Scientists find a new weapon against COVID-19 using genetics and maths to map early and future spread of the pandemic JW Mitchell Follow Apr 11 · 4 min read

Portrait of a US Air National Guardsman building a temporary hospital in Chicago USA. For the first time scientists have used genetic and mathematical analysis to map the early spread of COVID-19 — Photo: Atlas Photo Archive/USAF/Jay Grabiec

Scientists from Cambridge University in England and colleagues in Germany have for the first time used genetic networking techniques and mathematical modelling to map the early ‘evolutionary paths’ of COVID-19 in humans, as the pandemic spread out of Wuhan, China to Europe and North America. This could be a powerful weapon against the coronavirus, according to the researchers.

They analysed the first 160 complete virus genomes sequenced from human patients and have mapped part of the original spread of the deadly virus, which has now infected millions worldwide and killed thousands. This was done by studying the mutations of the coronavirus, which create different viral lineages. Their research was published this week in the journal Proceedings of the National Academy of Sciences (PNAS).

“There are too many rapid mutations to neatly trace a COVID-19 family tree. We used a mathematical network algorithm to visualise all the plausible trees simultaneously,” said geneticist Dr Peter Forster, lead author from the University of Cambridge in England, UK.

“These techniques are mostly known for mapping the movements of prehistoric human populations through DNA. We think this is the first time they have been used to trace the infection routes of a coronavirus like COVID-19,” Dr Forster added.

Researchers used virus genome data which was sampled internationally between the 24th December, 2019 and the 4th March, 2020. Their research on these genomes has revealed three distinct variants of COVID-19, which consist of closely-related clusters that they have labelled ‘A’, ‘B’ and ‘C’.

The scientists found that the type of COVID-19 closest to that found in bats was the type ‘A’, which they call the “original human virus genome”-the one that was present in Wuhan. Surprisingly, this was not the predominant virus type in Wuhan.

Their research shows that mutated versions of ‘A’ virus type were seen in Americans who had been in Wuhan and that of those patients treated there, a large number of A-type viruses were found in those from the US and Australia.

The main virus type in Wuhan is ‘B’ and this was prevalent in patients there from across East Asia. This variant did not travel from Wuhan without mutations, the scientists say. This implies that there was a “founder event” in Wuhan or “resistance” against this ‘B’ type of COVID-19 outside of East Asia, according to the researchers.

Interestingly, the research shows that the ‘C’ type COVID-19 is found in the first patients in France, Italy, Sweden and England, though completely absent from the study’s samples from mainland China. The ‘C’ type virus was found though in Hong Kong, South Korea and Singapore.

The data suggests that one of the first cases of COVID-19 in Italy was via the first documented German infection on the 27th January, 2020 and also that one other early Italian infection route was related to a “Singapore cluster”.

These ‘Genetic Networking’ techniques have accurately traced the infection routes, plus the mutations and viral lineages, the scientists say, joining the dots between known cases.

Phylogenetic methods such as these could be applied to the latest coronavirus genome sequencing — to help predict future global clusters of the disease and it’s transmission, the boffins argue.

“Phylogenetic network analysis has the potential to help identify undocumented COVID-19 infection sources, which can then be quarantined to contain further spread of the disease worldwide,” said Dr Forster, a fellow of the McDonald Institute of Archaeological Research at Cambridge, as well as the University’s Institute of Continuing Education.

The research says that variant ‘A’, most closely related to the virus found in both bats and pangolins, is described as “the root of the outbreak” by researchers. Type ‘B’ is derived from ‘A’, separated by two mutations, then ‘C’ is in turn a “daughter” of ‘B’. Also, that the localisation of the ‘B’ variant to East Asia could result from a “founder effect” -which is a genetic bottleneck that occurs when (in the case of a virus) a new virus type is established from a small, isolated group of infections.

Dr Forster argues that there is another explanation worth considering: “The Wuhan B-type virus could be immunologically or environmentally adapted to a large section of the East Asian population. It may need to mutate to overcome resistance outside East Asia. We seem to see a slower mutation rate in East Asia than elsewhere, in this initial phase.”

He added: “The viral network we have detailed is a snapshot of the early stages of an epidemic, before the evolutionary paths of COVID-19 become obscured by vast numbers of mutations. It’s like catching an incipient supernova in the act.”

Since the PNAS study was conducted, the research team says it has extended its analysis to some 1,001 viral genomes. Although it has yet to be peer-reviewed, Dr Forster says the latest work suggests that the first infection and spread among humans of COVID-19 occurred between mid-September and early December.

These phylogenetic network methods used by the researchers — which allow the visualisation of hundreds of evolutionary trees simultaneously in one simple graph — were pioneered in New Zealand in 1979, then developed by German mathematicians in the 1990s.

The method could become an important tool in the global fight against the deadly COVID-19 pandemic.