Post-Covid Syndrome: from Biology to Neuropsychology

Background. Postcovid syndrome or Long COVID is a new term introduced into medical practice by WHO after the COVID -19 pandemic. Long COVID affects patients who have recovered from COVID -19.

Objectives. The purpose of this work is to understand cognitive deficits caused by COVID-19 from the point of view of neuropsychology and pathophysiology.

Data Sources. Literature search was conducted in the following electronic databases: Pubmed, Google.scholar and Scopus databases. 63 articles were selected. Keywords for the literature review included “neuropsychiatry/neuropsychology”, “pathophysiology”, “COVID-19”, “SARS-CoV-2”.

Methods. Review and analysis of COVID-19 studies in terms of its relation to the appearance of cognitive deficits in patients.

Results. The SARS-CoV-2 virus enters the human body and affects the structures of the brain. Some of the symptoms such as fatigue, shortness of breath, problems with concentration and memory, loss or change of taste and smell, pain in muscles and joints as well as sleep disorders are preserved in post-COVID period and may be explained by the peculiarity of the virus interaction with central nervous system. Neuropsychological analysis of observed disorders based on the theory of three functional blocks of the brain by A. R. Luria helps to identify the affected zones of the functional systems of higher mental functions (HMF). Neuropsychological assessment makes it possible to plan rehabilitation programme or cognitive training, and help doctor in choosing an adequate drug therapy to compensate for cognitive impairment.

Conclusions. SARS-CoV-2 causes damage to brain structures such as the brainstem, limbic system, prefrontal cortex and olfactory tract, which explains the observed symptoms. Neuropsychological diagnostics makes it possible to identify the impaired component of the HMF in patients with post-COVID syndrome, to plan an adequate rehabilitation programme, as well as to choose drug therapy.

References

Alonso-Lana, S., Marquié, M., Ruiz, A., Boada, M. (2020). Cognitive and Neuropsychiatric Manifestations of COVID-19 and Effects on Elderly Individuals with Dementia. Frontiers in Aging Neuroscience, 12, 588872. https://doi.org/10.3389/fnagi.2020.588872

Ardila, A., Lahiri, D. (2020). Executive dysfunction in COVID-19 patients. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(5), 1377–1378. https://doi.org/10.1016/j.dsx.2020.07.032

Ayoubkhani, D., Khunti, K., Nafilyan, V., Maddox, T., Humberstone, B., Diamond, I., Banerjee, A. (2021). Post-covid syndrome in individuals admitted to hospital with COVID-19: Retrospective cohort study. The BMJ, n693. https://doi.org/10.1136/bmj.n693

Banerjee, D., Viswanath, B. (2020). Neuropsychiatric manifestations of COVID-19 and possible pathogenic mechanisms: Insights from other coronaviruses. Asian Journal of Psychiatry, (54), 102350. https://doi.org/10.1016/j.ajp.2020.102350

Barker-Davies, R. M., O’Sullivan, O., Senaratne, K. P. P., Baker, P., Cranley, M., Dharm-Datta, S., Bahadur, S. (2020). The Stanford Hall consensus statement for postCOVID-19 rehabilitation. British Journal of Sports Medicine, 54(16), 949–959. https://doi.org/10.1136/bjsports-2020-102596

Bilbul, M., Paparone, P., Kim, A. M., Mutalik, S., Ernst, C. L. (2020). Psychopharmacology of COVID-19. Psychosomatics, 61(5), 411–427. https://doi.org/10.1016/j.psym.2020.05.006

Brussow, H., Timmis, K. (2021). COVID‐19: Long covid and its societal consequences. Environmental Microbiology, 23(8), 4077–4091. https://doi.org/10.1111/1462-2920.15634

Capuano, R., Altieri, M., Bisecco, A., de Ambrosio, A., Docimo, R., Buonanno, D., Gallo, A. (2021). Psychological consequences of COVID-19 pandemic in Italian MS patients: Signs of resilience? Journal of Neurology, 268(3), 743–750. https://doi.org/10.1007/s00415-020-10099-9

Ceban, F., Ling, S., Lui, L. M. W., Lee, Y., Gill, H., Teopiz, K. M., McIntyre, R. S. (2022). Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain, Behavior, and Immunity, (101), 93–135. https://doi.org/10.1016/j.bbi.2021.12.020

Chen, R., Wang, K., Yu, J., Howard, D., French, L., Chen, Z., Xu, Z. (2021). The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains. Frontiers in Neurology, 11, 573095. https://doi.org/10.3389/fneur.2020.573095

Cilia, R., Bonvegna, S., Straccia, G., Andreasi, N. G., Elia, A. E., Romito, L. M., Eleopra, R. (2020). Effects of COVID ‐19 on Parkinson’s Disease Clinical Features: A Community‐Based Case‐Control Study. Movement Disorders, 35(8), 1287–1292. https://doi.org/10.1002/mds.28170

Collier, M. E., Zhang, S., Scrutton, N. S., Giorgini, F. (2021). Inflammation control and improvement of cognitive function in COVID-19 infections: Is there a role for kynurenine 3-monooxygenase inhibition? Drug Discovery Today, 26(6), 1473–1481. https://doi.org/10.1016/j.drudis.2021.02.009

Cuan-Baltazar, J. Y., Munoz-Perez, M. J., Robledo-Vega, C., Perez-Zepeda, M. F., Soto-Vega, E. (2020). Misinformation of COVID-19 on the Internet: Infodemiology Study. JMIR Public Health and Surveillance, 6(2), e18444. https://doi.org/10.2196/18444

Dai, X., Shao, Y., Ren, L., Tao, W., Wang, Y. (2022). Risk factors of COVID-19 in subjects with and without mental disorders. Journal of Affective Disorders, 297, 102–111. https://doi.org/10.1016/j.jad.2021.10.024

Daroische, R., Hemminghyth, M. S., Eilertsen, T. H., Breitve, M. H., Chwiszczuk, L. J. (2021). Cognitive Impairment After COVID-19 — A Review on Objective Test Data. Frontiers in Neurology, 12, 699582. https://doi.org/10.3389/fneur.2021.699582

Davies, D. A., Adlimoghaddam, A., Albensi, B. C. (2021). The Effect of COVID-19 on NF-κB and Neurological Manifestations of Disease. Molecular Neurobiology, 58(8), 4178–4187. https://doi.org/10.1007/s12035-021-02438-2

Day, G. S. (2021). Measuring the cognitive costs of the COVID-19 pandemic. Molecular Neurodegeneration, 16(1), 67. https://doi.org/10.1186/s13024-021-00492-x

Debnath, M., Berk, M., Maes, M. (2020). Changing dynamics of psychoneuroimmunology during the COVID-19 pandemic. Brain, Behavior, & Immunity — Health, (5), 100096. https://doi.org/10.1016/j.bbih.2020.100096

Desai, S., Sheikh, B., Belzie, L. (2021). New-Onset Psychosis Following COVID-19 Infection. Cureus, 13(9), e17904. https://doi.org/10.7759/cureus.17904

de Sousa Moreira, J. L., Barbosa, S. M. B., Vieira, J. G., Chaves, N. C. B., Felix, E. B. G., Feitosa, P. W. G., Neto, M. L. R. (2021). The psychiatric and neuropsychiatric repercussions associated with severe infections of COVID-19 and other coronaviruses. Progress in Neuro-Psychopharmacology and Biological Psychiatry, (106), 110159. https://doi.org/10.1016/j.pnpbp.2020.110159

Dinakaran, D., Manjunatha, N., Naveen Kumar, C., Suresh, B. M. (2020). Neuropsychiatric aspects of COVID-19 pandemic: A selective review. Asian Journal of Psychiatry, (53), 102188. https://doi.org/10.1016/j.ajp.2020.102188

El Sayed, S., Shokry, D., Gomaa, S. M. (2021). Post‐COVID‐19 fatigue and anhedonia: A cross‐sectional study and their correlation to post‐recovery period. Neuropsychopharmacology Reports, 41(1), 50–55. https://doi.org/10.1002/npr2.12154

Erausquin, G. A., Snyder, H., Carrillo, M., Hosseini, A. A., Brugha, T. S., Seshadri, S., the CNS SARS‐CoV‐2 Consortium. (2021). The chronic neuropsychiatric sequelae of COVID‐19: The need for a prospective study of viral impact on brain functioning. Alzheimer’s & Dementia, 17(6), 1056–1065. https://doi.org/10.1002/alz.12255

Esaulenko, I. E., Nikityuk, D. B., Alexeeva, N. T., Shevchenko, A. A., Sokolov, D. A., Klochkova, S. V., Kvaratskheliya, A. G., Filin, A. A., Tutel’yan, V. A. (2021). Pathomorphological and molecular biological aspects of blood vessel injury in COVID-19. Zhurnal Anatomii i Gistopatologii (Journal of Anatomy and Histopathology), 9(4), 9–18. https://doi.org/10.18499/2225-7357-2020-9-4-9-18 (In Russ.).

Garg, M., Maralakunte, M., Garg, S., Dhooria, S., Sehgal, I., Bhalla, A. S., Sandhu, M. S. (2021). The Conundrum of ‘Long-COVID-19’: A Narrative Review. Inter-national Journal of General Medicine, (14), 2491–2506. https://doi.org/10.2147/IJGM.S316708

Grolli, R. E., Mingoti, M. E. D., Bertollo, A. G., Luzardo, A. R., Quevedo, J., Reus, G. Z., Ignacio, Z. M. (2021). Impact of COVID-19 in the Mental Health in Elderly: Psychological and Biological Updates. Molecular Neurobiology, 58(5), 1905–1916. https://doi.org/10.1007/s12035-020-02249-x

Guedj, E., Campion, J. Y., Dudouet, P., Kaphan, E., Bregeon, F., Tissot-Dupont, H., Eldin, C. (2021). 18F-FDG brain PET hypometabolism in patients with long COVID. European Journal of Nuclear Medicine and Molecular Imaging, 48(9), 2823–2833. https://doi.org/10.1007/s00259-021-05215-4

Heneka, M. T., Golenbock, D., Latz, E., Morgan, D., Brown, R. (2020). Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimer’s Research & Therapy, 12(1), 69. https://doi.org/10.1186/s13195-020-00640-3

Hernandez-Vazquez, F., Garduno, J., Hernandez-Lopez, S. (2019). GABAergic modulation of serotonergic neurons in the dorsal raphe nucleus. Reviews in the Neurosciences, 30(3), 289–303. https://doi.org/10.1515/revneuro-2018-0014

Jasti, M., Nalleballe, K., Dandu, V., Onteddu, S. (2021). A review of pathophysiology and neuropsychiatric manifestations of COVID-19. Journal of Neurology, 268(6), 2007–2012. https://doi.org/10.1007/s00415-020-09950-w

Kas, A., Soret, M., Pyatigoskaya, N., Habert, M.-O., Hesters, A., Le Guennec, L., Houot, M. (2021). The cerebral network of COVID-19-related encephalopathy: A longitudinal voxel-based 18F-FDG-PET study. European Journal of Nuclear Medicine and Molecular Imaging, 48(8), 2543–2557. https://doi.org/10.1007/s00259-020-05178-y

Levine, A., Sacktor, N., Becker, J. T. (2020). Studying the neuropsychological sequelae of SARS-CoV-2: Lessons learned from 35 years of neuroHIV research. Journal of NeuroVirology, 26(6), 809–823. https://doi.org/10.1007/s13365-020-00897-2

Liu, Y.-H., Wang, Y.-R., Wang, Q.-H., Chen, Y., Chen, X., Li, Y., Wang, Y.-J. (2021). Post-infection cognitive impairments in a cohort of elderly patients with COVID-19. Molecular Neurodegeneration, 16(1), 48. https://doi.org/10.1186/s13024-021-00469-w

Luriya, A. R. (2018). Higher cortical functions of humans. St. Petersburg: Piter.

Machhi, J., Herskovitz, J., Senan, A. M., Dutta, D., Nath, B., Oleynikov, M. D., Kevadiya, B. D. (2020). The Natural History, Pathobiology, and Clinical Manifestations of SARS-CoV-2 Infections. Journal of Neuroimmune Pharmacology, 15(3), 359–386. https://doi.org/10.1007/s11481-020-09944-5

Mahalakshmi, A. M., Ray, B., Tuladhar, S., Bhat, A., Paneyala, S., Patteswari, D., Qoronfleh, M. W. (2021). Does COVID‐19 contribute to development of neurological disease? Immunity, Inflammation and Disease, 9(1), 48–58. https://doi.org/10.1002/ iid3.387

May, P. E. (2022). Neuropsychological Outcomes in Adult Patients and Survivors of COVID-19. Pathogens, 11(4), 465. https://doi.org/10.3390/pathogens11040465

Meier, I. B., Vieira Ligo Teixeira, C., Tarnanas, I., Mirza, F., Rajendran, L. (2021). Neurological and mental health consequences of COVID-19: Potential implications for well-being and labour force. Brain Communications, 3(1), fcab012. https://doi.org/10.1093/braincomms/fcab012

Melo Silva Junior, M. L. de, Souza, L. M. A. de, Dutra, R. E. M. C., Valente, R. G. de M., Melo, T. S. (2021). Review on therapeutic targets for COVID-19: Insights from cytokine storm. Postgraduate Medical Journal, 97(1148), 391–398. https://doi.org/10.1136/postgradmedj-2020-138791

Miners, S., Kehoe, P. G., Love, S. (2020). Cognitive impact of COVID-19: Looking beyond the short term. Alzheimer’s Research & Therapy, 12(1), 170. https://doi. org/10.1186/s13195-020-00744-w

Mosolov, S. N. (2021). Long-term psychiatric sequelae of SARS-CoV-2 infection. Sovremennaya Terapiya Psikhicheskikh Rasstroistv (Current Therapy of Mental Disorders), (3), 2–23. https://doi.org/10.21265/PSYPH.2021.31.25.001 (In Russ.).

Mukaetova-Ladinska, E. B., Kronenberg, G. (2021). Psychological and neuropsychiatric implications of COVID-19. European Archives of Psychiatry and Clinical Neuroscience, 271(2), 235–248. https://doi.org/10.1007/s00406-020-01210-2

Nakamura, Z. M., Nash, R. P., Laughon, S. L., Rosenstein, D. L. (2021). Neuropsychiatric Complications of COVID-19. Current Psychiatry Reports, 23(5), 25. https:// doi.org/10.1007/s11920-021-01237-9

Nalleballe, K., Reddy Onteddu, S., Sharma, R., Dandu, V., Brown, A., Jasti, M., Kovvuru, S. (2020). Spectrum of neuropsychiatric manifestations in COVID-19. Brain, Behavior, and Immunity, (88), 71–74. https://doi.org/10.1016/j.bbi.2020.06.020

Namdar, P., Mojabi, N. A., Mojabi, B. (2020). Neuropsychological and Psychosocial Consequences of the COVID-19 Pandemic. Neurophysiology, 52(6), 446–455. https://doi.org/10.1007/s11062-021-09903-7

Padala, K. P., Parkes, C. M., Padala, P.R. (2020). Neuropsychological and Functional Impact of COVID-19 on Mild Cognitive Impairment. American Journal of Alzheimer’s Disease & Other Dementiasr, (35), 153331752096087. https://doi.org/10.1177/1533317520960875

Pan, Y., Zhao, S., Chen, F. (2020). Letter to the Editor: “What Are the Long-Term Neurological and Neuropsychiatric Consequences of COVID-19?”. World Neurosurgery, (144), 310–311. https://doi.org/10.1016/j.wneu.2020.09.158

Pirker-Kees, A., Platho-Elwischger, K., Hafner, S., Redlich, K., Baumgartner, C. (2021). Hyposmia Is Associated with Reduced Cognitive Function in COVID-19: First Preliminary Results. Dementia and Geriatric Cognitive Disorders, 50(1), 68–73. https://doi.org/10.1159/000515575

Poloni, T. E., Medici, V., Moretti, M., Visona, S. D., Cirrincione, A., Carlos, A. F., Ceroni, M. (2021). COVID‐19‐related neuropathology and microglial activation in elderly with and without dementia. Brain Pathology, 31(5). https://doi.org/10.1111/bpa.12997

Riordan, P., Stika, M., Goldberg, J., Drzewiecki, M. (2020). COVID-19 and clinical neuropsychology: A review of neuropsychological literature on acute and chronic pulmonary disease. The Clinical Neuropsychologist, 34(7-8), 1480–1497. https://doi.org/10.1080/13854046.2020.1810325

Rogers, J. P., Chesney, E., Oliver, D., Pollak, T. A., McGuire, P., Fusar-Poli, P., David, A. S. (2020). Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: A systematic review and meta-analysis with comparison to the COVID-19 pandemic. The Lancet Psychiatry, 7(7), 611–627. https://doi.org/10.1016/S2215-0366(20)30203-0

Roy, D., Ghosh, R., Dubey, S., Dubey, M. J., Benito-Leon, J., Kanti Ray, B. (2021). Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic. Canadian Journal of Neurological Sciences / Journal Canadien Des Sciences Neurologiques, 48(1), 9–24. https://doi.org/10.1017/cjn.2020.173

Sinanovic, O. (2020). COVID-19 pandemia: neuropsychiatric comorbidity and consequences. Psychiatria Danubina, 32(2), 236–244. https://doi.org/10.24869/ psyd.2020.236

Singh, H., Singh, A., Khan, A. A., Gupta, V. (2021). Immune mediating molecules and pathogenesis of COVID-19-associated neurological disease. Microbial Pathogenesis, (158), 105023. https://doi.org/10.1016/j.micpath.2021.105023

Soriano, J. B., Murthy, S., Marshall, J. C., Relan, P., Diaz, J. V. (2022). A clinical case definition of post-COVID-19 condition by a Delphi consensus. The Lancet Infectious Diseases, 22(4), e102–e107. https://doi.org/10.1016/S1473-3099(21)00703-9

Steardo, L., Steardo, L., Verkhratsky, A. (2020). Psychiatric face of COVID-19. Translational Psychiatry, 10(1), 261. https://doi.org/10.1038/s41398-020-00949-5

Steardo, L., Steardo, L., Verkhratsky, A., Scuderi, C. (2021). Post‐COVID‐19 neuropsychiatric syndrome: Is maladaptive glial recovery to blame? Acta Physiologica, 233(2). https://doi.org/10.1111/apha.13717

Szczesniak, D., Gladka, A., Misiak, B., Cyran, A., Rymaszewska, J. (2021). The SARS-CoV-2 and mental health: From biological mechanisms to social consequences. Progress in Neuro-Psychopharmacology and Biological Psychiatry, (104), 110046. https://doi.org/10.1016/j.pnpbp.2020.110046

Tizenberg, B. N., Brenner, L. A., Lowry, C. A., Okusaga, O. O., Benavides, D. R., Hoisington, A. J., Postolache, T. T. (2021). Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19. Current Psychiatry Reports, 23(10), 68. https://doi.org/10.1007/s11920-021-01275-3

Troyer, E. A., Kohn, J. N., Hong, S. (2020). Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain, Behavior, and Immunity, (87), 34–39. https://doi.org/10.1016/j.bbi.2020.04.027

Tsapanou, A., Papatriantafyllou, J. D., Yiannopoulou, K., Sali, D., Kalligerou, F., Ntanasi, E., Sakka, P. (2021). The impact of COVID‐19 pandemic on people with mild cognitive impairment/dementia and on their caregivers. International Journal of Geriatric Psychiatry, 36(4), 583–587. https://doi.org/10.1002/gps.5457

Vindegaard, N., Benros, M. E. (2020). COVID-19 pandemic and mental health consequences: Systematic review of the current evidence. Brain, Behavior, and Immunity, (89), 531–542. https://doi.org/10.1016/j.bbi.2020.05.048

Wang, F., Kream, R. M., Stefano, G. B. (2020). Long-Term Respiratory and Neurological Sequelae of COVID-19. Medical Science Monitor, (26), e928996. https://doi.org/10.12659/MSM.928996

Wilkialis, L., Rodrigues, N. B., Cha, D. S., Siegel, A., Majeed, A., Lui, L. M. W., McIntyre, R. S. (2021). Social Isolation, Loneliness and Generalized Anxiety: Implications and Associations during the COVID-19 Quarantine. Brain Sciences, 11(12), 1620. https://doi.org/10.3390/brainsci11121620

Zaitsev, O.S. (2010). Selection of neuromethabolic drug in severe brain injury. Zhurnal nevrologii i psikhiatrii im. S.S.Korsakova (S.S. Korsakov Journal of Neurology and Psychiatry), 110(9), 66–69. URL: https://www.mediasphera.ru/issues/zhurnalnevrologii-i-psikhiatrii-im-s-s-korsakova/2010/9/031997-72982010913) (access date: 07.01.2023) (In Russ).

Zaitsev, O.S. (2021). Psychiatric aspects of traumatic brain injury and its consequences: A textbook. Мoscow: MEDpress-inform. (In Russ.).

Znazen, H., Slimani, M., Bragazzi, N. L., Tod, D. (2021). The Relationship between Cognitive Function, Lifestyle Behaviours and Perception of Stress during the COVID-19 Induced Confinement: Insights from Correlational and Mediation Analyses. International Journal of Environmental Research and Public Health, 18(6), 3194. https://doi.org/10.3390/ijerph18063194