Can I test for COVID-19 T-cells? Yes, you can.

In this article we bring you a summary of what we know about the immune response to SARS-CoV-2 and updated information on the latest T-Spot.COVID Test including a break-down overview of what is T-Spot technology, when to use a T-Spot Test, its accuracy, and how soon after infection and vaccination it is effective to take one.

What do we know about the immune response to COVID-19?

SARS-CoV-2 stands for Severe Acute Respiratory Syndrome Coronavirus 2. This is the virus that causes COVID-19, which as we know was first discovered in Wuhan, China in December of 2019 and declared a pandemic by the World Health Organization in March 2020.

COVID-19 is the contagious disease caused by the SARS-CoV-2 virus and continues to cause a varying degree of symptoms from mild to severe including difficulty breathing, pneumonia and sadly has resulted in hundreds of thousands of deaths globally. On the other end of the spectrum, some infected individuals suffer no symptoms at all and are therefore referred to as asymptomatic to the infection.

As the pandemic has progressed, different variants (mutations from the original SARS-CoV-2 infection) have also been discovered and the range of predominant mild and moderate symptoms has likewise changed from a dry, persistent cough and loss of smell and/or taste to a runny nose, sore throat, headache, and fever. These are also the current leading symptoms associated with the Delta variants. In terms of the immune response, the majority of people infected with COVID-19 generally develop a T cell and an antibody response against the virus within several weeks after initial exposure.

Why are T Cells important?

Our body has between 25 million and 1 billion T cells, which form an important part of the immune system. T cells do not attack general antigens but rather focus on specific foreign particles and circulate until they confront the specific foreign particle they are meant to attack.

T Cells produce a cellular-level immune response (which does not require existing antibodies) where Helper T cells – essential for all adaptive immune responses and, as the name suggests, helpers of other cells of the immune system – coordinate immune responses and activate B cells (or lymphocytes, one of the most important cells in the body that fight bacteria and viruses in response to a signal from a Helper T Cell) to form and release the proteins we know and refer to as antibodies, while Cytotoxic T cells kill virally infected host cells infected by the SARS-CoV-2 virus causing COVID-19. Antibodies attach to antigens and can also inhibit movement or stop some viruses from forming essential proteins.

What is the current situation regarding SARS-CoV-2 antibody testing?

Molecular and antigen tests are the primary testing methods used to confirm if someone is currently infected with COVID-19, as well as serology (antibody) testing that can highlight if there was a previous infection. Whilst useful in detecting the presence of a current and previous infection, these methods also have some limitations which might prevent giving a complete overview of someone’s immune response to COVID-19.

Antibody tests are helpful in revealing if someone has had an infection or a successful immune response to vaccination (Roche quantitative testing is the recommended test for vaccination response), though research indicates that antibody levels diminish or disappear over time. There is also evidence that some infected patients do not produce detectable levels of antibodies against COVID-19 so the use of antibody testing alone may not give the full picture of the incidence of the virus across populations.

In other words, you may be pretty sure that you had a previous infection for COVID-19 but either tested negative on PCR at the time, testing wasn’t available at that time or your antibody test came back negative. You may also have had the COVID-19 vaccine and tested negative for antibodies.

Understanding cell-mediated immunity may help to better understand the immune response to COVID-19 especially in individuals who do not produce a measurable antibody response, or whose antibody responses have decreased or disappeared over time. This testing method is called the T-Spot.COVID test.

What is a T-Spot.COVID test and how does the T-SPOT technology work?

The T-SPOT.COVID test has been developed using the standardised T-SPOT^® technology testing platform. It is important to note that the T-SPOT.COVID test’s function is to detect a T cell response to the infection and not to diagnose a current COVID-19 infection. As mentioned earlier, the test is intended to identify patients who generate an immune response to the infection even if their serological test is negative.

The T cell response to the virus is generally measured in the blood a few days after initial infection – current estimates being one week from onset of symptoms – with data from a US clinical study of the T-SPOT.COVID test showing 100% agreement with previous positive PCR Swab Test results at 7-14 days (in all 4 samples tested) and 0-6 days (in the one sample tested) after a PCR positive test.

However, precise timing remains to be confirmed.

In terms of the technology itself, the Oxford Immunotec’s T-SPOT technology is based on the established ELISPOT assay method for measuring cells with regulatory approval in over 50 countries including the UK, EU, US, China and Japan and with more than 20 million tests using T-SPOT technology shipped worldwide to-date.

The technology ensures this is the most sensitive and specific test for measuring T cells as the test works by washing, counting, and normalising cell numbers (to create what is known as a cell suspension), which means it standardises the number of cells and removes serum factors (the fluid component of blood that includes all proteins not used in blood clotting) that could unfavourably impact results. To do so, a blood sample is collected by routine phlebotomy then used to collect and isolate a specific subset of white blood cells.

A standard number of these cells are then added in specifically designed plates and stimulated with the specific antigen under study – in this case, the SARS-CoV-2 virus – with cells that respond to the antigen releasing a chemical messenger known as cytokine. Cytokines are a group of proteins, peptides, and glycoproteins secreted by specific sells of the immune system.

The cytokine antibodies released during the test are used to encapsulate the cytokine as it is released by the cells with a secondary labelled antibody also then added to bind the captured cytokine. In addition, a detection reagent is also included which reacts with the secondary labelled antibody in a response that produces spots akin to footprints of where the cytokine was released. These spots are then numbered and counted.

The T-SPOT.COVID test is CE marked and has been submitted to the FDA for Emergency use authorization.

What is the test’s accuracy?

The data from the previously mentioned US clinical study shows an average percent positive agreement between the T-SPOT.COVID test and PCR testing of 96.6 % (84/87) at <60 days after positive PCR result, and 83.3% (40/48) at >60 days after a positive PCR result. A group of patients residing in an endemic region presumed negative (defined as low risk of infection and no previous positive results to PCR testing) showed an overall negative agreement of 98.0 % (98/100)¹.

What does this mean?

A positive test result indicates that the individual tested has T Cells that are reactive to the afore-mentioned peptides specific to SARS-CoV-2 used in the T-SPOT.COVID test, which in turn indicates they are highly likely to have been exposed to the virus. As you have probably and correctly gathered, a negative result means the opposite and therefore the unlikelihood of having been exposed to the virus.

It is worth noting that the only way to understand the full immune response to COVID-19 is to test for both antibodies and T Cells.

Reference

1. T-SPOT.COVID package insert – PI-T-SPOT.COVID-IVD-UK-V3