Neeraja Venkateswaran and Roma Venkateswaran explain the importance of testing as a tool against COVID-19

An outbreak of 27 cases of atypical viral pneumonia was first reported on 31 December 2019, in Wuhan, China. On that day, the Avian Flu Diary blog noted that “while it may turn out to be something relatively innocuous, the dedicated newshounds at FluTrackers began posting numerous reports out of China…on an outbreak of an – as yet – unidentified viral pneumonia in Wuhan; the capital and largest city (pop. 11 million) in Hubei Province”

By the end of January 2020, the enormity of the current outbreak began to attract scrutiny. On 11 February, the World Health Organization (WHO) announced a name for the new coronavirus disease: COVID-19 (Coronavirus Disease, 2019). The virus causing the disease was named SARS-CoV-2 by the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses.

Declared a pandemic
COVID-19 was declared a pandemic by WHO on March 11. By then, the disease had spread to over 110 countries and territories around the world and there were more than 118,000 diagnosed cases. By 8 June 2020, COVID-19 had spread to at least 188 countries and had caused over 7 million infections and more than 405,000 deaths.
 

Testing to combat the spread
Until a vaccine or antiviral drugs become available, social control measures, diagnostic testing, and contact tracing will play a vital role in preventing the transmission of this disease.

While public behaviour modification is important, enforcement can be difficult in democratic societies, so researchers in various fields from around the world have underscored the importance of testing in containing the spread of COVID-19.

While there has been discussion and authorisation of antigen testing, the laboratory diagnosis of infection with SARS-CoV-2 in suspect cases currently relies upon using real-time polymerase chain reaction (PCR) methods to detect nucleic acids from viral RNA in nasopharyngeal, oropharyngeal, and throat swab samples.

Underscoring the importance of data sharing in this pandemic, the early availability of the complete ~30Kb genome of SARS-CoV-2 allowed nucleic acid tests to be quickly and widely created. In the United States, over 70 molecular tests have received emergency use authorisation from the Food and Drug Administration (FDA).
 

Acute phase
This acute phase testing is critical for understanding the current presence of the virus in a community, recommending behaviour modification such as isolation, and informing therapeutic approaches. However, low viral load, missing the viral replication window, or incorrect sampling may contribute to false-negative results for molecular testing.

Because of resource scarcity, molecular tests are often not performed on pre-symptomatic or asymptomatic subjects who may remain silent carriers of the disease, which can hinder efforts to contain the virus.
 
Antibody testing
As we enter the later phases of this pandemic, it is particularly important to understand susceptibility and transmission at the population level. Serological, or antibody, testing is essential for both diagnostic and surveillance studies.

A positive serology test indicates that an individual has previously been in question if this positive result demonstrates immunity to further infection, it is likely that the presence of antibodies lessens the chance of infection and transmission of COVID-19.

How serology works
How do serology tests work? When exposed to foreign or infectious agents (antigens) like SARS-CoV-2, the immune system usually makes antibodies to help the body fight off the invader. These antibodies, also known as immunoglobins, come in various types.

In the case of SARS-CoV-2, serology testing seeks to detect and measure antibodies called Immunoglobulin G (IgG) because they are more unique to this virus, unlike IgM and IgA which have yet to be established as a specific indicator of infection for SARS-CoV-2. While nucleic acid testing detects viral RNA directly, serology testing indirectly looks for SARS-CoV-2 by measuring the body’s reaction to infection.

Available tests
Several rapid serological tests based on lateral flow assay technology have recently become commercially available, only some of which are extensively validated. There are also only a few validated laboratory-based assays currently available.

These ELISA-based tests analyse IgG antibody response to a single antigen, or antibody-inducing part, of SARS-CoV-2. There is a building body of evidence now suggesting that sensitivity and specificity of human IgG detection after SARS-CoV-2 infection can be improved by assessing antibody response to more than one antigen target.

FleximmArray
Tetracore have developed and commercialized the FlexImmArray SARS-CoV-2 Human IgG Antibody test. This is a multiplex test for detecting human IgG antibodies to three different antigens of SARS-CoV-2 in human plasma and serum samples.

These antigens include the spike and nucleocapsid proteins of the virus, which are known to be highly immunogenic, meaning that the body usually produces high levels of antibodies when exposed to these antigens.

This test has shown 100% specificity in a study of about 1,000 samples. The high specificity is attributed to the use of three unique antigens, as antibodies to all three antigens must be detected for the sample to test positive.

High specificity
High specificity of serology testing is especially important in the case of SARS-CoV-2. This is because the chance that an individual positive test result is true, known as the positive predictive value, is dependent on both the specificity of the test and the prevalence of the disease in the population.

If a positive serology test result is to be used as a sign of individual protection, as has been discussed in countries like Germany and in contexts like healthcare workers, then the positive predictive value of the test must be as high as possible. Especially when disease prevalence is low, a highly specific result is necessary to provide a high positive predictive value.

Vital roles of testing
At an individual level, serologic tests generally should not be used to signify protection, but are used to support the diagnosis of COVID-19, identify donors for therapeutic uses of convalescent plasma, and investigate efficacy and the need for boosters in vaccine development studies.

At the population level, antibody tests can help map the disease’s seroprevalence, contribute to research about the relationship between antibody presence and immunity to the virus, and provide data to policy makers about the risks of business and community reopening.

There is not one magic bullet to stop this pandemic. We must continue to observe social and behavioural control measures both at individual and community levels. New antiviral drugs will be useful in providing relief to the infected and vaccines will help prevent infection.

Testing and contact tracing will widely help in containment and early diagnosis of a local outbreak and aid in the mitigation of transmission. Applying these efforts in conjunction can successfully bring an end to the COVID-19 pandemic.

Tetracore laboratories are working tirelessly to develop assays for high throughput testing for serology.

©Tetracore, Inc