistant Staphylococcus aureus (MRSA) growing normally in upper panel and tolerant to an antibiotic in lower panel (Photo courtesy of Nathalie Balaban and Jiafeng Liu).

Rapid UTI, Sepsis Tests Use Digital PCR

(ESBLs) as a model system, and demonstrated that their technology developed by Velox Biosystems (Irvine, CA, USA; www.veloxbio. com) can simultaneously achieve unprecedented high sensitivity (10 CFU per mL) and rapid sample-to-answer assay time (one hour).

In head-to-head studies, by contrast, real time PCR and Bio-Rad ddPCR (Bio-Rad, Hercules, CA, USA; www.bio-rad.com) only exhibited a

limit of detection of 1,000 CFU per mL and 50–100 CFU per mL, respectively.

In the study, the team spiked whole-blood samples with a strain of Escherichia coli containing a synthetic resistance gene and was able to detect bacteria and resistance within one hour. The detection required no culture or sample processing, with a limit of detection of less than 10 colony-forming units per milliliter.

The group was also able to demonstrate multi-

plexing ability for two targets per droplet. The study also detailed strategies to overcome the PCR inhibitory effects common to whole blood, a method to enhance the ability to partition blood into droplets by diluting it, and determined that the ideal fluorophore to get past the autofluorescence of blood was a dye called Quasar 670 from LGC Biosearch Technologies (Teddington, UK; www.biosearchtech.com).

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LabMedica International June-July/2020

Modular Targeted Capture Assay Detects Clinically Significant Oncology Alterations

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LabMedica International

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Medical Laboratory Scientists at the University of Washington Medical Center (Seattle, WA, USA; www.uwmedicine.org) used DNA samples for the validation of their OncoPlex Cancer Gene Panel version 6 (UWOPXv6) were derived from 108 unique specimens from 29 different adult and pediatric neoplasms including central nervous system (CNS) malignancies, leukemia/lymphoma, melanoma, sarcoma, and carcinomas of the lung, breast, endometrium, bowel, and prostate, in addition to five germline samples. UW-OncoPlex is a multiplexed mutation assay for tumor tissue that assesses mutations >350 genes related to cancer treatment, prognosis, or diagnosis.

The team described the validation of OncoPlex version 6 (OPXv6) for the detection of single nucleotide variants (SNVs), insertions and deletions (indels), copy number variants (CNVs), structural variants (SVs), microsatellite instability (MSI), and tumor mutational burden (TMB) in a panel of 340 genes.

All samples had prior molecular characterization via orthogonal clinical tests including both laboratory-developed amplicon-based and hybridcapture-based NGS assays and/ or a custom commercial RNA sequencing assay (FusionPlex, ArcherDx, Boulder, CO, USA; https://archerdx.com).

DNA was extracted using one or more kits from Qiagen (Qiagen, Valencia, CA, USA; www.qiagen.com) depending on specimen type and nucleic acid extraction desired. Libraries were prepared from genomic and cell-free DNA, hybridized to a custom panel of xGen Lockdown probes, and sequenced on Illumina platforms (Illumina, San Diego, CA, USA; www.illumina.com). Sequences were processed through a custom bioinformatics pipeline, and variant calls were compared to prior orthogonal clinical results.

The scientists reported that the performance characteristics of OPXv6 are excellent for all tested variant classes (SNVs, Indels, SVs, and CNVs), both using standard protocols and in the setting of decreased DNA input and multiple methods of nucleic acid extraction. Accuracy was 99% for SNVs â&#x2030;Ľ5% allele fraction, 98% for indels, 97% for SVs, 99% for CNVs, 100% for MSI, and 100% for TMB. Library preparation turnaround time decreased by 40%, and sequencing quality improved with a 2.5-fold increase in average sequencing coverage and 4-fold increase in percent on-target.

The authors concluded that OPXv6 demonstrates improvements over prior UW-OncoPlex versions including reduced capture cost, improved sequencing quality, and decreased time to result. The modular capture probe design also provides a

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nimble laboratory response in addressing the expansions necessary to meet the needs of the continuously evolving field of molecular oncology.

The study was published on February 3, 2020 in the journal Practical Laboratory Medicine.

Image: Copy number variants (CNVs) detection directly by UW-OncoPlex sequencing; depicted are examples from a melanoma and colon cancer sample (Photo courtesy of Noah G. Hoffman, MD, PhD).

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The scanR High-Content Screening Station combines the modularity and flexibility of a microscope-based setup with the automation, speed, and throughput demanded by highcontent screening. lINkXPRESS COM

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The Sofia SARS Antigen Fluorescent Immunoassay (FIA) uses advanced immunofluorescence-based lateral flow technology in a sandwich design for qualitative detection of nucleocapsid protein from SARSCoV-2.

The m24sp is an instrument for laboratories with midthroughput requirements offering automated flexibility.

It is an automated bench-top system with a small footprint and reliable extraction using mSample Preparation chemistry.

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Ovarian Cancer Protein Contributes to Alzheimer's Disease Neurodegeneration

lzheimer's disease is a complex neurological disorder with pathological hallmarks of hyperamyloidosis (senile plaques), neurofibrillary tangles containing hyperphosphorylated tau, and extensive neurodegeneration in the brain.

Alzheimer's disease (AD) pathogenesis remains elusive and no effective therapy is available. Neurodegeneration, including synaptic damage and neuronal loss, forms the basis of dementia in AD, and certain brain regions are more vulnerable during disease progression.

Scientists at the Houston Methodist Research Institute (Houston, TX, USA; www.houstonmethodist.org) and their colleagues reported on a new role of ovarian cancer immune-reactive antigen domain containing 1 (OCIAD1). Originally discovered for its effect on ovarian cancer metastasis and stem cell metabolisms, the group found the OCIAD1 protein in human brain cells, and determined it impairs neurons and damages synapses in the brain, contributing to neurodegeneration in Alzheimer's disease.

The investigators culled through archived bioinformatics data of brain tissue from deceased Alzheimer's patients, as well as mouse models by blending computational methods with laboratory studies. They determined that OCIAD1 plays a role in the disease's progressive neurodegeneration by impairing mitochondria function. Known as the powerhouse of cells, damage to mitochondria results in the trickle-

Affordable COVID-19 Panel Aims to Serve Emerging Countries

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The IgG kits use Spike protein antigens to ensure clinical relevance and specificity, while the IgM kits employ a combination of Spike and Nucleocapsid antigens.

The performance and accuracy of the tests have been validated by multiple studies conducted at public and private laboratories, as well as universities. Aside from being CE marked, and pending EUA authorization in the USA, the ErbaLisa COVID-19 tests have also been approved by regulatory bodies across the globe, from ANVISA in Brazil to the ICMR in India.

Erba Mannheim is now focused on making these tests available to labs across emerging markets in Asia, Latin America, and Middle East/Africa. With ongoing challenges in the supply of reliable COVID-19 tests, and most large IVD concerns still bent on serving European and North American needs, Erba Mannheim's kits fill a crucial need across the emerging world.

down cell death effect in the brain leading to neuron damage.

Higher levels of OCIAD1, found in vulnerable brain areas and dystrophic neurites, were correlated with disease severity. Multiple early AD pathological events, particularly Aβ/GSK-3β signaling, elevated OCIAD1, which in turn interacts with BCL-2 to impair mitochondrial function and facilitates mitochondria-associated neuronal injury.

Notably, elevated OCIAD1 by Aβ increases cell susceptibility to other AD pathological challenges.

Xuping Li, PhD, an instructor of Neurodegeneration in Oncology and co-corresponding author, said, “We applied a system biology strategy to see if we could find a different mechanism of neurodegeneration in Alzheimer's disease. We identified OCIAD1 as a new neurodegeneration-relevant factor, predicted its function, and demonstrated it mediates the long-term impact of amyloid beta on cells and synaptic damages by impairing mitochondria function.” The study was published on January 12, 2020 in the journal EBioMedicine.

Image: In the brain of mice with Alzheimer's, areas near amyloid plaques (A) appear with fewer neural networks (B), dying neurons (C) and higher OCIAD1 (D). In cultured neuronal cells, the OCIAD1 proteins (E) appear in the mitochondria (F) (Photo courtesy of Houston Methodist Research Institute).

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Artificial Intelligence Improves Prostate Cancer Diagnosis

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rostate cancer is a frequently occurring type of cancer, but not always aggressive: more men die with prostate cancer than from prostate cancer. However, its treatment has many consequences for the quality of life of patients, so determining aggressiveness is an important step in choosing a treatment.

To determine the aggressiveness of the cancer, biopsies are taken from the prostate, which are scored by a pathologist. This 'Gleason score' is then used to classify biopsies into five groups - the Gleason Grade Groups - which indicate the risk of dying from prostate cancer.

However, this is a subjective process; whether and how a patient is treated may depend on the pathologist who assesses the tissue.

A team of scientists from the Radboud University Medical Center (Nijmegen, The Netherlands; www.radboudumc.nl) developed an AI system that examines those biopsies the same way a pathologist does.

The AI system also determines the Gleason score, and then the system can classify a biopsy according to the Gleason Grade Groups. By means of deep learning, the system examined thousands of images of biopsies to learn what a healthy prostate is, and what more or less aggressive prostate cancer tissue looks like. A semi-automatic labeling technique was used to circumvent the need for manual annotations by pathologists, using pathologists' reports as the reference standard during training. The system was developed to delineate individual glands, assign Gleason growth patterns, and determine the biopsy-level grade.

The investigators collected 5,759 biopsies from 1,243 patients. The developed system achieved a high agreement with the reference standard and scored highly at clinical decision thresholds: benign versus malignant (area under the curve 0.99), grade group of 2 or more (0.978), and grade group of 3 or more (0.974). In an observer experiment, the deep-learning system scored higher (kappa 0.854) than the panel (median kappa 0.819), outperforming 10 of 15 pathologist observers.

On the external test dataset, the system obtained a high agreement with the reference standard set independently by two pathologists (quadratic Cohen's kappa 0.723 and 0.707) and within inter-observer variability (kappa 0.71).

The authors concluded that their automated deep-learning system achieved a performance similar to pathologists for Gleason grading and could potentially contribute to prostate cancer diagnosis. The system could potentially assist pathologists by screening biopsies, providing second opinions on grade group, and presenting quantitative measurements of volume percentages. The study was published on January 8, 2020 in the journal The Lancet Oncology.

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Image: Photomicrograph of a histological biopsy of a prostatic adenocarcinoma, conventional (acinar) type, the most common form of prostate cancer (Photo courtesy of Nephron).

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PCR SYSTEM

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C-PEPTIDE ASSAY

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The SARS-CoV-2 Total (COV2T) Assay detects both IgM and longer-lasting IgG antibodies with high sensitivity of recent and prior infection, allowing for identification of patients who have developed an adaptive immune response.

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Homologous Recombination Defects Prevalent in African-American Cancer Patients

n the USA, African-Americans have the highest cancer incidence and lowest survival across multiple cancer types. The reasons for these persistent trends are not clear.

Lung cancer, the second most common cancer in the USA and the leading cause of cancer-related death, has persistent disparities in both incidence and mortality African-Americans have the highest lung cancer incidence and mortality rates compared with other racial or ethnic groups.

Scientists from the National Cancer Institute (Bethesda, MD, USA; www.cancer.gov) and their associates generated and compared genomewide copy number profiles for 222 non-small cell lung cancer samples obtained from 126 African-American and 96 European-American patients.

DNA was extracted from fresh, frozen micro-dissected primary lung tumor tissues using the Qiagen DNeasy Blood and Tissue kit spin column procedure (Qiagen, Hilden, Germany; www.qiagen.com). Isolated primary lung tumor DNA was initially quantified using a DS-11 spectrophotometer (DeNovix, Wilmington, DE, USA; www.denovix.com).

Subsequent Qubit fluorometer (Thermo Fisher Scientific, Waltham, MA, USA; www.thermofisher.com) analyses were performed to assess DNA integrity and ensure the presence of intact double-stranded DNA in all samples.

The team estimated the tumors' genomic instability by determining the portion of their genomes that harbored a non-diploid copy number.

They found that lung squamous cell carcinomas from African-Americans had higher genomic instability compared to those from European Americans. They did not, however, uncover significantly higher genomic instability in lung adenocarcinomas from American Americans, as compared to European Americans.

The team extended their analysis to 6,492 tumors from The Cancer

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The team also demonstrated that the technology can be broadly applicable for targeted detection of a wide range of antibiotic resistant genes found in both Gram-positive (vanA, nuc, and mecA) and Gramnegative bacteria, including ESBLs (blaCTX-M-1 and blaCTX-M-2 families) and CREs (blaOXA-48 and blaKPC), as well as bacterial speciation (E. coli and Klebsiella spp.) and pan-bacterial detection, without requiring blood culture or sample processing. The study was first published on December 16, 2019 in the journal Lab on a Chip.

Genome Atlas to find that tumors from African-American patients had a higher burden of genomic instability as well as of homologous recombination deficiencies. In particular, 11 of the 17 cancer types analyzed exhibited higher homologous recombination deficiency in African-Americans. Additionally, a mutational signature associated with homologous recombination deficiency was more prevalent among these tumors. In both a pan-cancer analysis and a lung squamous cell carcinoma-specific one, they found that African-American patients had significantly higher germline homologous recombination deficiencies than European-American patients. Pan-cancer, they found pathogenic variants in BRCA2, PALB2, and BARD1, among other genes, to be enriched in AfricanAmerican patients.

Higher homologous recombination deficiency in lung squamous cell carcinoma and other cancers hints that these tumors could potentially respond to poly ADP ribose polymerase (PARP) inhibitors and that African-American patients in particular might be more likely to respond to PARP inhibitor treatments. While PARP inhibitors are not commonly used to treat lung cancer, the scientists noted, they have been shown in some studies to be effective in combination with chemotherapy. The study was published on January 13, 2020 in the journal Nature Cancer.

Image: The DS-11 Series of Spectrophotometers are used to perform fast quantification of nucleic acids and proteins (Photo courtesy of DeNovix).

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Diagnostic Assay for leukemic Stem Cells

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LabMedica International

cont’d from cover

show resistance to these procedures. The cause of relapse or resistance to treatment is sometimes due to the existence of leukemic stem cells capable of starting cancer again, and in turn, for being resistant to chemotherapy. However, identifying them is a challenge since there are no specific markers to detect and isolate them.

Scientists at the Josep Carreras Leukaemia Research Institute (Badalona, Spain; www.carrerasresearch.org) and their colleagues carried out a prospective hospital-based cohort study that included 43 newly diagnosed patients with acute myeloid leukemia. There were 30 males, and 13 females; with a median age of 63 years, (range 26– 91) in the study cohort. A total of 12 out of 43 patients underwent allogeneic stem cell transplant (ASCT) following chemotherapy.

The team used flow cytometric cellular alkaline phosphatase (ALP) activity within primitive leukemic cells which allowed them to identify two groups of patients at diagnosis according to the numbers of leukemic blasts expressing ≥ 12% of ALP+ cells (27 patients, Group A) and less than 12% of ALP+ cells (16 patients, Group B). All 38 EDTA-anticoagulated bone marrow and five blood samples were prepared using a modified previously developed method aimed at avoiding the lysis of erythrocytes during sample preparation, which can result in unwanted damage to leukocytes, and conceivably to leukemic cells.

DNA content cell cycle and stem cell Side Population analysis was accomplished by flow cytometry. Stained cells were diluted with Hank’s Balanced Salt Solution (HBSS) (1,000 µL final volume) prior to sample acquisition. All cell measurements were done using the Attune Acoustic Focusing Cytometer and the Attune NxT Acoustic Focusing Cytometer (Thermo Fisher Scientific, Eugene, OR, USA; www.thermofisher.com).

The scientists reported that differences in outcome for complete response, relapse or treatment resistance, and exitus were statistically analyzed and were significant, when comparing the two groups. The overall survival (OS) and event-free survival (EFS) differences between Group A and B were statistically significant. The survival of Group A patients was significantly shorter than those for Group B. The AML patients had a median value of 18.33% ALP+ blast cells (range 0.26–96.93). Twenty-seven patients in Group A had a median value of 23.76% of ALP+ blast cells ranging from 13.83 to 96.63), and 16 patients in Group B had a median value of 4.99% of ALP+ blast cells ranging from 0.26 to 11.98.

The authors concluded that flow cytometric cellular ALP activity at diagnosis may be used to estimate relapses and disease persistence more accurately. The limitations of the study include the small number of patients enrolled and a short follow-up, due to its prospective nature. The study was published on December 10, 2019 in the journal Oncotarget.

Image: The Attune NxT Acoustic Focusing Cytometer is ideal for immunophenotyping and signaling studies, cell cycle analysis, detection of rare events, stem cell analysis, cancer and apoptosis studies, microbiological assays, and more (Photo courtesy of Thermo Fisher Scientific)

Bone Marrow Donors May Transfer Pathogenic Mutations to Patients

cont’d from page 19

said, “We didn't expect this many young, healthy donors to have these types of mutations. We also didn't expect 100% of the harmful mutations to be engrafted into the recipients. That was striking. This study raises concerns that even young, healthy donors' blood stem cells may have harmful mutations and provides strong evidence that we need to explore the potential effects of these mutations further.” The study was published on January 15, 2020 in the journal Science Translational Medicine.

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Biomarkers Identified for Delirium Risk and Severity

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Novel Reliable Assay for Tuberculosis and lTBI Tested

n estimated seven million hospitalized Americans suffer from the acute confusion and disorientation, characteristics of delirium, including a majority of patients in medical or surgical intensive care units (ICUs).

Individuals who experience delirium in the ICU are more likely to have more hospital-associated complications, longer stays and higher risk of readmission. They are more likely to experience cognitive impairment and also have a greater likelihood of dying for up to a year after their hospital stay than ICU patients who did not experience delirium.

Scientists at the Regenstrief Institute (Indianapolis, IN, USA; www.regenstrief.org) and the Indiana University School of Medicine (Indianapolis, IN, USA; https://medicine.iu.edu) carried out an observational study at three hospitals that included 321 participants. The team analyzed the associations between biomarkers collected at delirium onset and deliri-

uberculosis (TB), caused by Mycobacterium tuberculosis (MTB) complex organisms, is still one of the most prevalent human infections worldwide estimated in 2018 with 1.2 million deaths among human immunodeficiency virus (HIV)-negative people and an additional 251,000 deaths from TB among HIV-positive people.

Additionally, 1.7 billion people in the world’s population harbor a latent tuberculosis infection (LTBI) and thus they are at risk of developing active TB disease during their lifetime Consequently, urgent action is required to improve the diagnosis of both active TB and latent infection in order to set-up new screening tests for MTB that can be used for public health

um-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality.

After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C- Image: Biomarkers, including interleukin-6, have been isolatreactive protein, and S-100β lev- ed that can identify delirium risk and severity (Photo courtesy els in quartile 4 were negatively of Blood Tests London). associated with delirium-/comaand -10, tumor necrosis factor-α, C-reactive profree days by one week and 30 days post enrolltein, and S-100β levels in quartile 4 were also ment. Insulin-like growth factor-1 levels in quarassociated with delirium severity by one week. tile 4 were not associated with delirium-/comaCont’d on page 27 free days at both time points. Interleukin-6, -8,

to detect and treat individuals who are at high risk of developing active TB. Clinical scientists at the University of Florence (Florence; Italy; www.unifi.it) and their colleagues consecutively enrolled a total of 250 subjects that included 151 healthy subjects, 66 active TB patients and 33 subjects with LTBI. Diagnosis of active TB cases relied on clinical, microbiological and radiological findings. A group of 139 blood donors was recruited in Blood Center, Almaty, Kazakhstan; they were designated as “conditionally healthy” since all were negative by annual fluorographic examination.

The blood of all the patients was tested with LIOFeron TB/LTBI assay (Lionex GmbH

(Braunschweig, Germany; https://lionex. com), containing MTB alanine dehydrogenase, able to differentiate active TB from LTBI diagnosis. This assay is an interferon-gamma release assay (IGRA) and the optical density (OD) was quantified at 450 nm with a spectrophotometer (Multiskan Go, Thermo Scientific, Waltham, MA, USA; www.thermofish er.com). For comparison the assay was compared with the QuantiFERON-TB Gold Plus assay (Qiagen, Hilden, Germany; www.qia gen.com).

The investigators reported that the two assays demonstrated an excellent concordance of their results with patients’ diagnosis of MTB Cont’d on page 35

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Proteogenomic Characterization of Endometrial Carcinoma Analyzed

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E

ndometrial cancer is a cancer that arises from the endometrium which is the lining of the uterus or womb.

It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body.

Endometrial cancer occurs most commonly after menopause. Approximately 40% of cases are related to obesity. Endometrial cancer is also associated with excessive estrogen exposure, high blood pressure and diabetes. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain.

A large team of scientists led by those at the New York University School of Medicine (New York, NY, USA; https://med. nyu.edu) described their characterization of 95 prospectively collected endometrial carcinomas comprising 83 endometrioid and 12 serous tumors, and 49 normal tissues.

For their study, the investigators performed whole-exome, whole-genome, and total and miRNA sequencing on each tumor and normal sample, along with DNA methylation analyses. They also quantified the relative levels of the proteins and post-translational modification (PTM) sites across the samples.

The tumors were classified into four genomic subtypes: POLE, a rare ultramutated subtype with endometrioid histology and good prognosis; microsatellite instability (MSI), a hypermutated endometrioid subtype; copy-number (CNV) low, which consists of most of the rest of the endometrioid cases; and CNV-high, comprised of all serous and the most aggressive endometrioid cancers. The cohort included seven POLE, 25 MSI, 43 CNV-low, and 20 CNVhigh tumors. Protein and PTM levels dif-

cont’d from page 26

Image: Proteogenomic Characterization of Endometrial Carcinoma (Photo courtesy of the Clinical Proteomic Tumor Analysis Con-

Biomarkers Identified for Delirium Risk and Severity

At hospital discharge, interleukin-6, -8, and -10 retained the association, but tumor necrosis factor-α, C-reactive protein, and S100β lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100β levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality.

The authors concluded that biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium

27

fered between genomic subtypes.

The team reported that about 61% of all somatic mutations were found in the seven POLE tumors, while the MSI tumors carried 88% of all indels in the cohort. Additionally, they identified INPPL1, KMT2B, and JAK1 as putative significantly mutated genes (SMGs) in the MSI subtype. In another analysis, the team looked at TP53 mutations, finding them in 23 tumors in the cohort, including all serous carcinomas.

Rather than grouping all TP53-mutated tumors together and looking for a single molecular phenotype, they segregated them by mutation type and location and identified several proteomic and phosphoproteomic signatures.

The team also compared proteomic and transcriptomic changes between the cancer subtypes. They generated a score for each sample based on the DNA damage response (DDR) marker phosphoproteins and found that DDR-high samples were enriched for serous tumors and therefore the CNV-high subtype, but that DDR-high endometrioid tumors came from the CNV-high, POLE, and MSI genomic subgroups. This indicated that active DNA damage signaling is largely independent of genomic subtype.

The authors concluded that integrating comprehensive quantitative measurements of protein, phosphorylation, and acetylation with genomic and transcriptomic measurements not only has provided novel insights into fundamental biological processes associated with carcinogenesis, but also has provided intriguing leads for new therapeutic approaches in endometrial cancer, including potential criteria for selecting the most appropriate therapies. The study was published on February 13, 2020 in the journal Cell.

LabMedica International

LabMedica International June-July/2020

severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization should be considered.

Babar Khan, MD, who led the study, said, “If you can tell which patients will have higher delirium severity and longer duration and therefore greater probability of death, there are important treatment implications. Analyzing biomarkers to stratify risk for delirium is a promising approach with the potential to be applied regularly in ICU patients in the near future.” The study was published on January 16, 2020 in the journal Critical Care Medicine.

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T Cells Function as a Team to Fight Infection LabMedica International

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hen faced with an infection, T cells normally follow a remarkably reproducible response pattern of expansion, contraction, and memory formation. Population-intrinsic and -extrinsic regulation of T cells occur, but are not mutually exclusive.

Conventional T cell response is often measured by extrinsic signals, such as those sent by regulatory T cells or dendritic cells, which can be variable and thus difficult to use to infer population size. Alternatively, if a population of T cells mutually controls each other, then the strength of regulatory signals scales with population size in an intrinsic manner.

An international team of scientists collaborating with Albert-Ludwigs University (Freiburg im Breisgau, Germany; www.unifrei burg.de) used time-lapse microscopy, genetic perturbation, bioinformatic predictions, and mathematical modeling to investigate if CD8+ T cells use quorum regulation to control their population dynamics. The scientists found that activated T cells mutually promote their expansions when they are present at low densities, but they also limit further proliferation once sufficient numbers have been reached.

This mechanism leads to efficient amplification of initial immune reactions and also prevents potentially dangerous immunopathologies.

Specifically, CD28 and interleukin-2 (IL-2) induced CD80 expression by activated T cells, which could in turn bind to CD28 to augment IL-2 production. This positive feedback loop perpetuated T-cell expansion. However, at some point it becomes necessary to limit this amplification. This is accomplished through a negative feedback circuit acting via cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), by blocking ligand binding of CD28 and IL-2.

This evidence supports a mechanistic explanation of how T-cell population dynamics are regulated in a cell density manner by receiving signals from a variety of cell types.

The team found that Intercellular Adhesion Molecule 1 (ICAM-1)-mediated cell clustering enabled CD8 + T cells to collectively regulate the balance between proliferation and apoptosis. Mechanistically, T cell expressed CD80 and CD86 interacted with the receptors CD28 and CTLA-4 on neighboring T cells; these interactions fed two nested antagonistic feedback circuits that regulated IL-2 production in a manner dependent on T cell density as confirmed by in vivo modulation of this network.

Accordingly, CD8 + T cell-population-intrinsic mechanisms regulate cellular behavior, thereby promoting robustness of population dynamics.

Jan Rohr, MD, the senior author of the

hronic kidney disease (CKD) is estimated to affect about 10% of the general adult population and is even more prevalent in diabetic patients. It is estimated that 20%–40% of individuals with diabetes have moderate to severe CKD, ranking diabetes as the leading cause of end-stage renal disease (ESRD) and an important risk factor for morbidity and mortality in dialysis patients.

It is known that good glycemic control predicts better clinical outcomes for patients with diabetes, by limiting morbidity and mortality associated with cardiovascular complications and end-organ damage. It has been suggested that the relationship between glycated hemoglobin A1c (HbA1c) and blood glucose concentration is altered as the glomerular filtration rate (GFR) declines.

Scientists at the South African Medical Research Council (Cape Town, South Africa; www.mrc.ac.za) and their colleagues assess whether the agreement between fasting glucose and glycated proteins is affected by chronic kidney disease (CKD) in a communitybased sample of 1,621 mixed-ancestry South Africans. A standard oral glucose tolerance test (OGTT) was performed by drawing a blood sample after an overnight fast, as well as two hours after a 75 g oral glucose load, to determine plasma glucose and serum insulin concentrations.

Plasma glucose levels were measured by

enzymatic hexokinase method (Beckman AU, Beckman Coulter, Midrand, South Africa; www. beckman.com) and serum insulin with a paramagnetic particle chemiluminescence assay (Beckman DXI). HbA1c was analyzed with high-performance liquid chromatography (Bio-Rad Variant Turbo, Bio-Rad, Cape Town, South Africa; www. bio-rad.com), whereas hemoglobin was measured on a Coulter LH 750 hematology analyzer and fructosamine was determined by immunoturbidimetry on an ABX Pentra 400 autoanalyzer (Horiba Medical, Irvine, CA, USA; www.horiba.com).

The investigators reported that of those 96 with CKD, 79%, 16% and 5% where in stages 3, 4 and 5, respectively. Those with CKD had higher levels of HbA1c (6.2% versus 5.7%), glycated albumin (15.0% versus 13.0%) and fructosamine levels (269.7 versus 236.4 μmol/L), compared to those without CKD. Higher fasting glucose levels were associated with higher HbA1c, glycated albumin and fructosamine, independent of age, gender, and CKD. However, the association with HbA1c and glycated albumin differed by CKD status, at the upper concentrations of the respective markers.

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study, said, “We showed that these immune cells perceive and regulate each other. The immune cells act as a team and not as autonomously acting individualists. This principle of density control of immune cells is simple and very effective. This makes it reliable and at the same time hopefully accessible for therapeutic approaches.” The study was published on February 11, 2020 in the journal Immunity.

Image: This photomicrograph depicts T cells interacting with each other. Cell surfaces are labeled in red, cell nuclei in blue, and receptors mediating communication in green (Photograph courtesy of Immunity).

Glycemic Markers Influenced by Chronic kidney Disease

The authors concluded that though HbA1c and glycated albumin perform acceptably under conditions of normoglycemia, but their findings suggest that these markers significantly underestimate true glycemic levels in people with CKD, not on dialysis. The results suggest that fructosamine may potentially be a more reliable marker of glycemic levels in those with CKD with elevated fasting blood glucose. The study was published on January 30, 2020 in the journal BMC Nephrology.

Image: The ABX Pentra 400 is a compact clinical chemistry benchtop autoanalyzer (Photo courtesy of Horiba Medical).

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Blood Test Predicts Parkinson's Progression

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cont’d from cover

markers that could identify those at highest risk of early cognitive decline would enhance our understanding of disease progression and give valuable insights into the underlying pathophysiological mechanisms.

Scientists at Newcastle University (Newcastle Upon Tyne, UK; www.newcastle.ac.uk) and their associates examined the association of blood-derived markers of cell senescence and inflammation with motor and cognitive function over time in an incident PD cohort. Participants (154 newly diagnosed PD patients and 99 controls) underwent physical and cognitive assessments over 36 months of follow up.

The team analyzed whether markers of cellular senescence such as telomere length (TL), p16 and p21 expression, as well as inflammatory markers in blood samples taken close to diagnosis can be predictive of cognitive and motor progression of the disease over the next 36 months. Mean leukocyte TL and the expression of senescence markers p21 and p16 were measured at two time points (baseline and 18 months).

Investigators also selected five inflammatory markers from existing baseline data using Meso Scale Discovery (Rockville, MD, USA; www.mesoscale. com) electrochemiluminescent immunoassays, including the V-PLEX human pro-inflammatory panel. For the isolation of DNA, blood samples were collected using EDTA vacutainers (BD Diagnostics, Oxford, UK; www.bd.com). For the isolation of RNA, blood samples were collected in PAXgene Blood RNA Tubes (PreAnalytiX, Qiagen, Manchester UK; www.qiagen.com). The collection tubes were stored at –80 °C. The quantification of expression levels of p21 and p16 was performed by RT-qPCR analysis on a 7900HT Fast Real Time PCR system (Applied Biosystems, Foster City, CA, USA; www.thermofisher.com).

The team reported that their study demonstrated that PD patients had shorter telomeres at baseline and 18 months later compared to age-matched healthy controls. Those PD patients, who had developed dementia after three years, also had significantly shorter telomeres compared to individuals who were dementia-free at this time.

Baseline p16 levels were associated with faster rates of motor and cognitive decline over 36 months, while a simple inflammatory summary score at baseline best predicted cognitive score 36 months later in PD patients. A baseline inflammatory score consisting of five different cytokines gave the best prediction for cognitive scores of PD cases three years later, while lower p16 gene expression predicted a more rapid dis-

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ease progression over the same period in relation to both cognitive and motor scores.

Roger Barker, MBBS, MRCP, PhD, a Professor of Clinical Neuroscience and a co-author of the study, said, “Being able to reliably predict the clinical path a patient with newly diagnosed PD will follow would greatly help in terms of planning their treatment now and in the way we do trials of diseasemodifying interventions in the future. This study provides an example of how this could be done using a simple blood sample.” The study was published on January 13, 2020 in the Journal of Parkinson's Disease.

LabMedica International

Image: The V-PLEX Proinflammatory Panel 1 Human Kit measures 10 cytokines that are important in inflammation response and immune system regulation as well as numerous other biological processes (Photo courtesy of Meso Scale Discovery).

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lipocalin 2 Identified as Biomarker for Differential Diagnosis of Vascular Dementia

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esults obtained by a study conducted by several European research institutes suggest that lipocalin 2 is a promising biomarker for the differential diagnosis of vascular dementia.

Vascular dementia (VaD) is caused by a defect of blood flow arrival to the brain, which consequently generates neuronal damage. Currently, the clinical diagnosis of VaD is based on imaging criteria, and specific biochemical markers have not been identified.

In this regard, investigators at Bellvitge Biomedical Research Institute (Barcelona, Spain; www.idibell.cat) and collaborators at four other European centers evaluated the potential diagnostic use of cerebrospinal fluid (CSF) lipocalin 2 (LCN2), a secreted glycoprotein that has been suggested as mediating neuronal damage in vascular brain injuries.

LCN2 is a secreted glycoprotein involved in innate immunity and highly expressed in the central nervous system in response to injury and inflammatory stimuli. It has been discussed as a potential marker for Alzheimer’s disease (AD). Studies in humans have shown slightly elevated levels of LCN2 in plasma of patients with mild cognitive impairS TOR Y IBU APPL R T DIS ED TO IT INV

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ment (MCI) and in CSF of patients with multiple sclerosis. LCN2 has also been discussed as an attractive blood-based biomarker of inflammation, ischemia, and, in particular kidney injury. Lipocalin-2 is typically assessed for clinical or research purposes using ELISA or immunoturbidimetric assays.

For the current study, the investigators analyzed CFS samples from 472 patients in four European countries. Results revealed that LCN2 was significantly elevated in VaD compared to controls, Alzheimer’s disease (AD), other neurodegenerative dementias, and cognitively unimpaired patients with cerebrovascular disease. LCN2 discriminated VaD from AD without coexisting VaD with high accuracy.

To determine the role of lipocalin 2 in the brain of patients with vascular dementia, brain tissue samples were examined. These studies showed that glial cells were expressing lipocalin 2, and its expression pattern was different in vascular dementia or Alzheimer's disease.

The investigators concluded that their results indicated that CSF LCN2 was elevated in patients with VaD compared to controls, cognitively unimpaired patients with VBI (vertebrobasilar insufficiency), and other forms of dementia. The high diagnostic accuracy highlighted its potential as a biomarker for VaD in the differential diagnosis of dementia.

The lipocalin 2 study was published in the January 30, 2020, online edition of the journal Nature Communications.

Direct Oral Anticoagulants Determined by RDT in Urine Samples

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he rapid determination of the presence of direct oral anticoagulants (DOACs) in a patient remains a major challenge in emergency medicine and for rapid medical treatment decisions. All DOACs are excreted into urine.

Emergency situations with a need for point-of-care testing for the presence or absence of DOACs include emergent or urgent major surgical interventions, clinically relevant bleeding, or thrombotic episodes with known or unknown anticoagulant therapy, as well as the evaluation of unconscious patients or those unable to inform clinicians about their anticoagulant therapy.

An international team of scientists led by the Ruprecht Karls University of Heidelberg (Heidelberg, Germany; (www.uni-heidelberg.de) carried out a prospective, open-label, controlled, nonrandomized, multicenter study in Germany on subjects treated with a DXI (apixaban, edoxaban, and rivaroxaban) or the DTI dabigatran were included. The subjects were recruited from 18 outpatient care units specialized in oral anticoagulation.

Urine samples (4 mL) were transferred into polyethylene terephthalate tubes (V-Monovette Urine Z 4mL, Sarstedt AG, Nümbrecht, Germany; www.sarstedt.com) using plastic syringes. The DOAC Dipstick test (DOASENSE GmbH, Heidelberg, Germany; www.doasense.de) was performed on the urine sample at the time of collection by site personnel.

Next, barcodes were attached to the duplicate samples and recorded in the case report form. The samples were frozen immediately at –25 °C, transferred without interrupting the cold chain to a central laboratory for LC-MS/MS analysis. The chromatography system consisted of an ACQUITY H-Class UPLC System connected to an Autosampler, quaternary HPLC-Pump, Xevo TQ-S mass spectrometry detector, and a CSH C18 Column (Waters GmbH, Eschborn, Germany; www.waters.com).

The authors concluded that the present study shows that DOAC Dipstick test sensitively and specifically determines the presence of both Xa and IIa inhibitors in urine samples, if compared with the gold standard of LC-MS/MS. The evaluation of the DOAC Dipstick test in emergency medicine and other patient groups is ongoing. The study was published in the January 2020 issue of the journal Thrombosis and Haemostasis.

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Genetic Risk Factors Found in Gestational Diabetes

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estational diabetes mellitus (GDM) is a common pregnancy complication affecting 6%â&#x20AC;&#x201C;15% of pregnancies globally. Although the condition resolves after delivery in most cases, women with a history of GDM have a more than sevenfold increased risk of developing type 2 diabetes (T2D) compared with women with a normoglycemic pregnancy.

Individual single nucleotide polymorphisms (SNPs) and genetic risk scores (GRSs) capturing the cumulative risk conferred by these SNPs have been associated with T2D risk in the general population.

However, as women with a history of GDM already have an elevated baseline genetic risk for T2D compared with the general population.

The role genetic factors play in the development of T2D among women with a history of GDM may differ from that in the general population.

A team of scientists at the at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Rockville, MD, USA; www.nichd.nih.gov) sought to gauge whether genetic risk scores could distinguish women with a history of gestational diabetes who develop T2D from those who do not. They applied this score to two population cohorts, one from the USA and one from Denmark, to find that women with high genetic risk scores were more likely to go on to develop T2D. Their findings also indicated that eating healthy could mitigate some of that risk.

Genotyping was performed using the TaqMan quantitative polymerase chain reaction (PCR) method (Applied Biosystems, Foster City, CA, USA; www.thermofisher.com) in 1,855 study participants from the USA and 603 from Denmark. In all, 112 candidate SNPs were selected based on previous genome- wide association studies (GWAS) of T2D. Genotyping was additionally performed using highdensity SNP markers platforms, including, HumanHap, Infinium, OncoArray or Infinium HumanCoreExome (Illumina, San Diego, CA, USA; www.illumina.com).

Based on recent genome-wide association studies in European populations, the scientists identified 59 SNPs associated with T2D risk that they bundled into a genetic risk score for the condition. They then genotyped 2,434 white women with a history of gestational diabetes from the US Nurses' Health Study II and the Danish National Birth Cohort and determined their genetic risk scores. Of the women in the study, 601 developed T2D during the median follow-up period of 21 years for the US cohort and 13 years for the Danish cohort.

A high genetic risk score was associated with increased risk of developing T2D in both the US and Danish cohorts. When broken up by quartiles, the highest-scoring group was 19% more likely to develop T2D than the lowest scoring group. Every five risk alleles were associated with a 7% increase in T2D risk in the US cohort and 9% increase in risk in the Danish cohort.

The authors concluded that in a study based on two independent populations with a long follow- up period, they observed a significant association of genetic risk factors with the development of T2D. The magnitude of association, however, was modest. The study was published on February 13, 2020 in the journal BMJ Open Diabetes Research & Care.

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Image: Illumina microarrays are a robust system that allow investigators to find variants in simple nucleotide polymorphisms (SNPs). The microarrays are subsequently scanned in the iScan system (Photo courtesy of LABSERGEN LANGEBIO).

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Genetic Biomarkers Detect Incipient Tuberculosis, Predict Progression of the Disease

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to predict the disease at a very early stage and before symptoms arise.

To this end, they conducted a systematic review of published gene signatures found in blood samples from patients with TB compared to healthy individuals. Culture-confirmed and clinically or radiologically diagnosed pulmonary or extrapulmonary tuberculosis cases were included.

The investigators tested 17 candidate mRNA signatures in a pooled dataset from four studies comprising 1126 samples. This dataset included 183 samples from 127 incipient tuberculosis cases in South Africa, Ethiopia, The Gambia, and the United Kingdom. Results revealed that eight signatures (comprising one to 25 transcripts), which predominantly reflected interferon and tumor necrosis factor-inducible gene expression, had equivalent diagnostic accuracy for incipient tuberculosis over a two-year period.

The eight signatures achieved sensitivities of 24.7 to 39.9% over 24 months and of 47.1 to 81.0% over three months, with corresponding specificities of more than 90%. However, when using biomarker thresholds maximizing sensitivity and specificity with equal weighting to both, no signature met the min-

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imum Wold Health Organization (WHO) target product profile parameters for incipient tuberculosis biomarkers over a two-year period. Thus, blood transcriptional biomarkers reflected short-term risk of tuberculosis and only exceeded WHO benchmarks if applied to three to six-month intervals.

Senior author, Dr. Mahdad Noursadeghi, professor of infectious diseases at University College London, said, "About one-quarter of the world's population is thought to have been infected with the bacteria that cause TB. The majority of these individuals remain well and cannot transmit the disease. However, we currently do not know which people are most likely to develop TB disease after being infected. If we can identify these individuals, we can treat their infection more easily and prevent it from spreading to others. Our findings establish the gene signatures in blood which show most promise for identifying people who are at risk of disease. Future development of a blood test based on these findings could make an im-

portant contribution to efforts to reduce the impact and spread of this deadly infection."

The incipient TB study was published in the January 17, 2020, online edition of the journal The Lancet Respiratory Medicine.

Image: Photomicrograph of a sputum specimen showing the presence of numerous Mycobacterium tuberculosis bacteria (Photo courtesy of [U.S.] Centers for Disease Control and Prevention)

Identification of Rickettsial Biomarker Facilitates Early Diagnosis of Tick-borne Spotted Fevers

protein biomarker has been identified that enables the rapid and specific early diagnosis of tick-borne rickettsial diseases such as Rocky Mountain spotted fever and Mediterranean spotted fever.

The causative agent of these diseases is Rickettsia conorii, a Gram-negative, obligate intracellular bacterium of the genus Rickettsia. It is a member of the spotted fever group and the most geographically dispersed species in the group, recognized in most of the regions bordering on the Mediterranean Sea and Black Sea: Israel, Kenya, and other parts of North, Central, and South Africa, and India.

R. conorii causes the human disease called boutonneuse fever, Mediterranean spotted fever, Israeli tick typhus, Astrakhan spotted fever, Kenya tick typhus, Indian tick typhus, or other names that designate the locality of occurrence while having distinct clinical features. The disease presents as an eschar (dry, dark scab), acute fever, headache, and maculopapular rash. After entering the body, rickettsiae can cause vascular leakage, such as pulmonary or cerebral

edema. The prevailing vector is the brown dog tick, Rhipicephalus sanguineus.

Since there are no available tests for diagnosis of early R. conorii infection, Mediterranean spotted fever is often not diagnosed and left untreated, resulting in significant mortality. To address this critical need, investigators at the University of Texas Medical Branch (Galveston, USA; www.utmb. edu) applied a quantitative proteomics approach for analyzing the molecules secreted by primary human umbilical vein endothelial cells that had been infected with R. conorii.

Results revealed that of the 104 proteins whose abundance changed significantly in the R. conoriiâ&#x20AC;&#x201C;infected human umbilical vein endothelial cellsâ&#x20AC;&#x2122; secretome (the set of proteins expressed by an organism and secreted into the extracellular space), 46 proteins were up-regulated: 45 were host secreted proteins (including cytokines), and one was a rickettsial protein, the putative Nacetylmuramoyl-l-alanine amidase RC0497.

RC0497 is an enzyme that hydrolyzes the link between N-acetylmuramoyl residues and L-amino acid residues in cer-

tain cell-wall glycopeptides. Proteins with sequence highly homologous to RC0497 were found to be shared by many species of the spotted fever group rickettsiae, but not typhus group rickettsiae.

The investigators developed an immunoprecipitation (IP) enrichment-selected reaction monitoring (SRM) assay to detect the small amount of circulating RC0497, and this assay was validated as a diagnostic approach in a cohort of humans presenting with acute rickettsial infections.

"The detection of RC0497 has the potential to diagnosis a wide variety of rickettsial spotted fever infections, including Rocky Mountain spotted fever," said senior author Dr. Yingxin Zhao, assistant professor of internal medicine at the University of Texas Medical Branch. "The rickettsioses represent an important unmet need in human and veterinary medicine. Rickettsioses are a spectrum of potentially lethal diseases whose diagnosis and definitive treatment require a high index of suspicion."

The study was published in the January 16, 2020, online edition of the American Journal of Pathology.

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Glycoprotein-Specific Direct Platelet Autoantibody Testing in Immune Thrombocytopenia

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utoantibodies directed against platelet glycoproteins have long been accepted as a major pathophysiologic mechanism in immune thrombocytopenia (ITP), but platelet autoantibody (PA) testing has previously shown poor sensitivity for ITP diagnosis.

Direct assays for platelet autoantibodies, which measure antibodies on platelets, as opposed to indirect assays, which measure free antibodies in plasma, that are capable of detecting glycoprotein-specific autoantibodies are considered optimal for PA testing Hematologists at the Massachusetts General Hospital (Boston, MA, USA; www.mgh.harvard.edu) performed a comprehensive retrospective study of PA testing in adult patients with ITP strictly applying the criteria of the 2012 International Society on Thrombosis and Haemostasis (ISTH) and 2011 American Society of Hematology (ASH) guidelines. Of 986 PA assays performed, 485 assays in 368 patients met criteria and were included.

All PA assays meeting inclusion criteria were performed by using the commercially available PakAuto assay (Immucor, Brookfield, WI, USA; www.immucor.com), a direct and indirect solid-phase enzyme-linked immunosorbent assay (ELISA)-based test measuring antibodies against GPIIb/IIIa, GPIb/IX, and GPIa/IIa. This direct glycoprotein-specific PA assay measures antibodies eluted from the surface of platelets. A result was positive if optical density values were equal to or greater than two times the value obtained for the mean of the negative controls for the corresponding glycoprotein.

The scientists reported that the sensitivity and specificity of a positive test result for diagnosis of active ITP (n = 228 patients) were 90% and 78%, respectively. Sensitivity and specificity of a negative test result for

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Tumor DNA Platform Classifies Colorectal Cancer

clinical remission (n = 61 assays) were 87% and 91%. Antibodies against both glycoprotein IIb (GPIIb)/IIIa and GPIb/IX were required for the presence of antibodies against GPIa/IIa in patients with ITP. Logistic regression analysis revealed that more positive autoantibodies predicted more severe disease (relative to nonsevere ITP, relative risk ratio for severe ITP and refractory ITP was 2.27 and 3.09, respectively. Sixty-four patients with ITP had multiple PA assays performed longitudinally: all 10 patients achieving remission converted from positive to negative serologic results, and evidence for epitope spreading was observed in 35% of patients with ongoing active disease.

The authors concluded that glycoprotein-specific direct PA testing performed using ISTH recommendations in patients meeting ASH diagnostic criteria is sensitive and specific for ITP diagnosis and reliably confirms clinical remission. More glycoproteins targeted by autoantibodies predicts for more severe disease. The study was published on December 31, 2019 in the journal Blood Advances.

Image: The NEO Iris is a fully automated immunohematology analyzer for in vitro diagnostic testing of human blood (Photo courtesy of Immucor)

ost colorectal cancers are due to old age and lifestyle factors, with only a small number of cases due to underlying genetic disorders.

Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases.

The detection of circulating tumor DNA in the blood is a noninvasive method that may help detect cancer at early stages if the correct markers for evaluation are known. A new machine learning platform can identify patients with colorectal cancer (CRC) and helps predict their disease severity and survival.

Scientists at the Sun Yat-sen University Cancer Center (Guangzhou, China; www.uicc.org) and their colleagues first identified CRC-specific methylation signatures by comparing CRC tissues to normal blood leukocytes. They then created a diagnostic model based on nine methylation markers associated with colorectal cancer, which they identified by studying plasma samples from 801 patients with colorectal cancer as well as 1,021 controls.

This model accurately distinguished patients from healthy individuals with a sensitivity and specificity of 87.5% and 89.9%, respectively, and outperformed a clinically available blood test named serum carcinoembryonic antigen (CEA). Furthermore, a modified prognostic model helped predict the patients' risk of death over a follow-up period of 26.6 months on average, especially when combined with established clinical characteristics such as tumor location. The team found that a single circulating tumor DNA methylation marker, cg10673833, could yield high sensitivity (89.7%) and specificity (86.8%) for detection of CRC and precancerous lesions in a highrisk population of 1,493 participants in a prospective cohort study.

The authors concluded that they had showed the value of circulating tumor DNA (ctDNA) methylation markers in the diagnosis, surveillance, and prognosis of CRC. The study was published on January 1, 2020 in the journal Science Translational Medicine.

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Semi-Automatic Isoelectric Focusing Evaluated for Apolipoprotein E Phenotyping

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lasma apolipoprotein E (apoE) mainly arises from liver hepatocytes (75%), but the brain (astrocytes, oligodendrocytes, microglia, astrocytes) also synthesizes apoE found in the cerebrospinal fluid.

ApoE is a major component of lipoproteins which participates in the transport and clearance of lipids. ApoE4 status is a risk factor for Alzheimer’s and other neurodegenerative diseases, whereas apoE2 and also apoE4 increase the risk for cardiovascular disease.

A team of biochemists from the Sorbonne University (Paris, France; www.sorbonne-universite.fr) collected blood samples from 40 patients in the course of familial hypercholesterolemia screening or mixed dyslipidemia diagnosis. These patients had given their informed consent including genetic determination and APOE genotypes were already determined

by Sanger sequencing of a polymerase chain reaction (PCR) fragment encompassing the two polymorphic sites (rs429358 and rs7412).

The scientists used the Hydragel 18 Apo E Isofocusing kit (Sebia, Lisses, France; www.sebia.com) which is a qualitative kit for detection and identification of the different apoE phenotypes. A ready-to-use agarose gel containing ampholytes (pH gradient: 5–8) is used to perform a semi-automatic electrophoresis on a Sebia Hydrasys 2 Scan, followed by a specific immunofixation with anti-apoE antiserum. The “apoE isofocusing visualization” kit included antiserum diluent, stock solutions of anti-apoE antiserum and peroxidase-labeled antibody, and reagent for revelation (TTF1 and TTF2 developing solutions).

The team reported that the sera from the genotyped patients included in the study allowed them to test the following isoforms: E3/E3 (18 sera), E3/E4 (16 sera), E2/E2 (four sera) and E4/E4 (two sera). All phenotypes tested were 100% concordant to the genetic isoforms, even if all the possible phenotypes are not found in their population. Precision of the tech-

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nique was verified with the repeatability and the reproducibility tests for the different isoforms, since tests gave similar results. In addition, the reproducibility tests led them to perform three freezing-thawing cycles on serum samples and a 100% concordant interpretation with genotyping was maintained. There was no interference of hemolysis, glucose or hypertriglyceridemia at the respective concentrations of 45.3 μmol/L hemoglobin, 25.1 mmol/L glucose and 9.5 and 4.8 mmol/L triglycerides for the determination of the phenotype profile.

The authors concluded that this qualitative, semi-automatized method could yield a novel and simple tool to phenotype apoE isoforms. Validated on a cohort of patient samples with known genotype, it could be used either for screening and stratification of a patient cohort, or for clinical analysis when genetic material cannot be obtained. It could be a useful and supplementary tool helping the clinician in the diagnosis of dyslipidemic and neurodegenerative diseases. The study was published in the January 2020 issue of the journal Practical Laboratory Medicine.

Image: The Sebia Hydragel 18 Apo E Isofocusing showing different apoE isoforms from 16 patients tested. The “control serum” provided in the Sebia kit is included in each series, together with two already typed serum samples as internal controls (as an example, E3/E2 and E4/E4) (Photo courtesy of Sorbonne University).

D‐Dimer levels Predict Ischemic Stroke in Infective Endocarditis

nfective endocarditis (IE) is a life-threatening disease, especially in developing countries. IE may present many extra-cardiac symptoms or signs, in which neurological complications are the most prominent and severe.

The manifestations of these neurological complications include ischemic stroke, hemorrhagic stroke, mycotic aneurysms, brain abscesses, meningitis, and encephalitis. Ischemic stroke, characterized by the interruption of cerebral blood flow, is a dominant and frequent neurological complication of left-sided IE, as well as the main stroke type among all stroke cases in IE. Infectious disease specialists at the Tianjin Medical University General Hospital (Tianjin, China; www.tjmugh.com.cn) enrolled in a prospective study, a total of 173 consecutive patients with IE from January 2016 to December 2018. All patients were hospitalized for the first time with a definite diagnosis of IE based on the modified Duke criteria. The primary diagnosis of ischemic stroke was mainly based on clinical neurological symptoms and imaging manifestations on brain magnetic resonance imaging (MRI).

The team performed the measurement of plasma D-dimer on admission using the VIDAS D-dimer assay (bioMérieux, Marcy-l'Étoile, France; www.biomerieux-diagnostics.com), which has shown comparable sensitivity and specificity. The normal range of plasma D-dimer is 0-500 μg/L. Other hematological and biochemical data, such as white blood cell (WBC) count and C-reactive protein (CRP), were also detected from peripheral blood samples collected on the next morning after admission. In addition, to identify causative organisms, at least three sets of blood cultures were obtained from all patients before the initiation of antibiotic therapy.

The scientists reported that ischemic stroke was observed in 38 (22%) patients during 6-month follow-up since definite diagnosis of IE. Patients with ischemic stroke had significantly higher levels of plasma D-dimer than those of patients without stroke (4,982 versus 2,205 μg/L). Positive results of blood cultures were obtained from 107 (62%) patients. Streptococcus identified in 40 (23%) patients was the most common microorganism, accounting for 37% of all positive blood cultures. The secondary dominant

causative agent was Staphylococcus aureus, isolated in 33 (19%) patients and 31% of all positive blood cultures.

In addition, Staphylococcus aureus infection (Hazard Ratio (HR): 1.96), mitral valve vegetation (HR: 1.52), and higher levels of on-admission plasma D-dimer (HR: 1.35) were significantly associated with ischemic stroke.

Moreover, D-dimer levels ≥3,393 μg/L served as a strong predictor for ischemic stroke in patients with IE, and the sensitivity and specificity were 78% and 83%, respectively.

The authors concluded that their study revealed that higher levels of onadmission plasma D-dimer showed high sensitivity and specificity in the prediction of ischemic stroke, which occurred mostly in the first three months after the diagnosis of IE. On the one hand, as a traditional and inexpensive biomarker, plasma D-dimer may help clinicians identify high-risk IE patients for ischemic stroke in a simple and quick way. The study was published on February 3, 2020 in the Journal of Clinical Laboratory Analysis.

Image: Blood test for D-dimer showed high sensitivity and specificity in the prediction of ischemic stroke in patients with infective endocarditis (Photo courtesy of Blue Horizon).

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Blood Biomarkers Associated with Acute Sports-Related Concussion

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uring the past decade, several candidate biomarkers have emerged as potential diagnostic markers of traumatic brain injury (TBI) and an estimated 90% of brain injuries are classified as mild TBI. Early work has identified select biomarkers with favorable performance in the context of mild TBI, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain (NF-L), and S100B. High sensitivity and negative predictive value of UCH-L1, GFAP, NF-L, and tau biomarkers to predict intracranial injury present on acute-phase head computed tomography have been reported.

Neurosurgeons at the Medical College of Wisconsin (Milwaukee, WI, USA; www.mcw.edu) and their multidisciplinary colleagues conducted a multicenter, prospective, case-control study of 504 collegiate athletes with concussion, contact sport control athletes, and non–contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute post injury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and seven days after return to play. Data analysis was conducted from March 1 to November 30, 2019.

The team collected non-fasting blood samples by venipuncture at baseline and all post injury time points. Single molecular array technology (Simoa; Quanterix Corporation, Billerica, MA, USA; www.quanterix .com) was used to measure serum biomarker levels. Multiplex technology simultaneously quantified UCH-L1, tau, NF-L, and GFAP. The mean coefficients of variance for each protein were the following for data included in the analyses: 9.02% for UCH-L1, 7.92% for tau, 4.59% for NF-L, and 3.07% for GFAP. The scientists included in the study a total of 264 athletes with concussion (mean age, 19.1 ± ±1.24 years); 211 (79.9%) male), 138 contact sport controls (mean age, 19.03±1.27 years); 107 (77.5%) male, and 102 non–contact sport controls (mean age, 19.39 ±1.25) years; 82 (80.4%) male). Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.0460.396 pg/mL) at the acute post injury time point compared with preseason baseline.

While Nf-L interaction was not considered significant as a concussion indicator, findings support its use as a measure for the seriousness of an

LabMedica International

injury and triggered neuronal damage. Nf-L was the only marker elevated days after return-to-play (RTP) in more severely injured athletes with loss of consciousness (LOC) or post-traumatic amnesia (PTA).

The authors concluded that the results suggest that blood biomarkers can be used as study tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in sport-related concussion (SRC). The study was published on January 24, 2020 in the journal JAMA Network Open.

Image: The Quanterix SR-X Ultra-Sensitive Biomarker Detection System uses single molecular array technology (SIMOA) (Photo courtesy of Quanterix Corporation).

Novel Reliable Assay for Tuberculosis and lTBI Tested

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infection. Receiving Operating Characteristic (ROC) analysis for QuantiFERON-TB Gold Plus showed sensitivity and specificity respectively of 98% and 97% in diagnosing active TB patients and 85% and 94% in diagnosing LTBI subjects. LIOFeron TB/LTBI assay showed sensitivity and specificity respectively of 90% and 98% in diagnosing active TB patients and 94% and 97% in diagnosing LTBI subjects.

The authors concluded that the LIOFeron TB/LTBI assay displayed the same high accuracy as the QuantiFERON-TB Gold Plus test in diagnosing MTB infection/TB disease, and demonstrated higher sensitivity than QuantiFERON-TB Gold Plus test in LTBI detection. The study was published in the February, 2020 issue of the International Journal of Infectious Diseases.

Image: The LIOFeron TB/LTBI is a novel interferon-gamma release test for diagnosing latent tuberculosis (LTBI)/TB infection (Photo courtesy of Lionex GmbH).

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lung Cancer liquid Biopsy Guides MRD-Directed Adjuvant Therapy

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inimal residual disease (MRD) is the name given to small numbers of leukemic cells (cancer cells from the bone marrow) that remain in the person during treatment or after treatment when the patient is in remission or have no symptoms or signs of disease.

Circulating tumor DNA is tumor-derived fragmented DNA in the bloodstream that is not associated with cells. Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD is unclear.

Oncology specialists at Stanford University (Stanford, CA, USA; www.stanford.edu) and their associates from different institutions applied cancer personalized profiling by deep sequencing (CAPP-Seq) ctDNA analysis to 218 samples from 65 patients receiving chemoradiation therapy for locally advanced non-smallcell lung cancer, including 28 patients receiving consolidation immune checkpoint inhibition (ICI).

The study found that patients with ctDNA evidence of MRD after chemoradiation therapy who then received consolidation ICI had significantly better outcomes than patients with signs of MRD who did not receive consolida-

tion ICI therapy. In contrast patients with undetectable ctDNA after chemoradiation therapy had what the authors called "excellent outcomes" whether or not they received consolidation ICI. Importantly though, one of these patients who showed complete clearance of ctDNA also suffered a significant adverse event, pneumonitis, related to the consolidation ICI. According to authors, the results as a whole provide evidence for the potential utility of using ctDNA tests to define which patients should get immunotherapy treatment, and which might safely avoid it and its potential complications.

Maximillian Diehn, MD, PhD, an associate professor of radiation oncology and a senior author of the study, said, â&#x20AC;&#x153;Our Capp-seq method appears to be very sensitive and to have excellent clinical performance in these locally advanced lung cancer patients, where with a panel design we can find a significant number of mutations in the average patient. However, applying the same method in sarcoma, for example, would likely fail, because these tumors don't show many recurrent mutations.â&#x20AC;?

omen harboring heterozygous germline mutations of BRCA2 have a 50% to 80% risk of developing breast cancer, yet the pathogenesis of these cancers is poorly understood. Breast cancers arising in women who inherit heterozygous mutations in BRCA2 are associated with a high prevalence of genomic alterations and aggressive clinical behavior.

Because of the high risk of these cancers in BRCA2 mutation carriers, many such women elect to undergo bilateral mastectomy for breast cancer prevention. However, despite the unmet need for more effective breast cancer prevention approaches in this setting, the stepwise evolution from an otherwise normal BRCA2 heterozygous mutant (BRCA2mut/+) cell to an invasive malignancy has not been defined.

Medical scientists from the Massachusetts General Hospital (Boston, MA, USA; www. mgh.harvard.edu) performed single-cell, wholegenome sequencing on cell populations sorted from breast tissue samples from more than twodozen BRCA2 mutation-positive women who had undergone bilateral prophylactic mastectomies. The participants had just one affected copy of the breast- and ovarian-cancer linked gene.

The teams compared genetic profiles in these breast cell populations to those from matched control individuals, and were able to track down alterations that were over-represented in the BRCA2-deficient cells. For example, with this ap-

proach, they uncovered sub-chromosomal aneuploidy in more than one-quarter of luminal progenitor cells from BRCA2 mutation carriers. In breast epithelial cells, meanwhile, the heterozygous BRCA2 changes coincided with a jump in DNA damage, along with reduced apoptotic pathway or replication checkpoint activity.

The investigators focused on heterozygous BRCA2 mutation carriers who were breast cancer-free and had no previous exposure to chemotherapy, along with control individuals matched for factors ranging from age to hormone exposure and menopausal status who donated breast tissue samples after elective breast reduction surgeries. With the help of cell marker-based flow cytometry using a FACSAria flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA; www.bd.com) the team distinguished between mature luminal, luminal progenitor, and basal epithelial cell populations in the breast tissue samples from participants with or without BRCA2 mutations.

The scientists used single-cell genome sequencing and algorithmic analyses to identify copy number shifts and other somatic alterations in each cell type, identifying patterns supported

by RNA sequencing, single-cell polymerase chain reaction (PCR), and other follow-up analyses. In samples from 26 women with BRCA2 mutations and 28 without, they also saw an apparent expansion in the proportion of luminal progenitor cells with reduced stress and DNA damage response in samples from aging BRCA2

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The authors concluded that their results suggest that consolidation ICI improves outcomes for non-small-cell lung cancer patients with MRD and that ctDNA analysis may facilitate personalization of consolidation therapy.

The study was published on January 20, 2020 in the journal Nature Cancer.

Image: Workflow of cancer personalized profiling by deep sequencing (CAPP-Seq) circulating tumor-DNA analysis (ctDNA) (Photo courtesy of Rashedul Islam Rony, PhD).

Single-Cell Sequencing Identifies Breast Cancer Risk

mutation carriers.

The authors concluded that although the early genomic changes they observed were likely to include many passenger events, they nevertheless may provide a quantifiable hallmark of the preneoplastic BRCA2 carrier state. Tracking the prevalence of DNA-damaged cells in the clinical setting could possibly improve risk prediction for these women, who are faced with the difficult choice of whether to undergo mastectomy long before cancer develops. The study was published on January 29, 2020 in the journal Science Advances.

Image: Summary of findings in primary BRCA2mut/+ breast tissues: Epithelial progenitor cells of heterozygous germline BRCA2 carriers exhibit DNA damage, failed replication stress, and damage responses, together with attenuated apoptosis. Loss of heterozygosity (LOH) analyses suggests that these findings may reflect a haploinsufficient phenotype for BRCA2 in vivo (Photo courtesy of Massachusetts General Hospital).

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Edited by Katherina Psarra MSc, PhD IFCC members may send news to: Prof. Katherina Psarra IFCC Office, Via C. Farini 81 20159 Milano, Italy. E-mail: enews@ifcc.org

IFCC young Scientists Produce International Video Showcasing Global COVID-19 Effort

NEWS

By Marie Lenski, IFCC Task Force for Young Scientists Corresponding Member for the Société Française de Biologie Clinique (SFBC)

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aboratory Medicine professionals, including young scientists, have a central contribution during the current health crisis. With their professional commitment, they are at the forefront during COVID-19 pandemic, adding value to patient care and well-being, as well as to protection of the population. In this context, the need of improving visibility and promoting involvement of Laboratory Medicine professionals at an international level was identified. In this common and global objective, young scientists from IFCC-TF-YS participated in making a video underlying their role during the crisis.

This initiative, as well as the edition of the video, was conducted by a union of young medical biologists from France SJBM, with the support of the national representative society SFBC and IFCC-TFYS. Each participant recorded a 5second video, under laboratory environment, with masks and white coats, with the name of their country, or a part of the following sentence: "Today, as tomorrow, the creative and scientific force of the Laboratory Medicine professionals is mobilizing for your health. All over the world, we are devoting all our energy to fight COVID-19 pandemic. Your health and safety, our priority." All 5-second videos were then gathered in a final 2-minute video, that is viewable following this link on Youtube or facebook.

Young scientists made a significant contribution in that project.

Young scientists working in public and private sectors and university researchers from twenty different countries participated in this collective and dynamic initiative. The video was promoted on various networks and so far generated over 140,000 views.

IFCC-TFYS would like to thank and congratulate all the participants, who made it possible with their involvement. IFCC-TFYS is thankful to all senior members and authorities for their unconditional support to young scientists’ projects. That contribution permitted to enhance communication between young scientists all over the world, and to make the Task Force a stronger group. Other YS projects are under development.

Among others, the TFYS has planned to organize the first of its PRESS own kind “Young Scientist Forum” at IFCC WorldLab Seoul for participation, networking and education supported by IFCC-EB. Looking forward to meeting you at WorldLab Seoul (5-6 January, 2021).

NOW AVAILABLE ONLINE

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NEWS S

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

Editorial

By Katherina Psarra, MSc, PhD

Dear colleagues, ummer is here. Try to enjoy yourselves as much as possible, but don’t lose touch with the IFCC. Pay attention to the new strategic plans of our President, Prof. Khosrow Adeli, and respond to his invitation for outreach.

Communication is very important especially in these times of “keeping distance”. This is why our Communications and Publications Division, through Rojeet Shrestha’s hard work with social media, even with the new one, Telegram, doesn’t

permit you to just relax. Every-day you can be in touch with IFCC. UNIVANTS' call to action invites all teams to share their best practice and measurable benefits to patients, clinicians, health systems and payors. Deadline for applications is quickly approaching, don’t miss out! Dr. Gouget’s new article with a lot of valuable thoughts about the situation we are all facing will keep you company and will certainly provoke some discussions and ideas. Why don’t you report on your societies’ response to the pandemic? It would be really interesting to learn about our respective lessons and challenges. Don’t forget summer, though. Some vacation and free time are what we all need. Enjoy!

Coming Together in Social Media to Honor Medical lab Professionals Fighting COVID-19

Rojeet Shrestha, MS, Ph.D. Assistant Professor (Medical Lab Sciences), Faculty of Health Sciences, Hokkaido University, Japan

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aboratory Medicine professionals play a vital role in quality health care by providing accurate results to aid diseases diagnosis, screening, predicting, and monitoring. Laboratory professionals are the diverse group of multidisciplinary expertise that include, but not limited to, clinical chemists, microbiologists, pathologists, molecular biologists, medical technologists, laboratory technicians, lab assistants, and research scientists. Combined contributions of all result in the diagnosis and management of most clinical conditions. Despite the importance of these healthcare professionals, they usually remain in shadow in public attention and are mostly confined behind the scenes. With the beginning of this devastating COVID-19 crisis, the importance of laboratory professionals has risen more than ever. Lab professionals around the globe are working around the clock performing diagnostic tests to fight against the virus.

Hundreds of millions of tests have been performed to identify the infections so that appropriate healthcare management can be efficiently done. Laboratory professionals are the unsung heroes in this battle against COVID19, therefore, they need special recognition and appreciation for their immense contribution in saving millions of lives.

Medical Laboratory Professionals Week

provides the profession with a wonderful opportunity to increase the public understanding and appreciation for clinical laboratory professionals. At least, 17 world-renowned clinical laboratory organizations officially celebrate the last full week of April every year as Medical Laboratory Professionals Week.

IFCC also took this opportunity to sincerely thank all the medical laboratory professionals around the world through its social media with a message – “We appreciate your dedication to fight against COVID-19. We need you now more than ever”. The greetings were posted on all our social media platforms – Facebook, Twitter, LinkedIn, and Instagram. We are happy that it has been well received by lab professionals and general public with post reaching to over 200,000 users with over 20,000 engagements in Facebook alone. Furthermore, with the kind help of our young professionals around the globe, we were able to translate this message to over 25 different languages [see picture]. Thousands of lab professionals were happy to share the content in their native languages increasing public awareness of the importance of clinical laboratory sciences and clinical laboratory scientists. This is something that we have never done before and would not have been possible without support, generosity, and teamwork of the IFCC Taskforce

Stay connected here

Social media posts in various languages

for Young Scientists. We would like to appreciate all members who helped us in delivering “thank you” messages to laboratory professionals in their native languages. We would like to specially thank Santiago Fares (IFCC TS-YS), Monica Spalvieri (IFCC CPR), Maria Eugenia (Germany), Geraldine Dayrit (Philippines), Élodie Lebredonchel (France), Gabriel Lima-Oliveira (Portugal), Itai Chitungo (Zimbabwe), Tamar Ramishvili (Georgia), Ashish Agravatt (Hindi), Manel Chaabane (Tunisia), Giulia Sancesario (Italy), Dwi Yuniati (Indonesia), Rinat Drori (Hebrew), Rojeet Shrestha (Nepal), Sibtain Ahmed (Urdu, Pakistan), Saifuddin Khaled (Bangladesh), Lucy Liu (China), Miljan Savkovic (Serbia), Magdalena Krintus (Poland), Borai Anwar (Arabic) and many more who helped the translation anonymously.

We hope this activity provided us an opportunity to unite during this unprecedented time to celebrate the vital role that we laboratory professionals play in this pandemic.

Please stay connected with us through social media – Facebook, Twitter, LinkedIn, Instagram and Telegram!

LabMedica International June-July/2020

38

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

NEWS

MESSAGE FROM THE PRESIDENT By khosrow Adeli

A

•

President, IFCC

s promised, I am writing to follow up on our new proposed strategic plans for IFCC over the next three years. In the June newsletter, I provided a glimpse of our new strategic plan that I have been working on together with members of the IFCC Executive Board over the past few months. In this issue of the newsletter, I would Prof. Khosrow Adeli, PhD, to like explain in more detail three of FCACB, DABCC, FAACC the key strategic plans and would like to seek feedback from all of you (IFCC officers, IFCC national societies and regional federations, as well as our corporate members) as we finalize and initiate implementation of these plans into practice with your support and participation.

In partnership with all IFCC divisions and functional units, the IFCC Executive Board will strive to enhance IFCC’s leadership position in the field of laboratory medicine by implementing a number of important new programs.

A detailed outline of our top three strategic priorities is listed below: DIRECTLY IMPACT PATIENT CARE AND OUTCOMES

• VISION: IFCC should be more proactive and directly impact global healthcare in developing nations;

• First Key Project: IFCC Global Newborn Screening Program: • • •

Development of an IFCC Program in Collaboration with WHO, Gates Foundation, industry, others; Rationale: Lack of newborn screening programs in many developing countries is leading to major health consequences and a burden on healthcare delivery and costs. Development of new programs in developing countries will significantly enhance child health and reduce infant mortality.

Scientific Oversight by a new IFCC Taskforce on Global Newborn Screening Operational Coordination with an industry partner (NBS provider) DIRECTLY CONTRIBUTE TO GLOBAL LAB QUALITY

• VISION: IFCC should directly assist clinical laboratories

improve internal and external quality assurance and become a key resource for evidence-based laboratory reference intervals for both adults and children.

Key Projects: • IFCC External Quality Assurance Program in developing countries

T

in developing countries

• Global Reference Interval Consortium: An IFCC global data • • •

base of adult and pediatric reference intervals as a key resource for laboratories around the world Rationale: There is a critical need globally for improved internal and external quality assurance and the IFCC has a clear mandate and obligation to help improve quality beyond training and education. A more direct role on the ground in developing countries is essential to achieve these goals Scientific Oversight by a new IFCC Taskforce on Global Lab Quality Operational Oversight by an industry partner (EQA provider)

MAJOR EXPANSION OF IFCC ELEARNING / DISTANCE LEARNING PROGRAM

• VISION: IFCC should be the largest provider of free

eLearning/Distance Learning Programs Globally; With a Focus on Developing Countries & Young Scientists, Students, Trainees.

Key Projects: • A new strategy to develop and deliver webinars via eAcademy or a new platform; • Live global webinars (monthly) starting in September 2020; biweekly live webinars in 2021 and future years; • Rationale: Distance learning/eLearning is a major mandate of the IFCC organization to provide both live and recorded webinars given by experts around the world. This is an important way by which IFCC can give back to the national societies around the world and their members especially young scientists and trainees. The current system to deliver webinars is not working and a major overhaul is required to ensure delivery of timely webinars to the membership; Scientific Oversight by a new IFCC Taskforce on • eAcademy/eLearning • Operational Delivery by a full-time coordinator working with a webinar/video conferencing company

I invite each of you to review these proposed strategic plans and provide feedback and comments. Your input will be greatly appreciated as we finalize and initiate implementation of these plans into practice with your support and participation.

Please email me at: president@ifcc.org with your feedback, questions, or concerns.

Till next time ☺ khosrow

IFCC Information Guide on COVID-19 With Weekly Updates

he IFCC is pleased to publish an online resource providing key information on laboratory guidelines, biosafety, and other important resources to assist member societies around the world and their clinical laboratories as they face the challenges posed by the COVID-19 outbreak.

The page is constantly updated with the most recent information.

The next update will be available on 13 July 2020, and updates will continue on a biweekly basis.

Coronavirus disease 2019, abbreviated to COVID-19, is an emerging global pandemic caused by severe acute respiratory

39

• IFCC Internal Quality Assurance On-site Training Program

LabMedica International June-July/2020

syndrome coronavirus 2 (SARS-CoV-2). As the number of individuals infected with COVID-19 continues to rise globally and healthcare systems become increasingly stressed, it is clear that the clinical laboratory will play an essential role in this crisis, contributing to patient screening,diagnosis, monitoring/treatment, as well as epidemiologic recovery/surveillance. This guide aims to organize relevant available information on laboratory screening, testing protocols, diagnosis, and other general information on COVID-19 for laboratory professionals, including links to helpful resources and interim guidelines. It will be continually updated as new guidelines and literature become available.

NEWS

VIEWPOINT

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

Social Distancing and The Truth of Masks

by Dr. Bernard Gouget

D

Chair-IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MHBLM), co-Chair IFCC -TF on History, SFBC-International Committee, President-Human Health Care Committee-Cofrac, President-Committee for selection of the French Reference Medical Laboratories, MoH.

uring the COVID-19 pandemic, modeling has been frequently put forward and numerical simulation has been used at different scales, from the reproduction of the virus on an atomic scale to that of the flows of infected populations. Several projects using AI have sought to virtually test the effect of several thousand drugs and anticipate the effects of deconfinement with the goal of modeling R0 coming out of confinement and its evolution, creating flows of contaminated air to recreate virus transmission from one individual to another and simulate the efficacy of various face shields and masks qualities for protection from someone who sneezes and to determine distancing measures.

Therefore, a profile of populations with the highest risk of being infected according to their behavior can be created and the status of populations that have not been tested can be predicted..

On the basis of simulations, many countries have fashioned their national responses and started to relax their coronavirus lockdowns. Some countries have almost completely suppressed the virus. Other countries have experienced and are still experiencing large outbreaks. Several countries have taken drastic measures and have seen life get back to normal. Other versions of spring lockdown associated with tracing systems for individuals have been more flexible, like in Sweden, although the model could be questioned. However, the pandemic is still a major concern worldwide, with an epicenter that has moved to the countries of South America and in South Africa. The coronavirus crisis is far from being over. Other economic, social, environmental or political crises will follow and we must expect to experience a succession of crises, or a pile of crises all at once, that will severely test the capacities of governments as well as our social fabric, our organizations, our economic and health structures, and more generally, our democratic institutions. These crises will not be isolated, but will be part of a group of larger transformations, especially climate change and digital transformations, as well as the increase in inequality, rise of populism, crisis of representative democracy, migratory movements, disputing medical science or upheaval in the media and social networks. All these transformations contribute to and, simultaneously, will be exacerbated by the crisis that we are going through, which will ultimately be a only first warning.

After several weeks of deserted public spaces and empty streets, crowds are gathered in the streets again, not to celebrate victory over the virus but to protest the murder of George Floyd, who died after 8 minutes and 46 seconds of suffocation. The question of breathing and suffocation is again at the heart of new and bitter current events. Protestors are gathered tightly together in the large cities of many countries, despite the injunctions to "social distance", chanting and demanding justice. The police reacted with tear gas and piled them up in paddy wagons or in jail, forcing proximity. These mobilizations are part of a long tradition that blends activism and art, and reflects the need to reconnect with a collective solidarity to fight for respect for a population dehumanized by discrimination. Die-in protests reproduce the posture of George Floyd's body on the ground, immobilized by handcuffs and a police officer's knee, tirelessly repeating "I Can’t Breathe!" or, on the model initiated by Colin Kaepernick, the football player who showed his opposition to racial discrimination and violence, taking a knee on the ground. Standing in a crowd for long periods, breathing chemicals that force to cough and gag, raises the risk of increased transmission of SARS-CoV-2. This particular form of mass, in-person

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The views and positions expressed in the IFCC News section are those of the IFCC or the individual authors, and do not necessarily represent the views or positions of LabMedica magazine or its publishers.

protest—and the corresponding police response—is a “perfect set-up” for transmission of the virus. The body is at the heart of the performance of revolt in order to revive the memory of pain and trauma. This is played out in the context of COVID-19, where the frightening accounts of people in intensive care are shared, suffering from lungs affected by this disease that produces severe respiratory failure, possibly leading death. This moment is also one where masks visually mark an obstruction of the mouth and nose. Air literally and figuratively can no longer circulate. This risk of transmission is complicated with the moral stakes of current events. Two racial inequalities are encountered during protests: one, a pandemic in which people of color die at nearly twice the rate in the American population, and two, anti-Black brutality.

The protests are uncontestably risky, and national authorities such as the centers for disease control and prevention have warned that the gatherings could cause new clusters. The protesters themselves are not unaware of the pandemic risk. In the videos, the majority of protesters appear to wear masks.

The photos and videos of the protests show both large and tightly packed crowds and protesters who respect social distancing and volunteers distributing hand sanitizer and water among the crowd.

With these latest events, while facial recognition and temperature taking were used as tools for fighting the pandemic, IBM has just strongly opposed the use of any technology, including facial recognition technology offered by other suppliers, for mass surveillance, profiling, violations of human rights and fundamental freedoms or any other objective that would not be in accordance with their values and principles of trust and transparency Everything has been said about the COVID-19 epidemic and how to protect yourself from contamination. The expressions "social distancing" or "physical distancing" have become part of everyday language. We are faced with a situation in which, we now know--although laboratory diagnosis has been shown to be essential both from the diagnostic viewpoint and regarding the immune response of patients recovered from COVID-19-that medical responses, vaccine and treatments are still uncertain. Also, the greatest role in the immediate future is allotted to preventive measures, for which the cooperation of the population is essential. These measures, and especially data relating to virus transmission, have been the subject of a massive communication campaign which has undoubtedly achieved its purpose.

Nevertheless, we can wonder why health standards, however validated, disseminated and rehashed in all the media, do not generate more conformity, when they are not simply ignored.

This can be illustrated by one of the most prominent aspects of social distancing, the question of wearing a mask. According to all appearances, the mask is a device seeking to protect health, both that of the person wearing it and those they encounter. However, wearing the mask has many other meanings. When they become mandatory, the mask is not only a vector for health, it is a sign of respect for public order. Not wearing it becomes an infraction. But the mask can also paradoxically mean mistrust or trust, one thing or its opposite. Trust, because it is a gesture of respect and collective participation in the fight against virus transmission. Mistrust also, since the mask is often, rightly or wrongly, conceived by its wearer as a means of protection from others. Wearing a mask, beyond its participation in physical distancing, brings us back to ancestral fears and old epidemics. Not wearing it can also be classified as a rebellion, affirmation of freedom, opposition to government orders and denial, even though the strength of the epidemic is universally recognized. In all cases, wearing the mask functions as a message that is not necessarily about preserving health. If we want to encourage people to wear it in all situations where there is a risk and make it a social obligation, we must work to make it desirable. Even as the peak of the epidemic moves away from Europe but continues to be severe elsewhere, this should lead us to caution, vigilance and respect for preventative measures. We must not relax our efforts. It is necessary to continue to wear a mask when the situation requires it and to respect a safe distance as much as possible.

Naturally, we are not immune to a second wave and we must take action to anticipate and avoid it. Epidemics will surprise us still. But we have learned a lot from this first wave, and if people have at least learned that hygiene is not just cleanliness or disinfection, but a set of relevant and well-targeted preventive measures, we will have made great progress. Coronavirus has a stable genome that is protected from replication errors. In other words, whether or not a second wave occurs depends on almost everyone.

Now, there is still an unknown aspect: we do not know what will happen when the seasonal flu epidemic and a second wave of COVID-19 coexist.

So, let us prepare ourselves.

LabMedica International June-July/2020

40

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

NEWS

2020 UNIVANTS of Healthcare Excellence Awardsâ&#x20AC;Ś Donâ&#x20AC;&#x2122;t Miss Out!

I

t is not too late to be recognized for your valued best practices of healthcare excellence. The prestigious UNIVANTS of Healthcare Excellence Award Program is accepting applications until the deadline of August 31, 2020. These awards are valued opportunities for global recognition to integrated care teams who have partnered across disciplines to improve clinical care in measurably impactful ways. This award, now in its third year, is designed to encourage collaboration and utilization of laboratory data in insightful ways to solve and improve outcomes.

The program has been made possible through the collaboration across leading healthcare organizations with like-minded in-

IFCC Annual Report 2019 Now Available Online At the IFCC Website

The IFCC Annual Report 2019, compiled by Dr. David Kinniburgh, IFCC Secretary, is now available online at the IFCC Website, www.ifcc.org.

In the IFCC Annual Report you will find reports from IFCC Officers on key projects covering a wide range of clinical, scientific, educational, and communication-related topics.

National or Area Societies and Regional Federation reports are also included, allowing the opportunity to communicate their activities to other members.

Download your copy of the 160page fact-filled publication and read how the IFCC mission "Advancing excellence in laboratory medicine for better healthcare worldwide" has been the guiding principle for our work in 2019.

Link: https://www.ifcc.org/media /478502/ifcc-2019-annual-report.pdf

41

LabMedica International June-July/2020

terests, reinforcing the importance of unity and/or partnerships both within and outside the clinical laboratory. Partners of the program include the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), AACC, EHMA (European Health Management Association), Modern Healthcare, Health Information and Management Systems Society (HIMSS), National Association of Healthcare Quality (NAHQ) and the Institute of Health Economics (IHE); each through partnerships with Abbott Laboratories. With a shared vision to celebrate healthcare excellence, the award is intended to inspire healthcare professionals around the world.

The award is open to all healthcare professionals and teams regardless of their affiliation with the partner organizations. All partners, excluding Abbott, independently assess every application to determine global and area winners. Area categories this year include Best of Asia Pacific, Best of Europe, Best of Latin America and Caribbean, and Best of Middle East and Turkey, and Best of North America.

All teams are invited to share their best practice and measurable benefits to patients, clinicians, health systems and payors. For more information and/or to submit an application for the 2020 UNIVANTS of Healthcare Excellence Awards, please visit www.UnivantsHCE.com.

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ECE 2020 – 22nd European Congress of Endocrinology. Sep 5-9; Virtual Venue; Web: www.ese-hormones.org

ASCP 2020 – Annual Meeting of the American Society for Clinical Pathology.

Sep 9-11; Virtual Venue; Web: www. ascp.org

India Lab Expo & Analytica Anacon India. Sep 17-19; Hyderabad, India; Web: www.analyticaindia.com

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BCLF 2020 – 28th Balkan Clinical Laboratory Federation Meeting. Sep 30 - Oct 3; Sofia, Bulgaria; Web: www.bclf2020.org OCTOBER 2020

BSACI 2020 – Annual Conference of the British Society for Allergy and Clinical

JIB 2020 – Journées de l’Innovation en Biologie. Nov 4-5; Paris, France; Web: jib-innovation.com

Immunology. Oct 1-2; Virtual Venue; Web: bsacimeeting.org

SIOP 2020 – 52nd Annual Congress of the International Society of Paediatric Oncology (SIOP). Oct 14-17; Virtual Venue; Web: siop-congress.org

15th Baltic Congress of Laboratory Medicine. Nov 5-7; Riga, Latvia; Web: www.balmriga.com

Analytica 2020. Oct 19-22; Munich, Germany; Web: www.analytica.de

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ASHI 2020 – 46th Annual Meeting of the American Society for Histocompatibility & Immunogenetics. Oct 19-23; Anaheim, CA, USA; Web: www.ashihla.org

Analytica China 2020. Nov 16-18; Shanghai, China; Web: www. analyticachina.com

CMEF 2020 – China International Medical Equipment Fair. Oct 19-22; Shanghai, China; Web: www.cmef.com.cn

41st Annual Meeting of the American College of Toxicology (ACT). Nov 15-18; Virtual Venue; Web: www.actox.org

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ASHG 2020 – American Society of Human Genetics. Oct 27-31; Virtual Venue; USA; Web: www.ashg.org

MEDLAB Asia Pacific 2020. October 2830; Bangkok, Thailand; Web: www. medlabasia.com

11th African Congress of Immunology – Federation of African Immunological Societies (FAIS). Nov 29 – Dec 3; Lilongwe, Malawi; Web: www.faisafrica.com

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DECEMBER 2020

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Advertising Index

Vol. 38 No.4 7/ 2020 Page

AACC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41 Alcor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27 Awareness Technology . . . . . . . . . . . . . . . . . . .25 Biofire . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 Biohit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19 BioRad . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 Diasys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 EliTechGroup . . . . . . . . . . . . . . . . . . . . . . . . . . .33 Erba Mannheim . . . . . . . . . . . . . . . . . . . . . . . . . .5 Erba Mannheim . . . . . . . . . . . . . . . . . . . . . . . . . .7 Euroimmun . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31 Greiner-Bio . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23 ICE 2020 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43 Instrument Laboratory . . . . . . . . . . . . . . . . . . . .44 TradeMed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29 Mayo Clinic Laboratories . . . . . . . . . . . . . . . . . . .9 NG-Biotech . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Serosep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30 Veda Lab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13 Vicotex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35 Vircell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17 YHLO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11 Provided as a service to advertisers. Publisher cannot accept responsibility for any errors or omissions.

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