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Editorials

Post-acute COVID-19: Psychological sequelae

September 2, 2021

Shivam Gulati, M.D., Steven Lippmann, M.D.

Introduction

Post-COVID-19 syndrome includes illness presentations during or following an infection that persist longer than 12 weeks and not otherwise diagnosed (1).  Manifestation of this so-called “long-covid” can exist throughout the body, including the nervous system. Psychological aspects are often the first symptoms, sometimes even before recognizing COVID-19 disease. Fear of potential infection, mental trauma during illness, and sustained turmoil after recovery are observed in some people. Longer-term effects vary and might include tiredness, flashbacks about time spend isolated, stress by dyspnea or being ventilated, and/or the results of social, occupational, educational, and/or financial problems.

Pathophysiology

The psychiatric pathophysiology remains unclear. Particles are detected in the brain of patients with other coronavirus infections (2). Despite no proof that SARS-CoV-2 also invades neurons, this virus might induce alterations in the central nervous system parenchyma and arteries (2). Such effects on the blood–brain and blood–cerebrospinal fluid barriers may cause neuronal inflammation (3,4). Immune activation is linked to cognitive and behavioral abnormalities (5). Prolonged brain inflammation decreases the capacity to react to new antigens, and an accumulation of memory T cells might result in long-term COVID-19 clinical sequelae (6). Physiological deconditioning might occur after a period of inactivity, bedrest, or a sedentary lifestyle, and posttraumatic stress disorder could result in post-COVID-19 “brain fog” (7). This form of cognitive dysfunction sometimes follows even moderate illness severity; it indicates that dysautonomia may be part of the pathophysiology (8,9). Prolonged cognitive dysfunction reportedly arises in 20-40% of patients discharged from intensive care units (10).

Manifestations

COVID-19 survivors sometimes complain about recurrent malaise, diffuse myalgia, depressive symptoms, and non-restorative sleep as a post-viral syndrome (11,12). Migraine-like headaches can occur and are resistant to conventional analgesics (13-15). Late-onset cephalgias also can arise. Brain fog, with attention, memory, receptive language, and/or executive dysfunctions is documented, with or without clinical fluctuations (16-18). Such symptoms may last for months to years after an infection (19).

One month after hospitalization, 56% of Italian COVID-19 survivors evidenced either posttraumatic stress disorder (PTSD), depression, anxiety, insomnia, and/or obsessive-compulsive symptomatology (20). Following severe cases of COVID-19 infection, up to 40% of patients experienced depression and/or anxiety (21-24).

In post-acute COVID-19 Chinese subjects, about 25% had anxiety, depression, and/or sleep problems at half year follow-up assessments. PTSD was identified in 30% of affected individuals who required hospitalization, with an early onset or months later (24).

Next     

Research about the psychological impact of COVID-19 is on-going. New post-disease manifestations continue to be observed in post-COVID-19 clinics. The implications of new variant coronavirus forms are yet to be understood.

References     

  1. NICE, COVID-19 rapid guideline: managing the long-term effects of COVID-19, (2020). Last accessed August 28, 2021
  2. Desforges, M., Le Coupanec, A, Stodola, J.K., et al. “Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis.” Virus Research 2014; 194:145-15
  3. Romero-Sánchez, C. M., Díaz-Maroto I., Fernández-Díaz E, et al. “Neurologic manifestations in hospitalized patients with COVID-19.” Neurology 2020; 95(8): e1060-e1070
  4. Reichard, R. R., Kashani K. B., Boire N. A., et al. “Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology.” Acta Neuropathologica 2020;140(1): 1-6
  5. Bortolato, B., Carvalho, A. F., Soczynska, J. K., et al. “The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments.” Current Neuropharmacology 2015;13(5): 558-576
  6. Aiello, A., Farzaneh, F., Candore, G., et al. “Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically?” A Review of Potential Options for Therapeutic Intervention.” Frontiers in Immunology 2019;10: https://doi.org/10.3389/fimmu.2019.02247. Last accessed August 2, 2021
  7. Kaseda, E. T., Levine, A. J. “Post-traumatic stress disorder: A differential diagnostic consideration for COVID-19 survivors.” The Clinical Neuropsychologist 2020; 34(7-8): 1498-1514
  8. Novak, P. “Post COVID-19 syndrome associated with orthostatic cerebral hypoperfusion syndrome, small fiber neuropathy and benefit of immunotherapy: a case report.” e-Neurological Sci 2020;21: 100276
  9. Miglis, M. G., Goodman B. P., Chémali, K. R., et al. “Re: ‘Post-COVID-19 chronic symptoms’ by Davido et al.” Clinical Microbiology and Infection 2021; 27(3): 494
  10. Sakusic, A., Rabinstein, A. A. “Cognitive outcomes after critical illness.” Current Opinion Critical Care 2018 ;24(5): 410-414
  11. Fauci, A. International AIDS conference (2020), YouTube https://www.youtube.com/ watch?v=UMmT48IC0us &feature=emblogo, Last accessed August 28, 2021
  12. Nordvig, A. S., Fong, K. T., Willey, J. Z., et al. “Neurology.” Clinical Practice 2021; 11(2): e135-e146
  13. Belvis, R. “Headaches during COVID-19”: The Journal of Head and Face Pain 2020 60(7):1422-1426
  14. Arca, K. N., Starling, A. J. “Treatment refractory headache in the setting of COVID-19 pneumonia: migraine or meningoencephalitis?” SN Comprehensive Clinical Medicine 2020 ;2(8):1200-1203
  15. Bolay, H., Gül, A., Baykan, B.,”COVID-19 is a real headache”: Journal of Head and Face Pain 2020; 60(7):1415-1421
  16. Heneka, M. T., Golenboc, K. D., Latz, E., et al. ”Immediate and long term consequences of COVID-19 infections for the development of neurological disease.” Alzheimer’s Research & Therapy 2020;12(1): PMID 32498691
  17. Ritchie, K., Chan, D., Watermeyer, T. ”The cognitive consequences of the COVID-19 epidemic: collateral damage? Brain Communications 2020; 2(2):fcaa069. Last accessed August 28, 202118.
  18. Kaseda, E. T., Levine, A. J. “Post-traumatic stress disorder: a differential diagnostic consideration for COVID-19 survivors.” The Clinical Neuropsychologist 2020; 34(7-8): 1498-1514
  19. Postolache, T. T., Benros, M. E., Brenner, L. A., et al. ”Targetable biological mechanisms implicated in emergent psychiatric conditions associated With SARS-CoV-2 infection.” JAMA Psychiatry 2021; 78(4):353
  20. Mazza, M. G., De Lorenzo, R., Conte, C., et al. ”Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors.” Brain Behavior Immunology 2020; 89:594-600
  21. Lam, M. H.-B. ”Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: long term follow up.” Archives Internal Medicine 2009;169(22):2142
  22. Lee, S. H., Shin, H.-S., Park, H. Y., et al. ”Depression as a mediator of chronic fatigue and post-traumatic stress symptoms in Middle East respiratory syndrome survivors.” Psychiatry Investigation 2019;16(1): 59-64
  23. Lee, A. M., Wong, J. G., McAlonan, G. M., et al. “Stress and psychological distress among SARS survivors 1 year after the outbreak.” Canadian J Psychiatry 2007; 52(4):233-240
  24. Rogers, J. P., Chesney, E., Oliver, D., et al.” Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.” Lancet Psychiatry 2020; 7(7):611-627

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