Despite many questions remaining about the level and duration of protection that antibodies may provide against SARS-CoV-2 infection, there has been a surge in demand for tests that can detect these antibodies and identify individuals who have already been infected with the virus. Over the past few months, several such tests have been developed, providing researchers and public health experts with tools to conduct serosurveillance and track the spread of disease.

Technology Networks spoke to Jeff Hawkins, Dr Jerry Yeo, and Dr Abhijit Datta, to hear about one example – Truvian’s Easy Check COVID-19 IgM/IgG™ – which was recently granted FDA Emergency Use Authorization (EUA). We also learned about the importance of high sensitivity and specificity, and how the information provided by antibody tests can be used appropriately during the COVID-19 pandemic.

Anna MacDonald (AM): Can you give us an overview of serology and some of the advantages and limitations associated with the use of antibody tests?

Jeff Hawkins (JH): Serology is the study of blood in relation to the body’s immune response. Serology tests can detect the presence of antibodies made by our immune systems to fight certain infections, in this case antibodies (IgM and IgG) against the SARS-CoV-2 virus that causes COVID-19. Health experts stress the critical role of antibody testing in the fight against COVID-19.

Jerry Yeo (JY): Serology testing is a valuable tool for understanding SARS-CoV-2 exposure and necessary from a public health response perspective to estimate the number of people who have been infected in various regions and settings.

With respect to lateral flow technology, there is a great deal of potential to tap, being that it’s very practical, especially for deployment in off-site environments, or in countries where there is limited access to healthcare. The beauty is that it’s simple to use, stable, and no equipment is needed to run these systems. The technology is quickly deployable, and results are accurate, while significantly faster than with sophisticated technology.

Lab tests have three attributes that we look for: speed, cost and accuracy. Often, most tests only have two out of three, in any combination. Unfortunately, this has been common throughout this pandemic. Truvian’s Easy Check COVID-19 IgM/IgG™ antibody test was able to deliver on all three of these attributes.

In terms of limitations with testing, access – including availability and cost – has been an issue we continue to deal with on a global level. Affordable testing leads to more access, which results in a more empowered society. Lateral flow technology, for instance, is drastically more affordable than traditional laboratory tests run on larger analytical systems.

AM: Can you explain what the sensitivity and specificity of an antibody test is, and why these measures are so important?

JH: One way to explain sensitivity and specificity is:

— Sensitivity is when the antibodies are there, how often do you detect them?
— Specificity is when the antibodies are not there, how often do you correctly call the sample negative.

In looking at our data, with 98.4% sensitivity, we are going to detect those antibodies. And with 98.9% specificity, there is only a 1% chance that we detected something that wasn’t related to COVID-19.

The importance of high sensitivity and specificity is that there are few false negatives/positives, providing us more accurate data about a person’s exposure to SARS-CoV-2.

AM: Several antibody tests have received FDA EUA during the COVID-19 pandemic. How important do you think fast track processes such as this are? How can the risks of potentially subpar products reaching the public be minimized?

JH: The COVID-19 pandemic has shined a spotlight on the many issues with diagnostics in the U.S. and around the world. Inaccurate antibody testing has reminded us of the dire need to transform healthcare. This transformation must include the development of more reliable and scientifically backed serological tests, which are critical to ending any global health crisis.

Due to concerns regarding the accuracy of antibody tests, and in keeping in line with our own high standards, Truvian has taken the time to ensure performance criteria is met, and exceeded, by working with established leaders in the scientific and medical communities. In times of crisis, collaboration is key. Scientifically accurate, fast-result antibody testing available at scale is vital for reopening the nation without igniting a surge of cases. To support this cause, we have recently developed and received FDA EUA for our Easy Check COVID-19 IgM/IgG™ antibody test, which has been rigorously validated in multiple independent studies.

Consumers deserve better testing solutions and are demanding change. Now, it is our time as an industry to answer their call. I will argue that antibody tests need to be put through a more thorough validation process, screened by third party studies, and backed in reality; even at the expense of timely delivery and profits. I am committed to driving this transformation forward with credible, scientifically-viable solutions. It is becoming too common for companies and “bad actors” to rush out products that are not fully vetted, or are missing the rigorous scientific backing consumers both demand and need.

AM: While scientists work to learn more about the development and duration of human immunity to SARS-CoV-2, how can the information provided by antibody tests be used appropriately?   

Abhijit Datta (AD): Serology (antibody) tests do not detect the virus causing COVID-19 disease. They detect the human body’s response to an infection. As the body tries to fight infection, it produces IgM and IgG antibodies against the virus antigens. IgM are produced earlier than IgG and individual responses can vary by 14 days. It is generally understood that antibodies are produced and can last for weeks or months. This is an important consideration to understand that the timing of testing may impact results. When even a highly accurate antibody test is administered too early, post symptom onset (PSO), it will not be useful because the antibodies are not yet present.

It is assumed and studies in primates suggest a certain degree of immunity is conferred by the presence of antibodies; however, it is not known exactly how protective the antibodies are and how long they can last. A qualitative serology test to detect specific antibodies to SARS-Cov-2 infection, after sufficient days PSO, is thus useful to:

●       Add to the meaning of a positive genetic test by confirming the result or by flagging a false negative

●       Understand community spread of past infections in serosurveys that inform public health officials 

In special populations, such as skilled nursing facilities or meat plants or employees in a building, serosurveys allow health experts to compare the infection rates to larger community level rates for better return-to-work guidance. A second generation of antibody tests is in the pipeline that aims to determine the level of protection or immunity in the body by detecting neutralizing antibody levels.

The usefulness of the antibody test in serosurveys is limited by sensitivity, specificity and the prevalence rate. In communities where there is a very low infection rate of <1%, even highly sensitive and specific antibody tests are not going to be completely accurate which is reflected in the positive predictive value (PPV). However, in hot spots, with high infection rates, the PPV is higher and can significantly assist public health officials in making decisions.

AM: How else could antibody test results be used as part of the response to the COVID-19 pandemic?

JH: The medical community is trying to understand how long an individual’s immune response lasts. Does the duration of immune response relate to the severity of the infection? This is a question we can help answer if testing is available at scale and at low cost.

As blood donations from those who have been previously infected may be useful in treating people who are currently ill or may become ill with future outbreaks, we need to help our blood banks quickly identify people who are carriers of antibodies to COVID-19 and prioritize donations from those who are able.

While the scientific and medical communities are just beginning to scratch the surface on the utility and actionability of antibody testing for COVID-19, what we do know is that information is power, and devoid of data we are powerless. Truvian is joining the battle against this pandemic; leading with viable and thoroughly tested science to do our part in helping to bring the pandemic to an end.

AM: Can you tell us about Easy Check and some of the benefits it offers?

JH: The Easy Check COVID-19 IgM/IgG antibody test is a lateral flow immunochromatographic assay for detection of SARS-CoV-2 IgM/IgG antibodies in human blood specimens. This test differentiates IgM and IgG immunoglobins (antibodies) specific to SARS-CoV-2 in a single test, rapidly and affordably.

The test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. These insights can help individuals understand their exposure history and help people and companies evaluate risk factors when making crucial decisions about returning to work or participating in day-to-day activities without putting others at risk. Easy Check COVID-19 IgM/IgG antibody test provides significant benefits over traditional lab-based diagnostic technologies:

● Compact lateral flow device
● Fast and easy to use
● Exceeds the FDA’s standards and requirements
● Results you can trust: 98.4% Sensitivity, 98.9% Specificity
● Testing sponsored by the National Cancer Institute (NCI): 100% Sensitivity, 97.5% Specificity
● Cross Reactive Study: 0% cross-reactivity with 15 other infectious diseases including HIV and other coronaviruses
● Requires only a small sample (10uL of whole blood, serum or plasma)
● Obtain results at 10 minutes
● No ancillary equipment or training required
● Affordable economy of scale vs. expensive lab approaches with longer turnaround times
● Meet service level needs

AM: The test differentiates IgM and IgG immunoglobins. Why is this important?

JH: With respect to IgM/IgG immunoglobins and their importance, the SARS-CoV-2 infection elicits development of IgM and IgG antibodies, which are the most useful for assessing antibody response. In SARS-CoV-2 infections, IgM and IgG antibodies can arise nearly simultaneously in serum within 2 to 3 weeks after illness onset.

Present IgM antibodies indicate that a patient has an active or recent infection with SARS-CoV-2. IgG antibodies develop later following infection, and generally do not begin to appear until seven to ten days after infection. When IgG antibodies are present, it often indicates a past infection but does not exclude recently infected patients who are still contagious, especially if detected with IgM antibodies. The importance of lgG and lgM testing is to minimize the likelihood of false positive test results.

Jeff Hawkins and Drs Abhijit Datta and Jerry Yeo were speaking to Anna MacDonald, Science Writer, Technology Networks.

Jeff Hawkins is President and Chief Executive Officer, Truvian.
Dr Abhijit Datta, PhD, is a Scientist, Medical Device Executive and Advisor to Truvian.
Dr Jerry Yeo, PhD, DABCC, FAACC is Professor of Pathology and Medical Director of Clinical Chemistry at the University of Chicago. He conducted a number of studies with Truvian’s Easy Check COVID-19 IgM/IgG test that were designed to evaluate the performance, including clinical sensitivity, clinical specificity, and cross-reactivity of the test.