How A Change in Immune Cell Metabolism Contributes to Severe COVID-19

Illustration of energy metablism in cell.

There is still a lot we don’t know about COVID-19 and the virus, SARS-CoV-2, that caused the pandemic and changed the way we live. But there are two things we do know about the disease: 1) Patients with diabetes and high blood glucose levels are more likely to develop severe COVID-19 symptoms with higher mortality.  2) Patients that experience an uncontrolled inflammatory response, called the cytokine storm, also develop more severe COVID-19 symptoms. The fact that both high glucose levels and an exaggerated immune response drive severe disease suggests that the two may be linked. But how? The answer may lie in the metabolism of immune cells in the lungs of COVID-19 patients, according to a recent study published in Cell Metabolism.

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XpressAmp™ Direct Amplification: Simplified and Accelerated Time to qPCR Results

As the SARS‐CoV‐2 pandemic continues to rage across the United States and around the globe, the demand for COVID‐19 testing is increasing. The vast majority of the COVID-19 assays use RT‐qPCR to detect the viral RNA in patient samples such as nasopharyngeal swabs, which are collected and stored in viral or universal transport media (VTM/UTM). The general workflow for these COVID‐19 assays can be broken down as follows:

  1. Collect and store patient samples
  2. Ship samples to testing laboratory
  3. Extract RNA from samples
  4. Amplify and analyze samples

While many companies who manufacture the products that are used in these steps have been able to adapt and significantly increase their production capacities, there are still gaps between the supply of these products and the global test demand. Both the sample collection and storage step and the RNA extraction/purification step have a tendency to bottleneck and experience supply constraints. One way to address these bottlenecks and expand production capacity for these in‐demand products is to evaluate the viability of skipping a step in the workflow, without hindering the ability to detect viral RNA from samples.

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Answers to the Most Common Questions from “Battling the Novel Coronavirus” Online Event

This post was written by guest blogger, Nitin Kapoor, from our Promega India branch office.

The COVID-19 crisis has led to substantial worldwide efforts to develop drug treatments and vaccines effective against SARS-CoV-2.  Termed a novel Coronavirus, SARS-CoV-2 belongs to the same family as that of SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) viruses that were responsible for epidemics in 2003 and 2012 respectively (Lu et al. 2020)

India reported more coronavirus infections than any other country in the world during July 2020. Records topped 50,000 new cases each day. 

Recognizing the need for a fast development of assays to detect SARS-CoV-2 and identify exposed individuals and to support research into better understanding the coronavirus, Promega’s branch office in India developed a how to “Battle against Novel Coronavirus” live virtual event that was hosted by its associate partner, Biotecnika. The virtual event featured scientists and business professionals focused on SARS-CoV-2 Detection and Assay Development. Around 9,000 attendees from the scientific community attended the live event and had the unique opportunity to ask Promega scientists questions about the virus, its products, and vaccine development.

Several of the most often asked questions from the event participants are highlighted below:

How is RT-PCR testing different from serological testing for COVID-19?

SARS-CoV-2  is an RNA virus so the first thing we will be able to detect is the presence of SARS-CoV-2 RNA. Testing for antibodies is called serological testing. Such a test can identify who has been infected with the new coronavirus but it cannot necessarily identify an active infection. The antibodies are detected later, after symptoms developed, and are believed to stay on in the blood for at least a few months. Serologiocal tests are used for checking epidemiology, not for diagnosing an active infection.

With all of the COVID-19 cases, there is a need for quick turnaround on tests. How can the Maxwell Instrument help?

The Maxwell® RSC instrument is a compact, automated RNA extraction platform that processes up to 48 samples simultaneously in less than 35 minutes, so in typical 8-hour shift instrument can process up to 400 samples. The Maxwell® RSC 48 Instrument is for research use only.

How can your Lumit™ technology be used to understand immune response to SARS-CoV-2?

Technologies built around the Lumit platform can be used in immunoassays in which NanoBiT® subunits are conjugated to a pair of secondary antibodies. The target analyte can be detected by adding an antibody mix either containing two primary antibodies against the target analyte along with SmBiT- and LgBiT- conjugated secondary antibodies, or by adding SmBiT- and LgBiT- conjugated primary antibodies. Binding of the primary/Lumit™ secondary antibody complexes to their corresponding epitopes brings NanoBiT® subunits into proximity to form an active NanoLuc® luciferase that generates light in proportion to the amount of target protein. 

Additionally our NanoLuc® and NanoBiT™ technologies are being used to create reporter viruses used in vaccine and therapeutic research and development (2,3).

What is your opinion about upcoming vaccine?

COVID-19 is one of the biggest global health concerns, with massive economic burden. With no clear remedies to treat the disease, researchers are racing against the clock to trial COVID-19 vaccines. Promega supports scientists, working to understand the molecular mechanisms by which emerging viruses infects and to develop accurate detection methods, therapeutics, and vaccines.

We support scientists working to develop vaccines and to answer questions about viral pathology and treatment, including: 

  • How does the binds to and enters cells?
  • How does the body respond to the virus?
  • What treatments can be used to alleviate symptoms?
  • How can immunity to the virus be gained?

“Promega technologies are used in studies monitoring key steps in viral pathogenesis,” said Rajnish Bharti, Promega India General Manager, “including detecting virus interactions with host cell surface receptors, tracking and monitoring production of viral nucleic acids and proteins within the cell, and monitoring host cell viability and metabolism.”

You can view the online recording of the webinar below:

Literature Cited

  1. Lu R. et al. (2020) Genomic characterization, and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395:565–574. doi: 10.1016/S0140-6736(20)30251-8. [PubMed]
  2. Hooper, K. (2020) Choices for Measuring Luciferase-Tagged Reporter Pseudotyped Viral Particles in Coronavirus Research. Promega Connections [Internet: https://www.promegaconnections.com/choices-for-measuring-luciferase-tagged-reporter-pseudotyped-viral-particles-in-coronavirus-research/ ]
  3. Arduengo, M. (2020) The Path Brightens for Vaccine Researchers: Lumienscent Reporter Viruses Detect Neutralizing Antibodies. Promega Connections [Internet: https://www.promegaconnections.com/luminescent-reporter-viruses/ ]

Nitin Kapoor, Manager of Marketing Services for Promega Biotech India, Ltd. joined Promega in Oct 2017. Nitin Kapoor has 9 years of expertise in Sales and Marketing in Life Sciences, Pharma/ Biotech, Molecular Diagnostics and Forensic domain. His specialties are Product management ,  Sales force effectiveness, Market Research, Brand positioning & Competitor analysis. Before joining Promega  he has worked with companies like Qiagen , ThermoFisher Scientific & GE Health care.
He has completed MBA Biotech Gold Medallist from Amity University Noida . He is also an Author for Book: ‘Issue Related with Marketing of GM Food’ LAP publisher and is co-author for research paper on ‘Marketing of Nanobiogarments’ in IJMRA, Volume 2, Issue 4.

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From Drug Use to Viral Outbreaks, How Monitoring Sewage Can Save Lives

Most of us, after we flush the toilet, don’t think twice about our body waste. To us, it’s garbage. To epidemiologists, however, wastewater can provide valuable information about public health and help save lives.

History of Wastewater-Based Epidemiology

Wastewater-based epidemiology (WBE) is the analysis of wastewater to monitor public health. The term first emerged in 2001, when a study proposed the idea of analyzing wastewater in sewage-treatment facilities to determine the collective usage of illegal drugs within a community. At the time, this idea to bridge environmental and social sciences seemed radical, but there were clear advantages. Monitoring wastewater is a nonintrusive and relatively inexpensive way to obtain real-time data that accurately reflects community-wide drug usage while ensuring the anonymity of individuals.

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What We Know About the COVID-19 and the SARS-CoV-2 Virus

David Goodsell image of SARS-2-CoV
Image by David Goodsell

In the nine months since the first cases of COVID-19 were noticed in Wuhan, China, the virus has spread around the globe and infected over 22 million people. As with all emerging infectious diseases, we often find ourselves with more questions than answers. However, through the tireless work of researchers, doctors and public health officials worldwide, we have learned a lot about the virus, how it spreads and how to contain it.

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Questions about Immunity? This Infographic Might Help

If you are the “family scientist” you may find yourself answering questions about things like antibodies, immunity and serology from friends and family curious about the COVID-19 pandemic and all of the news they are seeing. Whether you are an oceanographic cartographer or a seasoned immunologist, we hope that this infographic about antibody testing helps.


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The Path Brightens for Vaccine Researchers: Luminescent Reporter Viruses Detect Neutralizing Antibodies

Developing a vaccine that is safe, effective, easily manufactured and distributed is a daunting task. Yet, that is exactly what is needed in response to the COVID-19 pandemic.

Vaccine development, safety and efficacy testing take time. The mumps vaccine is thought to be the quickest infectious disease vaccine ever produced, and its development required four years from sample collection to licensing (2). However, there are many reasons to anticipate quicker development for a COVID-19 vaccine: Researchers are collaborating in unprecedented ways, and most COVID-19 scientific publications are free for all to access and often available as preprints. As of August 11, 2020, researchers around the globe have more than 165 vaccine candidates in development, 30 of which are in some phase of human clinical trials (1). The range of vaccine formulations available to scientists has expanded to include RNA and DNA vaccines, replication-defective adenovirus vaccines, inactivated or killed vaccines and subunit protein vaccines. Equally important is that vaccine developers and researchers have greater access to powerful molecular biology tools like bioluminescent reporters that enable quicker testing and development.

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Using the Power of Technology for Viral Outbreaks

Artist’s rendition of a virus particle.

When the world is experiencing a viral pandemic, scientists and health officials quickly want data-driven answers to understand the situation and better formulate a public health response. Technology provides tools that researchers can use to develop a rapid sequencing protocol. With such a protocol, the data generated can help answer questions about disease epidemiology and understand the interaction between host and virus. Even better: If the protocol is freely available and based on cheap, mobile sequencing systems.

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Connecting and Collaborating: How Scientists Across the Globe are Supporting Each Other During The COVID-19 Pandemic

Many research labs around the world have temporarily closed their doors in response to the COVID-19 pandemic, while others are experiencing unprecedented need for reagents to perform viral testing. This urgency has led many scientists to make new connections and build creative, collaborative solutions.

“In labs that are still open for testing or other purposes, there’s certainly heightened anxiety,” says Tony Vanden Bush, Client Support Specialist. “I feel that right now, I need to help them deal with that stress however possible.”

Last week, Tony was contacted by a lab at the University of Minnesota that was preparing to serve as a secondary COVID-19 testing facility for a nearby hospital lab. The two labs needed to process up to 6,000 samples per day, and the university lab was far short of that capacity.

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Emergency Use Authorization: The What, the Why and the How

This blog is written by guest blogger, Heather Tomlinson, Director of Clinical Diagnostics at Promega.

Finding safe and effective treatments for human diseases takes time.  Medication and diagnostic tests can take decades to discover, develop and prove safe and effective.  In the United States, the FDA stands as the gold-standard gatekeeper to ensure that treatments and tests are reliable and safe. The time we wait in review and clearance means less risk of ineffective or unsafe treatments.

And yet, in a pandemic, we are behind before we even start the race to develop diagnostic tests, so critical for understanding how an infectious disease is spreading. That is when processes like the FDA’s fast track of Emergency Use Authorization (EUA) are critical. Such authorization allows scientists and clinicians to be nimble and provide the best possible test protocol as quickly as possible, with the understanding that these protocols will continue to be evaluated and improved as new information becomes available. The EUA focuses resources and accelerates reviews that keep science at the fore and gets us our best chance at staying safe and healing.

The Maxwell 48 RSC Instrument and the Maxwell RSC Total Viral Nucleic Acid Isolation Kit are now listed as options within the CDC EUA protocol.

For scientists working around the clock, the FDA’s EUA process is ready to review and respond. Getting an EUA  gives clinical labs a very specific and tested resource to guide them to the tools and tests to use in a crisis.

Typically the Centers for Disease Control (CDC) will develop the first test or protocol that receives FDA EUA in response to a crisis like a pandemic.  For COVID-19 the CDC 2019-Novel Coronavirus Real-Time RT-PCR Diagnostic Panel received FDA EUA clearance in early February. This is the test protocol used by the public health labs that work with the CDC and test manufacturers around the world.

Throughout a crisis such as the current pandemic, scientists continually work to improve the testing protocols and add options to the EUA protocols. This enables more flexibility in the test protocols. Promega is fortunate to play a part of the CDC EUA equation for diagnostic testing. Our GoTaq® Probe 1-Step PRT-qPCR System is one of a few approved options for master mixes in the  CDC qPCR diagnostic test,  and now our medium-throughput Maxwell 48 Instrument and Maxwell Viral Total Nucleic Acid Purification Kit  have been added to the CDC protocol as an option for the RNA isolation step as well. These additions to the CDC EUA means that laboratories have more resources at their disposal for the diagnostic testing which is so critical to effective pandemic response.

The Emergency Use Authorization provides the FDA guidance to strengthen our nation’s public health during emergencies, such as the current COVID-19 pandemic. The EUA allows continual improvement of an authorized protocol through the collaborative efforts scientists in all academia, government and industry to identify and qualify the most reliable technologies and systems, giving labs more flexibility as new products are added as options.

Dr. Tomlinson is the Director for the Global Clinical Diagnostics Strategic Business Unit at Promega Corporation with over 15 years of experience in clinical diagnostic test development. She is responsible for leading the team that drives strategy in the clinical market for Promega. Her background is in infectious disease diagnostic testing, with a focus on HIV drug resistance and evolution.  Her recent work has been in oncology companion diagnostic test development.  Heather has is an accomplished international presenter, delivering conference presentations in the United States, Europe, Asia, and Africa.

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