COVID-19 (SARS-CoV-2) Information

A collection of blogs discussing the COVID-19 pandemic, testing and SARS-CoV-2 research.

Two COVID-19 Waves in Brazil Driven by Separate Lineages of SARS-CoV-2

Posted on by Jordan Villanueva

The Brazilian state of Amazonas experienced two distinct waves of COVID-19 infections in 2020. After the first wave, a team from the University of Sao Paolo projected that the city of Manaus would reach the theoretical threshold for herd immunity by the end of the summer. However, a second COVID-19 wave erupted in December 2020, coinciding with the rise of Variant of Concern (VOC) P.1.

3d model of coronavirus covid-19

New research published in Nature Medicine examined the different lineages of COVID-19 present in Brazil over time and determined that the two waves were driven by different variants. The first wave was driven by the variant B.1.195, which was imported from Europe in the spring. The second wave was largely driven by VOC P.1. The Nature Medicine study is the first to use viral sequences from samples collected throughout 2020 to explore the epidemiological and virological factors behind the two distinct COVID-19 waves.

Detecting VOC P.1 in Amazonas Samples

The researchers started by generating whole-genome sequences of 250 SARS-CoV-2 samples collected between March 2020 and January 2021. The survey showed that 20% of the sequences belonged to the B.1.195 lineage, and these mostly corresponded with the first exponential growth phase. 24% of the samples belonged to the P.1 lineage, and all of these samples corresponded with the rise of the second exponential growth phase. The largest share belonged to B.1.1.28 (37%), which replaced B.1.195 as the dominant variant in Brazil shortly after the first wave until the rise of VOC P.1.

The team also used real-time RT-PCR to analyze 1,232 positive samples collected in Amazonas between November 1, 2020 and January 21, 2021. The assay was designed to detect a deletion in NSP6, which is a signature mutation of VOC P.1. None of the samples collected before December 16 showed the NSP6 deletion, but it was common in samples starting in mid-December. Combining the two analysis methods, the team found the P.1 lineage in 0% of samples collected in November 2020, but by January 1-15 it was present in 73.8% of samples.

This data supports the theory that VOC P.1 first emerged in December 2020 and was the dominant lineage driving the second wave in Amazonas.

Two COVID-19 Waves: Virological and Epidemiological Factors

In addition to tracking the prevalence of lineages throughout the pandemic, the researchers also offered suggestions for how Amazonas experienced two distinct waves of COVID-19 infections.

Using computer modeling, the team found a significant reduction in reproductive efficiency (Re) of lineages B.1.195 and B.1.1.28 in April-May 2020, around the same time that Amazonas increased social distancing measures. Transmission rates remained low until the interventions were relaxed in September 2020. This suggests that the reduction in cases was not a result of herd immunity. Instead, nonpharmaceutical interventions (NPI) limited the first wave and contained the spread through the summer.

Using real-time RT-PCR, the researchers found that the viral load of P.1 infections was nearly ten times the viral load of non-P.1 infection. They also referenced other research that found that VOC P.1 has a stronger affinity for the human receptor ACE2 than B.1.195 and B.1.1.28. P.1 is clearly a highly transmissible VOC, and it evolved in an ideal environment for rapid spread. Amazonas had relaxed social distancing measures by late 2020, P.1 was able to quickly reach extremely high infection rates.

The study did not directly address theories that P.1 evades immunity developed from prior infections, but they concluded that a combination of epidemiological and virological factors allowed P.1 to drive a second wave of COVID-19 in Amazonas starting in December.

The paper includes a supplementary note suggesting that NPIs instituted in Manaus in January 2021 significantly reduced transmission rates of VOC P.1. The team ends the paper by reiterating the importance of adequate social distancing measures to limit the spread of COVID-19 and prevent the emergence of new Variants of Concern.

Read the entire paper here.

This study used the Maxwell® RSC Viral Total Nucleic Acid Purification Kit to extract viral RNA from samples. Learn more about the kit and its uses during the COVID-19 pandemic here.

Antibody Response Differ in Adults, Kids and Potential Cross-Reactive Coronavirus Antibodies

Posted on by Kari Kenefick
B cell and B cell receptor cartoon. The B cell receptors are important for antibody response.
Drawing of a B cell and the B cell receptor. The receptor shows the characteristic Y shape of an immunoglobulin molecule.

B cells are the immune cells that produce antibodies (immunoglobulins or Ig) to detect intruding pathogens. B cells produce a variety of classes of antibodies. Generally during an immune response to a pathogen, whether viral or bacterial, B cells produce immunoglobulins (Ig) IgM and IgD, and later in the response, IgG and IgA, that are specific to the intruding organism. These Igs capture and aid in neutralizing the pathogen.

Ig classes can be studied by sequencing the B cell receptor (BCR), which binds antigen specifically. BCRs are formed via irreversible gene segment rearrangements of variable, diversity and joining (VDJ) genes. Ig classes can be diversified through somatic hypermutation and class-switch recombination of these gene segments (1).

B cell receptors with high sequence similarity can be found in individuals exposed to the same antigen, demonstrating that antigen exposure can result in similar B cell clones and memory B cells between individuals, both adults and children (1).

However, B cell immune responses can differ between adults and children. For example, children use more B cell clones that form neutralizing antibodies to HIV-1. And children infected with SARS-CoV-2 generally have milder illness than infected adults. SARS-CoV-2-infected children have lower antibody titers to the virus and more IgG-specific response to SARS-CoV-2 spike protein than to the nucleocapsid protein (1). These differences can contribute to faster SARS-CoV-2 clearance and lower viral loads in children versus adults.

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Understanding Inflammation: A Faster, Easier Way to Detect Cytokines in Cells

Posted on by Johanna Lee

Inflammation, a process that was meant to defend our body from infection, has been found to contribute to a wide range of diseases, such as chronic inflammation, neurodegenerative disorders—and more recently, COVID-19. The development of new tools and methods to measure inflammation is crucial to help researchers understand these diseases.

This diagram shows how the Lumit™ Immuno assay can be used to detect cytokines.

Cytokines—small signaling molecules that regulate inflammation and immunity—have recently become the focus of inflammation research due to their role in causing severe COVID-19 symptoms. In these severe cases, the patient’s immune system responds to the infection with uncontrolled cytokine release and immune cell activation, called the “cytokine storm”. Although the cytokine storm can be treated using established drugs, more research is needed to understand what causes this severe immune response and why only some patients develop it.

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Drug Repurposing Screens: Redeploying Old Dogs for New Tricks

Posted on by Promega

This blog was written by guest author, Amy Landreman, PhD.

Drug repurposing, identifying new uses for approved or investigational drugs, is an attractive strategy when looking for new disease treatments. Because the compounds have already gone through some level of pre-clinical optimization and safety testing, this approach can reduce risk, reduce cost, and speed up the timeline for further drug development. An additional benefit of this approach is that it can result in new biological insights or a better understanding of disease mechanisms since these compounds usually already have some level of mechanistic characterization. Indeed, there are now a number of compound collections openly available specifically for the purpose of facilitating drug repurposing efforts. For example, the ReFRAME (Repurposing, Focused Rescue, and Accelerated Medchem) library is a collection of 12,000 compounds developed by Scripps Research Center and has been screened to identify novel candidate therapeutics for Cryptosporidium infection (1). The Broad Institute also offers a drug repurposing hub that contains an annotated collection of over 7,000 compounds.

Drug repurposing libraries, although often smaller than novel compound small molecule libraries, are designed for implementation into high-throughput screening workflows in order to efficiently triage compounds for the desired result. Effective compound screens require assays that can be scaled to 384 or 1536-well microplate formats and implemented in batch or continuous processing workflows. The firefly luciferase reaction has been leveraged to create many assays that are well-suited to these types of high-throughput screening approaches. In particular, the generation of “Glow” assays that have stable luminescent signals and homogenous assay design is a good fit. The signal stability allows for multi-plate processing and because the reagent is added directly to cells in culture, pre-processing steps are eliminated allowing for automated workflows. Assay reagents such as the CellTiter-Glo® Cell Viability Assay and the ADP-Glo™ Kinase Assay are commonly used in screening efforts including those done with repurposing libraries.  In addition, there are several firefly luciferase reporter assay reagents such as Steady-Glo® and Bright-Glo™ Luciferase Assays that have been optimized for high-throughput detection of firefly luciferase activity making them well-suited to repurposing screens.

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What Is A Viral Variant?

Posted on by Jordan Villanueva

Every time a genome is replicated, there’s a chance that an error will be introduced. This is true for all life forms. On a small scale, these mutations can lead to genetic diseases or cancers. On a much larger scale, random mutations are an important tool of evolution.

During the COVID-19 pandemic, the SARS-CoV-2 virus has picked up many mutations as it spread around the world. Most of these mutations have been inconsequential – the virus didn’t change in any significant way. Others have given rise to variants such as B.1.1.7 and B.1.351, which present complications for public health efforts. By studying the evolution of the virus, we can monitor how it’s spreading and predict the characteristics of variants as they are detected.

SARS-CoV-2 variant
David Goodsell Painting of SARS-CoV-2 Virus
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A SARS-CoV-2 NanoLuc® Reporter Virus for Rapid Screening of Antivirals

Posted on by Johanna Lee
nanoluc invivo imaging

Before the COVID-19 global pandemic began, Dr. Xuping Xie, Assistant Professor of the University of Texas Medical Branch at Galveston, TX has been studying viruses, such as Dengue and Zika, for more than 10 years. Once the pandemic hit in early 2020, he was prepared to join the fight against the virus. “There was an urgent need to know: Is there a quicker way to develop therapeutics or antibodies to target SARS-CoV-2?” says Dr. Xie. “That’s why we immediately launched our SARS-CoV-2 project.”

His goal was to create an assay that could 1) screen for antiviral drugs and 2) quickly measure neutralizing antibody levels. The assay could be used to determine the immune status of previously infected individuals and to evaluate various vaccines under development. To achieve this, he wanted to create a reporter virus that is genetically stable and replicates similarly to the wild-type virus in cell culture. 

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COVID-19 Therapies: Are We There Yet?

Posted on by Ken Doyle

A year after COVID-19 was declared a pandemic, collaborative efforts among pharma/biotech and academic researchers have led to remarkable progress in vaccine development. These efforts include novel mRNA vaccine technology, as well as more conventional approaches using adenoviral vectors. While vaccine deployment understandably has captured the spotlight in the fight against COVID-19, there remains an urgent need to develop therapeutic agents directed against SARS-CoV-2.

COVID-19 therapeutic drugs

In the March 12 issue of Science, an editorial by Dr. Francis Collins, director of the U.S. National Institutes of Health (NIH), examines lessons learned over the past 12 months (1). Collins points out that many clinical trials of potential therapeutics were not designed to suit a public health emergency. Some were poorly designed or underpowered, yet they received considerable publicity—as was the case with hydroxychloroquine. Collins advises developing antiviral agents targeted at all major known classes of pathogens, to head off the next potential pandemic before it becomes one. A news feature in the same issue discusses the current state of coronavirus drug development (2).

The present crop of drug candidates is remarkably diverse, including repurposed drugs that were originally developed to treat diseases quite different from COVID-19. Typically, however, the mainstream candidates belong to two broad classes: small-molecule antiviral agents and large-molecule monoclonal antibodies (mAbs).

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Impact of COVID-19 Pandemic on Cancer Diagnosis—When Fewer Cases of Cancer is Not Good News

Posted on by Kelly Grooms

The year 2020 was a year filled with things we didn’t do. The global COVID-19 pandemic meant we didn’t gather with family and friends; we didn’t attend concerts or sporting events; we didn’t even go to work or school in the same way. We also didn’t go to the doctor, and as a result, many countries and organizations are reporting that there was an alarming drop in the number of new cancer cases (1–6). Unfortunately, while fewer diagnosis might sound like a good thing, there is no evidence that the actual rate of new cancer occurrence is declining (7).  

COVID-19 Restrictions Impact Cancer Screening and Diagnosis

The drop in cancer diagnosis happened after countries began to put into place new restrictions intended to slow the spread of the SARS-CoV-2 virus. These measures often included limiting or pausing many routine screenings and doctor visits, which also limited or paused opportunities to diagnosis cancer. The resulting decline in new cancer diagnosis was dramatic. In the United States, there was a 46.4% decline in the number of newly diagnosed cases of six of the most common cancer types (breast, colorectal, esophageal, gastric, lung and pancreatic) per week between March 1, 2020 and April 18, 2020 (1,2,8).

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From Primate Models to SARS-CoV-2 Sequencing and Testing

Posted on by Jordan Villanueva

As the SARS-CoV-2 virus spread around the world in early 2020, many researchers shifted their focus to support the global endeavors to address the challenge. For two professors at the University of Wisconsin, their efforts started with animal models to study pathogenicity and grew into massive SARS-CoV-2 sequencing and COVID-19 testing projects.

Virologists David and Shelby O'Connor (shown running along Lake Mendota) have worked extensively in SARS-CoV-2 Sequencing and COVID-19 Testing

“Being a scientist in this field gives a sense of purpose, but also a sense of obligation and responsibility,” says David O’Connor, PhD. “You always want to feel like you’re living up to that.”

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Engineering a Safer SARS-CoV-2 for Use in the Research Laboratory

Posted on by Sara Klink
This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses such as SARS-CoV-2. Photo Credit: Alissa Eckert, MS; Dan Higgins, MAM CDC
SARS-CoV-2 illustration from CDC; Photo Credit: Alissa Eckert, MS; Dan Higgins, MAM
E = envelope; M = membrane

A worldwide pandemic requires scientific research to understand the viral pathogen. The focused efforts of global scientists are even more necessary in the face of a novel coronavirus like SARS-CoV-2, the causative agent of COVID-19. However, because SARS-CoV-2 causes human disease, research efforts are restricted by the need for physical laboratories that are equipped to handle the required level of containment and personnel trained to handle pathogens in these facilities. But what if we could bypass the restrictive facility requirements by engineering a synthetic, replication-defective version of SARS-CoV-2 that more researchers could use to study the pandemic coronavirus, expanding the capacity to test and develop methods to attenuate its devastating effect on humans?

The challenge is to develop a derivative of SARS-CoV-2 that reflects how it behaves in the cell but is compromised such that it is unable to infect cells more than a single time. That is, the virus can get into a cell or be introduced into cells and replicate but is unable to produce infectious virus would offer a pathway to expand research capacity without the use of special laboratory facilities. This replication-defective SARS-CoV-2 could be created to encode as much or as little of the genome needed to examine its lifecycle without becoming a fully infectious virus. In fact, this replication-defective version of SARS-CoV-2 could include additional genetic elements that could be used to control its expression, track the virus in cells and measure the level of its replication. This task has been undertaken by Dr. Bill Sudgen’s group at the University of Wisconsin–Madison McArdle Laboratory for Cancer Research, explained by graduate student Rebecca Hutcheson during her presentation “Making the Virus Causing COVID-19 Safe for Research”.

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