Cognitive consequences of COVID-19: results of a cohort study from South America

ABSTRACT

Background: Neurological and psychiatric manifestations associated with SARS-CoV-2 infection have been reported throughout the scientific literature. However, studies on post-COVID cognitive impairment in people with no previous cognitive complaint are scarce. Objective: We aim to investigate the impact of COVID-19 on cognitive functions in adults without cognitive complaints before infection and to study cognitive dysfunction according to disease severity and cognitive risk factors. Methods: Forty-five post-COVID-19 patients and forty-five controls underwent extensive neuropsychological evaluation, which assessed cognitive domains such as memory, language, attention, executive functions, and visuospatial skills, including psychiatric symptomatology scales. Data were collected on the severity of infection, premorbid medical conditions, and functionality for activities of daily living before and after COVID-19. Results: Significant differences between groups were found in cognitive composites of memory (p=0.016, Cohen’s d= 0.73), attention (p<0.001, Cohen’s d=1.2), executive functions (p<0.001, Cohen’s d=1.4), and language (p=0.002, Cohen’s d=0.87). The change from premorbid to post-infection functioning was significantly different between severity groups (WHODAS, p=0.037). Self-reported anxiety was associated with the presence of cognitive dysfunction in COVID-19 subjects (p=0.043).

Conclusion: Our results suggest that the presence of cognitive symptoms in post-COVID-19 patients may persist for months after disease remission and argue for the inclusion of cognitive assessment as a protocolized stage of the post-COVID examination. Screening measures may not be sufficient to detect cognitive dysfunction in post-COVID-19 patients.

RESUMEN

Antecedentes: Las manifestaciones neurológicas de la infección por SARS-CoV-2 han sido reportadas en la literatura científica. Sin embargo, los estudios cognitivos post COVID-19 en personas sin queja cognitiva previa son escasos. Objetivo: Nuestro objetivo es investigar el impacto cognitivo del COVID-19 en adultos sin quejas cognitivas previas a la infección y estudiar el desempeño cognitivo de acuerdo a la severidad de la enfermedad y a los factores de riesgo cognitivo. Métodos: Cuarenta y cinco pacientes post COVID-19 y cuarenta y cinco controles sanos apareados por edad, género y educación realizaron una evaluación neuropsicológica, que evalúa memoria, lenguaje, atención, funciones ejecutivas, habilidades visuoespaciales, incluyendo además escalas de sintomatología psiquiátrica, y la recopilación de datos sobre la severidad de la infección, la salud premórbida y la funcionalidad. Resultados: Se encontraron diferencias significativas entre los grupos en los compuestos cognitivos de memoria (p=0,016, d de Cohen= 0,73), atención (p<0,001, d de Cohen= 1,2), funciones ejecutivas (p<0,001, d de Cohen=1,4) y lenguaje (p=0,002, d de Cohen=0,87). El cambio del funcionamiento premórbido al funcionamiento posterior a la infección, fue significativamente diferente entre los grupos de gravedad (WHODAS; p=0,037). La ansiedad autoinformada se asoció con la presencia de disfunción cognitiva en los sujetos de COVID-19 (p=0,043). Conclusión: Nuestros resultados sugieren que los síntomas cognitivos en pacientes post COVID-19 pueden permanecer hasta tres meses después de la remisión de la enfermedad. Este estudio aboga a favor de incluir la evaluación cognitiva como una etapa protocolizada del examen post COVID-19. Es posible que las medidas de cribado no sean suficientes para detectar la disfunción cognitiva en los pacientes post COVID-19.

Keywords:

COVID-19 - Neuropsychology - Cognitive Dysfunction - Executive Function - Memory

Palabras clave:

COVID-19 - Neuropsicología - Disfunción Cognitiva - Función Ejecutiva - Memoria

Authors’ contributions:

LC: conceptualization, formal analysis, investigation, methodology, visualization, writing of original draft, review and editing; IC: conceptualization, formal analysis, methodology, software, supervision, visualization, writing of original draft, review and editing; NC, MAC, GK, CM, MA: investigation, methodology, project administration and writing of original draft; RA: conceptualization, resources, supervision, review and editing; LC, IC: joint first authors.

Publication History

Received: 16 August 2021

Accepted: 11 October 2021

Article published online:
30 January 2023

• REFERENCES

• 1 Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q. et al. Correction for Khan et al., "Emergence of a Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2: Biology and Therapeutic Options". J Clin Microbiol 2020; 58 (08) e01297-e01220 https://doi.org/10.1128/JCM.01297-20
• 2 Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C. et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020; 382 (23) 2268-2270 https://doi.org/10.1056/NEJMc2008597
• 3 Mao L, Jin H, Wang M, Hu Y, Chen S, He Q. et al. Neurologic manifestations of hospitalized patients with Coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; 77 (06) 683-690 https://doi.org/10.1001/jamaneurol.2020.1127
• 4 Ellul MA, Benjamin L, Singh B, Lant S, Michael BD, Easton A. et al. Neurological associations of COVID-19. Lancet Neurol 2020; 19 (09) P767-P783 https://doi.org/10.1016/S1474-4422(20)30221-0
• 5 Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun 2020; 87: 34-39 https://doi.org/10.1016/j.bbi.2020.04.027
• 6 Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alz Res Therapy 2020; 12 (01) 69 https://doi.org/10.1186/s13195-020-00640-3
• 7 Mazza C, Ricci E, Biondi S, Colasanti M, Ferracuti S, Napoli C. et al. A nationwide survey of psychological distress among italian people during the COVID-19 pandemic: immediate psychological responses and associated factors. Int J Environ Res Public Health 2020; 17 (09) 3165 https://doi.org/10.3390/ijerph17093165
• 8 Hampshire A, Trender W, Chamberlain SR, Jolly AE, Grant JE, Patrick F. et al. Cognitive deficits in people who have recovered from COVID-19. EClinicalMedicine 2021; 39: 101044 https://doi.org/10.1016/j.eclinm.2021.101044
• 9 Triana RM, Martínez CC, Almeida TM, González MÁÁ, Vaillant TZ, Barreto YR. Cognitive performance in convalescent covid-19 patients. Rev Cuba Hematol Immunol Hemoter 2020; 36 special issue 1-17
• 10 Hosp JA, Dressing A, Blazhenets G, Bormann T, Rau A, Schwabenland M. et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain 2021; 144 (04) 1263-1276 https://doi.org/10.1093/brain/awab009
• 11 Ortelli P, Ferrazzoli D, Sebastianelli L, Engl M, Romanello R, Nardone R. et al. Neuropsychological and neurophysiological correlates of fatigue in post-acute patients with neurological manifestations of COVID-19: Insights into a challenging symptom. J Neurol Sci 2021; 420: 117271 https://doi.org/10.1016/j.jns.2020.117271
• 12 Alemanno F, Houdayer E, Parma A, Spina A, Del Forno A, Scatolini A. et al. COVID-19 cognitive deficits after respiratory assistance in the subacute phase: a COVID-rehabilitation unit experience. PLoS One 2021; 16 (02) e0246590 https://doi.org/10.1371/journal.pone.0246590
• 13 Brutto OHD, Wu S, Mera RM, Costa AF, Recalde BY, Issa NP. Cognitive decline among individuals with history of mild symptomatic SARS-CoV-2 infection: a longitudinal prospective study nested to a population cohort. Eur J Neurol 2021; 28 (10) 3245-3253 https://doi.org/10.1111/ene.14775
• 14 Zhou J, Liu C, Sun Y, Huang W, Ye K. Cognitive disorders associated with hospitalization of COVID-19: results from an observational cohort study. Brain Behav Immun 2021; 91: 383-392 https://doi.org/10.1016/j.bbi.2020.10.019
• 15 Miskowiak KW, Johnsen S, Sattler SM, Nielsen S, Kunalan K, Rungby J. et al. Cognitive impairments four months after COVID-19 hospital discharge: pattern, severity and association with illness variables. Eur Neuropsychopharmacol 2021; 46: 39-48 https://doi.org/10.1016/j.euroneuro.2021.03.019
• 16 Pan American Health Organization / World Health Organization. Epidemiological Update: Coronavirus disease (COVID-19). Washington (DC): PAHO/WHO; 2021
• 17 Brucki SMD, Corazza LA, de Queiroz AP, Barros MP, Tatsch JFS, Riso IL. et al. Neurological complications in COVID-19 patients from Latin America. Brain 2021; 144 (03) e29 https://doi.org/10.1093/brain/awaa440
• 18 Amalakanti S, Arepalli KVR, Jillella JP. Cognitive assessment in asymptomatic COVID-19 subjects. Virusdisease 2021; 32 (01) 1-4 https://doi.org/10.1007/s13337-021-00663-w
• 19 Raman B, Cassar MP, Tunnicliffe EM, Filippini N, Griffanti L, Alfaro-Almagro F. et al. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine 2021; 31: 100683 https://doi.org/10.1016/j.eclinm.2020.100683
• 20 Woo MS, Malsy J, Pöttgen J, Zai SS, Ufer F, Hadjilaou A. et al. Frequent neurocognitive deficits after recovery from mild COVID-19. Brain Commun 2020; 2 (02) fcaa205 https://doi.org/10.1093/braincomms/fcaa205
• 21 WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020; 20 (08) e192-e197 https://doi.org/10.1016/S1473-3099(20)30483-7
• 22 Serrano CM, Sorbara M, Minond A, Finlay JB, Arizaga RL, Iturry M. et al. Validation of the Argentine version of the Montreal cognitive assessment test (MOCA): a screening tool for mild cognitive impairment and mild dementia in elderly. Dement Neuropsychol 2020; 14 (02) 145-152 https://doi.org/10.1590/1980-57642020dn14-020007
• 23 Reitan RM. Validity of the trail making test as an indicator of organic brain damage. Percept Motor Skill 1958; 8 (03) 271-276 https://doi.org/10.2W466/pms.1958.8.3.271
• 24 Richardson JTE. MMeasures of short-term memory: a historical review. Cortex 2007; 43 (05) 635-650 https://doi.org/10.1016/s0010-9452(08)70493-3
• 25 Wechsler D. Wechsler memory scale-revised manual. San Antonio (TX): The Psychological Corporation; 1987. 150.
• 26 Craft S, Newcomer J, Kanne S, Dagogo-Jack S, Cryer P, Sheline Y. et al. Memory improvement following induced hyperinsulinemia in Alzheimer's disease. Neurobiol Aging 1996; 17 (01) 123-130 https://doi.org/10.1016/0197-4580(95)02002-0
• 27 Rey A. L'examen Clinique En Psychologie. 2. Paris: Presse Universitaires de France; 1964
• 28 Possin KL, Laluz VR, Alcantar OZ, Miller BL, Kramer JH. Distinct neuroanatomical substrates and cognitive mechanisms of figure copy performance in Alzheimer's disease and behavioral variant frontotemporal dementia. Neuropsychologia 2011; 49 (01) 43-48 https://doi.org/10.1016/j.neuropsychologia.2010.10.026
• 29 Berg EA. A simple objective technique for measuring flexibility in thinking. J Gen Psychol 1948; 39: 15-22 https://doi.org/10.1080/00221309.1948.9918159
• 30 Stroop JR. Studies of interference in serial verbal reaction. J Exp Psychol 1935; 18 (06) 643-662 https://doi.org/10.1037/h0054651
• 31 Butman J, Allegri RF, Harris P, Drake M. Spanish verbal fluency. Normative data in Argentina. Medicina (B Aires) 2000; 60 (05) 561-564
• 32 Head H. Aphasia and Kindred Disorders of Speech (2 Volumes). New York (NY): Hafner Publishing Company; 1963
• 33 Ivanova I, Salmon DP, Gollan TH. The multilingual naming test in Alzheimer's disease: clues to the origin of naming impairments. J Int Neuropsychol Soc 2013; 19 (03) 272-283 https://doi.org/10.1017/S1355617712001282
• 34 Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G. et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 1989; 39 (09) 1159-1165 https://doi.org/10.1212/WNL.39.9.1159
• 35 Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67 (06) 361-370 https://doi.org/10.1111/j.1600-0447.1983.tb09716.x
• 36 Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 2006; 5 (09) P735-P741 https://doi.org/10.1016/S1474-4422(06)70537-3
• 37 WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020; 20 (08) e192-e197 https://doi.org/10.1016/S1473-3099(20)30483-7
• 38 Whiteside DM, Oleynick V, Holker E, Waldron EJ, Porter J, Kasprzak M. Neurocognitive deficits in severe COVID-19 infection: case series and proposed model. Clin Neuropsychol 2021; 35 (04) 799-818 https://doi.org/10.1080/13854046.2021.1874056
• 39 Ermis U, Rust MI, Bungenberg J, Costa A, Dreher M, Balfanz P. et al. Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients. Neurol Res Pract 2021; 3 (01) 17 https://doi.org/10.1186/s42466-021-00116-1
• 40 Tolentino JC, Gjorup ALT, Schmidt GJ, Schmidt SL. Early attention impairment in a patient with COVID-19. Psychiatry Clin Neurosci 2021; 75 (02) 66-67 https://doi.org/10.1111/pcn.13178
• 41 Robinson OJ, Vytal K, Cornwell BR, Grillom C. The impact of anxiety upon cognition: perspectives from human threat of shock studies. Front Hum Neurosci 2013; 7: 203 https://doi.org/10.3389/fnhum.2013.00203
• 42 Rogers JP, Chesney E, Oliver D, Pollak TA, McGuire P, Fusar-Poli P. 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 (07) P611-P627 https://doi.org/10.1016/S2215-0366(20)30203-0
• 43 Kanmogne GD, Fonsah JY, Umlauf A, Moul J, Doh RF, Kengne AM. et al. Effects of HIV infection, antiretroviral therapy, and immune status on the speed of information processing and complex motor functions in adult Cameroonians. Sci Rep 2020; 10 (01) 14016 https://doi.org/10.1038/s41598-020-70981-4
• 44 Raper J, Kovacs-Balint Z, Mavigner M, Gumber S, Burke MW, Habib J. et al. Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques. Nat Commun 2020; 11 (01) 2534 https://doi.org/10.1038/s41467-020-16320-7