The Delta Variant poses a unique challenge to global health. We’ve compiled answers to some of the most common questions about Delta and other SARS-CoV-2 variants.
What is a variant?
A variant is a form of a virus that is genetically distinct from the original form.
“All organisms have mutation rates,” says Luis A Haddock, a graduate student at University of Wisconsin – Madison. “Unfortunately for us, viruses have one of the highest mutation rates of everything that currently exists. And even more unfortunately, RNA viruses have the highest mutation rates even among viruses.”
Luis works in the Friedrich Lab at UW-Madison, which has been sequencing SARS-CoV-2 genomes from positive test samples since the beginning of the pandemic. SARS-CoV-2 is constantly evolving, and sequencing can help us follow it through time and space. Most of the variants don’t behave any differently. A single nucleotide substitution might not even change the amino acid sequence of an encoded protein. However, occasionally a mutation will alter the structure or function of a protein.
The Promega Corporate Responsibility Report captures a variety of stories of how we’ve supported our employees, customers and communities over the past year. For example, in 2020, 735 million samples were tested for SARS-CoV-2 using Promega reagents. We launched a new scholarship to support students from underserved backgrounds, and we completed our three largest solar arrays on our Madison, WI campus. As we look to the future, we recognize that there are always more opportunities to reduce our environmental impact. That’s why we’re setting our most ambitious sustainability goals ever.
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.
New research published in Nature Medicineexamined 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.
In 2020, Promega North America launched the Diversification Of Our Research Scientists (DOORS) Scholarship to recognize and empower students from underrepresented backgrounds. Ten students received $5,000 towards tuition and other costs associated with their education, as well as connections with mentors from Promega. Here are two of their stories.
Almost 90% of the human genome is transcribed into RNA, but only 3% is ultimately translated into a protein. Some non-translated RNA is thought to be useless, while some play a significant yet often mysterious role in cancer and other diseases. Despite its abundance and biological significance, RNA is rarely the target of therapeutics.
“We say it’s undruggable, but I would say that ‘not-yet-drugged’ is a better way to put it,” says Amanda Garner, Associate Professor of Medicinal Chemistry at the University of Michigan. “We know that RNA biology is important, but we don’t yet know how to target it.”
Amanda’s lab develops systems to study RNA biology. She employs a variety of approaches to analyze the functions of different RNAs and study their interactions with proteins. Her lab recently published a paper describing a novel method for studying RNA-protein interactions (RPI) in live cells. Amanda says that with the right tools, RPI could become a critical target for drug discovery.
“It’s amazing that current drugs ever work, because they’re all based on really old approaches,” Amanda says. “This isn’t going to be like developing a small molecule kinase inhibitor. It’s a whole new world.”
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.
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.
“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.”
New variants of COVID-19 are causing global concern. Mutations in the viral genome can affect its transmissibility and pathogenicity, and structural changes to the spike protein could reduce the effectiveness of some of the vaccines that are being distributed in several countries. A new preprint available on bioRxiv suggests that the COVID-19 variant B.1.1.7, which was first documented in the United Kingdom, is still susceptible to the neutralizing antibodies produced in response to several vaccines, including the Moderna mRNA-1273 and the Novavax NVX-CoV2373.
John Longshore admits that he was not a big Promega customer before the COVID-19 pandemic. His team uses a wide variety of suppliers to assemble the types of testing protocols needed to serve over 50 hospitals. However, when he began to face supply chain disruptions in early 2020, he needed a supplier he could depend on to support the rapid scale-up of COVID-19 testing, and Promega rose to the occasion.
“When we started working with Promega for bulk isolation reagents, our ask was, ‘Can you supply us with 15,000 isolation reagents per week?’” John says. “The answer was yes, and we have gotten everything we’ve asked for on the dates that it was promised.”
The 2020 Promega Award for Biochemistry ceremony was a bit different this year. Promega Beijing typically announces the award recipients in a ceremony at the biannual meeting of the Chinese Society of Biochemistry and Molecular Biology (CSBMB). As a result of the COVID-19 pandemic, the 2020 conference was moved online. Despite the unusual circumstances, Promega Beijing held a virtual ceremony to grant the award to Dr. Peng Chen and Dr. Haitao Yang.
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