Key biological pathway reveals insights into long COVID brain fog

Researchers from UNSW Sydney and St. Vincent’s Hospital have identified a key pathway, involved in inflammation, which appears to be activated in people with long COVID who have symptoms of ‘brain fog’.

Patients who took part in this study had mild to moderate acute COVID-19 and were enrolled in the St Vincent’s COVID-19 ADAPT study, a longitudinal study led by Professor Gail Matthews.

“Together, this study and a previous study in the ADAPT program show that long COVID brain fog is associated with a dysregulation of the immune response,” says Associate Professor Lucette Cysique, lead author of the study. “The current study specifically found that an important metabolic pathway – the kynurenine pathway – is linked to the cognitive changes we’re seeing in this group of patients.”

The study, published in Annals of Clinical and Translational Neurology, helps demonstrate that there is a biological change underlying brain fog in people who have long COVID as a result of mild acute COVID-19 infection.

“I think when patients go to the doctor’s with brain fog, it may be dismissed as a psychological problem. Our study speaks to the contrary, that there is a real biological mechanism behind long COVID brain fog,” A/Prof. Cysique says.

The discovery opens up possibilities for identifying and treating people who are experiencing the cognitive effects of long COVID and perhaps long COVID in general. “These findings lay the foundation for the kynurenine pathway as a potential diagnostic and monitoring marker, as well as a possible therapeutic target,” A/Prof. Cysique says.

Significantly, no other blood biomarkers, sex, or clinical factors – such as pre-existing or COVID-associated mental health, disease severity or respiratory function, and olfaction – were associated with cognition.

In April 2023, the government announced new research funding for long COVID as a result of the long COVID parliamentary enquiry. It shows that the government recognises long COVID as a serious issue that demands urgent solutions.

This study has opened the door for further research into potential biomarkers and future therapies for those living with long COVID. “The long COVID clinics are still full of patients and the hospitals are still struggling with the issue,” says A/Prof. Cysique. “We hope that our study can provide some hope to people who are suffering from long COVID.”

The team are keen to continue building on their research by extending the study cohort to vaccinated patients and to continue the investigation up to 24 months after the infection date.