Study sheds light on how virus-fighting cells develop during long COVID

A new long-term study into long COVID has investigated how a certain population of white blood cells, called memory T cells, are established and develop as part of the body’s defence to fight off the disease.

The study, led by researchers from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and published today in PNAS, found that despite the long COVID diagnosis, memory T cells that recognise SARS-CoV-2, the virus that causes COVID-19, can be established and maintain their ability to fight subsequent infections after two years.

T cells fight off viral infections by killing cells that are infected with the virus. They play a special role in the body’s immune defence system, in that they can remember their encounters with the virus and become long-term memory T cells for protection against subsequent infections, even when the virus mutates. 

Dr Louise Rowntree, a first author on the paper and Senior Research Fellow at the Doherty Institute, said the study included 31 people from Australia and Hong Kong with long COVID.

“In this study, we looked at memory T cells that can recognise SARS-CoV-2 in people with long COVID over a period of two years following SARS-CoV-2 infection and subsequent COVID-19 vaccination,” she said.

“We found that these SARS-CoV-2 memory T cells can be established and maintain key features over that period. Our findings are novel, as long-term T cell immunity in people with long COVID is understudied.”

The symptoms of long COVID are varied, and can include weakness, fatigue, impaired concentration and chest pain, and can last between 12 weeks to two years.

Dr Oanh Nguyen, Senior Research Fellow at the Doherty Institute, who co-led the study, said the recall of T cell memory is necessary for a more rapid recovery from COVID, and the establishment of these robust T cell responses is important for protection against subsequent infections of newer strains. 

“We know that long COVID is a rare disease following a COVID-19 infection, but it can hugely impact a person’s daily life, as well as substantially impacting the healthcare system,” she said.

“While research into underlying mechanisms is evolving, immunity is an area that remains understudied, and this is an important step in understanding how the body responds.”

Laureate Professor Peter Doherty, an author on the study, said this manuscript represents important research.

“Applying the lessons learned and technologies developed to study the cellular immune response in human influenza has allowed us to move fast on analysing this aspect of our immune response in COVID-19,” said Professor Doherty.

“That opens an important portal for understanding where we need to go with future therapies and vaccines.”

Additional information: 

• Peer review: Rowntree L.C., et al. SARS-CoV-2-specific CD8 T cells from people with long COVID establish and maintain effector phenotype and key TCR features over 2 years. PNAS (2024). DOI: https://doi.org/10.1073/pnas.2411428121

• Funding: This study was supported by NHMRC, APPRISE network for SETREP-ID, Snow Medical, Jack Ma Foundation, TRS RGC and MRFF.

• Collaboration: This study by Dr Louise Rowntree and Dr Jennifer Audsley was co-led by Laureate Professor Peter Doherty, Dr Irani Thevarajan, Associate Professor Sophie Valkenburg, Professor Katherine Kedzierska and Dr Oanh Nguyen, in collaboration with HKU-Pasteur Research Pole at The University of Hong Kong, The Chinese University of Hong Kong, Monash University, La Trobe University and Austin Health.

About the Peter Doherty Institute for Infection and Immunity

Finding solutions to prevent, treat and cure infectious diseases and understanding the complexities of the immune system requires innovative approaches and concentrated effort. This is why The University of Melbourne – a world leader in education, teaching and research excellence – and The Royal Melbourne Hospital – an internationally renowned institution providing outstanding care, treatment and medical research – have partnered to create the Peter Doherty Institute for Infection and Immunity (Doherty Institute); a centre of excellence where leading scientists and clinicians collaborate to improve human health globally.