Professor Sir Gordon Duff emphasises the importance of UK strengths in the fight against Covid-19

By Sarah Cartledge - World Healthcare Journal

Professor Sir Gordon Duff is one of the UK’s most respected scientists and was co-chair of the SAGE committee during the H1N1 swine flu epidemic of 2009. Currently the Principal of St Hilda’s College Oxford, with interests in inflammation, immunology, cytokines, biomedicine, public health and genetics, he has published more than 400 research articles as well as government reports on medicines, vaccines, and public health. He is also co-inventor of some 35 patented technologies in inflammation and biotechnology.

But the presence of the SARS-Cov-2 coronavirus has baffled and continues to baffle, scientists such as himself. “When we were faced with swine flu, we knew a little about it because of seasonal flu, so we had vaccines ready to adapt and enough antivirals to keep people out of ICUs. We also had a preparedness committee that ensured that the right things had been stockpiled at reasonable levels,” he says.

“With Covid-19, we knew nothing about it until it arrived - how it transmits, its virulence and the kind of illness it causes in different people. So, the UK couldn’t stockpile as we knew so little about it before it hit us. ”

Thus, his focus is on the medical countermeasures to Covid-19, as opposed to the public health and epidemiological countermeasures. “We seem to be plateauing or reducing in case numbers and mortality, and we have avoided exceeding our capacity to treat the critically ill. Now, we need to coordinate and consider our strengths here in the UK in bioscience generally, but also at that border between basic science and clinical medicine, the translational space. ”

The importance of testing

One of Britain’s key strengths lies in long-established institutions such as NHS Blood and Transplant that takes blood on a daily basis from volunteer donors. Another is the National Institute for Biological Standards and Control, a centre of the MHRA. “This is where you start,” he says.

“Some of those donors will have had the virus, so it is possible to assess samples with high antibody titres - high concentration of specific antibodies to SARS-CoV-2 in their blood which can be used as positive controls in antibody tests, and ultimately biological standards for the antibody. They can be ampouled and sent around the world to allow other regions to standardise against them. In that way, we achieve international standards, and this work is already well underway. ”

A large part of the early problem with antibody tests was the lack of standardisation, resulting in many false negatives potentially false positives. But just last week, the Swiss pharmaceutical company Roche has announced a new test with specificity greater than 99.8 per cent, and a sensitivity of 100 per cent.

The company aims to provide high double-digit millions of tests in May alone for countries accepting the CE mark, and in the US under Emergency Use Authorisation, further ramping up capacities thereafter. This breakthrough can help assess patients’ immune response to the virus, and as more is understood about immunity to SARS-CoV-2, the test may be able to determine who has built up immunity to the virus.

“Now we are on a better trajectory towards reliable tests, so the challenge is to scale up the production and distribution on a global scale,” says Sir Gordon. This feeds in very strongly in how to deal with the next wave, which many experts feel is inevitable once the restrictions around lockdown are loosened.

“A lot of the medical countermeasures are based on very first principles that should not be bypassed. You start with your standards and then go on to make proper tests, likewise with vaccines and other countermeasures, such as antivirals.

“This is an area that needs consistent momentum. In the UK there is a huge strength in fundamental bioscience. We are world leaders in many areas and, while some of this expertise is being harnessed, we need to harness it more.

“Once we understand how the virus gets into cells, how it replicates, and the pathways that lead to illness - probably largely mediated by the person’s own immune response to the virus - then we will understand more about where good targets may be to interrupt the pathway of viral infection, replication, and pathogenesis. There will be lots of new targets and we have to be agile and nimble at defining them in both the virus and the human host. ”

But, he acknowledges that at this point it amounts to more than just the science. “It becomes about funding, coordination, regulation, production scale-up and distribution. Good regulation is key because ultimately the dictum remains ‘first do no harm”, even, perhaps especially, when we are in a global emergency. So, new products must be independently assessed as having a positive benefit-to-risk ratio on the best available data. Even though we can expedite the process, it is important to do it right because, if not, we are more likely to fail than to succeed. Then the credibility of the scientific response is damaged. ”

The vaccine question

One of the earliest potential vaccines has been identified by Professor Sarah Gilbert at Oxford University, continuing previous research work on coronaviruses by adapting the adenovirus vehicle to carry the antigens of Covid-19.

“I’m not involved, but I have huge confidence in her assessment, so I’m optimistic,” says Sir Gordon. “Creating an effective and safe vaccine is a critical part of the global public health effort, but we may not get on top of this virus for some time. However, I think we will be able to live with it and control it better by possibly reducing the severity of the clinical illness with new or re-purposed drugs. ”

The UK has other global strengths, such as the National Institute for Biological Standards and Control. “It underpins much of the world’s vaccines and biological medicines because it sets international standards and supplies over 90 per cent of the world’s needs,” says Sir Gordon. “It is a very competent organisation with a history going back to NIMR in the 1920s when the first international standards for insulin were created by Henry Dale. I would put them right at the epicentre of UK efforts to develop medical countermeasures in pandemics. ”

The NIBSC plays a major role in assuring the quality of biological medicines worldwide through the provision of biological reference materials, by testing products, and carrying out research. It is the standardised testing assessed by NIBSC and the broader MHRA that Sir Gordon considered key to rapid development and safe use of diagnostics, biological medicines and vaccines.

“Even when we identify those who have antibodies, we still don’t know the level of protection they give and how long that will last. This will take more time, but once we have the correct positive controls in our tests, we will know the results from different places can be compared, no matter where the test is done, and which testing kit is used. Ultimately, these will become international standards. ”

Global response body

Currently, the data that exists is not in a form to produce accurate information. “Most of the learnings will come out in the months and years ahead, so in retrospect, it will be quite easy to see what worked and what didn’t. But at this point, it is important to collect the relevant data and frequently to review the generalisable learnings,”

“People are comparing the approach to clampdowns and isolation in different countries, but the populations and health services vary from country to country. Many places defined cases as probably because the patient had the symptoms in the middle of an outbreak, whereas others are very strictly sticking to the people who have positive viral presence via the PCR test. It is apples and oranges in terms of data. ”

In his opinion, it will take at least a year to collate the minimum vital information - but the full picture will take much longer to crystallize. “My feeling is that Covid-19 will still be with us as a health risk for several years yet, and could even become seasonal-like flu, but we will have come up with antivirals, treatments for the illness, especially critical illness, and effective vaccines,” he says.

“We must avoid a humanitarian disaster where rich countries stockpile vaccines and critical strategic reagents. The WHO needs a global body to work out a cohesive international response to this, and any future pandemic, but we must have a good national response before the UK can contribute everything that we have learned to the global response. We must keep on our foot on the pedal and not lose momentum. ”

The issue of face masks

It’s a thorny debate, but one that people want to engage with as a means of feeling in some control of this pandemic. Many governments have now mandated the usage of face coverings and ‘homemade’ masks whilst in public or on transportation, but the question is, how much of a benefit does wearing them provide?

“High-quality masks are fully justified for patient-facing staff trained in their use. Those masks are incinerated afterwards,” says Sir Gordon. “The only rationale for wearing masks is that it holds up virus passing in either direction.

“The benefit of poor quality masks for general use is less clear, especially with a virus that may survive in the mask for many hours, possibly replicating in cells that survive in the conditions that the masks create. There is, too, the question of how to dispose of those masks safely? Making it someone else’s problem isn’t a good answer.

“Perhaps miscellaneous face coverings make people feel safer, not to be dismissed as an outcome; we see prints of people wearing beaks during the bubonic plagues. But I think with the current pandemic, more studies are needed on the personal and public health benefits of masks for everyday use. ”

“Until then, social distancing remains a rational defence, until a good vaccine comes along. ”

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