Vaccines are helping bring the spread of the virus under control, and mitigate its worst effects. However, many people are still suffering from COVID-19 and long COVID.
It’s vital that we continue to find more effective treatments for COVID-19.
UK Research and Innovation (UKRI) has supported pioneering clinical trials and research projects to test new and established therapies at all stages of the disease. This is helping to preserve life and health here in the UK and around the world.
Treatments will continue to play a vital role in the fight against this unpredictable disease, according to Peter Horby, professor of emerging infectious diseases at the University of Oxford.
It’s clear that treatments will always be needed, particularly for viral respiratory infections like COVID.
Vaccines will never be a 100% solution, even when we reach widespread coverage.
We could see evolution of the coronavirus so that there is a poor match between virus and vaccine, some people won’t respond to vaccination, while others won’t be able to be vaccinated or don’t want it.
Large-scale clinical trials
COVID-19 is a disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). So, when the pandemic first struck doctors were unsure exactly how best to treat it.
There were lots of ideas – and, in the case of drugs like hydroxychloroquine, lots of media hype – but no solid data about how well any of them worked.
Clinical trials were urgently required, and UKRI played a leading role in establishing and funding a research pipeline in partnership with the NHS and the NIHR.
Three large-scale national clinical trials launched, each of which addresses a different part of the patient journey.
UKRI funded two of them from inception:
- the RECOVERY trial
- the PRINCIPLE trial.
The RECOVERY trial
The RECOVERY trial launched in April 2020 and within months showed that the cheap, widely available steroid dexamethasone, could cut the risk of dying by a third in hospitalised patients who already require oxygen.
This finding has helped save hundreds of thousands of lives around the world.
The RECOVERY trial continues to swap potential treatments in and out of the trial. It established that lopinavir-ritonavir and the much-touted antimalarial drug hydroxychloroquine were both ineffective.
The PRINCIPLE trial
The PRINCIPLE trial was part-funded by UKRI and since its launch has recruited over 5,000 patients.
It is led by the University of Oxford and is finding treatments for recovery from COVID-19 at home, instead of in hospital.
In April 2021, the trial reported that asthma drug budenoside shortens recovery time for non-hospitalised patients with COVID-19.
The PRINCIPLE trial also proved that the antibiotics azithromycin and doxycycline aren’t effective for people being treated at home.
Who decides what goes on trial?
The RECOVERY and PRINCIPLE trials are platform trials. This means patients can be efficiently recruited and randomised to receive one of a range of different treatments. There is flexibility to swap therapies in or out as required.
Decisions therefore have to be made on an ongoing basis about which treatments to include in each of these trials. This task fell to the UK COVID-19 Therapeutics Advisory Panel (UK-CTAP), managed by UKRI.
UK-CTAP has ceased its operations as of September 2021. See some of the highlights of what UK-CTAP achieved in the last 15 months (PDF, 254KB).
Patrick Chinnery, Chair of UK-CTAP and Medical Research Council (MRC) Clinical Director, explains how the panel reached its conclusions on which potential COVID-19 treatments to prioritise:
As well as damaging the lungs, the disease can also have an overwhelming effect on the immune system and cause blood clots, so we’re looking at drugs covering a range of disease mechanisms and modes of action.
For each potential treatment we’ll examine whether there is a plausible mechanism of action against COVID-19 or its complications, any evidence that it might work in COVID-19 patients, and whether it’s being tested anywhere else in the world.
We’ll also consider whether it’s a medicine that could actually be used in the NHS if it works – is it available, affordable and able to be manufactured at scale?
UK-CTAP evaluated all the proposed treatments that are put forward, and only recommended those where there is a strong case based on objective scientific evidence. As might be expected, this means that there are many ideas that didn’t pass the test.
Putting COVID-19 treatments to the test
The NIHR Clinical Research Network has been central to delivering all of the trials across the NHS.
The rapid evaluation and approval of new drugs has enabled tens of thousands of patients to be recruited at an incredible pace. This has been done by:
- the Medicines and Healthcare products Regulatory Agency (which looks at safety)
- the Health Research Authority (which looks at the ethical aspects).
In turn, this speed and scale is leading to much-needed answers about which treatments do – and, importantly, don’t – help people with COVID-19.
Trialling completely new treatments
While the RECOVERY and PRINCIPLE trials are testing existing therapies to find out if they have benefits for COVID-19 patients, the AGILE trial is focused on new antiviral therapies.
AGILE is taking brand new drugs into small-scale, first-in-human trials.
Saye Khoo, Professor of Pharmacology at the University of Liverpool and leader of the AGILE trial platform said:
To see the kind of antiviral effect against coronavirus that we have for viruses like HIV or hepatitis C, we’re going to need new drugs that specifically target the SARS-CoV-2 virus.
New therapies are added to AGILE according to recommendations from UK-CTAP.
In February 2021 it was announced that new funding from UKRI and NIHR meant the trial would be expanding to five additional centres in the UK.
Using the virus’s lifecycle to advantage
A team of MRC-funded scientists identified key cellular factors that are crucial for the infection of SARS-CoV-3, the virus that causes COVID-19.
The team from the universities of Glasgow and Oxford and the Rosalind Frankin Institute published their findings in the journal Molecular Cell.
They say that by identifying key cellular proteins that play a critical role in promoting or inhibiting virus infections, it will be possible to develop novel antiviral treatments or repurpose available drugs.
Dr Alfredo Castello, from the MRC-University of Glasgow Centre for Virus Research said:
We are extremely excited by our findings.
With just the first available inhibitor we tested in cell models, we were able to inhibit the virus replication, so the possibility for new treatment options is positive.
Moreover, in parallel studies, we found that many of these proteins also participate in the infection of other RNA viruses, so there is potential for discovering treatments with broad-range of action and that could be ready should a new coronavirus emerge.
We hope the study paves the way to identify the best potential therapeutic targets.
Research projects finding treatments
Scientists from the University of Bristol and start-up Halo Therapeutics are developing antiviral treatments that could prevent the virus from entering the body.
The team reported a breakthrough discovery in Science magazine. They found that exposing SARS-CoV-2 to linoleic acid locks the virus’s spike protein into a closed shape. This:
- blocks the virus’s entry into cells
- slows down its replication inside cells
- prevents it from spreading and infecting people.
Professor Christiane Berger-Schaffitzel from Bristol’s School of Biochemistry and Halo’s chief scientific officer added:
Our vision is that at the first sign of the disease, whether you come into contact with someone who has COVID-19 or you have early symptoms, you would self-medicate at home to stop the virus in its tracks and prevent you from getting ill.
The research was part-funded by the Biotechnology and Biological Sciences Council (BBSRC).
A pipeline of research
The UK’s suite of platform trials for COVID-19 treatments, underpinned by investment from UKRI and NIHR, has highlighted the benefits of a joined-up approach to clinical research that can extend far beyond the pandemic.
UKRI’s support has provided a way of prioritising drugs and linking together all the platforms so that promising treatments can go forward into bigger trials, as well as unlocking administrative jams and building trust across the research community and industry.
As Patrick Chinnery noted:
I think the challenges of COVID-19 have shaken up the system in a very positive way and really highlighted some myths about how we do clinical research.
It’s shown us the speed at which we can move from having an initial concept through to launching a trial, which would typically take 18 months and we managed to do in weeks.
Last updated: 2 March 2022