Brain Inflammation and COVID-19 Deaths

For more than a year, some patients with COVID-19 have complained of neurological and cognitive issues that in many cases have lingered far longer than the disease itself—memory problems, “brain fog,” mood disorders, sleep problems, and even hallucinations. A recent study provides further support for a link between COVID-19 and the brain, as a team of scientists delved into the brain tissue of people who died of COVID-19 and made the unsettling discovery that it contained evidence of inflammation and neuronal distress.

The study, conducted by Stanford University researchers, examined the brain tissue of 8 people who died from COVID-19, along with brain tissue from 14 people who died from non-COVID-19 causes. The people who had died from COVID-19 ranged in age from 55 to 79, and none had been diagnosed with Alzheimer’s disease, Parkinson’s disease, or any other neurodegenerative disorder.

The team employed RNA sequencing to generate information on 65,309 individual brain cells harvested from the COVID-19 patients as well as the controls. “Baseline inflammation varies by person, but we consistently found unusually strong inflammation in nearly all the severe COVID-19 patients compared to the controls, including 1 control patient that died of influenza,” Andrew Yang, PhD, a postdoctoral research fellow in neurology and neurological sciences and lead author of the study, told Contagion. “This suggests to us a consistent pattern of COVID-19-associated brain inflammation in severe cases.”

The blood-brain barrier, which normally prevents toxins from entering the brain, appeared to be vulnerable to inflammatory signals provoked by the virus, enabling inflammatory responses in the brain. This indicates that COVID-19 does not need to directly enter the brain tissue in order to create havoc; indeed, no Covid-19 particles were found in the brain samples studied. “[T]he data suggests that peripheral inflammation triggered by COVID-19 can still be relayed into the brain, triggering neuroinflammation and downstream issues,” Yang said. “These issues include brain circuit dysfunction preferentially in the neurons evolutionarily expanded in humans that support higher-level cognitive function. This would be consistent with long-COVID symptoms like brain fog.”

Yang and his team found molecular changes in the cerebral cortex, which is involved in cognitive functions like decision making and memory. Damage in the outer layer of the cerebral cortex—an imbalance between the excitatory and inhibitory neurons—was of the kind seen in cognitive disabilities and dementia-like conditions. The scientists also found an overabundance of T cells, or pathogen killers, in the brains of COVID-19 patients; normally, they’re scant.

While it remains to be seen whether people who survive COVID-19 will be at higher risk for neurocognitive and neurodegenerative conditions in the future, the current study offers a framework for further work exploring the link between COVID-19 and brain dysfunction. “It’s unclear exactly how much we can extrapolate our findings in severe patients to survivors, especially mild cases, but we now have concrete mechanisms to look out for and study,” Yang said.

Because the contents of cerebrospinal fluid and brain matter are often similar, an examination of this fluid in living Covid-19 patients may yield clues about individuals’ propensity to develop brain disorders down the line, according to Tony Wyss-Corey, PhD, professor of neurology and neurological sciences at Stanford who is a senior author of the study.