Analyses for getting to grips with the pandemic

Even though the first wave of the COVID-19 pandemic has passed its peak in Switzerland, coronavirus diagnostic procedures are as important as ever. For one thing, the continuing aim is to test people who may have become infected so that, if infection is confirmed, they can isolate themselves to prevent the epidemic from flaring up again. For another, it is now time to investigate how many people’s immune systems have produced antibodies in response to the coronavirus in question, SARS-CoV-2 (including in undetected cases of infection). Scientists suspect that once people have contracted the virus, they gain at least temporary immunity to re-infection.

Although experimental research at ETH Zurich has been temporarily suspended, some scientists are working in coordination with the Vice President for Research on the further development of tests that can detect either the pandemic virus itself or antibodies that recognise the virus according to the lock-and-key principle.

Fast and economical virus test

Laboratories worldwide routinely detect the virus itself by way of its genetic fingerprint (RNA sequence). For this they usually employ the PCR method, which can determine whether genetic material from the pandemic pathogen is present in, say, a throat swab. In this method, short sections of viral DNA are replicated in a process of thermal cycling, which exposes the sample to repeated cycles of heating and cooling. The method also requires certain laboratory chemicals that have become scarce worldwide in the current situation.

In recent years, ETH Professor Wendelin Stark’s group has developed an improved, cost-effective PCR device that works with tiny metal sample containers rather than the plastic containers that are currently standard. The new device can heat and cool the sample much faster, which speeds up the process considerably. And because the containers are smaller, the scientists needed only one-fifth of the quantity of reagents. Stark and his colleagues have already arranged for their device to go into full-scale production, and they are now planning to apply for official approval. Once this is granted, they can begin marketing the device.

Determining the fingerprint

Meanwhile, ETH Professor Sai Reddy and the Genomics Facility at the Department of Biosystems Science and Engineering at ETH Zurich in Basel are employing a different method to detect the virus: deep sequencing. This relatively new method is extremely sensitive – Reddy estimates it to be much more sensitive than PCR – and it can analyse around 5,000 samples at a time. Another great advantage of this technology is that it also provides the exact genetic fingerprint (RNA sequence) of the virus for each sample. Because the pathogen undergoes minute changes over time, this data is ideal for phylogenetic analyses of the virus to determine its family tree.

A bioinformatics method developed by ETH Professor Niko Beerenwinkel will also be used in the analysis and quality control of the deep sequencing raw data. He developed this method in recent years to detect whether a patient is carrying different genetic variants of a virus at the same time. In the case of HIV, for example, this kind of intra-host diversity influences decisions about treatment. Beerenwinkel would like to investigate whether such diversity also plays a role for SARS-CoV-2.

Unreported cases and geographical spread

ETH Professor Tanja Stadler is responsible for the phylogenetic analyses. She has started a collaboration with a large Swiss laboratory diagnostics company headquartered in the Basel area. This company will anonymise all the virus samples it has examined and make them available to the Genomics Facility Basel, which will determine their genetic fingerprint. Phylogenetic analyses will enable Stadler to calculate epidemiological parameters, including the number of undetected cases – people who have been infected but have not been tested and therefore do not appear in any statistics.

In addition, Stadler’s methods will make it possible to trace the geographical spread of the virus almost in real time. She will be able to show, for example, how many of the people who became ill were infected within the Basel area and how many were infected elsewhere and then brought the virus into the region. Information of this sort does not allow conclusions to be drawn about individuals, but it could supplement the information obtained from the identification of people with the infection and their contacts – known as contact tracing – and help the authorities to adapt measures to combat the pandemic if necessary.

Virus on surfaces

The pandemic virus is transmitted directly from person to person via droplets. At present, the science is largely unclear as to how big a risk there is of contracting the virus from things like payment terminals or handles on doors, shopping trolleys or in public transport. Similarly, no research has yet been carried out into how widespread the pandemic virus is on such surfaces in Switzerland. ETH Professor Barbara Treutlein wants to look into this question by collecting with her team a large number of samples in Basel and to examine them – both by way of sequencing in the Genomics Facility Basel and using another relatively new virus detection method known as loop-mediated isothermal amplification.

Viral proteins for antibody tests

Various groups at the University Hospital Zurich and the University of Zurich are currently focused not on detecting the pandemic virus itself, but on testing blood serum to see if it contains antibodies to the virus. Laboratory tests make use of viral proteins to determine whether serum samples contain antibodies that attach to those viral proteins according to the lock-and-key principle.

ETH Professors Nenad Ban and Kaspar Locher and their groups are already working or planning to produce certain viral proteins in sufficient quantities and high purity using biotechnology. They will pass the proteins on to colleagues at the University of Zurich, who will develop appropriate antibody detection tests and make them available to the University Hospital Zurich for analysis.