Frequency and profile of objective cognitive deficits in hospitalized patients recovering from COVID-19

Jaywant, Abhishek; Vanderlind, W. Michael; Alexopoulos, George S.; Fridman, Chaya B.; Perlis, Roy H.; Gunning, Faith M.

doi:10.1038/s41386-021-00978-8

Cited by 248Long-Term Effects of COVID-19Intensive Care Unit Cognitive DisordersCOVID-19 Clinical Research Studies

Frequency and profile of objective cognitive deficits in hospitalized patients recovering from COVID-19

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Jaywant, Abhishek, Vanderlind, W. Michael, Alexopoulos, George S., Fridman, Chaya B., Perlis, Roy H., Gunning, Faith M.·2021·Neuropsychopharmacology

DOI 10.1038/s41386-021-00978-8PMC PMC7884062

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Abstract

Early reports and case series suggest cognitive deficits occurs in some patients with COVID-19. We evaluated the frequency, severity, and profile of cognitive dysfunction in patients recovering from prolonged COVID-19 hospitalization who required acute inpatient rehabilitation prior to discharge. We analyzed cross-sectional scores from the Brief Memory and Executive Test (BMET) in a cohort of N = 57 COVID-19 patients undergoing inpatient rehabilitation, calculating the frequency of impairment based on neuropsychologist diagnosis and by age-normed BMET subtests. In total, 43 patients (75%) were male, 35 (61%) were non-white, and mean age was 64.5 (SD = 13.9) years. In total, 48 (84%) were previously living at home independently. Two patients had documented preexisting cognitive dysfunction; none had known dementia. Patients were evaluated at a mean of 43.2 (SD = 19.2) days after initial admission. In total, 50 patients (88%) had documented hypoxemic respiratory failure and 44 (77%) required intubation. Forty-six patients (81%) had cognitive impairment, ranging from mild to severe. Deficits were common in working memory (26/47 [55%] of patients), set-shifting (21/44 [47%]), divided attention (18/39 [46%]), and processing speed (14/35 [40%]). Executive dysfunction was not significantly associated with intubation length or the time from extubation to assessment, psychiatric diagnosis, or preexisting cardiovascular/metabolic disease. Attention and executive functions are frequently impaired in COVID-19 patients who require acute rehabilitation prior to discharge. Though interpretation is limited by lack of a comparator group, these results provide an early benchmark for identifying and characterizing cognitive difficulties after COVID-19. Given the frequency and pattern of impairment, easy-to-disseminate interventions that target attention and executive dysfunctions may be beneficial to this population.

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The changes in working memory, set-shifting, divided attention, and processing speed in recovering COVID-19 patients were not associated with intubation length, psychiatric and clinical diagnosis.
“not being associated with intubation length, psychiatric and clinical diagnosis [142].”
From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [142]
A recent article showed changes in working memory, set-shifting, divided attention, and processing speed in a cohort of 57 patients recovering from moderate or severe COVID-19.
“A recent article showed changes in working memory, set-shifting, divided attention, and processing speed in a cohort of 57 patients recovering from moderate/severe patients with COVID-19”
From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [142]

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Toniolo, S., the Management Group of the EAN Dementia and Cognitive Disorders Scientific Panel, Scarioni, M., Lorenzo, F. D., Hort, J., Georges, J., Tomić, S., Nobili, F. M., & Frederiksen, K. S. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210335 · Cited by 85 · see citing works
Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection Part 1: Cognitive functioning
Whiteside, D. M., Basso, M. R., Naini, S. M., Porter, J. N., Holker, E. G., Waldron, E. J., Melnik, T. E., Niskanen, N., & Taylor, S. E. (2022) · The Clinical Neuropsychologist · doi:10.1080/13854046.2022.2030412 · Cited by 86 · see citing works
“The existing literature on cognitive dysfunction following COVID-19 has mostly focused on relatively short-term outcomes (e.g., Almeria et al., 2020; Jaywant et al., 2021; Whiteside et al., 2021; Zhou et al., 2020); thus, this is one of the first studies to examine longer-term outcomes in both…”
Background
Cognitive Impairment in Non-critical, Mild-to-Moderate COVID-19 Survivors
Henneghan, A. M., Lewis, K., Gill, E. R., & Kesler, S. R. (2022) · Frontiers in Psychology · doi:10.3389/fpsyg.2022.770459 · Cited by 83 · see citing works
Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life
Miskowiak, K. W., Pedersen, J. K., Gunnarsson, D. V., Roikjer, T. K., Podlekareva, D. N., Hansen, H., Dall, C. H., & Johnsen, S. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.12.122 · Cited by 79 · see citing works
“2022), other studies found high frequencies of impairment across executive function, attention and memory (Bungenberg et al. 2022; CostasCarrera et al. 2022; Crivelli et al. 2022; Jaywant et al. 2021; Krishnan et al. 2022; Lopez-Leon et al. 2021; Mazza et al. 2021; Miskowiak et al. 2021; Miskowiak et al. 2022).”
Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer's disease via cGAS-STING
Gao, D., Hao, J.-P., Li, B., Zheng, C.-C., Miao, B.-B., Zhang, L., Li, Y., Li, L., Li, X., & Zhang, L. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175809 · Cited by 79 · see citing works
Neurotropism of SARS-CoV-2 and neurological diseases of the central nervous system in COVID-19 patients
Veleri, S. (2021) · Experimental Brain Research · doi:10.1007/s00221-021-06244-z · Cited by 76 · see citing works
Multi‐disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post‐acute sequelae of SARS‐CoV‐2 infection (PASC)
Fine, J. S., Ambrose, A. F., Didehbani, N., Fleming, T. K., Glashan, L., Longo, M. T., Merlino, A., Ng, R., Nora, G. J., Rolin, S. N., et al. (2021) · PM&R · doi:10.1002/pmrj.12745 · Cited by 70 · see citing works
SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?
Awan, H. A., Diwan, M. N., Aamir, A., Ali, M., Giannantonio, M. D., Ullah, I., Shoib, S., & Berardis, D. D. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10153441 · Cited by 67 · see citing works
Functional connectivity underlying cognitive and psychiatric symptoms in post-COVID-19 syndrome: is anosognosia a key determinant?
Voruz, P., Cionca, A., de Alcântara, I. J., Nuber‐Champier, A., Allali, G., Benzakour, L., Thomasson, M., Lalive, P. H., Lövblad, K., Braillard, O., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac057 · Cited by 68 · see citing works
Long COVID Neuropsychological Deficits after Severe, Moderate, or Mild Infection
Voruz, P., Allali, G., Benzakour, L., Nuber‐Champier, A., Thomasson, M., de Alcântara, I. J., Pierce, J. E., Lalive, P. H., Lövblad, K., Braillard, O., et al. (2022) · Clinical and Translational Neuroscience · doi:10.3390/ctn6020009 · Cited by 69 · see citing works
“Fourth, to our knowledge, only two studies have so far explored the short-term impact (10 40 days post-hospital discharge) of SARS-CoV-2 infection on cognition by using a validated and standardized methodology with face-to-face interviews [21,22].”
Postacute/Long COVID in Pediatrics
Morrow, A. K., Ng, R., Vargas, G., Jashar, D. T., Henning, E., Stinson, N., & Malone, L. A. (2021) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000001896 · Cited by 68 · see citing works
“On neuropsychological testing, patients are demonstrating impaired performance primarily with attention as opposed to other domains, such as executive functioning or working memory, which has been reported in the adult literature.(39,47) Elevated anxiety and depression symptoms are also commonly reported.”
Background
Neurocognitive deficits in severe COVID-19 infection: Case series and proposed model
Whiteside, D. M., Oleynick, V. C., Holker, E. G., Waldron, E. J., Porter, J. N., & Kasprzak, M. (2021) · The Clinical Neuropsychologist · doi:10.1080/13854046.2021.1874056 · Cited by 65 · see citing works
“Similarly, another paper on medRxiv by Jaywant et al. (2020) used the Brief Memory and Executive Test (BMET) and identified attention and executive functions as the most commonly affected cognitive domains among medically-stable inpatients recovering from COVID-19.”
MethodResult
COVID-19 causes neuronal degeneration and reduces neurogenesis in human hippocampus
Bayat, A., Azimi, H., Moghaddam, M. H., Ebrahimi, V., Fathi, M., Vakili, K. G., Mahmoudiasl, G., Forouzesh, M., Boroujeni, M. E., Nariman, Z., et al. (2022) · APOPTOSIS · doi:10.1007/s10495-022-01754-9 · Cited by 64 · see citing works
Brain functional connectivity alterations associated with neuropsychological performance 6–9 months following SARS‐CoV ‐2 infection
Voruz, P., Cionca, A., de Alcântara, I. J., Nuber‐Champier, A., Allali, G., Benzakour, L., Lalive, P. H., Lövblad, K., Braillard, O., Nehme, M., et al. (2022) · Human Brain Mapping · doi:10.1002/hbm.26163 · Cited by 60 · see citing works
“…et al., 2021; Raman et al., 2021; Solaro et al., 2021; Udina et al., 2021), memory functions (Almeria et al., 2020; Hampshire et al., 2021; Jaywant et al., 2021; Whiteside et al., 2021; Woo et al., 2020), attention (Alemanno et al., 2021; Almeria et al., 2020; Hampshire et al., 2021),…”
Background
WITHDRAWN: SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer’s-like neuropathologyPreprint
Shen, W., Elahi, M., Logue, J., Yang, P., Baracco, L., Reece, E. A., Wang, B., Li, L., Blanchard, T. G., Han, Z., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.31.478476 · Cited by 60 · see citing works
Multidomain cognitive impairment in non-hospitalized patients with the post-COVID-19 syndrome: results from a prospective monocentric cohort
Schild, A., Goereci, Y., Scharfenberg, D., Klein, K., Lülling, J., Meiberth, D. U., Schweitzer, F., Stürmer, S., Zeyen, P., Şahin, D., et al. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11444-w · Cited by 56 · see citing works
Cognitive Symptoms of Post–COVID-19 Condition and Daily Functioning
Jaywant, A., Gunning, F. M., Oberlin, L. E., Santillana, M., Ognyanova, K., Druckman, J. N., Baum, M., Lazer, D. M. J., & Perlis, R. H. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.56098 · Cited by 54 · see citing works
Self-citation
Cognitive domains affected post‐COVID ‐19; a systematic review and meta‐analysis
Fanshawe, J. B., Sargent, B., Badenoch, J., Saini, A., Watson, C. J., Pokrovskaya, A., Aniwattanapong, D., Conti, I., Nye, C., Burchill, E., et al. (2024) · European Journal of Neurology · doi:10.1111/ene.16181 · Cited by 48 · see citing works
Cognitive Impairment after Post-Acute COVID-19 Infection: A Systematic Review of the Literature
Perrottelli, A., Sansone, N., Giordano, G. M., Caporusso, E., Giuliani, L., Melillo, A., Pezzella, P., Bucci, P., Mucci, A., & Galderisi, S. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12122070 · Cited by 46 · see citing works
“Another cognitive domain severely affected following SARS-CoV-2 infection was the speed of processing that were impaired in 9 studies [46,54,63,65,76,81,83,91,100] out of 26.”
Multidisciplinary outpatient rehabilitation of physical and neurological sequelae and persistent symptoms of covid-19: a prospective, observational cohort study
Albu, S., Zozaya, N. R., Murillo, N., García‐Molina, A., Chacón, C. A. F., & Kumru, H. (2021) · Disability and Rehabilitation · doi:10.1080/09638288.2021.1977398 · Cited by 47 · see citing works
Objective and subjective cognition in survivors of COVID-19 one year after ICU discharge: the role of demographic, clinical, and emotional factors
Godoy-González, M., Navarra‐Ventura, G., Gomà, G., de Haro, C., Espinal, C., Fortià, C., Ridao, N., Rebanal, N. M., Oliveras-Furriols, L., Subirá, C., et al. (2023) · Critical Care · doi:10.1186/s13054-023-04478-7 · Cited by 42 · see citing works
Neuropsychological deficits in patients with persistent COVID-19 symptoms: a systematic review and meta-analysis
Sobrino-Relaño, S., Balboa-Bandeira, Y., Peña, J., Ibarretxe‐Bilbao, N., Zubiaurre‐Elorza, L., & Ojeda, N. (2023) · Scientific Reports · doi:10.1038/s41598-023-37420-6 · Cited by 42 · see citing works
Long-term cognitive impairments following COVID-19: a possible impact of hypoxia
Dondaine, T., Ruthmann, F., Vuotto, F., Carton, L., Gelé, P., Faure, K., Deplanque, D., & Bordet, R. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11077-z · Cited by 39 · see citing works
“[13] showed that 81% of patients with a severe form of COVID-19 (77% had been intubated for a mean duration of 13 days) had a cognitive impairment, although the latter might have resulted from the care received in the intensive care unit (ICU) [14, 15].”
Background
Neurological and (neuro)psychological sequelae in intensive care and general ward COVID ‐19 survivors
Klinkhammer, S., Horn, J., Duits, A., Visser‐Meily, J. M. A., Verwijk, E., Slooter, A. J. C., Postma, A. A., Heugten, C. M. V., & NeNeSCo Study Group (2023) · European Journal of Neurology · doi:10.1111/ene.15812 · Cited by 39 · see citing works
“Preselection of patients with cognitive complaints or neurological symptoms, as employed by some studies, could have also led to a higher prevalence of dysfunction [36].”
Background
Cognitive Assessment in SARS-CoV-2 Patients: A Systematic Review
Biagianti, B., Di Liberto, A., Nicolò Edoardo, A., Lisi, I., Nobilia, L., de Ferrabonc, G. D., Zanier, E. R., Stocchetti, N., & Brambilla, P. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.909661 · Cited by 41 · see citing works
Vascular Dysfunctions Contribute to the Long-Term Cognitive Deficits Following COVID-19
Shabani, Z., Liu, J., & Su, H. (2023) · Biology · doi:10.3390/biology12081106 · Cited by 40 · see citing works
“In addition, a recent cross-sectional report studied the connection between COVID-19 disease and cognitive signs in 57 hospitalized participants and found a high prevalence of cognitive impairment (>80% of the sample), primarily in the fields of attention and executive function [28].”
Background
Frequency of Abnormally Low Neuropsychological Scores in Post-COVID-19 Syndrome: the Geneva COVID-COG Cohort
Voruz, P., de Alcântara, I. J., Nuber‐Champier, A., Cionca, A., Allali, G., Benzakour, L., Lalive, P. H., Lövblad, K.-O., Braillard, O., Nehme, M., et al. (2022) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acac068 · Cited by 35 · see citing works
“Although research has highlighted a high frequency of neuropsychological deficits in various cognitive functions (Almeria et al., 2020; Jaywant et al., 2021; Krishnan et al., 2022), authors have not envisaged the possibility that this frequency could be comparable with that observed in a normative population (Binder e…”
BackgroundResult
Mechanisms of coronavirus infectious disease 2019-related neurologic diseases
Klein, R. S. (2022) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001049 · Cited by 33 · see citing works
SARS‐CoV ‐2, aging, and Post‐COVID ‐19 neurodegeneration
Strong, M. J. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15736 · Cited by 34 · see citing works
“…these neurological deficits which are often present to the same degree as that observed in the acute or subacute phase (Alemanno et al., 2021; Ali et al., 2022; Del Brutto et al., 2021; Graham et al., 2021; Hampshire et al., 2021; Jaywant et al., 2021; Pistarini et al., 2021; Woo et al., 2020).”
Background
COVID-19 and Neurodegenerative Diseases: Prion-Like Spread and Long-Term Consequences
Baazaoui, N., & Iqbal, K. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220105 · Cited by 32 · see citing works
“Indeed, at the time of the discharge, nearly 81% of the survivors of an acute respiratory distress syndrome exhibited cognitive impairment and that after 3 months 40% of them who were critically ill had at least mild cognitive deficits and 26% had moderate cognitive deficits [76].”
Background
Disentangling the cognitive, physical, and mental health sequelae of COVID-19
Wild, C. J., Norton, L. E., Menon, D. K., Ripsman, D., Swartz, R. H., & Owen, A. M. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100750 · Cited by 32 · see citing works
“21 17–20,23– 26 Second, how does the emergence of cognitive deﬁcits following COVID-19 infection relate to the severity of the primary”
Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson’s Disease?
Krey, L., Huber, M. K., Höglinger, G. U., & Wegner, F. (2021) · Brain Sciences · doi:10.3390/brainsci11121654 · Cited by 31 · see citing works
The negative impact of COVID-19 on working memory revealed using a rapid online quiz
Baseler, H. A., Aksoy, M., Salawu, A., Green, A., & Asghar, A. U. R. (2022) · PLoS ONE · doi:10.1371/journal.pone.0269353 · Cited by 31 · see citing works
“Using this methodological approach, short-term memory deficits have been reported for COVID-19 in some studies, although these investigations have been limited to small cohorts (6–87 patients) [5,15,16,18,19].”
MethodResult
Subjective and Objective Cognitive Impairments in Non-Hospitalized Persons 9 Months after SARS-CoV-2 Infection
Kirchberger, I., Peilstöcker, D., Warm, T. D., Linseisen, J., Hyhlik-Dürr, A., Meisinger, C., & Goßlau, Y. (2023) · Viruses · doi:10.3390/v15010256 · Cited by 31 · see citing works
“[36] found mild to severe cognitive impairment in 81% of 57 COVID-19 patients 7 days after diagnosis.”
Background
Description and Functional Outcomes of a Novel Interdisciplinary Rehabilitation Program for Hospitalized Patients With COVID-19
Patel, N., Steinberg, C., Patel, R., Chomali, C., Doulatani, G., Lindsay, L., & Jaywant, A. (2021) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000001897 · Cited by 30 · see citing works
Self-citation
Cognitive impairment and functional change in COVID-19 patients undergoing inpatient rehabilitation
Patel, R., Savrides, I., Cahalan, C., Doulatani, G., O’Dell, M. W., Toglia, J. P., & Jaywant, A. (2021) · International Journal of Rehabilitation Research · doi:10.1097/mrr.0000000000000483 · Cited by 30 · see citing works
“Seventeen patients were not administered our cognitive measure because (1) they were 59 admitted prior to knowledge of COVID-19-related cognitive deficits and the implementation of 60 our screening protocol; (2) clinicians deemed it could not be reliably administered due to 61 language barriers; or (3) clinicians deem…”
BackgroundSelf-citation
The Effects of Extrinsic and Intrinsic Factors on Neurogenesis
Jiang, M. H., Jang, S. E., & Zeng, L. (2023) · Cells · doi:10.3390/cells12091285 · Cited by 31 · see citing works
Neurological manifestation in COVID-19 disease with neuroimaging studies.
Ghaderi, S., Olfati, M., Ghaderi, M., Hadizadeh, H., Yazdanpanah, G., Khodadadi, Z., Karami, A., Papi, Z., Abdi, N., Jalali, S. S. S., et al. (2023) · PubMed Central · Cited by 28 · see citing works
Citicoline and COVID-19-Related Cognitive and Other Neurologic Complications
Turana, Y., Nathaniel, M., Shen, R., Ali, S., & Aparasu, R. R. (2021) · Brain Sciences · doi:10.3390/brainsci12010059 · Cited by 33 · see citing works
“With regard to COVID-19 severity, 88% of the patients had hypoxemic respiratory failure and 77% required intubation [16].”
Background
Dementia Clinical Care in Relation to COVID-19
Bianchetti, A., Rozzini, R., Bianchetti, L., Coccia, F., Guerini, F., & Trabucchi, M. (2022) · Current Treatment Options in Neurology · doi:10.1007/s11940-022-00706-7 · Cited by 29 · see citing works
Rehabilitation Strategies for Cognitive and Neuropsychiatric Manifestations of COVID-19
Rolin, S. N., Chakales, A., & Verduzco‐Gutierrez, M. (2022) · Current Physical Medicine and Rehabilitation Reports · doi:10.1007/s40141-022-00352-9 · Cited by 29 · see citing works
Perceived Cognitive Deficits in Patients With Symptomatic SARS-CoV-2 and Their Association With Post–COVID-19 Condition
Liu, T. C., Yoo, S., Sim, M., Motwani, Y., Viswanathan, N., & Wenger, N. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.11974 · Cited by 30 · see citing works
The unique contribution of depression to cognitive impairment in Post-Acute Sequelae of SARS-CoV-2 infection
Brown, L. A., Ballentine, E., Zhu, Y., McGinley, E. L., Pezzin, L. E., & Abramoff, B. A. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100460 · Cited by 30 · see citing works
Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment
Zhao, J., Xia, F., Jiao, X., & Lyu, X. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1367974 · Cited by 28 · see citing works
Cognitive remediation therapy for post-acute persistent cognitive deficits in COVID-19 survivors: A proof-of-concept study
Palladini, M., Bravi, B., Colombo, F., Caselani, E., Pasquasio, C. D., D'Orsi, G., Rovere, P. Q., Poletti, S., Benedetti, F., & Mazza, M. G. (2022) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2022.2075016 · Cited by 28 · see citing works
“…the specific cognitive domains, previous studies found that executive function and verbal fluency were among the most affected cognitive domains (Almeria et al., 2020; Beaud et al., 2021; Hampshire et al. 2020; Helms et al., 2020; Jaywant et al., 2021) both in acute and sub-acute stages.”
BackgroundResultInfluential
Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories
Llana, T., Méndez, M., Zorzo, C., Fidalgo, C., Juan, M. ‐., & Méndez-López, M. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1082811 · Cited by 28 · see citing works
“, 2021), memory is the predominant function altered, but also executive functions and visuospatial function (Ardila and Lahiri, 2020; Beaud et al., 2021; Jaywant et al., 2021; Llana et al., 2022).”
Background
Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection part 2: Psychological functioning
Whiteside, D. M., Naini, S. M., Basso, M. R., Waldron, E. J., Holker, E. G., Porter, J. N., Niskanen, N., Melnik, T. E., & Taylor, S. E. (2022) · The Clinical Neuropsychologist · doi:10.1080/13854046.2022.2030411 · Cited by 27 · see citing works
“In addition to finding cognitive deficits in nearly half of patients, 40% of the participants also reported psychiatric symptoms, with 23% having an adjustment disorder, 3% with major depressive disorder (MDD), and 11% with anxiety or mood disorders (Jaywant et al., 2021).”
Background
Chronic neuropsychiatric sequelae of SARS‐CoV‐2: Protocol and methods from the Alzheimer's Association Global Consortium
de Erausquin, G. A., Snyder, H. M., Brugha, T. S., Seshadri, S. S., Carrillo, M. C., Sagar, R., Huang, Y., Newton, C. R. J. C., Tartaglia, M. C., Teunissen, C. E., et al. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12348 · Cited by 26 · see citing works
Cognitive impairment in health care workers recovering from COVID-19 infection: a cross-sectional comparative study
Omar, A. K. A.-E., Dahesh, S. M. A., Ellakwa, D. E., Gomaa, M. K., Abdulsamad, B., Hanafy, R., Metwally, H. G. A., Mohammad, R. N. E. M., Badawy, S. S., Saleh, R. M. E., et al. (2022) · Middle East Current Psychiatry · doi:10.1186/s43045-022-00245-6 · Cited by 27 · see citing works
Neuropsychological Pattern in a Series of Post-Acute COVID-19 Patients in a Rehabilitation Unit: Retrospective Analysis and Correlation with Functional Outcomes
Pietro, D. A. D., Comini, L., Gazzi, L., Luisa, A., & Vitacca, M. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18115917 · Cited by 26 · see citing works
“In a series of 57 patients, deficits were common in working memory, set-shifting, divided attention and processing speed, without significant association with intubation length [5].”
Background
Case-control study of neuropsychiatric symptoms in electronic health records following COVID-19 hospitalization in 2 academic health systems
Castro, V. M., Rosand, J. M., Giacino, J. T., McCoy, T. H., & Perlis, R. H. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01646-z · Cited by 26 · see citing works
“For example, a small study suggested that the pattern of neuropsychiatric deficits immediately following hospitalization was non-specific and resembled that observed in individuals without COVID-19 [10].”
ResultInfluentialSelf-citation
Long-covid cognitive impairment: Cognitive assessment and apolipoprotein E (APOE) genotyping correlation in a Brazilian cohort
Tavares-Júnior, J. W. L., Oliveira, D. N., da Silva, J. B. S., Feitosa, W. L. Q., Sousa, A. V. M., Cunha, L. C. V., Gaspar, S. D. B., Gomes, C. M. P., de Oliveira, L. L. B., Moreira-Nunes, C. A., et al. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.947583 · Cited by 26 · see citing works
“The most affected cognitive impairment group domain in ACE-R sub-items was the memory, as found in other studies (56, 57), which is relevant because limbic structures may suffer from inflammation (58).”
Result
Memory alterations after COVID-19 infection: a systematic review
Llana, T., Zorzo, C., Méndez-López, M., & Méndez, M. (2022) · Applied Neuropsychology Adult · doi:10.1080/23279095.2022.2123739 · Cited by 26 · see citing works
“The long-COVID-19 syndrome neuropsychological deficits affect attention, frontal/executive functions, memory, and visuospatial function (Ardila & Lahiri, 2020; Beaud et al., 2021; Jaywant et al., 2021).”
Background
Clinical features and cognitive sequelae in COVID-19: a retrospective study on N=152 patients
Manera, M. R., Fiabane, E., Pain, D., Aiello, E. N., Radici, A., Ottonello, M., Padovani, M., Wilson, B. A., Fish, J. E., & Pistarini, C. (2021) · Neurological Sciences · doi:10.1007/s10072-021-05744-8 · Cited by 25 · see citing works
“Furthermore, ICU admission being shown to affect global cognition but not specific instrumental domains further supports the notion that COVID-19-related cognitive deficits are likely to reflect a decrease in general cognitive efficiency—which is typical of critical illnesses also affecting the CNS [15].”
Background
Markers of limbic system damage following SARS-CoV-2 infection
Thomasson, M., Voruz, P., Cionca, A., de Alcântara, I. J., Nuber‐Champier, A., Allali, G., Benzakour, L., Lalive, P. H., Lövblad, K., Braillard, O., et al. (2023) · Brain Communications · doi:10.1093/braincomms/fcad177 · Cited by 25 · see citing works
Patients recovering from COVID-19 who presented with anosmia during their acute episode have behavioral, functional, and structural brain alterations
Kausel, L., Figueroa-Vargas, A., Zamorano, F. J., Stecher, X., Aspé-Sánchez, M., Carvajal-Paredes, P., Márquez-Rodríguez, V., Martínez-Molina, M. P., Román, C., Soto-Fernández, P., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-69772-y · Cited by 24 · see citing works
“Most of the research that has identified manifest cognitive deficits typically involves more severe respiratory cases of COVID-19 33–35 or those who present neurological symptoms during the acute episode.”
Background
Neuropsychological Outcomes in Adult Patients and Survivors of COVID-19
May, P. E. (2022) · Pathogens · doi:10.3390/pathogens11040465 · Cited by 24 · see citing works
“[21]), this neuropsychological pattern could be a by-product of the selected test battery.”
Background
Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients
Michael, B. D., Walton, D., Westenberg, E., García‐Azorín, D., Singh, B., Tamborska, A., Netravathi, M., Chomba, M., Wood, G. K., Easton, A., et al. (2021) · Journal of Neuropsychiatry · doi:10.1176/appi.neuropsych.22010002 · Cited by 25 · see citing works
Semantic-Powered Explainable Model-Free Few-Shot Learning Scheme of Diagnosing COVID-19 on Chest X-Ray
Wang, Y., Jiang, C., Wu, Y., Lv, T., Sun, H., Liu, Y., Li, L., & Pan, X. (2022) · IEEE Journal of Biomedical and Health Informatics · doi:10.1109/jbhi.2022.3205167 · Cited by 24 · see citing works
The functional and structural changes in the hippocampus of COVID-19 patients
Nouraeinejad, A. (2023) · Acta Neurologica Belgica · doi:10.1007/s13760-023-02291-1 · Cited by 25 · see citing works
“Studies have extensively illustrated that “long COVID” after discharge from hospital consist of an assortment of neuropsychiatric complaints, such as defective instant verbal memory and learning, deferred verbal memory difficulties, verbal fluency problems, working memory issues, anxiety, depression, and post-traumati…”
Background
Personalized Computerized Training for Cognitive Dysfunction after COVID-19: A Before-and-After Feasibility Pilot Study
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Neurocovid-19: efectos del COVID-19 en el cerebro
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Cognitive function following SARS-CoV-2 infection in a population-representative Canadian sample
Hall, P. A., Meng, G., Hudson, A., Sakib, M. N., Hitchman, S. C., MacKillop, J. M., Bickel, W. K., & Fong, G. T. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100454 · Cited by 22 · see citing works
“Several studies have reported reliable evidence of cognitive dysfunction among those previously infected with SARS-CoV-2 (Jaywant et al., 2021; Becker et al., 2021; Liu et al., 2021; Almeria et al., 2020; Hampshire et al., 2021).”
Cognitive impairment in post-acute COVID-19 syndrome: a scoping review
Cipolli, G. C., Alonso, V., Yasuda, C. L., de Assumpção, D., Cachioni, M., de Melo, R. C., Hinsliff‐Smith, K., & Yassuda, M. S. (2023) · Arquivos de Neuro-Psiquiatria · doi:10.1055/s-0043-1777115 · Cited by 22 · see citing works
Vitamin K in COVID-19—Potential Anti-COVID-19 Properties of Fermented Milk Fortified with Bee Honey as a Natural Source of Vitamin K and Probiotics
Ali, A. M., Kunugi, H., Abdelmageed, H. A., Mandour, A. S., Ahmed, M. E., Ahmad, S., & Hendawy, A. O. (2021) · Fermentation · doi:10.3390/fermentation7040202 · Cited by 20 · see citing works
“The occurrence of these disorders is higher in older patients [35,36,151,152].”
Background
Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: a multivariate causality model analysis
García-Grimshaw, M., Chirino‐Pérez, A., Flores-Silva, F. D., Valdés-Ferrer, S. I., Vargas-Martínez, M. D. L. Á., Jiménez-Ávila, A. I., Chávez-Martínez, O. A., Ramos-Galicia, E. M., Marché-Fernández, O. A., Ramírez-Carrillo, M. F., et al. (2022) · Neurological Sciences · doi:10.1007/s10072-021-05798-8 · Cited by 20 · see citing works
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Systematic Review and Meta-Analysis of Clinically Relevant Executive Functions Tests Performance after COVID-19
Velichkovsky, B. B., Razvaliaeva, A. Y., Khlebnikova, A. A., Manukyan, P. A., Kasatkin, V. N., & Barmin, A. V. (2023) · Behavioural Neurology · doi:10.1155/2023/1094267 · Cited by 22 · see citing works
“earlier systematic analyses [45, 46] and further validate their points by pooling effect sizes from studies with healthy control groups.”
Background
Akinetic Mutism and Coronavirus Disease 2019: A Narrative Review
Fusunyan, M. A., Praschan, N. C., Fricchione, G. L., & Beach, S. R. (2021) · Journal of the Academy of Consultation-Liaison Psychiatry · doi:10.1016/j.jaclp.2021.08.009 · Cited by 19 · see citing works
“Mild perfusion abnormalities persisted in these regions through 6-month follow-up, which may reflect a shared substrate between AM and longerlasting executive dysfunction observed in many postCOVID patients.(45)”
Background
Neurocognitive deficits in COVID-19 patients five months after discharge from hospital
Thornberg, U. B., Andersson, A., Lindh, M., Hellgren, L., Divanoglou, A., & Levi, R. (2022) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2022.2125020 · Cited by 19 · see citing works
“…other test batteries reporting 18% of patients scoring below a cut-o ﬀ of 2 SD on The Brief Memory and Executive Test (BMET) rapid letter-number matching (Jaywant et al., 2021), and approximately 40% below norms using symbol digits modality test (SDMT) (Ferrucci et al., 2021; Mazza et al., 2021).”
BackgroundMethodResultInfluential
Attention profile of physically recovered COVID-19 inpatients on the day of discharge
Filho, Á. D. C., van Duinkerken, E., Tolentino, J. C., & Schmidt, S. L. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.03.047 · Cited by 19 · see citing works
Neurocircuitry Hypothesis and Clinical Experience in Treating Neuropsychiatric Symptoms of Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2
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“7,8 While a direct causal relationship has not been established, many studies addressing neuropsychological pro ﬁ les of post-Covid infection had consistent results: signi ﬁ cantly lower scores in cognition with the lowest subscores in attention, verbal ﬂ uency, and executive function followed by…”
Long-term cognitive dysfunction after the COVID-19 pandemic: a narrative review
Shariff, S., Uwishema, O., Mizero, J., Thambi, V. D., Nazir, A., Mahmoud, A., Kaushik, I., Khayat, S., Maigoro, A. Y., Awde, S., et al. (2023) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000001265 · Cited by 18 · see citing works
“COVID-19 impairs cognitive function by affecting several domains, including problem-solving, attention, working memory, and executive functioning [7,52,]64 – 66 .”
Cognitive Deficits in the Acute Phase of COVID-19: A Review and Meta-Analysis
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The Effects of Royal Jelly Acid, 10-Hydroxy-trans-2-decenoic Acid, on Neuroinflammation and Oxidative Stress in Astrocytes Stimulated with Lipopolysaccharide and Hydrogen Peroxide
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“81% of patients) in patients who were cognitively intact before contracting COVID-19 [6,7].”
BackgroundInfluential
Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies
Hall, P. A., Ayaz, H., Meng, G., Hudson, A., Sakib, M. N., Quah, A. C. K., Agar, T. K., Lee, J. A., Boudreau, C., & Fong, G. T. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100595 · Cited by 16 · see citing works
“…studies have shown that symptomatic COVID-19 is associated with poorer performance on cognitive tasks (Becker et al., 2021; Hampshire et al., 2021; Jaywant et al., 2021), more self-reported symptoms of cognitive dysfunction (Hall et al., 2022b), and prospective changes in structural brain…”
The impact of COVID-19 on cognition in severe cases highlights the need for comprehensive neuropsychological evaluations in all survivors
Burdick, K. E., & Millett, C. E. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-00995-7 · Cited by 16 · see citing works
Dutch multicentre, prospective follow-up, cohort study comparing the neurological and neuropsychological sequelae of hospitalised non-ICU- and ICU-treated COVID-19 survivors: a study protocol
Klinkhammer, S., Horn, J., Visser‐Meily, J. M. A., Verwijk, E., Duits, A., Slooter, A. J. C., & Heugten, C. M. V. (2021) · BMJ Open · doi:10.1136/bmjopen-2021-054901 · Cited by 15 · see citing works
“11 Furthermore, cognitive dysfunction may be associated with cognitive complaints.”
Acute and long-term neurological disorders in patients with coronavirus infection
Parfenov, V. A., & Kulesh, A. A. (2022) · Neurology neuropsychiatry Psychosomatics · doi:10.14412/2074-2711-2022-3-4-11 · Cited by 14 · see citing works
Long COVID: neurological manifestations - an updated narrative review
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“A systematic review selected studies that evaluated the recovery of anosmia in patients after 1, 2, and between 3–6 months after COVID-19, showing hyposmia in 37.4, 36.7, and 36.5% of patients, respectively 60 .”
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Neurocognitive and psychiatric post-coronavirus disease 2019 conditions: pathogenic insights of brain dysfunction following severe acute respiratory syndrome coronavirus 2 infection
García-Grimshaw, M., Sankowski, R., & Valdés‐Ferrer, S. I. (2022) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001046 · Cited by 15 · see citing works
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Kognitive Störungen und Schlafstörungen bei Long-COVID
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“All of these forms of cognitive impairment reflect fronto-striatal neuronal dysfunction (69, 70).”
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Greater executive dysfunction in patients post-COVID-19 compared to those not infected
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Cognitive Deficits in Patients with COVID-19 Infection during Their Hospital Stay: An Exploratory Study
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COVID-19 cognitive deficits after respiratory assistance in the subacute phase: A COVID-rehabilitation unit experience
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Authors: Jaywant, A., Vanderlind, W. M., Alexopoulos, G. S., Fridman, C. B., Perlis, R. H., & Gunning, F. M.
Affiliations: NewYork–Presbyterian Hospital (US)
Weill Cornell Medicine (US)
Harvard University (US)
Corresponding author: Gunning, Faith M.
ORCID: Jaywant, Abhishek
Vanderlind, W. Michael
Alexopoulos, George S.
Perlis, Roy H.
Gunning, Faith M.
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2021-02-15
Volume: 46
Issue: 13
Pages: 2235-2240
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/s41386-021-00978-8
PMC: PMC7884062
OpenAlex: W3132403899
Cited by: 248
References: 45
Citations by year: 2026: 12 · 2025: 19 · 2024: 35 · 2023: 64 · 2022: 84 · 2021: 34
FWCI: 25.96
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Neuropsychopharmacology (publishedVersion)
medRxiv (acceptedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords: COVID-19 pandemic, post-COVID cognitive impairment, cognitive impairment, inpatient rehabilitation, executive dysfunction, attention deficits, working memory, set-shifting, divided attention, processing speed, hypoxemic respiratory failure, intubation, hospitalized patients
MeSH terms: COVID-19, SARS-CoV-2, Cognition, Cross-Sectional Studies, Humans, Male, Middle Aged, Neuropsychological Tests, Cognitive Dysfunction

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Frequency and profile of objective cognitive deficits in hospitalized patients recovering from COVID-19

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