The Road to Recovery: Neuropsychiatric Symptoms of Long COVID

Hartej Gill, PhD(c)


December 27, 2021

Over 275 million individuals worldwide have tested positive for SARS-CoV-2 infection. Acute COVID-19 infection usually lasts up to 4 weeks, but a significant number of individuals continue experiencing symptoms beyond the initial course of illness (after an individual no longer tests positive for COVID-19). This was the case when speaking to family members recovering from COVID infection. Months following the initial infection, they insisted that they just did not feel like their true self. This included neurocognitive difficulties and a hard time getting back up to speed with their usual tasks. 

The lengthy recovery from COVID is not unique to individuals with previously existing health conditions or in older populations. The 23-year-old NBA All-Star Jayson Tatum, who is a prolific athlete in peak physical condition, admitted to an uphill battle during his COVID recovery over 1 month following his initial diagnosis. The persisting symptoms were accompanied by a drop in performance. It must be understood that the course of symptoms following COVID may be unique for each individual. Taken together, it can also be highlighted that the severity of symptoms following the initial diagnosis may be independent of one's current physical condition.


The course of symptoms following initial diagnosis is referred to as post-acute sequelae of COVID-19, or long COVID. Long COVID encompasses a wide range of physical and neurologic symptoms. For approximately 20%-70% of patients who have recovered from acute COVID-19 infection, lasting neuropsychiatric symptoms are a significant detriment to their well-being. 

Neuropsychiatric symptoms in post-acute COVID-19 infection include deficits in cognition, the development of mood or anxiety disorders, psychosis, or suicidal behaviors. These symptoms are generally unrelated to symptoms of COVID-19; however, some preliminary evidence indicates that the severity/duration of long COVID may be associated with symptom severity during acute COVID-19 infection, including persistent physical symptoms. For example, approximately 55% of people continue experiencing fatigue, dyspnea, joint pain, and chest pain following COVID.

A number of different mechanisms of action have been postulated for the development of neuropsychiatric symptoms in long COVID. Current lines of literature suggest that the inflammatory pathway may have an important role, where more severe forms of COVID-19 infection may be associated with a more dynamic immune response. This leads to an elevated release of proinflammatory cytokines, also referred to as a cytokine storm.

The cytokine storm may result in brain damage and exacerbates existing neuropsychiatric conditions and/or introduces new ones. Moreover, the changes may result in further alterations in neural functioning, particularly in brain regions involved in cognitive function. An additional proposed mechanism of action relates to iatrogenic harm, where the aggressive treatment of acute COVID-19 infection using methods such as intubation or nosocomial infections may contribute to poor patient outcomes and lasting disease trajectory. 

Taken together, existing lines of literature highlight the importance of evaluating long COVID impairment as an important part of COVID recovery. It is becoming apparent that COVID may negatively impact a person's long-term quality of life following the initial infection. Therefore, it is imperative for future research to understand the long-term effects of COVID on neurocognitive impairment to provide early and effective intervention. Current research is preliminary, and additional research will be needed to deepen our understanding of the underlying effects of long COVID. 

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

About Hartej Gill
Hartej Gill is a PhD candidate and researcher at the Canadian Rapid Treatment Center of Excellence and the Institute of Medical Science at the University of Toronto. He has expertise in mood disorders, investigating the etiology and pathophysiology of mental health disorders from both a clinical study and population health perspective, with over 50 peer-reviewed publications.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.