One of the main areas the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) was set up to tackle was that of future pandemics.

Of course, no one expected that just after the institute’s staff and researchers started moving into their home at the brand-new Jeffrey Cheah Biomedical Centre in October and November of 2019, a new virus would emerge and spread across the world like wildfire.

As we know, the SARS-CoV-2 virus surfaced in Wuhan, China, with the first cases being traced back to early December 2019.

The virus quickly spread out of China to various other countries, resulting in the World Health Organization (WHO) declaring the outbreak a Public Health Emergency of International Concern on Jan 30, 2020, and subsequently, a global pandemic on March 11, 2020.

With its raison d’etre being the focal point of research for immunity and infection within the University of Cambridge, the CITIID quickly went from being the newest institute on the university’s Biomedical Campus to the only research facility in the university allowed to stay fully open during the United Kingdom’s lockdown period.

Although they “weren’t quite ready”, as the institute’s director Professor Dr Ken Smith shares, all the researchers at the CITIID quickly and gamely pivoted from their own work to focusing on Covid-19 and the SARS-CoV-2 virus.

With many of the researchers also being clinical staff, Prof Smith added that they quickly realised they couldn’t do just purely academic research.

This was especially as such work would require assistance from clinical staff – in getting patient samples, for example – and add on to the already overburdened workload of the frontliners.

“So our initial priorities were to try and deliver research that would help the immediate response to the pandemic,” says the university’s Department of Medicine head, and consultant nephrologist and clinical immunologist.

One of the first things they did was to develop and set up the first point-of-care for Covid-19 testing.

When the pandemic started, every patient who came to Addenbrooke’s Hospital – the main teaching hospital and research centre affiliated with the University of Cambridge – had to wait for over 24 hours before their Covid-19 test results were known.

All of these patients would be placed in a waiting area during this period.

“So, instead of suspected patients spending a day in a ward mixed with non-Covid patients, waiting for their results, we would get their results in 10 minutes,” says Prof Smith.

This enabled patients to be quickly separated and segregated into the Covid-19 and non-Covid-19 areas of the hospital in order to receive the care they needed.

The institute also established the first healthcare worker screening programme in the UK, where Addenbrooke’s healthcare staff were screened after work every night.

“That meant we were able to send people home who were positive, and the hospital, which had been the biggest source of infection in the community during lockdown, could stop being a source of infection.

“We managed to almost wipe out inter-hospital infection,” he says.

Both of these programmes were made possible through the quick development of a PCR-based high throughput assay for SARS-CoV-2 screening at the institute.

A high throughput screening assay allows for the automated and rapid testing of large numbers of samples for certain biological properties, e.g. genes, antibodies or active compounds.

In this case, it allowed for the screening of genes from the SARS-CoV-2 virus.

Prof Smith shares that this was made possible from the experience and expertise of his colleagues, molecular microbiologist Prof Dr Stephen Baker and Department of Pathology deputy head (research) Prof Dr Ian Goodfellow.

“Ian had set up a field-based Ebola testing system in West Africa, using very rudimentary technology.

“And he used that experience to set up the rapid staff screening test we had.

“Because, of course, we couldn’t get most of the reagents we wanted because they were in short supply, so he set up an alternative sort of crude, but very effective, system.”

As this assay used different reagents from the ones the rest of the world was competing for, the CITIID team were able to get the supplies they needed at the necessary quantities quickly to set up both screening programmes.

Monitoring the spread

Another significant contribution researchers at the institute accomplished was to set up the Covid-19 Genomics UK Consortium (COG-UK).

Initiated by Department of Medicine professor of public health and microbiology Dr Sharon Peacock and senior research associate Dr Ewan Harrison, this was an effort to sequence the viral samples that were being collected by the institute.

Initially based at the CITIID, the work soon moved over to the Wellcome Sanger Institute – a non-profit genomics and genetics research institute based just outside Cambridge – and eventually, involved sites all over the UK.

“At its peak, they were sequencing 60,000 viral isolates (samples) a day, which allowed us to track outbreaks and to watch new variants come in and explore their spread over the country, and start to control those things,” shares Prof Smith.

For example, although much of the media attention at the time was on travellers coming in from China and attendees of Austrian ski parties that had generated Covid-19 clusters, the sequencing programme found that most of the initial Covid-19 UK cases were actually being brought in from Italy, France and Spain.

“That obviously then offers you a policy on how you can control travel (to minimise viral transmission).” he notes.

On a more local level, the sequencing programme allowed the tracing of six seemingly-unrelated Covid-19 patients living around Cambridge who had the exact same viral strain, back to a shared minibus they were all taking to go for dialysis at the same time.

This alerted the local authorities to this method of transmission and allowed for stricter monitoring of shared or public transport.

Continuing the work

While the institute continues to do work on the SARS-CoV-2 virus and Covid-19 – including monitoring vaccine efficacy on viral variants and leading the UK-wide study on long Covid – work on their other main objectives is slowly gathering steam again.

As Prof Smith shares: “Our strategy was very much to think about what were problems going to be in 20 years.

“And we thought they were going to be pandemics (and) they were going to be antimicrobial resistance – both of those things impacted by climate change.”

And while the timetable on pandemics certainly arrived much earlier than expected, in some ways it was a blessing in disguise.

“It was a great way to start a new institute, because everybody’s forced to work together.

“We met everyday at 5pm to discuss the strategy for the next day,” he shares.

“The another thing was we needed a huge increase in staff numbers to deliver things like the healthcare workers screening.

“And we were able to do that because all the other scientists on campus had been sent home, so we had hundreds of volunteers coming in to ferry samples, to assist on wards and to drive a lot of the technical work.

“So it wasn’t just us, we become a sort of nidus for a huge amount of voluntary activity across the campus,” he adds.

They even “adopted” three or four other research groups that were also researching Covid-19, but whose buildings had been locked down at that time.

Another advantage of the pandemic Prof Smith shares was that “the administrators got out of our way”.

“Normally, when you want to do an experiment, there are a series of bureaucratic hurdles you have to leap through that delays you by months.

“And those things that used to take months were suddenly truncated into days or weeks, and sensible decisions were made extremely quickly.

“My fantasy was that this situation would be maintained after the pandemic, but I was wrong,” he says with a smile.

“But the speed at which we made things work when we were focused was quite impressive,” he adds, noting that part of it was also due to having “built the perfect building and opened it eight weeks before the pandemic”.

Aside from the CITIID, the Jeffrey Cheah Biomedical Centre also houses the Wellcome-MRC Cambridge Stem Cell Institute, the Milner Therapeutics Institute and the Cambridge Centre for Myelin Repair.

It also has the largest biosafety level 3 lab in academia in the UK, according to Prof Smith.

Biosafety level 3 labs are used to study infectious agents or toxins that can be transmitted through air and cause potentially lethal infections.

Prof Smith met the media recently when he was in town to give a talk on “The Jeffery Cheah Biomedical Centre and the Cambridge Rapid Response to the SARS-CoV-2 Pandemic” in Sunway University as part of the Jeffrey Cheah Distinguished Speakers series.

This article was first published in The Star, 12 September 2022.