There is a potential to utilize T-cell diagnostics to diagnose the underlying post-viral syndromes by initially measuring the bodies adaptive immune resistance as well as monitoring the potential progression of an individual’s T-cell function following chronic antigen stimulation.

By Nigel McCracken, MSc, PhD

Post-viral syndromes are a wide range of complex conditions involving physical, cognitive, emotional, and neurological difficulties that vary in severity over time. These conditions frequently lead to a sense of tiredness and weakness, pain, difficulty concentrating, and headaches that linger after the viral infection has cleared. Symptoms may continue for weeks, months, or longer. Various microbial and viral infections are possible trigger factors for post-viral syndrome, including SARS-CoV-2, Epstein-Barr virus, cytomegalovirus, human herpes virus, enteroviruses, HPV, and Zika, among others.

The diagnosis of these conditions can be very difficult with sufferers often neglected by health care systems where they cannot identify a definitive diagnosis and treatment strategy.  The first point of diagnosis should be identifying that there is an issue and pinpointing the initial cause.  As an example, Long COVID represents a significant public health challenge in the post-COVID-19 era. Epidemiological studies indicate that 10-30% of individuals infected with SARS-CoV-2 experience persistent symptoms beyond the acute phase of the infection. These symptoms include:

  • Chronic fatigue
  • Cognitive dysfunction
  • Respiratory difficulties

These symptoms persistently affect patient health and quality of life. The heterogeneity of these symptoms complicates the diagnostic process, as they overlap with a range of other post-viral syndromes, posing a challenge to healthcare professionals.

Diagnosing Post-Viral Syndromes

The diagnostic tools currently available, primarily PCR and lateral flow tests, are optimized for acute viral infection detection and do not adequately address the chronic and complex nature of Long COVID. Consequently, many patients experience a diagnostic ambiguity, impacting their subsequent treatment and care. This challenge is exacerbated by the high prevalence of SARS-CoV-2 exposure, both through infection and vaccination, necessitating the development of diagnostic methods specifically tailored to Long COVID.

The exact reasons why people develop post-viral syndromes are still being studied and there is no definitive answer yet, but several factors are believed to play a role. These include problems with the immune system, including:

  • Ongoing chronic inflammation
  • Autoimmunity
  • Improper functioning of T-cells
  • The reactivation of viruses that were dormant in the body.

T-Cell Dysfunction

T-cell dysfunction is a broad term that has been used to describe the response of T-cells to chronic antigen stimulation and has been documented following numerous infections (HBV, HCV, SARS-CoV-2, ME, etc.). During an infection the virus enters cells and starts to multiply. The innate immune system initially generates antigen presenting cells which ingest the virus presenting fragments to components of the adaptive immune system which then stimulate other immune cells to fight the virus including specific cytokine producing T-cells that target and kill the affected cells. In some instances, chronic antigen stimulation causes the T-cells to still be active but function at lower levels to cause minimal damage to normal tissue. Over time this persistent stimulation of the T-cells causes a progressive exhaustion, which, without proper intervention, can further differentiate into a state of terminal exhaustion and dysfunction.

Unraveling T-Cell Dynamics for Post-Viral Syndromes

It has also been observed that after the immune system fights off a virus, the T-cells are sometimes significantly reduced in number. This decrease in T-cells can cause other viruses, especially those from the herpes family that were previously under control and dormant in the body, to become active again. When these viruses reactivate, they can turn into chronic infections, which lead to symptoms that tend to be much more severe than those experienced during the virus acute phase.

Low T-cell count or dysfunctional T-cells decreases the body’s ability to fight other pathogens and can even contribute to the reactivation of dormant viruses, which can lead to symptoms associated with post-viral syndromes through its effects on the cellular microenvironment, including oxidative stress and mitochondrial dysfunction.

Currently there are no diagnostics for the early detection of post-viral syndromes, including Long COVID. There is a potential to utilize T-cell diagnostics to diagnose the underlying post-viral syndromes by initially measuring the bodies adaptive immune resistance as well as monitoring the potential progression of an individual’s T-cell function following chronic antigen stimulation.

ABOUT THE AUTHOR

Nigel McCracken, MSc, PhD, is COO of Virax Biolabs.