As laboratories develop new services or adapt their existing workflows to support research and testing for Covid-19, LIMS software has become integral to the increase in sample throughput. LIMS also provides reporting tools and opportunities to automate experiments, such as PCR testing, allowing scientists to increase their efficiency in spite of Covid-19 restrictions.
All lab-based industries feel the pressure of Covid-19. Even those not directly working on the virus have to deal with reduced staff numbers in the laboratory, stricter regimes for cleaning and contamination, and increased requirements for collaboration and reporting remotely. Those that are working directly with Covid-19, either through vaccine development or environmental and personnel testing, need to be able to deliver increased numbers of samples and provide assurances that data integrity can be maintained.
Laboratory Informatics Management System (LIMS) software packages can help organisations quickly scale up their sample throughput and help mitigate remote working practices by providing remote access and in-built reporting tools, that let scientists and researchers share data with their colleagues more easily.
Human challenge models for Covid-19
Hvivo specialises in viral challenge studies and laboratory services supporting product development for customers developing antivirals, vaccines and respiratory therapeutics.
The company has now begun developing human challenge studies for Covid-19 to help scientists better understand the efficacy of a vaccine. Human challenge studies take healthy volunteers that are not from high-risk groups, inoculate them with a vaccine, then intentionally infect them with a particular virus so that their progress can be monitored. Hvivo then monitors patients for a given period of time to check viral load and viral shedding until they are healthy and can return home.
Adam French, director of laboratory operations, explains: ‘Hvivo runs human challenge studies where we take healthy volunteers and administer a virus, normally flu or HIV or RSV to test vaccines for treatment against those diseases.
‘We are also working with the UK government’s task force on setting up the first Covid-19 human challenge model, which we are doing in partnership with Imperial College London and the Royal Free Hospital.
‘For many years we have offered seasonal testing for seasonal coronaviruses and many other viruses, which means that we are in a fantastic position to be able to use those assays for Covid-19.’
Human challenge models enable companies to develop a better understanding of their vaccine in a small number of participants very quickly. As the subjects are inoculated and infected at a known point in time, the models can provide more accurate data than traditional field trials.
‘We have one of the largest units, at 24 bed units. We now have an additional facility with 19 rooms and we have 22 rooms at the Royal Free Hospital specifically for use with Covid. That combination is the biggest setup for viral challenge studies,’ said French.
‘We recruit healthy volunteers, just as you would have for any normal clinical trial. It is an in-patient model so they come into our facility, depending on the virus, for up to 15 days. They are admitted as fully-healthy fully-screened subjects. We monitor them and record their symptoms. We take samples to measure their viral load and the viral shedding, and then we can see that return back down to healthy. Once they are fully healthy – which is why they are with us for 15 days – they go home,’ added French.
Human challenge models sit between phase one and phase two trials. The information provided by the challenge model can then be used to help organisations make the decision to continue a vaccine’s development onto phase two trials.
As these trials can be very expensive, gathering as much good data as possible in a short time-frame is important for vaccine development and the companies that invest in them.
‘Compared to a field trial, you would need to give thousands of people the vaccine and then sit and wait to see if any of them catch it,’ said French. ‘You know exactly when they got it, so there is no guessing and you get the baseline samples immediately, whereas with the classic model they do not present until they are already ill and they have already had the virus for a number of days.
‘This allows the data to be very clean, so you can use a much smaller number of subjects. Instead of thousands and thousands, it could be only 60 or 80,’ added French.
Generating this data quickly enables companies to make swift decisions when developing vaccines. ‘Or, if the data is extremely good from the challenge study, it could enable them to get the funding they need to move on to phase three trials,’ said French.
These studies help organisations reduce risk and provide them with accurate data to quickly inform the decision-making process. But to scale up these human challenge models from 24 subjects to more than 60 requires Hvivo to rapidly increase the number of samples it can manage. To do this, the team adopted Labware LIMS to manage samples, increase automation, provide reporting tools and remote access to data.
‘LIMS systems are amazing tools and allow us to track samples and have instant access to the data. Back-end reporting tools are also critical for us, being able to feed into stats and having that data much sooner. Whereas, with the classic paper records there can be a gap of up to six weeks while you wait for that data to be usable and interpretable,’ stated French. ‘We take multiple samples each day for each subject, so all of that data needs to be put together each day and the graphs need to be produced.
‘For anyone working on anything to do with a covid vaccine, there is also that added pressure of getting that data out as quickly as possible, getting these vaccines ready faster than before,’ said French.
Environmental testing for the food industry
Campden BRI provides a wide range of analysis and testing services, and operational support for the food and beverage industry. Since the start of the pandemic they have been working to adapt existing expertise to develop services which can help.
Campden BRI helps organisations ensure their cleaning methods are working and can perform environmental testing to ensure that premises are free from contamination of the Sars-CoV-2 virus. The company is also now providing PCR testing for employees as part of this suite of services.
Martin D’Agostino, head of virology at Campden BRI notes that ‘one of the first tasks when I started in 2016, was to set up testing for detection of foodborne viruses. Things like norovirus, hepatitis A and hepatitis E virus.’
‘We have extensive experience in this area, working with food-borne viruses,’ added D’Agostino. Now the company has pivoted to help organisations in the food industry detect and prevent the spread of Covid-19.
‘When the Covid-19 issue came up, we wanted to diversify and be able to help the food industry out. While it may not be similar to other food-borne viruses, the impact on the food industry has been widespread. People are worried about the virus transferring from foods into people.’
D’Agostino notes that while normal environmental testing would be for something more common to the food industry, such as listeria, a lot of organisations were interested in being able to monitor if the virus was spreading to surfaces in a food industry environment.
‘Not only in food processing factories but also in retail environments like supermarkets. A lot of the enquiries that we got earlier on was advice on areas that might be contaminated with Sars-CoV-2,’ said D’Agostino.
‘People early on adapted fairly quickly by introducing enhanced cleaning regimes, making sure that the disinfectants they were using were suitable for use against this type of virus,’ notes D’Agostino. ‘But, as time went on, more evidence emerged to suggest that the virus can be transmitted through the air and by person to person. Organisations have become interested in the whole environment processes that can be used to clean areas.
‘Environmental swabbing can make sure that whatever cleaning regime you are using is effective. If you get a positive result after doing that you might have questions raised. It also suggests that there may be someone in that area who was asymptomatic and was then spreading the virus onto surfaces’ D’Agostino added. ‘If you pick up Sars-CoV-2 on an environmental surface, then chances are it has been fairly heavily contaminated.’
This testing helps organisations develop more effective cleaning regimes and provides assurances to staff that contamination can be avoided if the correct steps are taken. It also helps to minimise risk to staff and help keep the business functional, as the chances for outbreaks are reduced.
‘My colleagues have been using a surrogate virus, a virus that is very similar in shape and structure to the Sars-CoV-2 but it is a surrogate, so it is a safe alternative,’ This surrogate is a bacteriophage which means it can be grown on a host using an agar plate. That is another option to determine if a cleaning regime has been effective,’ notes D’Agostino. ‘They can actually go on-site and artificially infect a surface before and after cleaning. Looking at the numbers before and after to see how effective that cleaning regime has been.’
Towards the end of 2020 Campden BRI started looking at how it could provide more assurance. The decision was taken to set up a service for the testing of personnel.
Having the Labware LIMS in place meant Campden BRI could quickly scale up its PCR testing to enable this new service. The LIMS also helped ensure that the samples met with United Kingdom Accreditation Service (UKAS) regulation standards.
‘We have just launched the [personnel testing] service, so the total demand is still not known but we are looking to do between 150 and 300 per day. To process that number of samples we needed the LIMS in place,’ said D’Agostino.
‘There are a whole range of services that we can offer as part of a complete service. If people get positives in their environmental samples, that may trigger them to take on personnel testing. It is more difficult in a retail setting, because you do not know if that has been caused by a member of the public or the employees but you could use this testing to make sure.
‘It is very useful to have all the processes that LIMS has to be able to go to the UKAS accreditation service and demonstrate that we can handle that data correctly.
‘The first phase that we have gone through here has been a fairly basic setup, where we input the data manually to the LIMS system. At the moment we are not reading barcodes but associating the personal details with a barcode number. We then get a report once that has all been completed,’ said D’Agostino. ‘Our team is also working on being able to export a CSV file so we can easily copy the data across to Public Health England. That is another requirement of clinical swab testing.’
Phase two is more focused on automation. The ideal situation would be that a person could log on to a computer, input their personal details, then we would receive that sample and scan the barcode, which would automatically upload all of that information onto the LIMS system.
‘Another part of the work would be uploading that data to the PCR instrument, and then you could not only produce the report but also draft emails which would be a much more complete system,’ D’Agostino added.
