Now a 'worrisome New York variant — Columbia University

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A new SARS-CoV-2 lineage that shares worrisome similarities with other recent variants of concern is on the rise in New York City, according to a study by scientists at Columbia University Vagelos College of Physicians and Surgeons.

The prevalence of the new variant – called B.1.526 – has been steadily increasing since it first appeared in samples collected in November 2020. In January 2021, B.1.526 represented about 3% of samples analysed by the researchers, rising to 12.3% by mid-February. The cases they found are scattered throughout the New York City area.

The researchers also searched publicly available databases and found COVID-19 cases caused by B.1.526 and closely related strains are emerging predominantly in the north-eastern US, as suggested by other researchers. “It's not just one cluster, which means the lineage is probably spreading widely through the region,” says Dr Anne-Catrin Uhlemann, associate professor of medicine in the division of infectious diseases, who led the study with Dr David Ho, director of the Aaron Diamond AIDS Research Centre and the Clyde ‘56 and Helen Wu professor of medicine.

The researchers started to look for key mutations found in variants of concern in the New York City region in January and have analysed over 1,100 samples. “Initially, we thought we’d find a lot of the other known lineages,” Uhlemann says. Though a couple variants, originally identified in South Africa and Brazil, were detected, “we didn’t find the high numbers we expected. Instead we found high numbers of this home-grown lineage,” she says.

The impact of the new B.1.526 variant on transmissibility, disease severity, and risk of reinfection is not yet known.

But the Columbia study shows that B.1.526 shares some worrying characteristics with B.1.351, a variant first identified in South Africa, and P.1., first identified in Brazil, that are less susceptible to some treatments and vaccines.

Of prime concern is a change in one area of the virus’s spike protein, called E484K, that is present in all three variants. The E484K mutation is believed to weaken the body’s immune response to the virus.

A recent study by Ho found antibodies from vaccinated people are less effective at neutralizing the B.1.351 virus – and that the effect is primarily caused by the E484K mutation. The E484K mutation is also responsible, he found, for the drop in effectiveness of certain monoclonal antibody treatments against the B.1.351 variant.

Variants with the E484K mutation may also cause reinfection in people who were infected previously with earlier variants of the virus. In the current report, one of the individuals infected with the new B.1.526 variant had a previously documented SARS-CoV-2 infection without the E484K mutation, and the researchers are currently working to determine the potential origins of this local lineage.

In the coming weeks, the scientists plan to ramp up sequencing efforts to around 100 samples per day to continue surveillance of the new variants, including B.1.526.

“We are also finding many cases of the B.1.1.7 variant, originally identified in the UK, and it’s possible those cases will double – but it’s hard to know which variant will cause the biggest problem,” Uhlemann says. “Increasing our genomic sequencing effort will help us better understand the impact of the new variant and keep our eyes open for new variants that may pop up in our area.”

The researchers also are working to culture the live variant to learn more about its vulnerability to vaccines and monoclonal antibody treatments, and its potential for reinfection.

“The rise of these variants shows that we may be chasing after SARS-CoV-2 for some time,” Ho says. “Unfortunately, this pandemic may not go away so easily with the advent of the vaccines.”

“It’s worrying that in the New York City region, case numbers don’t seem to be declining as rapidly as in other areas of the country,” Uhlemann says, “Physical distancing and masks will slow the spread of all variants, and we need to double down on those efforts.”

 

Study details (1)
A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York

Medini K Annavajhala, Hiroshi Mohri, Jason E Zucker, Zizhang Sheng, Pengfei Wang, Angela Gomez-Simmonds, David D Ho, Anne-Catrin Uhlemann

Published in medRxiv on 23 February 2021

Abstract
Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution. Extensive mutations in the spike protein of variants B.1.1.7, B1.351, and P.1 have raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened. In vitro studies have shown that one mutation, E484K, plays a crucial role in the loss of neutralizing activity of some monoclonal antibodies as well as most convalescent and vaccinee sera against variant B.1.351. In fact, two vaccine trials have recently reported lower protective efficacy in South Africa, where B.1.351 is dominant. To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks. Whole genome sequencing further demonstrated that most of our E484K isolates (n=49/65) fell within a single lineage: NextStrain clade 20C or Pangolin lineage B.1.526. Patients with this novel variant came from diverse neighborhoods in the metropolitan area, and they were on average older and more frequently hospitalized. Phylogenetic analyses of sequences in the database further reveal that this B.1.526 variant is scattered in the Northeast of US, and its unique set of spike mutations may also pose an antigenic challenge for current interventions.

 

Study details (2)
Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization

Pengfei Wang, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D Kwong, Barney S Graham, John R Mascola, Jennifer Y Chang, Michael T Yin, Magdalena Sobieszczyk, Christos A Kyratsous, Lawrence Shapiro, Zizhang Sheng, Manoj S Nair, Yaoxing Huang, David D Ho

Published in bioRxiv on 25 January 2021

Abstract
The Covid-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization1,2, with more in the pipeline3–6. Furthermore, multiple vaccine constructs have shown promise7, including two with ~95% protective efficacy against Covid-198,9. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. Considerable viral evolution has occurred since, including variants with a D614G mutation10 that have become dominant. Viruses with this mutation alone do not appear to be antigenically distinct, however11. Recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK12 and B.1.351 in South Africa13 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD). It is modestly more resistant to convalescent plasma (~3 fold) and vaccinee sera (~2 fold). Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation, although some mAb combinations retain activity. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (~11-33 fold) and vaccinee sera (~6.5-8.6 fold). B.1.351 and emergent variants14,15 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

 

A report on the CIDRAP site notes that both Pfizer and Moderna have announced they are testing their mRNA vaccines against current variants, and in Moderna's case, it has shipped a new vaccine targeting the B1315 (South African) variant to the US National Institutes of Health (NIH).

Pfizer and BioNTech say they are testing if a third dose of their COVID-19 vaccine will trigger an enhanced immune response against new variants. They are also in talks with regulatory authorities about testing a new vaccine modified to target the B1351 variant.

"Leveraging the flexibility of our mRNA platform, we are moving quickly to test updates to the vaccines that address emerging variants of the virus in the clinic," Stephane Bancel, CEO of Moderna, is quoted as saying.

"Moderna is committed to making as many updates to our vaccine as necessary until the pandemic is under control. We hope to demonstrate that booster doses, if necessary, can be done at lower dose levels, which will allow us to provide many more doses to the global community in late 2021 and 2022 if necessary."

 

The Biden administration is taking the emergence of a new coronavirus strain in New York “very seriously,” CNBC reports White House chief medical advisor Dr Anthony Fauci said. In addition to the B.1.526 strain in New York, officials are monitoring four other variants.

The report says that as of Sunday, the CDC has identified 2,400 cases of the B.1.1.7 variant, first identified in the UK. The agency has identified 53 cases of the B.1.351 strain from South Africa as well as 10 cases of P.1, a variant first identified in Brazil.

California scientists are also monitoring a variant called B.1.427/B.1.429.

Fauci said that there are a lot of “unknowns” about the New York variant, but officials are looking at the strain “very carefully.”

 

The mutation has travelled extensively through the metropolitan New York region, and individual cases have also been found in 14 other states, including Texas, Wyoming and Maryland, according to Gregory Armstrong, director of the US Centres for Disease Control and Preventions Advanced Molecular Detection Programme in a Bloomberg report.

Recent research suggests B.1.526 needs to be closely watched “for its ability to evade both monoclonal antibody and, to a certain extent, the vaccine-induced antibody,” said Fauci, who also heads the National Institute of Allergy and Infectious Diseases.

Anthony West, a senior research specialist at CalTech, first raised the possibility that some portion of vaccine-induced immune response against the coronavirus “might be less effective because of the mutations” in the New York variant.

But the studies haven’t yet been peer-reviewed. And Eric Topol at the Scripps Research Translational Institute in California said that while the mutations noted in the variant probably have some impact, further significance remains unproven.

 

Columbia University material

 

medRxiv study (Restricted access)

 

bioRxiv study (Restricted access)

 

CIDRAP material

 

Full CNBC report (Open access)

 

Full Bloomberg report (Open access)

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