COVID-19: A Direct Viral Attack on the Brain


What are the long term psychiatric and neuropsychiatric complications of COVID-19?




In his presentation, “Psychiatric Complications of COVID-19” at the 2022 Annual Psychiatric Times™ World CME Conference in San Diego, John J. Miller, MD, explored the broad range of psychiatric and neuropsychiatric effects of COVID-19.

“We’ve all seen it and we’re still dealing with them,” said Miller. “The mental health crisis is not only for people with the infection itself, but care for their parents, their families, and us as clinicians.”

According to research, the most common psychiatric symptoms include depression, anxiety, insomnia, posttraumatic stress disorder (PTSD), fear, grief, phobias, social avoidance/isolation, increased substance abuse, suicidal ideation, psychosis, and obsessive-compulsive behaviors.1 One systematic review and meta-analysis of long term physical and mental sequelae found at least 1 sequelae symptom occurred in 50.1% of COVID-19 survivors for up to 12 months after infection. Some of the symptoms included cognitive deficits (19.7%), depression (18.3%), and PTSD (17.9%).2

“We know that any type of stress will only bring out underlying genetic and biological and epigenetic vulnerabilities,” Miller said.

As to neuropsychiatric symptoms, some of the most common are delirium (50% of COVID-19 ICU patients), confusion, fatigue, memory impairment, encephalopathy, seizures, cerebral vascular accidents, and more.3

“The bottom line is every person is going to have a different trajectory in terms of how their immune system, how their body, the probabilities of their genetics, other psychosocial circumstances, how their comorbidities will impact their journey through the virus.”

SARS-CoV-2 may traverse the olfactory mucosa—causing loss of smell, especially in the original variants—to gain access to infect the brain, potentially through the olfactory tract, vagal nerve, or trigeminal nerve. Damage to endothelial cells can lead to inflammation and thrombi, which can cause direct damage to the brain, Miller shared. He noted that astrocytes appear to be the primary brain cell type infected and can contribute to fatigue and “brain fog.”4,5

“It will probably take us another 5 or 10 years to figure out the real story. At the end of the day, we must say vaccinate, vaccinate, vaccinate, and remember our role as educators and health promoters is to be compassionate and provide accurate education to our patients and communities,” Miller concluded. “No one is safe until everyone is safe.”


1. Kalin NH. COVID-19 and stress-related disorders. Am J Psychiatry. 2021;178(6):471-474.

2. Zeng N, Zhao YM, Yan W, et al. A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action. Mol Psychiatry. 2022:1-11.

3. Manolis TA, Apostolopoulos EJ, Manolis AA, et al. COVID-19 infection: a neuropsychiatric perspective. J Neuropsychiatry Clin Neurosci. 2021;33(4):266-279.

4. Marshall M. COVID and the brain: researchers zero in on how damage occurs. Nature. 2021;595(7868):484-485.

5. Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. 2021;78(6):682-683.

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