COVID-19 research update

There are currently 289 worldwide interventional studies on COVID (that is trials that involve a drug or procedure to treat patients) and in total there are more than 1000 active trials of all types ongoing trying to improve the data and our understanding of this new disease. That is a huge research effort built up in a very short time. Below is a snap-shot of current research and how it will benefit the immunodeficiency community.

You can find out about the different phases of clinical trials here.

The COVAD study starts to look at COVID vaccine responses in patients affected by primary and secondary antibody deficiency

The UK Primary Immunodeficiency Network (UK PIN) are about to launch a research study to explore how effective COVID vaccinations are for people affected by primary and secondary antibody deficiency (PAD and SAD, respectively). This is a vital piece of research with the COVID vaccination programme now being rolled out nationally as it is not known, at present, what level of protection patients with antibody deficiency will develop after immunisation through antibody or T-cell responses.

The work will be funded by UK Research and Innovation (UKRI) and the aim is to involve over 1000 adults with PAD/SAD over the next six months by recruitment of patients through the collaboration of as many immunology centres as possible.

The research will also help to address some fundamental questions about how COVID is affecting the antibody deficiency community. These include finding out how common asymptomatic and symptomatic COVID infection occurs in this patient group, how often and for how long the virus persists and if COVID infection results in protective antibody or T-cell responses.

Professor Alex Richter of the University of Birmingham and Professor Siobhan Burns of University College London are co leading this project on behalf of UK PIN.  They say ‘We are delighted to launch this important project with the help of UKRI funding. It builds on our research indicating that people with antibody deficiency may be at an increased risk of severe COVID-19 infection.  At present we don’t know if this risk is due to the underlying immunodeficiency or due to other health complications associated with immunodeficiency.  The project will help address lots of important questions that will help inform how we care and manage patients in the context of their risk to COVID.‘

So how can patients take part?  Professor Richter says ‘We are seeking to recruit patients with PAD and SAD who have had COVID or who are eligible for COVID vaccination. The study will involve a questionnaire, diary, COVID swabs and blood tests’.

Dr Susan Walsh, CEO of Immunodeficiency UK, said ‘We are so pleased that this study is going ahead. Knowledge is power against this devastating virus and we need to learn so much more about COVID’s impact on the PAD and SAD communities and how beneficial vaccination is for these patient groups. We encourage all patients to ask their immunology teams if they are eligible to take part in this study.’

Posted 11th January 2021

Monoclonal Antibody Therapy for Covid-19

Monoclonal antibodies (Mabs) are a promising therapy because they can neutralise the SARS-CoV-2 virus, which causes COVID-19 and block its ability to infect a cell. This might be a lifesaving intervention in people who are unable to mount a strong natural immune response to the virus.

These man-made antibodies offer the possibility of immunotherapy similar to the use of convalescent plasma (see below) but with a more targeted and accurate action. They mimic the body’s natural immune response and target foreign agents,
like viruses. In COVID-19 they attach to the viral spike protein on the coronavirus preventing it from entering cells.

While a vaccine will ultimately help to protect the public, vaccination will not be an instantaneous event delivering vaccine to 100% of the population. The impact of a vaccine takes several weeks to generate a powerful antibody response in healthy people and may  generate a very limited response  in people who are immunodeficient.

Unlike conventional vaccines, Mabs can be used to treat patients infected with COVID-19 and to prevent infection for around 6-12 months. They are also likely to be effective in people with immunodeficiency disorders.

Mabs that neutralise the coronavirus are complicated to manufacture and produce and are therefore quite expensive. Several pharmaceutical companies worldwide have developed Mabs for use against COVID-19, including Regeneron
Pharmaceuticals. Eli Lilly and AstraZeneca.

AstraZeneca has produced a COVID-19 cocktail combining two monoclonal antibodies, AZD7442,  with potential to treat infected patients and to be given as a preventative treatment which will confer protection for 6-12 months.

Phase three trials of the AstraZeneca therapy have now started in the UK.  Trials are also underway in Europe and the US. These will evaluate the safety and effectiveness of the antibody therapy. The treatment can be injected or administered intravenously. Results are expected to be published in the first half of 2021, although the trial is expected to last for 12 months.

The UK Government has an in-principle agreement with AstraZeneca which it says secures access to a million doses of AZD7442 if it is successful in Phase 3 trials. It is unlikely to be available for general use before the end of 2021.

For more information on Mab therapies visit:
COVID-19 Long-Acting AntiBody (LAAB) combination AZD7442 rapidly advances into Phase III clinical trials
(astrazeneca.com)

RECOVERY COVID-19 phase 3 trial to evaluate Regeneron’s REGN-COV2 antibody cocktail | University of Oxford

Vaccine development

We all know how much a vaccine against COVID-19 is needed. This great article from the Wellcome Trust gives an insight into the stages involved and how the timescales of usual development are being dramatically speeded up to address the urgent need.  Thankfully, initiatives at Imperial College London and Oxford University are leading efforts to develop a vaccine and collaborative partnerships are being struck with pharmaceutical companies to ensure that infrastructure is in place for large-scale production if an effective vaccine is found.

Please see our statement on COVID vaccines and frequently asked questions about the use of vaccines for people with PID.

The RECOVERY project

This UK project aims to help identify the best treatments for COVID-19 through large randomised controlled trials. Treatments that are being looked at include: Hydroxychloroquine; Azithromycin; Kaletra and Tocilizumab. You can read more about the RECOVERY programme at https://www.gov.uk/government/news/worlds-largest-trial-of-potential-coronavirus-treatments-rolled-out-across-the-uk

Trials of ‘convalescent’ plasma treatment

Dr Matthew Buckland, Chair of Immunodeficeincy UK’s Medical Advisory Panel says ‘Plasma treatment for COVID is being considered based on a few promising cases in China and past experience with Severe acute respiratory syndrome coronavirus (SARS). Plasma from people who have cleared infection appears to help those who are sick clear infection more quickly. Trials are needed to see if it really helps people get out of hospital more quickly too. There have been lots of offers from people to donate. If it works it may be an option for immunodeficient patients who don’t make antibodies to get some passive protection or treatment.’

The NHS is calling on people who have recovered from COVID-19 to donate blood plasma, as part of a clinical trial to help work out how effective convalescent plasma is for treatment coronavirus patients.  Specific eligibility criteria apply and volunteers need to live near a donation centre.  Please encourage friends and family who have had COVID-19 and recovered to take part. Find out more at https://www.nhsbt.nhs.uk/how-you-can-help/convalescent-plasma-clinical-trial/

Anti-viral drug trials

The anti-viral drug Remdesivir is showing promise in the treatment of COVID-19. The results from the National Institutes of Health trial showed that the drug resulted in a faster time to recovery and a small reduction in death rate.  More trials are needed to fully confirm the data but very recently the Food and Drug Administration (FDA) in the USA has granted remdesivir emergency use status.

The anti-viral drug Favipiravir has also shown promise in an early study reducing the time to viral clearance.  Further trials are planned: https://www.sciencedirect.com/science/article/pii/S2095809920300631

DNA studies

The store of DNA in the UK Biobank is being used to study why the severity of symptoms for COVID-19 varies so much between affected individuals.  Read more at: https://www.bbc.co.uk/news/health-52243605

Posted 11th May 2020; updated 30th November 2020; updated 11th January 2021.