The science behind London’s Christmas blockade

On Saturday, Prime Minister Boris Johnson announced a highly restrictive lockdown to affect a third of England’s population, including most of south-east England and London. The closure has been widely reported, including in the New York Times, Washington Postand by Reuters.

Here I look at some of the science behind this decision. I have already written about molecular epidemiology. This is another example of the insights that genomic analysis can provide.

The key finding driving the British lockdown appears to be the rapid increase in the number of cases represented by a specific evolutionary branch of SARS-CoV-2, the virus that causes Covid-19. The lineage has been named B.1.1.7 by the COVID-19 Genomics Consortium UK. A report published online on the virological.org blog co-authored by ten leading experts in viral evolution explains the latest findings. Highlights include:

This lineage has been around for a while.

Patient samples from the B.1.1.7 lineage were collected for the first time in late September.

This means that it almost certainly originated from a single person. The original blog post has an interesting comment on this, including the conjecture that the new lineage arose in a person who was chronically infected.

There are seventeen non-synonymous mutations or deletions

These are the potentially important mutations. There are many mutations that can occur at the same time. As a background, the genetic code for SARS-CoV-2 is contained in its RNA. RNA is a “macromolecule” made up of nucleotides, each of which consists of a molecule of the sugar ribose, a phosphate group, and a nitrogen-containing “base”. In the case of SARS-CoV-2, the genome comprises a chain of 29,881 nucleotides. This nucleotide sequence is the blueprint for the amino acid sequences that are the building blocks of all the pieces that make up a virus particle. There is a certain redundancy in the genetic code, such that some mutations do not change the amino acid sequence, the so-called “synonymous” mutations, while others do, that is, the “not synonymous” ones. Synonymous mutations are like having multiple sets of plans leading to the same building. But non-synonymous mutations result in real changes in building materials. Here we have seventeen different changes to the virus that all happened at the same time.

Eight of these important mutations are found in the “S” gene

The S gene encodes a protein called a spike. The spike protein is essential for the transmission of SARS-CoV-2. It is found on the surface of the virus particle and has a characteristic called the receptor-binding domain. When the receptor-binding domain encounters an enzyme, called ACE2, that is embedded in the membrane of a host cell, then another enzyme, called TM serine protease 2 (TMPRSS2), allows the virus to enter the cell.

Possibly the most important of these mutations is one known as N501Y

The nomenclature N501Y means that mutations in the new variant cause the amino acid at site 501 to become tyrosine (symbol Y), whereas previous genotypes had encoded asparagine (symbol N). This amino acid provides one of the six contact points with the receptor-binding domain. This means that the N501Y mutation can affect how quickly the virus enters human cells. The N501Y mutation has been shown experimentally to cause SARS-CoV-2 to more easily infect mice. It has also emerged on several independent occasions, including in South Africa, as evolutionary virologist Emma Hodcroft from the University of Basel explains.

The new lineage, including the 17 major mutations, has grown very rapidly in Britain over the past six weeks.

The virological.org report only says that the B.1.1.7 lineage “has been growing rapidly for the past 4 weeks.” But, an analysis on nextstrain.org suggests that their rise to dominance in the UK started even earlier, in late October or early November, and it happened really fast. According to nextstrain analysis, this mutation is now found in over 75% of samples collected in the UK.

The B.1.1.7 lineage has now spread to other places as well.

According to virological.org, about a third of the genotypes in the B.1.1.7 lineage are from Kent (a county in England adjacent to London), one third from London, and one third from elsewhere in Great Britain, including Scotland and the United Kingdom . Welsh. In addition to this, Hodcroft reports that the lineage has also been detected in Denmark and Australia.

If you are in these places, it is almost certain that you are circulating in other parts of the world without being detected.

What does this mean for the Covid-19 pandemic?

The rapid expansion of the SARS-CoV-2 lineage B.1.1.7 is an interesting phenomenon that must have an explanation. Most likely, it has some kind of evolutionary advantage compared to other genotypes. The fact that the N501Y mutation makes SARS-CoV-2 more transmissible in mice suggests that this evolutionary advantage could have something to do with the virus’s ability to infect host cells, although this has yet to be established. This could be epidemiologically important, for example, if it results in a reduction in the infectious dose. Similarly, there is no evidence yet on the effects on the severity of the disease one way or another.

Given the close connections between the UK and many other countries, including the US, this mutation is expected to spread to other parts of the world. We must be vigilant.