Studying impact of COVID on brains
One of the hallmark features of COVID-19 offers an important clue about how the disease affects the brain.
Loss of smell, or anosmia, occurs in people with either mild or acute coronavirus infections. The condition is related to the olfactory bulb, a bundle of nerves in the brain that processes smell.
On the surface, loss of smell may seem like one of the mildest symptoms of a disease that can wreak havoc on the human body, causing respiratory failure and damage to multiple organ systems.
However, it is among an array of neurological problems that have been identified in COVID-19 patients, from issues with memory, concentration and regulation of bodily functions to intense delirium and even psychosis.
And the prevalence of anosmia, which long has been associated with viral illnesses, suggests the coronavirus has the potential to cause lasting effects on cognitive function.
“That was the hint that COVID-19 may be related to long-term neurological outcomes,” said Dr. Gabriel de Erausquin, a neurology professor with the Glenn Biggs Institute for Alzheimer’s and neurodegenerative Diseases at UT Health San Antonio.
It’s one reason an international group of researchers is undertaking a wideranging study of COVID-19’s impact on the central nervous system, tracking its long-term neurological effects on survivors.
A consortium that spans 40 countries plans to gather data from 30,000 to 40,000 people who will be divided into two groups: the infected and the unexposed.
The participants will be evaluated at six, nine and 18 months using cognitive tests, blood draws, brain scans and other clinical information.
Researchers will probe the disease’s effects on the brain, de Erausquin said, as well as its capacity to accelerate existing conditions, such as Alzheimer’s disease.
The work also will help identify risk factors and potential ways to prevent such problems, he added.
The research effort is being led by the Biggs Institute, with funding from the Alzheimer’s Association and guidance from the World Health Organization. Preliminary results are expected in early 2022.
Attack on brain
As the pandemic has progressed, evidence has grown to indicate that COVID-19 is neurotropic — adept at invading nerve cells.
In particular, the olfactory bulb is rich in ACE2 receptors, enzymes that the spikes of the coronavirus leverage to infect individual cells.
The structure, which is linked to the parts of the brain related to memory and emotion, is one of the few parts of the nervous system that is exposed to the outside, through the nasal cavity.
It’s also a point of entry for brain pathways that are targeted by other neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease.
In addition to loss of smell and taste, a subset of COVID-19 patients have experienced severe brain injuries.
COVID-19 is known to affect the vascular system, and some patients have suffered bleeding throughout the brain, says a review of the coronavirus’ neurological effects by de Erausquin published recently in the journal Alzheimer’s & Dementia.
Imaging also has identified changes in white brain matter and asymmetric olfactory bulbs. And the virus’ RNA has been found in the cerebrospinal fluid of COVID-19 patients who developed brain inflammation and damage, as well as in brain tissue during postmortem exams.
Brain inflammation is a prominent feature in neurodegenerative conditions, such as Alzheimer’s and Parkinson’s, both of which feature an early loss of smell, said Dr. Sudha Seshadri, director of the Biggs Institute, who co-authored the paper with de Erausquin.
“We have learned more and more about the fact that it does affect the brain in many ways,” she said.
Emerging evidence points to biological changes in COVID-19 patients, said Heather Snyder, vice president of medical and scientific relations at the Alzheimer’s Association.
It’s possible the strong immune response prompted by COVID-19 plays a role in weakening the bloodbrain barrier, a protective ring of cells that also plays a crucial role in other neurodegenerative diseases.
“It seems that it is attacking one of the areas of the brain that is a memory center, a main coordinator of a person’s memories across the board,” said Snyder, who also contributed to the paper.
History of problems
In studying COVID-19’s longer-term impacts, researchers are informed by a long history of respiratory viruses contributing to neurological conditions and psychiatric disorders.
In the wake of the 1918 flu pandemic, some people developed post-encephalitic Parkinsonism, a disease that leads to deteriorated motor and cognitive function. The 1957 flu pandemic was followed by a different set of neurological problems, de Erausquin said.
Cognitive and psychiatric issues also were observed in people who contracted the coronaviruses that caused SARS and MERS, epidemics that infected far fewer people than has COVID-19.
“Following infection, there’s been a connection to memory impairment, sleep disruption and other behavioral issues, anxiety and delirium, to name a few,” Snyder said.
Even so, only a study conducted over time with a large number of participants will give clinicians a full understanding of COVID-19’s specific implications for long-term cognitive health, de Erausquin said.
“Those are big questions that we don’t know the answer to, but we need to be asking them now so that we can get ahead and really understand what the impact is,” Snyder said.
When de Erausquin and Seshadri first started planning the consortium in the spring, they had no idea how widespread and severe the pandemic would become.
Even if the virus abated, they figured that studying its potential long-term effects would provide a wealth of information about it and other brain disorders, Seshadri said.
With the pandemic now infecting and killing more people than ever before, the research has taken on greater significance and urgency. And, Seshadri said, it may shed light on how critical illness and even abrupt lifestyle changes during the pandemic — to diet, exercise and social isolation — are linked to brain health.
‘Been through both’
The consortium is recruiting patients from South Texas, home to a large population of Hispanic residents, who are at a higher risk of developing Alzheimer’s and suffering severe complications from COVID-19.
The intersection of the two diseases has deep meaning for Robert Renteria.
The 77-year-old San Antonian, who contracted the virus in June, has a strong family history with Alzheimer’s. His father deteriorated to the point that he had to be admitted to a secure facility when he was in his mid-70s, and many of his extended family members have been stricken by the debilitating disease.
It took Renteria a month and his wife, Cynthia, six weeks to recover from COVID-19. Neither lost their sense of smell or needed to be hospitalized.
Months later, Renteria’s wife wakes up in the middle of the night to check that he’s still breathing. The couple didn’t gather with others for the holidays and are rigorous about following public health precautions, wearing masks and avoiding contact with strangers.
“We’re still looking over our shoulder,” he said.
Robert, who had seen UT Health San Antonio doctors for years due to his family history of Alzheimer’s, and Cynthia were eager to participate in the Biggs research. He hopes its results will help the world “get over both of these terrible diseases.”
“We’re dead set that we’re going to test as long as we can and help out however we can, because we’ve been through both,” Renteria said.