One year of Omicron: the vital work of a WHO reference lab in the surveillance and diagnosis of viruses

28 November 2022

26 November 2022 marked 1 year since the B.1.1.529 variant of the COVID-19 virus (SARS-CoV-2) was declared a “variant of concern” and assigned the name Omicron. Since then, the variant and its sublineages have become the predominant circulating SARS-CoV-2 variants, both in the WHO European Region and globally. 

WHO reference laboratories, such as those of the Erasmus University Medical Centre (Erasmus MC), in Rotterdam, the Netherlands, play a fundamental role in detecting virus variants and contribute to our knowledge of how viruses evolve and spread. They also help our understanding of what impact new emerging variants have on transmission, on our diagnostics, and on the effectiveness of our existing medical countermeasures, such as vaccines and therapeutics. WHO reference laboratories also serve to support confirmatory testing, and receive samples from across the European Region as countries work to establish their own capacities.

In their diagnostic and research work, the laboratory staff of Erasmus MC not only study SARS-CoV-2, but also monitor a whole range of other viruses that have the potential to be harmful to human health, from severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) to Ebola, HIV, influenza, herpes and monkeypox. As well as being a reference laboratory for COVID-19, Erasmus MC is also the WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research.

Recently, we visited their laboratories to get a better understanding of what they do, including seeing how they go about detecting and identifying viruses, how they are contributing to the development of vaccines, and what they are doing to monitor new SARS-CoV-2 variants and other potentially harmful emerging pathogens.

Click through the photo story to find out more.

WHO/Uka Borregaard
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Samples are received at the laboratory

Samples are sent in for testing from health facilities across the Netherlands – including Erasmus MC’s own hospital – and sometimes internationally. All kinds of samples are processed, including swabs from someone’s throat, blood (plasma and serum) or sometimes from organ biopsies.

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Amplifying (making copies) of the virus using polymerase chain reaction (PCR)

Sample vials are placed in special racks to be inserted into a DNA/RNA isolation machine and subsequently into PCR machines. The PCR machine is used to make millions of identical copies of an initially small segment of RNA (the genetic code of the virus). Genetic analysis is only really possible when you have large amounts of viral RNA, so this “molecular photocopying” is a necessary first step before detection of the virus can be carried out.

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A part of the sample is added to cell cultures to investigate the effect the virus infection has on these cells

The culture is monitored over several days to see if and how much the virus spreads. If the virus has damaged the cells in the culture, then this is indicative that the virus is likely to be causing disease in the person affected.

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Neutralization tests are used to compare the efficacy of antibodies in dealing with viral attack

Dr Corine Geurts van Kessel shows us the result of a serology test, where a number of serum samples are used to check how well various antibodies fight off (neutralize) particular viruses. A negative control, containing no antibodies, is used as a basis and is where you would expect to see the most viral activity. Such tests are particularly important for studying vaccine effectiveness and in the development of new vaccines, including for COVID-19, to see how well they perform against different variants.

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Sequencing helps the scientists understand the genetic code of the virus

The genome sequence of a virus is the order of bases or letters that makes up a virus’s genetic material, or its genome. If you were to write down the genome sequence of a particular coronavirus, for instance, it would be a series of about 30 000 letters. The technology to determine this has advanced massively in the last few years, so rather than having to rely on huge machines in laboratories, mobile pen-drive-like devices, like these, can be used with laptops to carry out direct, real-time DNA or RNA sequencing – ideal for in-the-field testing.

WHO/Uka Borregaard
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Virus samples are kept in cold storage to prevent degradation

A wide range of viruses and patient samples are stored at sub-zero temperatures. Having this “bank” of viruses means that the scientists can compare the genetic make-up of viruses in newly acquired samples, as well as keep an archive of “older” viruses and patient samples. New samples for testing are also stored here until the scientists are ready to study them. The cold temperatures ensure they do not degrade, so the scientists have an accurate record of the virus from when the sample was first taken.

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Colouring techniques and software help identify particular types of virus

A monitor displays an image of the microscope slide containing part of the sample, which goes through special staining techniques and use of specialized software to highlight parts containing the virus (shown in green). From the size and shape of these, the scientists can determine the type of virus they are dealing with.

 

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Special care is taken when handling the most infectious of viruses

Some viruses, such as SARS-CoV-2, need to be tested in laboratories with increased biosafety and biosecurity due to the higher risks associated with their handling. At Erasmus MC, the Biosafety Level 3 (BSL-3) laboratory is fitted with double doors and technicians are required to follow specific safety procedures, and wear additional protective clothing. Samples are only opened and tested within air-tight cabinets.

 

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Wild animal populations are also monitored for viruses that have the potential to be harmful to human health

The threat from zoonosis – the transmission of disease from animals to humans – is taken very seriously at Erasmus MC. Bird feathers are regularly collected by ornithologists and bird ringers from across the Netherlands and sent to the centre’s Wild Animals Surveillance Laboratory to test for a range of viruses, including avian influenza viruses. Through this careful monitoring, they can check on the spread of infectious disease in the wild bird population, and monitor for any potentially concerning virus mutations.

WHO/Uka Borregaard
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Keeping a particular eye on diseases in bats

Lineke is a veterinary pathologist at Erasmus MC. Her role involves dissecting and analysing tissue samples from the corpses of bats that have died naturally in the wild and been sent in to the laboratory by naturalists around the country. To date, no Dutch bats have been found to carry viruses that could be harmful to humans, but experience from other countries shows the importance of ongoing monitoring of bats. Indeed, it is believed that SARS-CoV-2, the virus behind the COVID-19 pandemic, originated in bats in China and made the leap into the human population at some point in late 2019.

 

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