Elevated tau in Long COVID patients raises risk for neurodegenerative diseases

A study of 227 individuals who experienced neuro cognitive difficulties post COVID-19 infection – such as headaches, vertigo, balance dysregulation, changes in taste/smell, and brain fog – displayed a significant increase in their blood plasma of a crucial protein called tau, which is found in nerves and especially in the brain. Excess levels of tau are linked to neurodegenerative diseases and found in many Alzheimer's patients.

Published this month in eBioMedicine, the study suggests that people who experience Long COVID neurocognitive symptoms could be at further risk for neurodegenerative diseases.

The research involves ongoing blood biomarker studies of 9/11 World Trade Center (WTC) responders who are monitored by clinicians and researchers at the Stony Brook WTC Health and Wellness Program. The research team analyzed plasma samples taken prior to the participants' COVID-19 infections and many months to years after having COVID-19. They measured a specific tau protein, pTau-181, which stands for phosphorylated tau, an abnormal type associated with dementia patients.

Overall, the cohort showed a 59 percent increase of tau (pTau-181) in their plasma post COVID-19 infection while or after experiencing neurocognitive symptoms, compared to their plasma tau levels pre-COVID-19.

All the participants are individuals with some form of Long COVID, or specifically for this study those with Neurological Post-Acute Sequelae COVID (N-PASC).

The presence of tau at higher levels in the blood is a known biomarker of lasting brain damage. Therefore, these study results imply that Long COVID could worsen with time and cause changes in neurological symptoms or lead to cognitive difficulties that become worse. Yet, we do not know if this increase in tau in our sample represents a biological course that could be similar to individuals who develop Alzheimer's or related diseases."

Sean Clouston, PhD, Corresponding Author and Professor in the Department of Family, Population and Preventive Medicine in the Renaissance School of Medicine (RSOM) and Program in Public Health, Stony Brook University

The 227 individuals with N-PASC were compared to 227 other WTC responders who either 1) did not contract COVID between their pre- and post-pandemic blood sample collection dates, or 2) developed COVID but did not develop any Long COVID symptoms, including neurological ones. This cohort served as the control group for the study.

Unlike those with N-PASC, any increased plasma tau levels in the control group from their pre-COVID tau levels was not evident based on testing.

Time could be an enemy

For those with N-PASC who had neurocognitive symptoms for more than 1.5 years, the tau level increases were worse. This finding, the authors write, "might portend worsened cognitive functioning as individuals age."

"We measured tau at an average of 2.2 years after COVID-19 infection, and our measurements taken ranged from six months to four years," adds Xiaohua Yang, First Author and Senior Research Program Manager at the Stony Brook WTC Health and Wellness Program. "This sampling timeframe represents a true long-term post-acute sequela of COVID-19."

Clouston and colleagues stress that other research steps need to be taken to determine if increased plasma levels of tau in those with N-PASC have any association with cognitive decline or neurodegenerative diseases.

"One important step is to validate our study results using neuroimaging tools to see if tau plasma level increases also represent increased levels in the participants' brains," explains Clouston.

Additionally, the authors also point out that the cohort for this study – WTC responders – also have had more environmental exposures than the general population. Therefore, findings in N-PASC individuals who are WTC responders could be much different from the general patient population.

"The long-term impact of COVID-19 may be consequential years after the infection and give rise to long-term illnesses including neurocognitive problems similar to what is seen in Alzheimer's disease," says Senior Author Benjamin J. Luft, MD, Director of the WTC Health and Wellness Program, an infectious diseases specialist, and the Edmund D. Pelligrino Professor of Medicine in the RSOM.

"This is one of the first studies to show that a virus may contribute to the development of abnormal tau production over time," he adds. "This has important implications for our understanding of the biological factors involved in the development of neurodegenerative disease. On a practical level, it has important implications for the development of effective vaccines and therapies to prevent an acute infection before it can embed itself in people and cause long-term disease."

The study was supported in part by funding from the Centers for Disease Control and Prevention's National Institute for Occupational Safety and Health (CDC/NIOSH CDC-75D30122c12222) and the National Institutes of Health's National Institute on Aging (NIH/NIA Ago49953).