Since the novel coronavirus, SARS-CoV-2, began to jump from human to human, it has mutated. The molecular machinery that the virus uses to read and make the genetic code is not good for proofreading; small typing errors made during the copying process cannot be corrected. Every time the virus lands in a new human victim, it infects a cell and makes an army of clones, some of which have genetic defects. Those error-bearing clones then go on to infect more cells, more people. Each cycle gives each infection more chance for errors. And over time, these bugs accumulate, those mutations.
Some of these changes are meaningless. Some are lost in the frenetic viral production. But some become permanent accessories, which are transmitted from virus to virus, human to human. Maybe it happens by chance; maybe it’s because the change helps the virus to survive in a small way. But collectively, viral strains with one notable mutation can begin to carry another. Collections of notable mutations are starting to pop up in viral genealogies, and sometimes they seem to have an advantage over their family members. This is when these different viruses – these variants – become alarming.
Scientists around the world have been closely monitoring mutations and variants since the pandemic began, and have seen some rise and fall without much effort. But in recent months, they have upset at least three variants. These variants of concern, or VOCs, have raised critical questions – and they are worrying – whether they can spread more easily than previous viral varieties, or they can evade therapies and vaccines or are even more lethal.
Here we will harm what we know and what we do not know about these variants. There are still many questions that still need to be asked. But researchers are working fast to address the most important unknowns. High on the list is whether the vaccines we already have will be effective against the variants. It seems likely so far that it will be. The virus nevertheless sends a clear message: with unbridled transmission that accelerates viral evolution, more variants will emerge and we need to be prepared.
As there is more data available per day, we will update this story with important findings as it comes. Before we get to the data, a brief remark about names: it is problematic to identify diseases or infectious agents – in this case virus variants – based on where they were identified. Such geographic associations may run the risk of creating stigma and may discourage reporting. Therefore, there is an active discussion in the scientific community about the best name of the current variants. In the meantime, it has become all too common to refer to their country of origin hereafter. We will try to avoid this as much as possible while making clear what variants we are talking about.
B.1.1.7
Alternative names: 501Y.V1 and VOC 202012/01
Geographical association: United Kingdom
Number of countries reporting cases: 70
Increased portability: Yes
Increased severity / mortality: A “Realistic Possibility”
Vaccine efficacy: Still effective
In early December 2020, researchers and officials in the UK began to warn about a new variant that appears to spread abnormally rapidly while carrying an unusually large number of mutations – 23. The first survey of the variant in the UK goes back to two samples taken from infected people on 20 September and 21 September. In a few weeks, the variant began to make up a larger and larger share of the total cases there. Researchers quickly suspected that the variant had become more transmissible – that is, that it could spread more easily from person to person.
Transmission
Data analyzes since December support the hypothesis, but researchers are still figuring out how much more transferable it is compared to previous versions. In early January, British researchers released preliminary results from a series of models that additionally calculated the variations of SARS-CoV-2’s observed reproduction number by 0.36 to 0.68. This means that people infected with B.1.1.7 will, on average, contract an infection. additional 0.36 to 0.68 people on top of how much they would be infected if they had a previous version of the virus. More recent estimates were approximately in this range, indicating that B.1.1.7 has an increase of 47% or 56% in the transfer.
B.1.1.7 has now been detected in more than 60 countries outside the UK, including the United States, where it has been found in at least two dozen states. A model study published by the U.S. Centers for Disease Control and Prevention on Jan. 15 estimated it would become the dominant tribe in the U.S. in March.
Mutations
Some of the mutations carried by B.1.1.7 help to explain the newfound ability of the virus. The variant contains a total of 23 mutations: 13 mutations that change the protein sequences of the virus (non-synonymous), four deletions and six synonymous mutations. Of the mutations of B.1.1.7, eight occur in the virus’ spike protein, the now infamous club-like protein that pushes out of the spherical particle of the virus. Spike is what the virus uses to bind and infect cells, which cause the protein to bind by a receptor on the outside of human cells called ACE2.
So far we know that at least three of B.1.1.7’s eight peak mutations may be relevant for the enhanced transmission of the variant. The most important among them is a mutation that changes one of the critical amino acids of the vein proteins – the amino acid at position 501 of the protein sequence of the vein. Specifically, the mutation changes the amino acid at 501 of an asparagine (N) into a tyrosine (Y), so the mutation is written as N501Y. The 501 amino acid is critical because it lies within the area of the peak that binds directly to ACE2 – called the receptor binding domain (RBD) – and it is one of only six major contact residues in the RBD. Laboratory experiments have suggested that changing from an N to a Y at 501 increases the peak’s ability to bind ACE2, and experiments in mice have linked the mutation to increased infectivity and disease.
After N501Y there is P681H. The mutation at position 681 – the change in the amino acid of a proline (P) to a histidine (H) – falls close to a unique furin cleavage site on SARS-CoV-2’s ear protein. For the SARS-CoV-2 to successfully enter a cell after ACE2 is bound, the vein protein must be cut by enzymes in its two subunits. The rupture changes the structure of the peak and activates it so that it can fuse itself with the cell membrane and dump the contents into the now infected cell. In animal studies, the furin cleft site appeared to promote the virus’ ability to invade cells. Researchers suspect that the new mutation may further promote entry.
Adrian DENNIS / AFP / Getty Images
The third peak mutation known to be significant is the deletion of six nucleotides in its genetic code, resulting in the loss of two amino acids at positions 69 and 70 in the vein protein. It is unclear what exactly this removal does for the virus, but it has occurred a number of times in different generations, suggesting that it offers an advantage. For now, there is one clear consequence for researchers: the removal confuses a diagnostic test for SARS-CoV-2. The test is a three-target RT-PCR test, meaning it works by detecting three fragments of the SARS-CoV-2 genome, including one in the gene encoding for peak. If this 69-70 deletion is present, the test will be negative for the spike gene but positive for the other two SARS-CoV-2 genetic sequences. This result is called “S gene dropout” and is now used to identify infections caused by B.1.1.7.
These three mutations are currently the most striking in B.1.1.7. There is scarce data on the other 20, but researchers are working fast to determine what each can do on their own or in combination with the other.
Severity / mortality
When researchers first raised concerns about B.1.1.7, all of these concerns were related to increased portability. Preliminary evidence looking at infection outcomes does not indicate that B.1.1.7 caused serious illnesses or more deaths than other virus strains. Some have nevertheless seen little consolation through this, as any increase in the total number of infections still leads to serious cases and deaths in absolute numbers.
The situation took a dark turn on 21 January when a British advisory group, NERVTAG, found preliminary evidence that ‘there is a realistic possibility that infection with VOC B.1.1.7 is associated with an increased risk of death in comparison with infection with -VOC viruses. ”
So far, some experts are not convinced by the preliminary evidence presented, and ask them for much more data before any conclusions are drawn. First, the complete data sets behind some of the analyzes done so far have not been published, and some trust that small numbers of deaths in people infected with B.1.1.7 are compared with larger numbers of deaths in people infected. with other tribes. Some experts also wonder if the calculated increase in deaths can be explained simply by congested hospitals rather than by a more lethal variant.
Vaccine efficacy
With increased infectivity and the possibility of being more lethal, a critical question raised by B.1.1.7 is whether the current vaccines we have – MRNA vaccines from Pfizer / BioNTech and Moderna – will work against the variant. So far, the answer seems to be yes.
On January 19, researchers from Pfizer and BioNTech released a non-peer-reviewed study in which they depleted antibody-laden blood of 16 people who gave their mRNA vaccine (BNT162b2) against a pseudovirus containing B.1.1.7’s mutated ear protein. contains. The researchers found that the antibodies of the vaccines were just as good at neutralizing the pseudovirus with B.1.1.7’s mutated ear protein as it was at neutralizing a pseudovirus with the ear protein of a SARS-CoV-2 virus. “These data … make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection,” the researchers concluded.
On January 25, Moderna also launched its own non-peer-reviewed study, which was similar in design. They tested the antibodies of eight people who gave their mRNA vaccine against a pseudovirus with B.1.1.7’s mutated ear protein. Again, the antibodies neutralized the pseudovirus at levels comparable to those seen with a pseudovirus with a reference peak protein.
Another similar study, led by researchers at Columbia University and released on January 26, found the same results. Antibodies from 12 people who received Moderna’s vaccine and 10 people who received Pfizer’s vaccine were able to neutralize a pseudovirus containing B.1.1.7’s mutated ear protein, with only a moderate decrease in potency compared to ‘neutralization of’ a pseudovirus with a reference seed protein.