COVID-19 Briefing for 3rd June 2020

Notes from a conversation held by Lara Marks with Stephen Baker, professor of molecular microbiology, Jeffrey Cheah Biomedical Centre, Cambridge University on Wednesday May 27 2020

Scope of COVID-19 screening tests

There is now a big push on to screen people here in the university and the hospital so that they can get back to work. A key question is who should get tested, where and how. In my personal opinion it isn't particularly valuable to screen everyone, because we will get a lot of asymptomatic people now that the peak of infection has diminished. There is also an issue as to whether our laboratory has the capacity to do such testing. It is one thing for us to undertake the diagnostic screening for the hospital as part of a research study but quite another to provide it as a service for the whole of the university. One of the problems is that our research laboratory is currently the only independent centre doing such diagnostic screening in the Cambridge area. Another question is how long we can continue such testing because, like others in the university, we also need to get back to doing our own work.

Not all COVID-19 tests are equal

Not all tests for COVID-19 are equal. There are limitations on how efficient the swabs are done, what technology is used and also what type of sample you are using. One of the problems with using saliva is that there may not be enough of the virus in the saliva in asymptomatic people so you may get a lot of false-negatives, this is currently being investigated. A more sensitive means for testing is to get a vigorous swab from the back of the throat and the nose, because that is where we get the most virus, followed by amplification of the specimen with PCR.

Swabs at the back of the throat and nose do involve a vigorous rub but this does not have to be painful. It depends on how it is done. All the people screened with our PCR test in the hospital perform the swab themselves. Not all of them are healthcare workers so not everyone has any training to take a swab. We give them instructions which tell them what to do. It involves them rubbing the back of their nose and throat. The process might cause some gagging but it is not strong. Below is a picture of the swab kit and the instructions we give out to people whose samples we test.

Serological testing

Where we really would like to focus our longer term efforts is serological testing. Doing the serological testing project is much more scalable for the laboratory than our PCR diagnostic testing system.

Our serological assays are already working, which means we can carry out serological testing. Such work is important for understanding the immune response to COVID-19. So far, the diagnosis of COVID-19 infection has largely been based around PCR assays for SARS-CoV-2 in symptomatic individuals. This approach is likely to have severely underestimated the true incidence of infection, as those who are asymptomatic or have mild symptoms would be undetected. Such testing also provides limited data on longer term population immunity.

Addenbrooke’s Hospital has already begun to roll out serological testing as a service for its staff. The aim is to get all of its staff members tested every 6 months. This will be done with a multiplex Luminex SARS CoV-2 assay, a high throughput assay, developed and optimised by Cambridge University Hospital's immunology laboratory. The assay uses a combination of SARS CoV-2 antigens (N, S, RBD) and measures IgG responses against the various antigens.

Our laboratory is not involved in the hospital’s serological testing. What we aim to do is get access to the hospital samples which do not show an antibody response and try to work out how that corresponds with our own validated serological ELISA assays. One of the advantages of working with the hospital is that it effectively provides a captive population who can be followed longitudinally. This means we will know how many have been exposed during this first pandemic wave and be able to look back at their records to see whether they had any symptoms or not or whether they were in fact asymptomatic. There will also be people who will have gone through our screening programme so we will know if they tested positive with our PCR test. The advantage of such a project with the hospital staff is it will allow us to infer ‘protection’ by antibody titre and the duration and efficacy of the immune response. It will also enable us to assess the serological impact of any potential vaccination or future waves of infection. Also, if there is a second wave of infection, we will be able to follow that and see who tests positive and gets exposed a second time around.

So, we have the potential to do a fairly large comprehensive project. This could be very exciting if it comes off. At the moment I am running around a lot trying to work out how we can do it. This is because it will involve a lot of work from different people to facilitate the project. One of the issues at the moment is getting buy in from all the parties to do it. Another is working out the right infrastructure so that we can get access to the hospital samples. Also, we can’t do very much without extra funding. We have sent out a bid to the Wellcome Trust on 22nd May for additional funding to match what we are seeking from Addenbrooke’s Charitable Trust. The money will enable us to carry out the downstream research outside of the hospital’s service.

ICU testing

We are continuing to test patients in the ICU in the hospital to check for cross-infections with COVID-19. This is using the pathogen microarray Taq technology. We are currently preparing a paper on that and now looking at how we can turn the research into a longitudinal service in non-COVID times and also putting in place the capacity to do the testing if a second wave of COVID hits Cambridge.

Moving forward

Our frustrations at the moment are trying to return to working as normal because this is proving very difficult to do. The challenge is the world isn’t normal anymore. However, we have got some important tools here for helping with the diagnosis of COVID-19, but we do not want to become a diagnostics laboratory. We want to get back to what we are really here for as a research laboratory. The issue is getting the balance between doing something useful and getting back to normal.

SARS-Cov-2 swabtest

Caption: Swab kit. Source: S Sridhar, et al, A blueprint for the implementation of a validated approach for the detection of SARS-Cov2 in clinical samples in academic facilities.

SARS-Cov-2 swabtest instructions

Instructions given to people tested for COVID-19 in Cambridge.

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