New Insights Into T Cell Exhaustion and Inflammation in Long COVID

In this Pharmaceutical Executive video interview, Nigel McCracken, chief operating officer, Virax Biolabs, discusses results from new data on the role of T cell dysfunction in post-acute infection syndromes (PAIS) at the World Immune Regulatory Conference in Switzerland. These syndromes are characterized by persistent, often debilitating symptoms that linger long after the initial infection has resolved. With growing recognition of the immune system’s role in driving these conditions, Virax's research focused on identifying biomarkers of immune exhaustion to better understand and potentially diagnose PAIS.

Pharmaceutical Executive: What implications do these findings have for the development of new diagnostic tools for conditions like long COVID, ME/CFS, and chronic Lyme disease?

Nigel McCracken: T cell exhaustion is well known to correlate with reduced cytokine production. Cytokines—key signaling molecules in the immune system—play various roles, including regulating or promoting immune responses. Some cytokines are regulatory and help dampen immune activity, while others are pro-inflammatory.

When we analyze patient samples from individuals with post-acute infection syndromes, such as long COVID, we observe significant differences in cytokine levels—particularly those involved in immune regulation and inflammation—compared to healthy volunteers without these symptoms.

Full Interview Summary: At the recent World Immune Regulatory Conference in Switzerland, Virax Biolabs presented pivotal findings on T cell dysfunction in post-acute infection syndromes (PAIS), such as long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and chronic Lyme disease. The team explored how persistent immune activation post-infection leads to T cell exhaustion, a phenomenon well-documented in oncology but now increasingly relevant in chronic infectious conditions. Their study demonstrated that prolonged antigen stimulation in vitro caused upregulation of key exhaustion markers—PD-1, LAG-3, TIM-3, TIGIT, and CD39—on both CD4+ and CD8+ T cells. These markers were associated with impaired cytokine production, helping to distinguish individuals with PAIS from healthy controls.

Virax’s post-acute assay, under development, measures T cell cytokine responses after stimulation with peptides derived from various viruses, including SARS-CoV-2 and latent viruses like herpes. This dual-layered approach allows for detection of general immune dysfunction and identification of specific viral triggers. Importantly, it highlights how chronic antigen exposure can leave the immune system in a prolonged inflammatory state, unable to fully clear infections or return to baseline.

Beyond PAIS, Virax aims to extend its immune diagnostic platform into broader areas such as transplant medicine and oncology. In transplant patients, monitoring latent viral reactivation and immune competence could prevent complications like organ rejection. In oncology, particularly with CAR-T therapies, understanding immune status could inform dosing strategies and predict efficacy and safety. The company is pursuing collaborations with academic research centers in the UK and US, while engaging with the FDA on clinical study pathways. Virax Biolabs seeks to shorten diagnostic timelines, enable earlier interventions, and expand the scientific understanding of immune dysfunction across multiple disease states.