Sequencing adapted from research use to monitoring the coronavirus pandemic

As the new, more transmissible coronavirus variants have arrived in Finland, the role of researchers and technology specialists at the University of Helsinki in controlling the pandemic has received increased emphasis. The monitoring of the virus variants was quickly initiated with the help of the University’s sequencing equipment and expertise. This rapid response was possible thanks to research projects launched in the beginning of the pandemic, good preparation, and collaboration between a range of operators.

The genomes of all viruses gradually accumulate mutations, of which only some are favourable to their spreading. To identify mutations, the genome of each virus sample must be determined through a technique known as sequencing. At the same time, information relevant to the epidemic is gained on chains of infection, the virus variants that have entered the country and their distribution.

In Finland, virus sequencing has been developed at the University of Helsinki’s Department of Virology by Professor Olli Vapalahti’s research unit specialised in viral zoonoses, where coronavirus sequencing has been carried out ever since the first Covid-19 diagnosis. Since last autumn, these efforts have been supported by the Institute for Molecular Medicine Finland (FIMM).

Before Christmas, after the emergence of new and more transmissible virus variants, sequencing claimed the spotlight in identifying variants, and as part of both diagnostics and controlling the pandemic. The number of samples coming to the University of Helsinki increased as well: in addition to samples from the Hospital District of Helsinki and Uusimaa region, all samples taken from travellers arriving in Finland, including positive samples collected at airports and ports, have, since December, been analysed at the University.

“In the past year, a total of roughly 1,600 positive coronavirus samples from the Hospital District of Helsinki and Uusimaa were analysed at the University of Helsinki. Our common goal is to increase the University’s sequencing capacity to 800 virus samples per week from the previous weekly rate of 200–300 samples,” says Katja Kivinen, head of the FIMM Technology Centre.

FIMM’s technical expertise assumed a nationally significant role

In normal circumstances, the sequencing laboratory of the FIMM Technology Centre concentrates on identifying gene defects in clinical specimens collected in conjunction with medical research. In the beginning of the coronavirus pandemic, however, the laboratory immediately started determining techniques suitable for sequencing the novel coronavirus.

“We knew that sequencing was the best option for monitoring the development and spread of new viral strains, and, through active preparations, we wanted to make sure that our laboratory would be able, if necessary, to assist the authorities in this work,” says Pekka Ellonen, head of the sequencing unit.

The equipment in use at the sequencing unit, which utilises what is known as next-generation sequencing technology, is also suited, without alteration, for sequencing viruses. As for detailed guidelines for the sequencing, they had been made openly available on the web by the international scientific community.

“It took about two weeks for our laboratory to deploy the technique. The validity of results was verified in cooperation with the Department of Virology, which had launched sequencing efforts early in the year under the direction of Teemu Smura

However, the information gained was mainly utilised in scientific research, until the new, more easily transmissible virus variants landed in Finland.

“We started to really get down to business in December. In a matter of only a few weeks, we established a working group spanning three laboratories involved in sequencing in the Helsinki area. We trained staff and harmonised procedures, as well as stored and distributed reagents purchased through joint procurement. Had each laboratory had to launch operations independently from scratch, we would have wasted as much as several months.”

In addition to training, FIMM has focused on sequencing hundreds of new virus samples since Christmas. Sequencing can be carried out with either conventional techniques in the case of smaller quantities of urgent samples or with next-generation techniques for larger quantities, requiring roughly a week’s response time.

According to Ellonen, capacity can still be further increased by prioritising resources.

Data obtained on the virus combined with patient data

All of the samples sequenced at the University of Helsinki eventually end up being further analysed by the Department of Virology. The analyses are coordinated by researchers Teemu Smura and Ravi Kant, together with the other bioinformatics specialists in the team.

Further analyses make it possible to cross-check the samples against international databases: such comparisons reveal the type of the virus and the mutations in its genome. The team employs an application developed together with CSC – IT Centre for Science, which has the capacity to analyse thousands of samples in a matter of hours.

These days, analysis results can be directly combined with patient data, enabling the identification of easily transmissible variants in real time. In December 2020 a new partnership was initiated with HUSLAB.

“We now know which virus type an infected individual is carrying,” says Tarja Sironen, associate professor of emerging infectious diseases.

Sironen notes that without smooth collaboration between different organisations, readily available practices and research capacity, it would be impossible to catch variants entering the country.

“Anticipation involves readiness for quick action. We are proud to have been able to respond so rapidly in December and capturing, at an early stage, the cases of virus variants coming to Finland. We have to be able to identify infections and chains of infection caused by the variants in the future, too. Soon that will be made easier by new coronavirus tests which are able to differentiate between variants,” Sironen explains.

Sironen hopes that combining sequencing data with patient data will, in the future, also help to investigate changes in the clinical picture and, for example, the number of further transmissions of the virus.

In addition, sequencing produces vast amounts of research data. According to Sironen, alongside the generation of sequencing data, it is important to culture in laboratory conditions viruses originating in clinical specimens, as this makes it possible to study the biological features of the coronavirus or, for example, identify antibodies.

“Research produces more tools for risk assessment and information on what kind of threat different virus variants pose,” she says.

Upward trend in sequencing since the autumn
  • In spring 2020 roughly 10% of the samples collected during the first wave of the pandemic in Finland were sequenced using the equipment of the University of Helsinki’s Department of Virology. At the time, researchers observed that several virus lineages had arrived in Finland.
  • Only a handful of these lineages survived through the wave, to be replaced in the second wave mainly by novel lineages coming from abroad.
  • Additionally, in the autumn, larger quantities of samples were sequenced at the Institute for Molecular Medicine Finland (FIMM). At the time, no significantly mutated viruses were seen in control samples.
  • The first variants of the virus were seen in Finland in samples taken in December.
  • Currently, hundreds of virus samples are sequenced at the University of Helsinki every week.
  • In the future, the most important variants can also be identified without sequencing, using specific PCR tests.