Category: Disease

The hunt for a home coronavirus antibody test

A person taking an antibody test

“No test is better than a bad test,” said Matt Hancock.

While we may tire of hearing slogans, the principle here is important.

Coronavirus antibody tests have been hailed as a game-changer for the pandemic and a way forward as we traverse these uncertain times. Antibodies are Y-shaped immune molecules produced by the body in response to an infection. They latch onto the offender – such as coronavirus – in a bid to thwart it. Your body keeps a record of the encounter, so that if it comes across the same pathogen in the future, it can quickly make more antibodies and launch an effective attack.

This is the basis for hedging bets on antibody testing for coronavirus. The idea is that the tests will flag people who have already had the infection and therefore might have protection from getting it again. And so these individuals could potentially be afforded greater flexibility than those vulnerable to the disease.

But it’s not that simple.

Despite being known for under a year, this is arguably one of the most studied viruses ever. Yet it’s still new, and there are many unknowns. Crucially, we don’t yet know whether having antibodies can prevent future infection. Or, even if they do, how long this immunity lasts – a month, a year, many years? These are all questions we must answer before a potentially dangerous over-reliance is placed on these tests.

With so many caveats, why are researchers at Imperial leading a major study of community antibody testing? While the tests’ power to indicate immunity is – as yet – far from clear, they have important uses beyond this. Rather than focussing on individuals, looking at widespread patterns at the population level could help to monitor the evolution of the epidemic, which will have important implications for easing of restrictions such as social distancing.

Antibodies vs antigens

Currently the most accurate way to look for antibodies is to perform a lab test called an ELISA, on a sample of blood. Antibodies are very selective about what they stick to – specific molecules called ‘antigens’ (in this case, bits of the coronavirus). In an ELISA, a blood sample is mixed with coronavirus antigens that are ‘glued’ onto a test surface. If antibodies are present in the sample, they stick to the antigens and this binding leads to a detectable signal, most commonly in the form of a colour change.

These lab-based tests are accurate and can tell us the exact amount of antibody in a sample, but they’re complicated to perform, and require expensive, specialised labs. This means it’s not feasible to roll out this kind of antibody testing at a national scale, when labs are already overburdened. That’s why Imperial’s REACT study is looking at the possibility of using home testing kits instead.

“The big advantage is that the home testing kits are really cheap to produce, easy to distribute and store at room temperature, and they completely bypass the lab,” says Barney Flower, Clinical Research Fellow at Imperial and member of the REACT study team. “The beauty is that you get participants to do the leg work and carry out the tests themselves, so it’s less of a capacity issue when resources are stretched.”

These home tests, called Lateral Flow Tests (LFTs), work in a similar way to ELISA, but everything is crammed into a small testing stick, which participants place a drop of blood onto. If antibodies are present, a signal will show up in a window on the testing stick, usually a coloured line.

An antibody testing stick
The antibody testing kits display coloured lines depending on the result

A flooded market

By May of this year, already more than 200 of these LFTs had reached the market. However, there was no guarantee of their accuracy.

“The tests have been validated for use in laboratories, but in general their performance has been tested in small numbers of individuals, often fewer than 50 patients,” Barney says. “And these were usually individuals who were in hospital with COVID-19, so quite sick, and therefore more likely to have a strong immune response to the virus, producing lots of antibodies.”

This presents an issue, given that many people who have been infected with the coronavirus don’t have symptoms, and most don’t end up in hospital. So it’s critical to ensure that these tests work in this key group. And it’s also important to make sure that the tests perform well when they’re carried out by individuals themselves, not a trained technician – which is usually how they’re scrutinised in formal validation tests.

Antibody test results: true or false?

There are two main criteria that researchers use to assess how well an antibody test works. Its sensitivity is how well it picks up people who have been infected. If a test is 95% sensitive, for example, then out of 100 individuals who have had COVID-19, five will be wrongly identified as having not been previously infected (false negatives). Specificity, on the other hand, concerns the test’s ability to correctly identify those who were not infected. So if a test’s 99% specific, out of 100 people who haven’t had COVID-19, one will be wrongly identified as having been infected (a false positive).

In the UK, our regulator of medicines and medical devices (the MHRA), set out guidelines which stated that antibody tests need to be at least 98% sensitive to be able to guide decision-making in the clinic.

“The tests we’ve been looking at have been far below that,” Barney says. “So they’re no good at the individual level. But if we can find a test that’s really specific, we can make adjustments in our calculations and get a fairly accurate picture of the proportion of people who have antibodies at the population level.”

An antibody testing kit
Study participants are asked to read the result of their test and submit a photograph so that researchers can review their interpretation

A testing conveyor belt

For the REACT programme, a team led by Professor Graham Cooke has been assessing a number of different commercially available tests, including the Wondfo test that the UK Government stockpiled early on in the epidemic. In the first phase, researchers carried out a small-scale study to test accuracy and usability (how well people can perform the test by themselves) on a group of around 270 healthy people, all NHS staff. Importantly, they’d all had a previous diagnosis of COVID-19 confirmed by a nose swab, but none of them had been hospitalised from the disease.

“The first test we tried out was throwing out negative results in four out of five participants – in a group who’d all had confirmed infection,” Barney says.

As well as testing the positive cases’ blood with the antibody kits, the researchers also performed an accurate lab ELISA to check if antibodies were detectable on the best test available. They found antibodies were present in more than 95% of cases.

They also tested the antibody kits on a batch of 500 blood samples taken from 2019 or earlier, i.e. preceding the pandemic and therefore COVID-19-free.

Together, this process is allowing the researchers to determine the tests’ sensitivity and specificity with a high degree of confidence.

“We’ve now developed a system where we can continually bring in new tests as they emerge, evaluate them on our bank of ‘known positive’ and ‘known negative’ samples, and if they look good we can test them in the clinic in more of a real-life scenario,” Barney says. “It’s like a lateral flow test conveyor belt.”

It’s how you use it

Another vital aspect of this work has been determining how usable these tests are by members of the public. Even if they perform well in controlled environments, they’re no good for use en masse if people can’t do them at home. A huge effort has been underway at Imperial, led by Prof Helen Ward, to involve and engage the public in this part of the project. Thousands of volunteers to date have given their time, offering valuable insight that’s not possible to gauge through lab testing alone.

While all of the LFTs work in the same way – placing a drop of blood onto a testing stick – there have been a number of issues with usability that this public involvement exercise has flagged up.

“This has been so important to highlight real issues with the tests,” Barney says. “One of the major things has been getting enough blood from the finger-prick, and successfully dropping this on the right part of the testing strip.”

At the start of the study, participants were provided with a plastic pipette to collect their blood after pricking their finger, which was then used to transfer a droplet of their blood onto the stick. But this soon proved a fiddly procedure, and now individuals are asked to place a drop of blood directly onto the test.

“We also found that health professionals tended to dive straight in and pay less attention to the instruction manual, and were therefore more likely to get it wrong!” Barney recounts. “Clear, simple instructions are so important!”

A person reading an antibody test instruction manual
The leaflet to guide people through the at-home antibody test was developed with the public

Blood, spit, spots

While this research continues, the REACT team has narrowed down their hunt for the best home LFT. After analysing 11 different LFTs in the lab, they found the best tests could correctly identify individuals with coronavirus antibodies over 80% of the time, while also correctly ruling out those who don’t in more than 98% of tested individuals.

Based on these findings, the team selected and rolled out a finger-prick test to more than 100,000 people across England, who tested themselves at home in June and July. Covering all 315 local authorities to ensure a nationally-representative sample, this major study found that just under 6% of the population had antibodies to coronavirus and had therefore likely already had COVID-19. It also revealed that the virus hadn’t spread evenly across the country, disproportionally affecting key workers and Black, Asian and minority ethnic individuals.

Watch the video below for the study highlights:

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The team is continuing further testing of LFTs on a group of 5,000 key workers to gather more data. This particular piece of work is also investigating whether other methods could also be used for antibody testing, such as saliva samples or drops of blood dried on paper.

While this research can’t tell us anything about possible immunity levels, its offering is a greater understanding of how the epidemic is progressing, and who is at greatest risk from the infection.

“What this can help us understand is how many people have been exposed to the virus,” Barney says.

“Comparing these numbers to deaths and numbers admitted to hospital, in different populations and different parts of the country, will help plan for future outbreaks.

“However, it’s still important to say that we don’t know what these antibodies mean for individuals yet. Do they offer protection? And if so, for how long? The future of mass antibody testing rests on what we can learn from research like this.”

If you’d like to learn more about the REACT studies, visit our website here.

Tackling Type 2 Diabetes in North West London

A medical record on a laptop demonstrating applications for diabetes

Type 2 Diabetes (T2D) is one of the greatest challenges currently facing the NHS, with growing levels of obesity contributing to a large increase in the numbers of people with the condition. The disease can lead to serious long-term health problems – including heart attack, stroke, kidney failure and sight loss – which have an enormous impact on the lives of patients and their families. And it is these complications that account for most of the healthcare activity and cost associated with T2D. (more…)

Malaria research: Scientist industry urged to not underestimate CRISPR’s risks

By IGHI guest blogger Chanice Henry, Editor, Pharma IQ & Pharma Logistics IQ

Similar to new Hollywood feature Rampage, a recent study has urged the life sciences industry not to underestimate the dangers that could hide within CRISPR Cas9.

Although the film has been criticised for wildly exaggerating the capabilities of the gene editing technique, it can be recognised for its effort to draw focus from the excitable buzz around CRISPR Cas9 towards the importance of considering the ethics and dangers associated with the tool.

A recent commentary piece also emphasised the importance of methodically debating the potential outcomes of CRISPR within the task of tackling Malaria.

Malaria is spread by the bite of female mosquitos holding the Plasmodium parasite. Plasmodium falciparum causes life threatening malaria.

Advances made so far

In the five years to 2015, 17 countries managed to eradicate malaria –including the likes of Senegal and Bolivia. In this period, mortality fell by 50% and incidences fell by 15% – preventing over 6 million deaths.

The World Health Organisation (WHO) recently launched “the world’s first malaria vaccine that has been shown to provide partial protection against malaria in young children.”  After establishing efficacy in Phase 3 clinical trials a vaccine implementation programme is due to commence within this year’s immunization projects in Ghana, Kenya and Malawi.

A long way to go

Government spend on malaria prevention has seen a dramatic increase over the past decade. Although, experts note that around $6.5 billion of funding by 2020 will be key to hitting the WHO’s 2030 goal to wipe out malaria in 35 countries and shrink incidents and deaths by 90%.

Statistics claim that malaria still kills one child every two minutes.

Sub-Saharan Africa, as noted by Tanvi Nagpal, housed around 80% of the world’s malaria cases in 2016. “Their high infection rates are compounded by insufficient domestic budgets and struggling health systems.”Reports recently emerged stating of one in four blood banks in certain areas of Sub-Saharan Africa host supplies infected with malaria causing parasites.

CRISPR Cas9  

Researchers are now turning to CRISPR Cas9 to stop the disease at the source of transmission – the mosquito.

What is CRISPR?

The genome-editing system based on CRISPR-Cas9 is becoming a valuable tool for different applications in biomedical research, drug discovery and human gene therapy by gene repair and gene disruption, gene disruption of viral sequences and programmable RNA targeting.  The tool permanently manipulates gene expression by using programmable DNA nuclease and can remove faulty genes from a DNA sequence. (more…)

Discovering the medicines of tomorrow: Four lessons from failed Alzheimer’s research

By guest blogger Chanice Henry, Editor, Pharma IQ

Even though drug development for Alzheimer’s Disease has a steep failure rate, the lessons learned from failed trials are of great benefit to future research.

Alzheimer’s is the most common form of dementia – the irreversible loss of memory and other cognitive functions which eventually makes daily tasks unmanageable.

As the life expectancy of the world’s population grows, the Alzheimer’s is becoming more common. Estimates suggest that  the number of affected US patients will climb from 5.3 million to almost 14 million by 2050.

In the fight against this disease many have dedicated their careers to revolutionise how the neurodegenerative disease is diagnosed and handled. Recent studies have created artificial intelligence that can identify the presence of Alzheimer’s two years before a doctor.

Progression has been made in the understanding of this progressive brain cell failure with “..promising targets for next-generation drug therapies under investigation in current research studies” according to the Alzheimer’s association.

However, the failure rates are high when it comes to creating new medical treatments to stop, slow or prevent Alzheimer’s. Between 2002 to 2012 there was a reported 99.6% failure rate within drug discovery for this condition.

Jeffrey Cummings notes that researchers have a duty to make sure that both the physical and financial efforts behind these failed trials are not in vain as they have a lot to contribute in the battle against Alzheimer’s.

Some key lessons from failed trials to incorporate into today’s R&D pipelines:

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Animal testing has long played a key role in the development of drugs and the understanding of how diseases function. However, animal models also have critical translation issues when results are compared to human trials. (more…)

Combining diverse expertise – Imperial College Network of Excellence in Malaria

By Dr Aubrey Cunnington, Clinical Senior Lecturer in Paediatric Infectious Diseases and Dr Jake BaumReader in Parasite Cell Biology, Faculty of Natural SciencesDepartment of Life Sciences, Imperial College London 

WHO/S. Hollyman

World Malaria Day is a good time to reflect on successes in the fight against malaria and the enormous challenges that still lie ahead. Malaria is a mosquito-transmitted parasitic disease, which causes illness ranging from severe flu-like symptoms to coma and death. Those at greatest risk are small children and pregnant women. It is an ancient enemy of mankind, and has exerted a powerful influence on our evolution. Malaria is a cunning foe, the parasites stay one step ahead of our immune systems allowing repeated infections to occur and they have a great capacity to develop resistance to antimalarial drugs.

(more…)

Malaria in 2017 – “It is too soon to be complacent”

By Professor Kathryn MaitlandProfessor of Tropical Paediatric Infectious Diseases, Director of Centre for African Research and Engagement, Imperial College London 

MosquitoApproximately 1200 African children are estimated to die from malaria every day, accounting for the vast majority of the global deaths from this disease. Over the past decade there has been an unprecedented increase in funding for malaria-control activities and vaccine development – the two major tools in ‘Roll back Malaria’ prevention and elimination programme. This has resulted in major scaling-up in the distribution of bed nets treated with long-lasting insecticides and public-private funding for late phase multi-site trials of the most promising anti-malaria vaccine candidate developed to date (RTS,S).

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Engaging with a public engagement project: Understanding TB from the experiences of the ill

By Bianca Masuku, Eh!woza

Students on a shoot day, interviewing a local resident in the neighbourhood of Nkanini.

Eh!woza is an evolving public engagement project focused on two infectious diseases (HIV and TB) that continue to burden communities within South Africa. The initiative is based at the recently awarded Wellcome Centre for Infectious Disease Research in Africa, and the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town. Previously described on this blog, this piece provides insights into an anthropological investigation of the work of Eh!woza, as well as the personal and lived experiences of persons affected by TB throughout South African communities.

(more…)

Tuberculosis in England: How research at Imperial is supporting the national strategy

By Dr Luis C. Berrocal-Almanza, Research Associate- Epidemiologist and Dr Alice Halliday, Research Associate, Imperial College London

World TB Day on 24 March commemorates the announcement by Dr Robert Koch in 1882 of his discovery of Mycobacterium tuberculosis (Mtb) as the cause of tuberculosis (TB), a disease that still affects approximately 10 million people and causes 1.8 million death globally each year. The Royal Society of Medicine commemorates this day with an annual TB meeting to review the most relevant advances in clinical, public health and scientific aspects of TB, organised by Professor Ajit Lalvani of the National Heart & Lung Institute, Imperial College London.

(more…)