Simple New 10-Minute Test Accurately Detects COVID-19 Immunity

SMART researcher Hoi Lok Cheng (right) performs a rapid neutralizing antibody test on a lab prototype. He co-authored a new paper reporting the development of a 10-minute test to detect immunity against SARS-CoV-2, the virus that causes Covid-19. Credit: Photo Courtesy of SMART

Paper-based blood test developed by SMART researchers can quickly determine the presence of SARS-CoV-2 neutralizing antibodies.

Researchers have successfully developed a rapid point-of-care test for the detection of SARS-CoV-2 neutralizing antibodies (NAbs). This simple test, requiring just a drop of blood from a fingertip, can be performed in under 10 minutes without the need for a lab or specially trained personnel. Currently, there are no comparable NAb tests commercially available in Singapore or elsewhere.

The work was led by the interdisciplinary Antimicrobial Resistance (AMR) research group of the Singapore-MIT Alliance for Research and Technology (SMART) and Nanyang Technological University, Singapore (NTU Singapore), alongside collaborators from National University Hospital, MIT and the Center for Life Sciences and Yong Loo Lin School of Medicine at the National University of Singapore.

To contain the transmission of SARS-CoV-2, countries have imposed strict measures to minimize social interaction and cross-border movements. Although they have been able to improve surveillance and prevent spread to some extent, these measures have had a serious impact on the economy and livelihoods, and the road to return to normalcy includes achieving herd immunity against the virus, either naturally or by mass vaccination. To evaluate herd immunity and the effectiveness of vaccine immunization programs, it is essential to screen populations on a faster and larger scale for the presence of SARS-CoV-2 NAbs.

As part of a body’s natural immune response, NAbs are generated by exposure to the virus or a vaccine. For effective prevention of viral infections, NAbs must be generated in sufficient quantities. The number of NAbs present in individuals indicates whether they have protective immunity against the virus and how likely they are to suffer serious consequences if infected. NAb testing can determine whether vaccinated individuals should be considered for booster shots for added protection against the virus.

Despite the availability of several diagnostic tests for Covid-19, the detection of SARs-CoV-2 NAbs is still generally performed in hospitals and specialized diagnostic labs. Currently, NAbs are often detected using virus neutralization tests, which require the handling of a live virus, a facility with strict biosecurity and containment measures, skilled personnel and a processing time of two to four days. Thus, these assays are not viable for testing and monitoring of large populations due to the lengthy process that can strain existing laboratory capabilities. By developing a more efficient way of testing, it is possible to test immediately at the point of care and mass surveillance of events or workplaces, specific places, high traffic points and critical access points such as immigration checkpoints.

“With the gradual opening of borders, economies and societies, having the right test and information will be crucial to not only plan this future, but also to ensure that it can be done safely without the current efforts to contain the spread. of the virus,” said Megan McBee, MIT research affiliate and scientific director at SMART AMR.

According to the research team’s data, published in Nature Communications Medicine, the newly developed rapid cellulose pull-down viral neutralization assay (cpVNT) detects SARS-CoV-2 NAbs in plasma samples within 10 minutes, using a vertical stream of paper-based test format and protein technology developed at SMART AMR and the lab of associate professor Hadley D. Sikes in the MIT Department of Chemical Engineering. This same protein technology has also been used to develop tests to detect other known viruses, such as the Zika virus and tuberculosis. Cellulose was used as a test material because it is cost-effective and easy to manufacture, and to avoid reliance on nitrocellulose, which is in high demand for its use in other rapid Covid-19 tests.

The test developed is easy to administer, non-invasive and provides fast results. To perform the test, a user mixes a drop of blood from the fingertip with the reaction solutions and places it on a paper strip, before placing it in a portable reading device that detects the NAb signals and reflects the results. This test offers an accuracy of up to 93 percent, higher than comparable laboratory-based methods currently in use.

“Schools and workplaces will also benefit greatly from the test. Whether a person should be eligible to receive a booster vaccine can also be assessed with this rapid test, as results are available within minutes from a blood sample taken from a fingertip. And if we can quickly determine immunity on a larger scale, the review and relaxation of Covid-related measures can be done in a more controlled, data-driven way,” said Sikes, who is also a principal investigator at SMART AMR and a co-corresponding author of the paper.

Co-corresponding author Professor Peter Preiser, a co-lead principal investigator at SMART AMR and the associate vice president for biomedical and life sciences at NTU Singapore, says: “In addition to detecting immunity to the current vaccine version of the SARS-CoV-2 virus, The NAb test can be modified to check immunity to the other variants of the virus, which can provide information about the potential efficacy of different vaccines against each variant, or whether to travel to areas with a high incidence of a specific variant.”

Further development of the test is underway for regulatory approval and production for public use. The team that developed the tests at SMART also spawned a biotech startup, Thrixen, which is developing the test into a commercial turnkey product.

Reference: “A Rapid, Simple Point-of-Care Assay for the Detection of SARS-CoV-2 Neutralizing Antibodies” by Patthara Kongsuphol, Huan Jia, Hoi Lok Cheng, Yue Gu, Bhuvaneshwari D/O Shunmuganathan, Ming Wei Chen , Sing Mei Lim, Say Yong Ng, Paul Ananth Tambyah, Haziq Nasir, Xiaohong Gao, Dousabel Tay, Seunghyeon Kim, Rashi Gupta, Xinlei Qian, Mary M. Kozma, Kiren Purushotorman, Megan E. McBee, Paul A. MacAry, Hadley D. Sikes and Peter R. Preiser, November 11, 2021, Communication Medicine.
DOI: 10.1038/s43856-021-00045-9

The major development of the rapid test took place at SMART AMR and NTU’s School of Biological Sciences. The research conducted at SMART is supported by the National Research Foundation (NRF) Singapore as part of its Campus for Research Excellence And Technological Enterprise (CREATE) program. The work was also supported by the National Medical Research Council under the Covid-19 Research Fund and the National Health Innovation Center under the Covid-19 Gap funding.

SMART is MIT’s research enterprise in Singapore, founded by the NRF in 2007. SMART is the first entity in CREATE developed by the NRF. SMART serves as an intellectual and innovation center for research interactions between MIT and Singapore and conducts pioneering research projects in areas of interest to both Singapore and MIT. SMART currently consists of an innovation center and five interdisciplinary research groups: AMR, Critical Analytics for Manufacturing Personalized-Medicine, Disruptive and Sustainable Technologies for Agricultural Precision, Future Urban Mobility and Low Energy Electronic Systems.

The interdisciplinary research group AMR is a translational research and entrepreneurship program addressing the growing threat of antimicrobial resistance. Leveraging talent and convergent technologies in Singapore and MIT, they are tackling AMR head-on by developing multiple innovative and disruptive approaches to identify, respond to and treat drug-resistant microbial infections. Through strong scientific and clinical collaborations, their goal is to provide transformative, holistic solutions for Singapore and the world.