COVID and Long-Term Brain Disorders: What We Know & How to Learn More

As doctors begin to see more and more patients with long-term impact from the COVID-19 virus (so called long-haulers), it’s important to consider what we know about similar viruses and use this evidence for treating patients who have contracted COVID-19 and are experiencing long-term brain disorders. It more than apparent that a new sector of medicine is quickly emerging dedicated to COVID-19 and long-term brain disorders.

COVID-19 and Long-term Brain Disorders

An article published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association reviews decades of published scientific evidence for Spanish flu and other viruses and makes a compelling case for SARS-CoV-2’s and the expected long-term effects on the brain and nervous system. This study includes dementia researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and coauthors from the Alzheimer’s Association and Nottingham and Leicester universities in England.

“Since the flu pandemic of 1917 and 1918, many of the flulike diseases have been associated with brain disorders,” said lead author Gabriel A. de Erausquin, MD, PhD, Msc, professor of neurology in the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio. “Those respiratory viruses included H1N1 and SARS-CoV. The SARS-CoV-2 virus, which causes COVID-19, is also known to impact the brain and nervous system.”

Dr. de Erausquin, an investigator with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, said it is becoming clear that the damage done by the pandemic will not be limited to acute effects, such as delirium in the hospital, but will have chronic consequences that impact many individuals’ quality of life and independence.

The question is to what degree and under what form. Even mild COVID-19 infections may have negative effects on the brain long term, Dr. de Erausquin said.

“As the Alzheimer’s & Dementia article points out, the under-recognized medical history of these viruses over the last century suggests a strong link to brain diseases that affect memory and behavior,” said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer and a coauthor on the paper. “In this difficult time, we can create a ‘silver lining’ by capitalizing on the Alzheimer’s Association’s global reach and reputation to bring the research community together to illuminate COVID-19’s long-term impact on the brain.”

COVID-19 and Long-Term Brain Disorders

The coronavirus is known to enter cells via receptors called ACE2. The highest concentration of ACE2 receptors is in the olfactory bulb, the brain structure involved in the sense of smell.

“The basic idea of our study is that some of the respiratory viruses have affinity for nervous system cells,” said senior author Sudha Seshadri, MD, professor of neurology in the Long School of Medicine at UT Health San Antonio and director of the Glenn Biggs Institute. “Olfactory cells are very susceptible to viral invasion and are particularly targeted by SARS-CoV-2, and that’s why one of the prominent symptoms of COVID-19 is loss of smell.”

The olfactory bulb connects with the hippocampus, a brain structure primarily responsible for short-term memory.

“The trail of the virus, when it invades the brain, leads almost straight to the hippocampus,” Dr. de Erausquin said. “That is believed to be one of the sources of the cognitive impairment observed in COVID-19 patients. We suspect it may also be part of the reason why there will be an accelerated cognitive decline over time in susceptible individuals.”

The authors point out that:

  • Intranasal administration of SARS-CoV-2 in mice results in rapid invasion of the brain.
  • Headache, hypogeusia (reduced ability to taste) and anosmia (loss of smell) appear to precede the onset of respiratory symptoms in the majority of affected patients.
  • SARS-CoV-2 can be found in the brain post-mortem.
  • Abnormal brain imaging that may be characterized by the appearance of lesions in different brain regions – and the appearance of other abnormal brain changes that may influence clinical presentation – has emerged as a major feature of COVID-19 from all parts of the world.
  • Abnormal imaging was seen in an individual whose only symptom was loss of smell.

NEW: International Brain Disorders Study from the Alzheimer’s Association

The Alzheimer’s Association is funding the initial work of a consortium of experts from more than 30 countries to understand how COVID-19 increases the risk, severity, pace and progression of neurodegenerative diseases such as Alzheimer’s and psychiatric diseases including depression. Consortium members will enroll study participants selected from a pool of millions of confirmed COVID-19 cases documented in hospitals worldwide. A second group of enrollees will consist of people participating in existing international research studies. Participants will be evaluated on a host of measures at their initial appointment and again at six, nine and 18 months. These measures include cognition, behavior and, when possible, brain volumes measured by magnetic resonance imaging.

COVID-19 and Long-term Brain Disorders


Consortium participants. Colored countries in the map represent those with at least one academic institution participating in the Consortium for Chronic Neuropsychiatric Sequelae of SARS‐CoV‐2

This consortium will link study teams from around the world that cover more than 22 million cases at the time of submission and will enroll two groups of individuals including people with confirmed cases of COVID‐19 sampled from hospitals that have been discharged to be evaluated for follow‐up at 6, 9, and 18 months. This study will also include people who are already enrolled in existing international research studies to add additional measures and markers of their underlying biology.

The study will collect information over the next two to three years. Initial results are expected in early 2022 for the first set of evaluations. The consortium is aided by technical guidance from the World Health Organization.

Conclusion/ “The increasing evidence and understanding of SARS‐CoV‐2’s impact on the CNS raises key questions on the impact for risk of later life cognitive decline, AD, and other dementia. Scientific leaders, including the Alzheimer’s Association and representatives from more than 30 countries—with technical guidance from the World Health Organization—have formed an international, multidisciplinary consortium to collect and evaluate the short‐ and long‐term consequences of SARS‐CoV‐2 on the CNS. This program of studies aims to better understand the long‐term consequences that may impact the brain, cognition, and functioning—including the underlying biology that may contribute to AD and other dementias.”

Click Here for Full-Text Study


Source: Gabriel A. de Erausquin, MD, PhD, Msc; Heather Snyder, Sudha Seshadri, MD et al. Chronic Neuropsychiatric Sequelae of COVID-19: the need for a prospective study of viral impact on brain functioning. First published: Jan. 5, 2021, Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association doi.org/10.1002/alz.1225