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Dr. Corinna Fiorotti
Posted by Dr. Corinna Fiorotti BioAgilytix Insight, Industry Update, Viruses

An Update on the Latest Science & Thinking on COVID-19 Testing

An Update on the Latest Science & Thinking on COVID-19 Testing

Since the official declaration of the COVID-19 pandemic in March, laboratory testing for the SARS-CoV-2 virus causing COVID-19 infection has been evolving rapidly. Methods that detect the presence of the virus and methods that detect antibodies produced in response to the infection are both needed to understand the true scope of the pandemic and to better forecast its course. Tracking infection and recovery through serological testing is particularly important because it is suspected that anywhere from 20% to 80% of those infected with COVID-19 are asymptomatic. Therefore, it is still unknown how widely the virus has spread, and identifying these undetected cases will help us to properly calibrate public health interventions.

The need for universal testing on a worldwide scale has led to a race for technology innovations for COVID-19 diagnostics – some of which are proving to be more accurate than others. In my recent webinar discussing the latest science and thinking on COVID-19 testing, I delved into the recent updates and advancements in both molecular and serological testing for the virus to improve quality, accuracy, and our ability to test a wider population. Below are some of the highlights of that discussion:

Understanding the Protein Composition of SARS-CoV-2
Coronaviruses are a large family of single-stranded RNA viruses that have a lipid envelope studded with club-shaped projections. They are of zoonotic origin and infect a wide variety of animals but of the four main genre of coronoaviruses (alpha, beta, delta, and gamma) only alpha and beta are known to be transmittable to humans. The SARS-CoV-2 virus, which causes the COVID-19 infection, belongs to the beta coronavirus genus and is comprised of four structural proteins: the nucleocapsid protein (NP), which holds the RNA genome, the spike protein (SP), the envelope protein (EP), and the membrane protein (MP) which together create the viral envelope.

The SP consists of two subnits, S1 and S2. S1 contains the receptor binding domain which is responsible for binding with the host cell receptor, ACE2, which is highly expressed on respiratory epithelial cells found in the lower respiratory tract. The SP is also the target of treatment options and vaccine endeavors because it is highly immunogenic and stimulates the production of high levels of neutralizing antibodies which are suspected to be protective to the virus. The SP as well as the NP appear to be important antigenic sites and thus have been utilized for the development of serological assays to detect COVID-19.

Rapid Development of Molecular and Serological Assays for COVID-19
The emergence of COVID-19 has brought with it very rapid development of testing solutions. Currently the gold standard test for active, acute phase of COVID-19 infection uses real-time PCR (RT-PCR) to detect the virus’ RNA genome. Most molecular tests rely on the detection of the EP, NP, SP, and RNA-dependent RNA polymerase gene. There is variation in the viral incubation time, with reports averaging 5-6 days and showing that viral load rapidly declines at about 9 days after disease onset. As the virus is cleared from the body, viral RNA is no longer available for detection, so RT-PCR may not be helpful much after the infection period. It also gives no indication of whether a patient has had the infection historically.

That is why serology tests have been designed to identify individuals that have already been infected and have recovered from COVID-19, including those that are asymptomatic and have developed an immune response. While not a diagnostic for acute illness, this testing can be useful to characterize immune response to the virus in a detailed, qualitative, and semi-quantitative manner. Measuring IgA, IgM, and IgG antibodies against SARS-CoV-2 and their relative levels can indicate the stage of COVID-19 infection. Detection of IgA and IgM antibodies tend to indicate a recent exposure to SARS-CoV-2, while detection of IgG antibodies indicates that exposure was some time ago. Studies have shown that using serological assays alongside molecular testing can significantly improve the accuracy of COVID-19 diagnosis by reducing false negative results and increasing positive detection.

It is important to note that the presence of IgG antibodies does not automatically equate to protective immunity against re-infection. Individuals infected with coronaviruses typically mount neutralizing antibodies, which might be associated with some level of protection for a determined period of time. Though antibody tests could be useful in determining whether a person has had COVID-19 and could now be immune to the coronavirus, it is still not clear if people gain complete immunity and if they do, how long they remain immune.

Updates on Regulatory Parameters Set Forth by the FDA
In an early effort to balance the urgent need for COVID-19 testing availability with testing accuracy, the FDA issued guidance in March that enabled companies to begin selling commercial antibody tests as long as they notified the agency of their plans and provided disclaimers including that they were not FDA approved. This resulted in a plethora of tests emerging almost overnight, with many providing unreliable results and accuracy issues that could lead to devastating public health outcomes. On May 4th the FDA revised its initial policy so that all serology tests will now require FDA authorization – even those already on the market.

As of June 11th , the FDA has granted Emergency Use Authorization (EUA) to 100 in vitro diagnostic (IVD) tests (77 molecular and 20 serological tests, 1 antigen detection, 1 home collection kit, and 1 immunoassay for IL-6) and 36 high complexity molecular-based laboratory developed tests (LDTs) for the detection and/or diagnosis of the virus causing COVID-19. IVDs made available under EUA have not undergone the same type of review as an FDA-approved or cleared IVD, and the EUA is in effect for the duration of the COVID-19 declaration which justifies the emergency use of IVDs, unless terminated or revoked. EUA is required for clinical application of SARS-CoV-2 molecular tests and serologic assays.

Where COVID-19 Testing is Heading Next
Concerns about testing capacity, including reagent shortages, have resulted in the CDC issuing guidance recommending testing be restricted to high-risk populations. However, with the demand for quicker tests in community settings growing, the market is moving toward point-of-care devices. Here sample collection type and timing is crucial to yielding accurate results and to enable testing efforts to scale. For example, the FDA recently authorized a molecular test from Rutgers Clinical Genomics Laboratory that uses saliva which can deliver results in approximately 24-48 hours. These tests have been shown to be as accurate as the swab-based tests and may help with the current shortage of testing swabs. Some companies have also created kits that allow individuals to swab themselves at home and then mail their sample to a laboratory for processing.

Overall, there have been tremendous advances in IVD assays for detection of SARS-CoV-2. With the unprecedented wave of research, data sharing, and open scientific collaboration happening to help us all understand, analyze, and track the spread of COVID-19, there is little doubt more progress will be rapidly made.

I invite you to watch the full webinar to hear more about these advancements and answers to additional questions you may have, such as: what platform technologies are being used for COVID-19 testing today, and how should results be interpreted?; how is antibody testing different from antigen testing?; how important is an antibody titer in the immune response test?; and other thoughtful questions asked by our audience during the session.

Thank you again to those that submitted your questions and to everyone who joined me for the live session. I welcome you to reach out with any additional inquiries or to discuss your COVID-19 testing needs and how BioAgilytix can support them.

Download the On-Demand Webinar

To access the full recording of the live webinar and Q&A session, click here.

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