Persistent Neurocognitive and Neuropsychiatric Symptoms Post-COVID

Although COVID-19 is primarily a respiratory virus, it also affects other organs and systems in the body, including the nervous system.¹ The mechanisms of injury to the brain and nervous system include chronic inflammation, changes in the integrity of the blood-brain barrier, hypoxia, and coagulopathies resulting in the formation of blood clots.^2,3

Long COVID and other terms, such as long haulers or post-COVID syndrome, have been used to describe symptoms persisting beyond 12 weeks that cannot be explained by another condition.⁴

Some individuals with long COVID report ongoing or continuous symptoms experienced during initial infection, whereas others report the onset of new symptoms not experienced during initial infection, or continuous remitting and relapsing of symptoms.⁵ Commonly reported neurocognitive and neuropsychiatric symptoms of long COVID can be found in the Table.⁶

Although some studies identify certain risk factors for developing long COVID, such as being hospitalized for COVID-19, female gender, obesity, increasing age, and the presence of 5 or more symptoms during the acute stage of illness, other studies report little relationship between the severity of the acute illness and the subsequent development of long COVID.^5,7

Since the World Health Organization declared COVID-19 a pandemic in early March 2020, approximately 107 million cases have been reported in the United States, resulting in more than 6 million hospitalizations related to COVID-19.⁸

According to data from the Household Pulse Survey, which was launched by the Census Bureau at the beginning of the pandemic, approximately 30% of individuals diagnosed with COVID-19 go on to develop long COVID.⁹ As is now evident, individuals with long COVID frequently report neurocognitive and neuropsychiatric symptoms.

Research

Mazza et al screened 402 adults diagnosed with COVID-19 at approximately 1 month post discharge from the hospital.¹⁰ They screened for psychiatric symptoms using a clinical interview and a battery of self-report questionnaires.

Their analysis found that a significant percentage of participants self-reported at the psychopathological range for anxiety (42%), sleep disturbance (40%), depression (31%), and posttraumatic stress disorder (28%; Figure).

A significant percentage of individuals with long COVID also report cognitive deficits, such as forgetfulness, trouble concentrating, and difficulty thinking.¹¹

Hampshire and colleagues examined the association between COVID-19 infection and cognitive performance in a large cross-sectional sample of 81,337 participants using a self-report questionnaire about COVID-19 infection and a web-based version of the Great British Intelligence Test.¹²

Their analysis showed that individuals who had recovered from COVID-19 exhibited significant deficits as compared with controls in several cognitive domains, including attention, working memory, problem-solving, and emotional processing. Significant cognitive deficits were seen in both hospitalized and nonhospitalized cases of COVID-19.

Research indicates that neurocognitive and neuropsychiatric symptoms of long COVID not only affect mental, emotional, and cognitive well-being, but it may also interfere with a person’s ability to engage in self-care (dressing, bathing, etc), driving, and the ability to return to work.^9,13

Similarities to Concussion/mTBI

With the similarities observed in neurocognitive and neuropsychiatric symptoms of long COVID and concussion/mild traumatic brain injury (mTBI), approaches to effectively manage concussion/mTBI may provide some insights to treatment.¹⁴

Effective management includes early identification and treatment, education about the condition, and optimistic expectations about recovery and outcome. Given the variation in reported symptoms and duration of symptoms, an individualized and symptom-focused approach is indicated.

Asking questions about how the condition is impacting the patient’s life (eg, “What aspects of your condition affect your life the most?” “What are you hoping to get back to?” “If you did not have these symptoms, what would you be doing today?”), as well as providing information about how to manage presenting symptoms (eg, headache, sleep disorder, changes in mood) is indicated.

For individuals with physical, cognitive, and psychiatric symptoms, a multidisciplinary team approach with coordination provided by a case manager may be necessary.

The core multidisciplinary team may include physician specialties (eg, physiatry, psychiatry, neurology), occupational therapy (to improve activities of daily living and monitor timing for return to work and driving), physical therapy (to manage pain, balance problems, vestibular issues), speech/language pathology (to treat cognitive-linguistic deficits), and counseling (to treat mood disturbance, sleep disorders, etc).

Concluding Thoughts

In conclusion, a large number of individuals infected with COVID-19 continue to experience symptoms after recovering from the initial viral infection and may seek treatment from mental health and rehabilitation providers. Persistent symptoms include neurocognitive and neuropsychiatric symptoms that can interfere with meaningful daily activities and roles.

Given the symptom overlap between concussion/mTBI and long COVID, best practices and evidence-based techniques for the treatment of concussion/mTBI can inform treatment approaches to manage symptoms and reduce the negative impact of long COVID.

Dr Seale is the regional director of clinical services at the Centre for Neuro Skills, which operates postacute brain injury rehabilitation programs in California and Texas. He is licensed in Texas as a chemical dependency counselor and psychological associate with independent practice. He also holds a clinical appointment at the University of Texas Medical Branch in Galveston in the Department of Rehabilitation Sciences.

References

1. Azizi SA, Azizi SA. Neurological injuries in COVID-19 patients: direct viral invasion or a bystander injury after infection of epithelial/endothelial cells. J Neurovirol. 2020;26(5):631-641.

2. Lahiri D, Ardila A. COVID-19 pandemic: a neurological perspective. Cureus. 2020;12(4):e7899.

3. Aghagoli G, Gallo Marin B, Katchur NJ, et al. Neurological involvement in COVID-19 and potential mechanisms: a review. Neurocrit Care. 2021;34(3):1062-1071.

4. Mahase E. Covid-19: what do we know about “long covid”? BMJ. 2020;370:m2815.

5. Nabavi N. Long covid: how to define it and how to manage it. BMJ. 2020;370:m3489.

6. Crook H, Raza S, Nowell J, et al. Long covid—mechanisms, risk factors, and management. BMJ. 2021;374:n1648.

7. Sykes DL, Holdsworth L, Jawad N, et al. Post-COVID-19 symptom burden: what is long-COVID and how should we manage it? Lung. 2021;199(2):113-119.

8. Long COVID or post-COVID conditions. CDC. Updated December 16, 2022. Accessed June 9, 2023. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/

9. Long COVID: Household Pulse Survey. National Center for Health Statistics. Reviewed May 17, 2023. Accessed June 9, 2023. https://www.cdc.gov/nchs/covid19/pulse/long-covid.htm

10. Mazza MG, De Lorenzo R, Conte C, et al. Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors. Brain Behav Immun. 2020;89:594-600.

11. Rass V, Beer R, Schiefecker AJ, et al. Neurological outcome and quality of life 3 months after COVID‐19: a prospective observational cohort study. Eur J Neurol. 2021;28(10):3348-3359.

12. Hampshire A, Trender W, Chamberlain SR, et al. Cognitive deficits in people who have recovered from COVID-19. EClinicalMedicine. 2021;39:101044.

13. Kumar S, Veldhuis A, Malhotra T. Neuropsychiatric and cognitive sequelae of COVID-19. Front Psychol. 2021;12:577529.

14. Junn C, Bell KR, Shenouda C, Hoffman JM. Symptoms of concussion and comorbid disorders. Curr Pain Headache Rep. 2015;19(9):46.