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The ASSURE® test kit detects antibodies produced by the human immune system in response to SARS-CoV-2 exposure in as little as 15 minutes.

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Assuring asymptomatic COVID-19 carriers are identified

6 Nov 2020

A*STAR researchers have developed a point-of-care rapid antibody test kit that can detect antibodies produced in response to SARS-CoV-2 infection in just fifteen minutes.

We’ve all heard the saying that early detection saves lives. It is why traditional public health strategies have relied on the speedy and accurate detection of diseases to contain their spread. But what happens when the disease you’re trying to control doesn’t allow for that? This is exactly the challenge presented by the COVID-19 pandemic.

Unlike the 2002-03 SARS epidemic, where the spread of the disease was brought under control due to its easily identifiable symptoms, things are not as straightforward with COVID-19. Researchers have had to contend with complications such as presymptomatic transmission, where people may be infectious before symptoms develop, as well as asymptomatic transmission, where people may infect others without ever developing symptoms at all.

These covert coronavirus carriers are a considerable concern, but thanks to A*STAR and MP Biomedicals, a new rapid antibody test kit may offer a way to identify them.


The case for antibody testing

The current gold standard for COVID-19 testing is the real-time reverse transcriptase polymerase chain reaction (RT-PCR) test, which screens for the presence of SARS-CoV-2 genetic material. Some RT-PCR test kits can take as little as 90 minutes to run, but the bottleneck for their overall speed and accuracy is their reliance on specialized resources such as equipment, reagents, trained personnel, and sample collection and preparation process. In light of this, there is a demand for easy-to-use test kits and devices that would allow for testing outside of laboratory settings. One such proposed strategy is antibody testing.

Antibodies are proteins produced by immune cells in response to foreign invaders like the SARS-CoV-2 virus. Even after the infection is cleared, these antibodies remain in the body to respond quickly if reinfection occurs. Antibody tests search for antibodies in blood or plasma, cutting down on the amount of time and work needed to amplify and detect viral genetic material that is the case in RT-PCR-based tests.

Furthermore, because they target antibodies that remain in the bloodstream long after recovery, antibody tests have proven valuable in contact tracing and retroactively discerning the links between cases in infection clusters, such as in the Grace Assembly of God cluster in Singapore. From this case, it is clear how a rapid antibody test kit can help identify those who have recovered from the virus but might still be contagious, even if they had been mildly symptomatic or completely asymptomatic.

Antibody tests also offer more information beyond past infections. They can assess the extent and length of COVID-19 infection in populations to provide valuable insight into viral epidemiology, or be used to screen donor blood for antibodies against SARS-CoV-2, and to identify those lacking antibodies as prime candidates for a potential vaccine.


The need for speed

A locally-developed test kit by A*STAR and diagnostic company MP Biomedicals Asia Pacific offers a truly fast and easy form of rapid antibody testing. Known as ASSURE®, the test kit can tell if someone has been previously exposed to SARS-CoV-2 in just 15 minutes and at a low cost. Moreover, ASSURE® is a point-of-care test kit, which means that the finger prick samples do not have to be processed in a laboratory and patients can receive their results almost immediately following the test.

ASSURE® looks for the presence of the Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies, which are produced by the immune system after viral exposure. To detect IgG and IgM, the kit development process was accelerated by using human monoclonal antibodies identified in March by a team of scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB), led by Associate Professor Yee-Joo Tan. Also, MP Biomedicals used proprietary synthetic SARS-CoV-2 proteins which could bind to the IgG and IgM antibodies if they are present in the sample and much like a pregnancy test, results are indicated by red lines in the result window of the test kit.

As a rapid antibody test, ASSURE® is not intended to accurately detect COVID-19 in the early acute phase of infection. Instead, by detecting the presence of the two different antibodies, ASSURE® can establish an estimated timeline of when the infection occurred. As IgG antibodies typically appear at later stages of infection, their presence in the test would indicate that the infection probably took place several weeks ago. In contrast, as IgM antibodies are produced by the body first, their presence could indicate a recent infection that most likely began less than 14 days ago. A repeat test can be done in the following week or two to confirm that IgM antibodies are no longer present.


The power of collaboration

Even more impressive than the speed and ease of how ASSURE® works is how fast it was assembled: the entire kit took MP Biomedicals about two months to develop from start to finish. Once the IMCB team identified the human monoclonal antibodies, MP Biomedicals then developed ASSURE® based on their lateral flow platform, while A*STAR’s Diagnostics Development (DxD) Hub co-developed the validation protocols and quality controls.

“The development was fast because of the close collaboration and trust between the different parties involved,” said Yongfeng Li, DxD Hub’s Chief Development Officer.

MP Biomedicals has a long history of developing rapid antibody tests for other diseases such as dengue and HIV, explained Li. Recognizing this, A*STAR and the National University Hospital (NUH) were quick to offer them support to adapt their rapid test platform for the fight against COVID-19.

Even so, ASSURE’s development wasn’t without its challenges. Li said that the urgency to launch the test kit in time, compounded by the shortage of clinical samples to optimize its performance were some of the stumbling blocks the teams had to overcome.

“As the project manager, DxD Hub had to pull together different component capabilities to assist in the development process,” Li said. “For example, we brought in IMCB to simulate the antibodies produced during COVID-19, which helped us to accelerate the optimization of the kit. We also helped by providing market intelligence and advice regarding verification and validation protocols, bringing in NUH to facilitate the clinical validation, and having Temasek Foundation help with scaling up local production and piloting its use in our local community.”

In these evaluations by NUH’s Department of Laboratory Medicine, ASSURE® demonstrated it could perform well with both serum and whole blood samples, with performance comparable to commercial tests. Now registered, ASSURE® has since been granted Provisional Authorization by the Health Sciences Authority and has been distributed to regions such as Europe, Africa and South America.

Asymptomatic transmission has been dubbed the Achilles heel of current strategies for controlling the spread of COVID-19. But with the insights they offer, rapid antibody tests like ASSURE® will be on hand to inform future public health interventions in a more cost-effective and user-friendly way.

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This article was made for A*STAR Research by Wildtype Media Group