In early 2020, researchers in the Clinical Microbiology unit of Turku University Hospital heard about the new Sars-CoV-2 virus. They were among the first ones to start developing the diagnostics. With a foundation in the strong diagnostic expertise at the University of Turku and Turku University Hospital (Tyks), the test developed in Turku has had a central role in the fight against the coronavirus.
– When we started developing the test, we thought that it was unlikely it would be needed, but we might as well develop it anyway. And look what happened and how wrong we were, says Antti Hakanen, Director of the Laboratory Division at Turku University Hospital, Chief Physician in Clinical Microbiology and Docent at the University of Turku.
– At the time, we couldn’t have even imagined that on the busiest days, we would analyse 2,500 respiratory samples per day, adds Kaisu Rantakokko-Jalava, Head of Section in Clinical Microbiology.
Chief Physician in molecular biology and virology at Turku University Hospital and Docent at the University of Turku Tytti Vuorinen reminds us that Turku University Hospital has always been on the frontlines. She herself has participated in the preparedness efforts against five threats: MERS, SARS, Ebola, avian influenza, and swine influenza. COVID-19 proved to be in a whole new category of its own.
– The pandemic has been so exceptional that I would have never guessed that I would face something like this during my career. If we didn’t have the virus diagnostic laboratories of Turku and Helsinki University Hospitals with the resources to develop tests of our own, coronavirus diagnostics in Finland would have been delayed by several months, says Vuorinen.
Internal and Active Expertise in Diagnostics
In April 2020, experts in Turku University Hospital already celebrated when the hospital acquired a fully automatic device, which was able to analyse 120–150 samples in eight hours. However, they soon discovered that the capacity was insufficient.
Meanwhile, the whole world needed testing machinery. Events that could take place in agent stories became a reality. Hakanen describes that the intelligence services of different countries went as far as stealing diagnostics equipment from each other in planes. At Turku University Hospital, the situation lead to waiting in line on the phone for an international company’s machine so that the hospital could achieve at least some level of diagnostic coverage.
– That’s when we started to realise that we need to do something completely new by ourselves. Turku is, after all, one of the places with active developed of our own diagnostics. Many countries have not been able to achieve functional diagnostics over this whole period, expresses Hakanen.
In Turku, the hospital’s own diagnostics, coronavirus PCR method was constructed from modules and put into action very quickly after the virus’ genotype was determined.
One of the impacting factors behind the decision to develop testing system was that the technology company PerkinElmer is located right next to Turku University Hospital. With the help of technology bought from there, Turku University Hospital started to develop their high-throughput PCR system. Equipment that has been manufactured locally has the benefit that maintenance staff are quickly available when needed, not for example still packing their luggage in another country. As opposed to the modular system used in Turku, those who have ordered large automatic devices from abroad have struggled at times when they have not been able to acquire reagents, suitable plastics and pipette tips.
– At Turku University Hospital, we have not experienced delays caused by equipment shortage; we are almost the only place that can say this, says Hakanen,
The PCR system was built as a result of a well-planned and well-managed project. The University’s expertise has been prominent in the development process.
– Things have not been done by accident. We are continuously thinking ahead, expresses Hakanen.
From Sample Collection to Laboratory Safely and Accurately
Coronavirus diagnostics at Turku University Hospital begins with collecting samples, a process which has been mainly created as a collaboration of the City of Turku and the Hospital District of Southwest Finland. The garage-type drive-in testing, for example, was launched quickly.
Next, the samples are delivered to a high safety level laboratory where the packages are opened and the samples are inactivated wearing protective equipment. At this stage, the samples no longer pose a threat of infecting people, and they can be safely moved out from the safety laboratory for extracting the nucleic acids (genome) of the virus.
The genome of the virus cannot be detected without amplification of nucleic acids. The extracted nucleic acids and the required reagents in the amplification are mixed. This is compared to the stage in baking when the flour and eggs are mixed.
The different stages of the process are conducted in their own, clean laboratory facilities. First, the constituents needed in the PCR clean room are combined together. Next, the automatic machine pipettes the constituents and the genome of the virus into test tubes. They are taken to the PCR duplication machines of the machine room to be duplicated. After the machines are finished, the results will be transferred on a computer. A doctor or hospital microbiologist will analyse the results and assess whether the sample is corona negative or positive. It is possible to complete around 2,500 of these self-developed tests per one working day.
– What is different between us and others is that we have a very long tradition in developing diagnostics; we have been doing this for a long time, says Hakanen.
The Reliability of the Testing Can Also Be Ensured
It is important to notice that the mutations of the virus can impact not only the vaccines or the spreading of the virus, but also the diagnostics. It possible that a strain of virus emerges that cannot be detected with the test. That is why the diagnostics process is also based on traditional Sanger sequencing, which allows the researchers to determine the whole genome of the virus and gives information about mutations in a couple of days. Furthermore, researchers in Turku are also developing next-generation sequencing, which would give reliable information about virus mutations in just a week. This method can be later sold to others.
During a normal year, the volume of clinical microbiology in Turku University Hospital is altogether 450,000 different tests under hundreds of different titles. The emergence of the coronavirus meant that by early June 2021, only the coronavirus tests amounted to 325,000 tests.
Vuorinen explains that under regular circumstances before the coronavirus outbreak, around 300 PCR tests were completed per week. In spring 2020, the number was 1,800 during the busiest weeks, which was considered a large number. Later over the course of the pandemic year, as many as 2,500 tests have been completed during one working day.
– The increase has been immense, says Vuorinen.
It is worth noting, that Turku did not purchase large devices worth of millions of euros. Instead, they have built their own, relatively cost-effective system. The work is based on decades of research and collaboration with universities.
Turku University Hospital, the Faculty of Medicine at the University of Turku, and the surrounding campus area form a multidisciplinary cluster of excellence in which research and the high-quality treatment based on it form a seamless entity. More than one thousand scientific studies are under way in these organisations, engaging approximately 1,500 experts. Approximately 200,000 patients receive treatment at Tyks every year. Visits to outpatient care total over 1.2 million and days at inpatient care almost 300,000. The University of Turku and the Hospital District of Southwest Finland are part of the Health Campus Turku network, which also includes Åbo Akademi University, Turku University of Applied Sciences, Novia University of Applied Sciences and Turku Science Park Oy.
Text: Sini Silvàn
Photos: Mikael Soininen
Translation: Lotta Junnila