Avian Flu Diary: CDC: Emerging SARS-CoV-2 Variants

#15,667

Yesterday's announcement from Colorado's Governor On The 1st Detection Of The COVID B.1.1.7 Variant In U.S. was fully expected given the rapid spread of this variant COVID strain around the world, and it is likely that variant is already circulating widely in the United States.

While between one and two million COVID PCR tests are conducted each day in the United States, the number of COVID viruses that undergo genomic sequencing - which is required to identify variants - only numbers in the hundreds.

As the following CDC report explains, work is underway to improve those numbers. But for now, genomic surveillance in the United States - and in many other places around the world - is pretty thin.

The following CDC update provides us with both details on the three most concerning variants currently on our radar (UK or B.1.1.7., South Africa or 501Y.V2, and Nigeria or B.1.207), along with a discussion of potential consequences from an evolving SARS-CoV-2 virus.

For now, we've seen no evidence that any of these variants increase the severity of illness, or that they would evade the current vaccines. There is some evidence, however, that B.1.1.7 and 501Y.V2 may be more transmissible.

Comparatively little is known about the variant reported in Nigeria, although once again there is no evidence that it is more severe, or even more transmissible, that past strains. Investigations into all three variants continue.

That said, these aren't the first - and are unlikely to be the last - COVID variants to appear. Viruses constantly evolve. Most will be evolutionary failures, or will convey no real advantage to the virus.

But we'd have to be naive to believe that this virus isn't capable of throwing us a curveball or two in the months and years ahead. In fact, its survival depends on it.

First yesterday's update from the CDC, and then a brief note about the words we use to describe variants.

Emerging SARS-CoV-2 Variants

Updated Dec. 29, 2020

Multiple SARS-CoV-2 variants are circulating globally. Several new variants emerged in the fall of 2020, most notably:

In the United Kingdom (UK), a new variant strain of SARS-CoV-2 (VOC 202012/01 or B.1.1.7) emerged with an unusually large number of mutations. This variant has since been detected in numerous countries around the world, including the United States (US) and Canada.
In South Africa, another variant of SARS-CoV-2 (501Y.V2 or B.1.351) emerged independently of VOC 202012/01. This variant shares some mutations with VOC 202012/01. Cases attributed to this variant have been detected outside of South Africa.
In Nigeria, another distinct variant strain of SARS-CoV-2 also emerged.

Scientists are working to learn more about these variants to better understand how easily they might be transmitted and whether currently authorized vaccines will protect people against them. Currently, there is no evidence that these variants cause more severe illness or increased risk of death. New information about the virologic, epidemiologic, and clinical characteristics of these variants is rapidly emerging.

CDC, in collaboration with other public health agencies, is monitoring the situation closely. CDC is working to detect and characterize emerging viral variants. Furthermore, CDC has staff available to provide on-the-ground technical support to investigate the epidemiologic and clinical characteristics of SARS-CoV-2 variant infections. CDC will communicate new information as it becomes available.

Emerging Variants

United Kingdom
Variant of Concern (VOC) 202012/01 (a.k.a. B.1.1.7)
This variant has a mutation in the receptor binding domain (RBD) of the spike protein at position 501, where amino acid asparagine (N) has been replaced with tyrosine (Y). The shorthand for this mutation is N501Y. This variant also has several other mutations, including:
69/70 deletion: occurred spontaneously many times and likely leads to a conformational change in the spike protein
P681H: near the S1/S2 furin cleavage site, a site with high variability in coronaviruses. This mutation has also emerged spontaneously multiple times.
ORF8 stop codon (Q27stop): mutation in ORF8, the function of which is unknown.
This variant is estimated to have first emerged in the UK during September 2020.
Since December 20, 2020, several countries have reported cases of the UK VOC 202012/01, including the United States and Canada.
Preliminary epidemiologic indicators suggest that this variant is associated with increased transmissibility (i.e., more efficient and rapid transmission).
Currently there is no evidence to suggest that the variant has any impact on the severity of disease or vaccine efficacy.
South Africa
501Y.V2 (a.k.a. B.1.351)
This variant has multiple mutations in the spike protein, including N501Y. Unlike the UK variant, VOC 202012/01, this variant does not contain the deletion at 69/70.
This variant was first identified in Nelson Mandela Bay, South Africa, in samples dating back to the beginning of October 2020, and travel-related cases have since been detected outside of South Africa.
Currently there is no evidence to suggest that this variant has any impact on disease severity or vaccine efficacy.
Nigeria
B.1.207
Analysis of sequences from the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer’s University, Nigeria, identified two SARS-CoV-2 sequences that share one non-synonymous mutation in the spike protein (P681H) in common with VOC 202012/01 (B.1.1.7). This variant does not share any of the other 22 unique mutations of VOC 202012/01 (B.1.1.7).
The P681H residue is near the S1/S2 furin cleavage site, a site with high variability in coronaviruses. This mutation also has emerged spontaneously multiple times and is present in VOC 202012/01 (B.1.1.7).
At this time, it is unknown when this variant may have first emerged.
Currently there is no evidence to indicate this variant has any impact on disease severity or is contributing to increased transmission of SARS-CoV-2 in Nigeria.

Why Strain Surveillance is Important for Public Health

CDC has been conducting SARS-CoV-2 Strain Surveillance to build a collection of SARS-CoV-2 specimens and sequences to support public health response. Routine analysis of the available genetic sequence data will enable CDC and its public health partners to identify variant viruses for further characterization.

Viruses generally acquire mutations over time, giving rise to new variants. Some of the potential consequences of emerging variants are the following:
Ability to spread more quickly in people. There is already evidence that one mutation, D614G, confers increased ability to spread more quickly than the wild-type[1] SARS-CoV-2. In the lab, 614G variants propagate more quickly in human respiratory epithelial cells, outcompeting 614D viruses. There also is epidemiologic evidence that the 614G variant spreads more quickly than viruses without the mutation.
Ability to cause either milder or more severe disease in people. There is no evidence that these recently identified SARS-CoV-2 variants cause more severe disease than earlier ones.
Ability to evade detection by specific diagnostic tests. Most commercial polymerase chain reaction (PCR) tests have multiple targets to detect the virus, such that even if a mutation impacts one of the targets, the other PCR targets will still work.
Decreased susceptibility to therapeutic agents such as monoclonal antibodies.
Ability to evade natural or vaccine-induced immunity. Both vaccination against and natural infection with SARS-CoV-2 produce a “polyclonal” response that targets several parts of the spike protein. The virus would likely need to accumulate multiple mutations in the spike protein to evade immunity induced by vaccines or by natural infection.
Among these possibilities, the last—the ability to evade vaccine-induced immunity—would likely be the most concerning because once a large proportion of the population is vaccinated, there will be immune pressure that could favor and accelerate emergence of such variants by selecting for “escape mutants.” There is no evidence that this is occurring, and most experts believe escape mutants are unlikely to emerge because of the nature of the virus.

[1] “Wild-type” refers to the strain of virus – or background strain – that contains no major mutations.

Strain Surveillance in the US

In the United States, sequence-based strain surveillance has been ramping up with the following components:
National SARS-CoV-2 Strain Surveillance (“NS3”): Since November 2020, state health departments and other public health agencies have been regularly sending CDC SARS-CoV-2 samples for sequencing and further characterization. This system is now being scaled to process 750 samples nationally per week. One strength of this system is that it allows for characterization of viruses beyond what sequencing alone can provide.
Surveillance in partnership with national reference laboratories: CDC is contracting with large national reference labs to provide sequence data from across the United States. As of December 29, CDC has commitments from these laboratories to sequence 1,750 samples per week and anticipates being able to increase this number.
Contracts with universities: CDC has contracts with seven universities to conduct genomic surveillance in collaboration with public health agencies.
Sequencing within state and local health departments: Since 2014, CDC’s Advanced Molecular Detection Program has been integrating next-generation sequencing and bioinformatics into the U.S. public health system. Several state and local health departments have been applying these resources as part of their response to COVID-19. To further support these efforts, CDC released $15 million in funding, with COVID supplemental funds, through the Epidemiology and Laboratory Capacity Program on December 18, 2020.
The SPHERES consortium: Since early in the pandemic, CDC has led a national consortium of laboratories sequencing SARS-CoV-2 (SPHERES) to coordinate U.S sequencing efforts outside of CDC. The SPHERES consortium consists of more than 160 institutions, including academic centers, industry, non-governmental organizations, and public health agencies.
Through these efforts, anonymous genomic data are made available through public databases for use by public health professionals, researchers, and industry.

Finally, a word about nomenclature.

I'm vaguely uncomfortable using terms like `the UK variant', or the `South African Strain' - and I'd be perfectly happy to call them B.1.1.7 and 501Y.V2 - if that didn't elicit a gigantic `Huh?' from most of the public.

The press, along with governments and public health agencies, have used the `UK' or `South African' descriptors for these variants from the start, and that is how most people differentiate them. The best I can do is to try to list both identifiers as often as possible, and hope that over time, the more accurate scientific names will prevail.

The fact that most people still refer to the 2009 H1N1 pandemic virus as `swine flu' more than a decade later (or worse, call African Swine Fever `Swine Flu'), illustrates the problem.

On a slightly more pedantic note, I'm seeing a lot of comments on twitter, and elsewhere, about the usage of `variant' vs. `strain' vs. `lineage' when describing these variant viruses. I'm aware there are subtle differences between these terms, and `variant' is the most appropriate appellation.

However, it is helpful when writing to have more than one way to describe these variants, and once again governments and public health agencies (and many journalists) have adopted both `strain' and `lineage' for these purposes. The CDC notes:

The press often uses the terms “variant,” “strain,” “lineage,” and “mutant” interchangeably. For the time being in the context of this variant, the first three of these terms are generally being used interchangeably by the scientific community as well.

While a `mutation' is a perfectly acceptable way to describe an amino acid change in a virus, calling the virus a `mutant' is misleading, and often inflammatory. In fact, I often refer to it disparagingly as the `M word', since it is often used in hyperbolic headlines.

With that said . . .

Cheers and and an early Happy New Year's to all my readers. Here's hoping 2021 be an improvement for all of us. - M.P.C.