A recent study published in eBioMedicine has found that individuals experiencing neurocognitive symptoms after COVID-19 infection, known as Long COVID, show a significant increase in the blood plasma levels of tau protein. This protein is associated with nerve cells and is especially present in the brain. Elevated tau levels are linked to neurodegenerative diseases, including Alzheimer’s.
The research focused on 227 World Trade Center (WTC) responders who developed neurological symptoms such as headaches, vertigo, balance issues, changes in taste or smell, and brain fog following COVID-19 infection. The study compared their plasma samples taken before contracting COVID-19 and months to years after infection. Researchers measured phosphorylated tau (pTau-181), an abnormal form of the protein commonly seen in dementia patients.
Results showed a 59 percent increase in pTau-181 among those with Long COVID neurocognitive symptoms compared to their pre-COVID levels. The participants were monitored by clinicians at the Stony Brook WTC Health and Wellness Program.
All participants had some form of Long COVID or specifically Neurological Post-Acute Sequelae COVID (N-PASC). They were compared to another group of 227 WTC responders who either did not contract COVID or had no long-term symptoms after infection. No similar increase in plasma tau was observed in this control group.
“The presence of tau at higher levels in the blood is a known biomarker of lasting brain damage,” said Sean Clouston, PhD, Corresponding Author and Professor at Stony Brook University’s Renaissance School of Medicine 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 study also found that those with N-PASC who experienced neurocognitive symptoms for more than 1.5 years had even greater increases in tau levels. The authors noted this “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 added 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 cautioned that because all subjects were WTC responders—who may have unique environmental exposures—the findings might differ from those seen among 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 at Stony Brook University.
“This is one of the first studies to show that a virus may contribute to the development of abnormal tau production over time,” Luft continued. “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.”
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The study received support from grants provided by CDC/NIOSH (CDC-75D30122c12222) and NIH/NIA (Ago49953).
