A recent study has found that individuals experiencing neurocognitive symptoms after COVID-19 infection, such as headaches, vertigo, balance issues, changes in taste or smell, and brain fog, show significantly higher levels of a protein called tau in their blood plasma. Tau is commonly associated with nerve cells in the brain and is linked to neurodegenerative diseases like Alzheimer’s.
The research was published in eBioMedicine and indicates that people with Long COVID who report ongoing neurological symptoms may be at greater risk for developing neurodegenerative conditions. The study focused on 227 participants who are part of the Stony Brook World Trade Center (WTC) Health and Wellness Program. Researchers analyzed blood samples collected from these individuals before they contracted COVID-19 and again several months to years after infection. They measured levels of pTau-181, a phosphorylated form of tau protein that is considered abnormal and often found in dementia patients.
Findings revealed a 59 percent increase in pTau-181 among those who experienced neurological symptoms following COVID-19 compared to their pre-infection levels. All participants had some form of Long COVID, specifically classified as 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,” said Sean Clouston, corresponding author and professor at Stony Brook University’s Renaissance School of Medicine (RSOM) and Program in Public Health. “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.”
The group with N-PASC was compared against another 227 WTC responders who either did not contract COVID-19 between sample collections or did not develop any Long COVID symptoms. This control group did not exhibit an increase in plasma tau levels over time.
Participants with N-PASC whose neurocognitive symptoms persisted for more than 1.5 years showed even greater increases in tau levels—a trend researchers say “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,” said 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 noted that further research is needed: “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.”
Researchers also highlighted that because all study participants were WTC responders—who have experienced additional environmental exposures—the findings may differ from those seen in the general 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,” said Benjamin J. Luft, MD, director of the WTC Health and Wellness Program.
“This is one of the first studies to show that a virus may contribute to the development of abnormal tau production over time,” Luft added. “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 research received support from grants provided by both CDC/NIOSH (CDC-75D30122c12222) and NIH/NIA (Ago49953).
