How phylogenetic testing helps experts establish links between Covid-19 cases

Phylogenetic testing helps scientists to deduce the index case of a cluster.
Phylogenetic testing helps scientists to deduce the index case of a cluster.ST PHOTO: KUA CHEE SIONG

SINGAPORE - Phylogenetic testing compares different virus genomes and helps scientists deduce the index case of a Covid-19 cluster.

In the case of the Jurong Fishery Port cluster, the authorities were able to determine that the strains relating to the cluster were of the Delta variant and similar to what was seen in imported cases from Indonesia.

Dr Sebastian Maurer-Stroh, executive director of the Bioinformatics Institute at A*Star, said a phylogenetic or "family" tree is created using viral mutations as markers to compare the virus genomes.

In this family tree, close relatives are grouped together and one can then see which cases had formed a cluster - in this way, one can then deduce the ancestor of a cluster, said Dr Maurer-Stroh.

Through real-time sharing of genomes globally via the Gisaid data-sharing platform, one can also understand transmission between countries by comparing the virus genome from different countries, he added.

Dr Gavin Smith, a professor in the Emerging Infectious Diseases Programme at Duke-NUS Medical School Singapore,  said phylogenetics is able to compare how related different virus genomes are, based on the similarities or differences in their RNA sequences.

"Because the Sars-CoV-2 virus has many different genetic mutations, computationally we are able to determine these relationships with a high degree of confidence," he said.

Associate Professor Raymond Lin, director of the National Public Health Laboratory at the National Centre for Infectious Diseases (NCID), added that the sequences should cover about 90 per cent of the whole virus genome for good phylogenetic analysis.

Phylogenetic tests had also suggested that the clusters linked to the Jurong Fishery Port and several wet markets may not have been due to a single point of introduction of infection, Singapore's director of medical services, Associate Professor Kenneth Mak, had said at a press conference on July 20.

Instead, exposure may have occurred over some time with multiple points of infection, as the genetic information for the variants was not identical across the different cases.

However, the authorities were not able to determine how long this period might have been and who could have been a specific super-spreader leading to the large cluster with more than 1,000 cases.

This means there were likely multiple infected people who had introduced multiple slightly different viruses, said Dr Smith.

"The high mutation rate of the Sars-CoV-2 virus means there are many differences that can be used to compare and distinguish between strains," he said.

Dr Mark Chen, a consultant at the National Public Health and Epidemiology Unit at NCID, said that while the viral sequences most closely resemble sequences reported in cases from Indonesia, only a small proportion of cases in the South-east Asian region have sequences that are publicly available.

"Moreover, the genetic sequences alone cannot tell us how the infection entered Singapore, and other investigations are ongoing into how this happened," he said.