The changing landscape of COVID-19 testing – the potential of T-cell response monitoring

The efforts to manage the pandemic have led to an unprecedented technological development culminating in the largest vaccination campaign in history.¹ The World Health Organization (WHO) has granted emergency use listing for 11 vaccines² and over 13 billion doses have been administered globally.³ In its first year, the vaccination campaign was estimated to have saved around 20 million lives.⁴ Furthermore, hundreds of diagnostic tests, including antibody, antigen and polymerase chain reaction (PCR) tests, were developed in record time.⁵  

While it is generally believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)  will become endemic and vaccines will provide protection from severe disease and death, a lot of uncertainty remains. First, predicting the evolutionary course of SARS-CoV-2 variants is exceedingly difficult due to the overlayed complexity of pre-existing immunity.⁶ Second, our understanding of the innate and adaptive immunologic mechanisms associated with coronavirus disease 2019 (COVID-19) is still incomplete.^7,8 COVID-19 is here to stay, and there will still be an ongoing need for new treatments and diagnostics.

Patient-centricity – a hallmark of COVID-19 management in the future

Understanding of the immunologic responses in these populations at risk for severe COVID-19 is central to making better informed decisions on COVID-19 management, in the context of regular clinical care and could be ascertained by development of new testing strategies. 

As the COVID-19 pandemic transitions to endemicity, understanding of the immunologic mechanisms underlying SARS-CoV-2 immunity in patients at high risk of severe COVID-19 becomes increasingly important (data as of February 17, 2023).^{1,3‑5,9‑11}

A holistic understanding of immunity against COVID-19 is key

The immune system provides protection from countless pathogens that are constantly evolving. B and T lymphocytes are the two major pillars of the adaptive immune response [Video].

Although vaccination reduces SARS-CoV-2 infection-related morbidity and mortality, emerging variants may have decreased susceptibility to antibody-mediated neutralization.^13,14 As SARS-CoV-2 is likely to continue evolving, we must use every tool at our disposal to enable normal social functioning while protecting individuals from severe disease and death. To accomplish this goal, a comprehensive understanding of the adaptive immune response to SARS-CoV-2 is needed.¹³ This understanding could be facilitated by development of new COVID-19 diagnostic tools for routine use (Figure 1). 

During COVID-19 vaccine development the role of neutralising antibodies (nAbs) has been a major focus and less emphasis has been applied on understanding the role of T cells, memory B cells, and non-nAbs that may confer protection^.13 As both humoral and cellular immunity collaborate for pathogen control, the development of a holistic understanding of the host response to pathogens like SARS-CoV-2 requires assessment of both antibodies and T cells.¹³

T-cell responses are less likely to be affected by virus variants. T-cell epitopes are derived from many viral antigens, including those that are under less selection pressure, while nAbs are predominantly targeting the spike protein. The spike protein shows a high number of mutations in emerging variants. T-cell responses are not only directed against spike but also the membrane, nucleocapsid, as well as non-structural proteins. In fact, >90% of CD4 + and CD8 + epitopes are 100% conserved across variants (including Omicron), and T cells of exposed donors or vaccinees effectively recognize SARS-CoV-2 variants (including Omicron).^22-25

The Elecsys^® IGRA SARS‑CoV‑2 assay for measurement of the T cell response complements Roche’s broad portfolio of COVID‑19 diagnostics

Elecsys^® IGRA SARS-CoV-2 is an immunoassay for the qualitative detection of the T cell-mediated immune response to SARS-CoV-2. The assay is based on the ability of antigen-specific T cells to produce the pro-inflammatory cytokine IFN‑γ after encountering the antigen, which is a well-established marker of T-cell activation.¹³ IFN‑γ release assays (IGRA) employing similar principles have proven useful in tuberculosis where the Mycobacterium tuberculosis–specific IGRA test has replaced the previously used tuberculin skin test.¹³ The Elecsys^® IGRA SARS-CoV-2 assay is intended as an aid in identifying individuals with an adaptive T cell response to SARS‑CoV‑2, indicative of past exposure to the virus or COVID-19 vaccination. It provides valuable information on the T cell responses of the patient, enabling the healthcare provider to make better informed decisions for patient care.

The assay uses a two-phased method to determine T cell immune response to SARS‑CoV‑2.

The Elecsys^® IGRA SARS-CoV-2 assay simplifies the determination of the cellular immune response to SARS-CoV-2 by automating a crucial part of the testing workflow.

It provides the physician with valuable information on the T-cell responses of their patients and can help inform clinical decisions in the next phase of the COVID-19 era. A better understanding of the holistic adaptive immune response in SARS-CoV-2-infected or -vaccinated individuals, and particularly the role played by T cells, will help future-proof our strategies against COVID-19. However, definitive verification for the protective role of T cells requires further research.¹³

Roche’s comprehensive response to the COVID-19 pandemic