Wednesday 6 May 2020
Genetic sequencing is critical to solving the pandemic (Gilnature)
On 16 July 1945, the world’s first atomic bomb was detonated 200 miles south of Los Alamos in New Mexico, on the Alamogordo Bombing Range. The bomb had taken 27 months to develop, at the highly secret Site Y, of what was known as the Manhattan Project. The Los Alamos National Laboratory was then heavily involved in US National Security and thrives even today. Consequently, whenever Los Alamos discovers something different, I sit up and listen. The laboratory has been thinking outside the routine box for a very long time indeed.
When Los Alamos published, on a preprint server not long ago, the finding that the SARS-CoV-2 virus had mutated, I was instantly all ears. Especially so, as a group from UK’s Sheffield was also involved. The spiky nature of the virus is important to it, as the spikes are its means of attachment to a victim. If the virus cannot attach, then the victim walks free.
Los Alamos, in its paper, stated:
“The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly became the dominant form.”
Los Alamos – anywhere that designed the atom bomb is worth taking seriously
Perhaps more worrying:
“D614G is increasing in frequency at an alarming rate, indicating a fitness advantage relative to the original Wuhan strain that enables more rapid spread.”
The Los Alamos report continues that the new mutation not only spreads faster than the original Wuhan virus, but it may make people vulnerable to a second infection after a first bout of the disease. Los Alamos has published this as an early warning to the world and based its report on a computational analysis of more than 6000 coronavirus sequences collected by the Global Initiative for Sharing All Influenza Data (GISAID), which is based in Munich (Germany).
The Los Angeles Times has reported that scientific reaction to this has been mixed. Peter Hotez of the Texas Children’s Hospital Center for Vaccine Development has summed it in one, by highlighting that the Los Alamos paper includes a lot of speculation and is not supported by experimental verification.
GISAID was critical to Los Alamos’ work. The idea of GISAID began in 2006, when mainstream media noticed human fatalities caused by the then deadly avian influenza. In those days, public access to the latest genetic sequences of the highly pathogenic virus (H5N1) was limited and restricted. This was because of the hesitancy of affected countries to share their information through traditional public archives. GISAID created a system that allowed sharing, while using proper scientific etiquette that would acknowledge and recognise submitters of any new data. Journalists may worry about theft of ideas, and scoops being attributed to the wrong person. Scientists are no different. Consequently, in 2008, the GISAID platform was created. Understandably, GISAID has today turned its attention to Covid-19.
As I look at the figures steadily emerging throughout the world, I cannot help but be impressed by the adaptability of SARS-CoV-2. Most folk agree that the thing started off in a bat. Although bats are mammals, and humans are as well, to make the shift from one to the other does imply adaptability, unless some laboratory gave it a helping hand. In mid-March 2020, the mutation D614G was being tracked at GISAID because of its high frequency. It was referred to as the “G clade” (G614), was seen in 29% of global samples, and was almost exclusive to Europe.
Mutant viruses, like turtles, are trying to keep ahead
A clade is a group of organisms that consists of a common ancestor and all its lineal descendants. Rodents, for example, are a clade. They are a branch of mammals that split off after the end of the period when the clade Dinosauria stopped being the dominant terrestrial vertebrate 66 million years ago. The original rodent population, and all its descendants, form a clade.
Throughout March 2020, G614 became increasingly common in Europe and by April dominated most samples. D614 had been dominant much earlier in the pandemic and was essentially being squeezed out by G614, which is the situation today. The problem, as I see it, is that the virus’ clear adaptability must make it hard to find a vaccine. You make one, the virus changes. You make another and the virus changes again. You would not want to play chess against SARS-CoV-2.
The beast is also very cunning in how it presents, as its high prevalence must in part be related to the lack of symptoms at onset. It takes a while to build up steam. You are feeling fine, looking fine and no one suspects you. Indeed, you do not even suspect yourself. Then away it goes. A common feature of so many sufferers of Covid-19 has been the report that when the disease starts, it seems to start quickly, although in fact you have been harbouring it for several days beforehand, and merrily giving it to your family and friends.
Not everyone is so alarmist. In the UK’s Daily Mail, I read that scientists at Arizona State University sequenced the viral genome in 382 patients from the state. In one sample only, however, they found a significant mutation. This was the same as was seen in the SARS virus in 2003. The mutation weakened the ability of the virus to fight a victim’s immune system and indicated the end of the five-month epidemic. Mind you, this mutation was only seen in one sample, but it shows what might be possible. One can but hope.
Sequencing is proving to be very useful in the UK and is being undertaken in a number of locations. Cambridge is one of them. Some of the first samples of the virus in UK, the Chinese visitors in York and the cluster in Brighton, were not related to anything being seen in the UK right now. There were multiple introductions of the virus in the UK, as this is such a popular country. For example, clusters in Wales were not purely Welsh. There were contributions from right around the world. London has seen the greatest viral diversity, which might be expected. At the 2011 census, 36.7% of the capital’s population was foreign-born. That is more than three million residents. If there happens to be a sudden expansion of a single viral lineage somewhere, then that area’s containment measures need to be looked at. A diversity of lineages suggests a pre-lockdown infection.
The situation this morning – 6 May 2020 (courtesy Center for Systems Science and Engineering at Johns Hopkins University)
Viral genome sequencing is a good way of working out how infections might be linked. There is a huge amount of sequencing data out there. For example, in mid-April a group from New York University analysed 236 SARS-Cov-2 specimens from cases in New York City. Most of the patients had no history of travel or known exposure. When the researchers compared their specimens with others, they found that the majority of the genome sequences were of European origin. It appears that Europe, unintentionally, did not do the USA a service and the virus was spreading unrecognised in the community for a considerable period before New York worked out what was happening.
For an easy, real-time view of how the virus is spreading globally, mutating as it travels, my favourite site is nextstrain.org. Take a look and worry. I am trying to work out if and when it will stop.
