What do we know about the new COVID-19 strain emergent in the UK?

As a new COVID-19 strain emerges in the southeast of England that appears to be more infectious than previous strains, what do we know about this version of the virus so far?

What is it and when did it first emerge?

It is a new strain of the SARS-CoV-2, that is expected to be more infectious than the previous dominant strain of the virus. It is referred to as the B.1.1.7 lineage of the virus or VUI-202012/01. The first strain of this new variant was detected 20 September 2020 in Kent in the southeast of England with another detected in London (UK) the following day.

How does it differ from previous strains?

All of the 14 alterations of note in this strain have been detected before. The novelty here is that some of the combinations of mutations have not been observed in a single strain. Four key changes have been highlighted in a preliminary characterization (yet to be peer reviewed) posted on the discussion forum Virological by the COVID-19 Genomics Consortium UK. These changes include:

• N501Y substitution mutation in the spike protein
• 69-70 deletion mutation in the spike protein
• P681H substitution mutation in the spike protein
• ORF8 Q27 stop mutation outside of the spike protein

The N501Y substitution is currently the best understood and impactful of these mutations. It alters one of the six key residues in the receptor-binding domain (RBD) of the spike and increases the binding affinity to human and murine ACE2 receptors – the protein through which SARS-CoV-2 binds and enters cells.

The 69-70 deletion mutation has previously been implicated in evading the human immune response while also occurring in association with other RBD mutations. This alteration was also observed in the mink mutated strain that was observed in Denmark just over a month ago.

The P681H substitution occurs in one of four residues component to the furin cleavage site on the spike. This site is known to play a role in the increased infection of respiratory epithelial cells and transmission of SARS-CoV-2 compared to other, closely related coronaviruses.

The ORF8 Q27 stop mutation disrupts the production of the protein ORF8, either truncating it or resulting in a completely inactive form of the protein. ORF8 is thought to play a role in the transmission of the disease and its inactivation is thought to allow further mutations to accrue in the virus, accelerating the rate at which it can attain mutations.

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How prevalent and transmissible is B.1.1.7?

At this stage, it is hard to be exact but the UK’s New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) has compiled the available information into a report. The report indicates that the new COVID-19 strain could currently have a growth rate of 71% higher than other strains of SARS-CoV-2. This indicates that the variant is spreading at a much higher rate than others. This does not necessarily mean that the variant is 71% more transmissible, as “super spreader events” can play a role in boosting this figure, but an increase in transmissibility is certainly a sensible explanation for this increased rate.

The report also suggests that the R value for the new strain could be anywhere from 0.39—0.93 higher than other strains. The R value indicates the number of people that one infected person is likely to infect. Again, the implication here is an increase in transmissibility.

How did this new strain evolve?

Viruses are continually mutating and SARS-CoV-2 has been noted to accrue new mutations at a rate of two a month. The Virological report speculates that this new COVID-19 strain could have developed while inside an immunodeficient patient. These patients, if chronically infected, host the virus for much longer periods of time, exhibiting detectable SARS-CoV-2 RNA for 2—4 months longer than a typical infection.

These patients receive multiple treatments such as remdesivir and convalescent plasma – blood plasma from someone who has had COVID-19 and that contains antibodies against the disease.  This treatment can act as a selection pressure and high rates of mutation are often observed in the viral genome of chronically infected immunodeficient patients.

Fortunately, this means that the virus has not had to evolve to defend against natural immune responses so will likely be no more resistant to a healthy immune response. However, resistance to antibody therapy may be increased as a result of the previously mentioned selection pressures.

This is currently the primary hypothesis for how this strain has evolved.

Is it any more dangerous and will the vaccine still work?

NERVTAG has noted that of the 1000 cases determined with the new COVID-19 strain, four people have died. More work needs to be done to establish if this is in-line with the regular mortality but currently it does not seem that the new variant is any more fatal or that it leads to a more severe disease progression. This remains to be confirmed empirically.

With regard to the efficacy of the vaccines, while one of the 14 notable mutations is in the RBD of the spike protein and a further six occur in the gene for the protein, the antibodies raised by the Pfizer vaccine are designed to attack the spike protein at many different locations. This makes it unlikely that the vaccine will be completely ineffective against the new variant, but the efficacy of the vaccine may be called into question.

The CEO of BioNTech – Pfizer’s partner in the development of the vaccine – has declared that he is “confident” that the vaccine will remain functional against the new strain as the spike protein remains mostly unchanged. Further studies will be enacted to ensure that this is the case.