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Bălăeţ M, Zadel A, Lingford-Hughes A, Paterson LM, Chamberlain SR, Trender W, Hellyer PJ, Hampshire A. Changes in recreational drug use, reasons for those changes and their consequence during and after the COVID-19 pandemic in the UK. Compr Psychiatry 2025; 140:152598. [PMID: 40250155 DOI: 10.1016/j.comppsych.2025.152598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 04/08/2025] [Accepted: 04/14/2025] [Indexed: 04/20/2025] Open
Abstract
Changes in drug use in the general population during the COVID-19 pandemic and their long-term consequences are not well understood. We employed natural language processing and machine learning to analyse a large dataset of self-reported rates of and reasons for drug use during the pandemic, along with their associations with anxiety, depression and substance use problems post-pandemic. Our findings revealed a transient decrease in drug use at the pandemic's peak, primarily attributed to reduced social opportunities. Conversely, some participants reported increased drug use for self-medication, boredom, and lifestyle disruptions. While users of psychedelics and MDMA had anxiety and depression rates similar to non-users, users of opioid agonists and depressants-representing one in ten active drug users-reported greater mental health challenges post-pandemic. These results suggest that a subset of active drug users with distinct profiles faces elevated risks, particularly for anxiety and depression, and may benefit from targeted support.
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Affiliation(s)
- Maria Bălăeţ
- Department of Brain Sciences, Imperial College London, London, UK; Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
| | - Ana Zadel
- Department of Biology, University of Lund, Sweden
| | - Anne Lingford-Hughes
- Department of Brain Sciences, Imperial College London, London, UK; Division of Psychiatry, Imperial College London, London, UK
| | - Louise M Paterson
- Department of Brain Sciences, Imperial College London, London, UK; Division of Psychiatry, Imperial College London, London, UK
| | - Samuel R Chamberlain
- Department of Psychiatry, Faculty of Medicine, University of Southampton, UK; Southern Health NHS Foundation Trust, Southampton, UK
| | - William Trender
- Department of Brain Sciences, Imperial College London, London, UK
| | - Peter J Hellyer
- Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Adam Hampshire
- Department of Brain Sciences, Imperial College London, London, UK; Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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2
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Samanci B, Ay U, Gezegen H, Yörük SS, Medetalibeyoğlu A, Kurt E, Şahin E, Doğan FU, Barbüroğlu M, Bilgiç B, Hanağası H, Gürvit H. Persistent neurocognitive deficits in long COVID: Evidence of structural changes and network abnormalities following mild infection. Cortex 2025; 187:98-110. [PMID: 40318391 DOI: 10.1016/j.cortex.2025.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 03/26/2025] [Accepted: 04/07/2025] [Indexed: 05/07/2025]
Abstract
This study aimed to investigate the neurocognitive deficits, structural brain alterations, and network abnormalities in individuals who had a mild SARS-CoV-2 infection, with and without brain fog, as a symptom of long COVID. A cross-sectional study was conducted involving 75 participants, categorized into three groups: 24 healthy controls (HCs), 26 COVID-19 survivors without brain fog (woFOG), and 25 with brain fog (wFOG). Neuropsychological assessments included the Free and Cued Selective Reminding Test (FCSRT) and Addenbrooke's Cognitive Examination-Revised (ACE-R). Structural and functional brain alterations were examined using voxel-based morphometry (VBM) and resting-state functional MRI (rs-fMRI). The wFOG group exhibited significant cognitive impairments, particularly in delayed free recall, attention, memory, and visuospatial skills, compared to both the woFOG and HC groups. Structural MRI analyses revealed reduced gray matter concentrations (GMC) in the left inferior temporal gyrus, left fusiform gyrus, and right orbital gyri in both COVID-19 groups relative to HCs. Additionally, the wFOG group exhibited further GMC reductions in the bilateral caudate nuclei, right putamen/pallidum, and amygdala compared to the woFOG group. rs-fMRI analyses demonstrated altered connectivity patterns in COVID-19 survivors, characterized by increased connectivity in the default mode network and visual networks, alongside decreased connectivity in the dorsal attention network. These findings indicate that even mild COVID-19 can result in persistent neurocognitive deficits, structural brain alterations, and functional network abnormalities, both in individuals with and without brain fog. The observed changes highlight the importance of long-term monitoring and targeted interventions to address potential cognitive and neurological consequences of long COVID.
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Affiliation(s)
- Bedia Samanci
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
| | - Ulaş Ay
- Neuroimaging Unit, Hulusi Behçet Life Sciences Research Laboratory, Istanbul University, Istanbul, Turkey; Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Haşim Gezegen
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Sanem Sultan Yörük
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Alpay Medetalibeyoğlu
- Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Elif Kurt
- Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Erdi Şahin
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Faruk Uğur Doğan
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehmet Barbüroğlu
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Başar Bilgiç
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Haşmet Hanağası
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Hakan Gürvit
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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3
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Takács J, Deák D, Seregély B, Koller A. Cognitive Slowing, Dysfunction in Verbal Working Memory, Divided Attention and Response Inhibition in Post COVID-19 Condition in Young Adults. Life (Basel) 2025; 15:821. [PMID: 40430247 DOI: 10.3390/life15050821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2025] [Revised: 05/17/2025] [Accepted: 05/18/2025] [Indexed: 05/29/2025] Open
Abstract
After COVID-19 infection, about 30% of people have clinically persisting symptoms, characterized as Post COVID-19 Condition (PCC). One of the most reported symptoms in PCC is cognitive dysfunction, yet there are only a few studies investigating long-term effects on different domains of cognitive function. A total of 107 young adults, university students aged 18-34 years, participated. In total, 68.2% had contracted SARS-CoV-2; 21.9% showed PCC. Three groups were compared: no-C19 (COVID-19-negative controls), C19 (COVID-19-recovered without PCC) and PCC. Attention and executive function were measured with the Vienna Test System (Schuhfried®, Mödling, Austria). In verbal working memory, the PCC group had a significantly lower performance with a moderate effect. The rate of below-average performance was higher in PCC (56.2%) compared to no-C19 (20.6%) and C19 (15.8%). In divided attention and response inhibition, PCC also showed lower performance, 62.5% and 37.5%, respectively, than no-C19 and C19. The co-occurrence of decreased cognitive functions was pronounced in PCC. The present study revealed significant long-lasting cognitive dysfunction in PCC in young adults, two years after COVID-19 infection. Verbal working memory was significantly impaired, and a lower performance was found in divided attention and response inhibition. In addition, there was an increased reaction time in most cognitive tasks, demonstrating cognitive slowing in young people with PCC.
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Grants
- TKP2020-NKA-17 MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND
- TKP2021-EGA-37 MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND
- OTKA K 132596 MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND
- TKP2021-EGA-25 MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND
- EKÖP-2024-151 MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND
- Post-Covid 2021-34 HUNGARIAN ACADEMY OF SCIENCES
- ÚNKP-22-4-II-SE-4 NEW NATIONAL EXCELLENCE PROGRAM OF THE MINISTRY FOR INNOVATION AND TECHNOLOGY FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND
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Affiliation(s)
- Johanna Takács
- Department of Social Sciences, Faculty of Health Sciences, Semmelweis University, 1088 Budapest, Hungary
| | - Darina Deák
- Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, 1088 Budapest, Hungary
| | - Beáta Seregély
- Department of Physiotherapy, Faculty of Health Sciences, Semmelweis University, 1088 Budapest, Hungary
| | - Akos Koller
- Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, 1088 Budapest, Hungary
- Department of Physiology, New York Medical College, Valhalla, NY 10595, USA
- Research Center for Sports Physiology, Hungarian University of Sports Science, 1123 Budapest, Hungary
- Department of Translational Medicine, Faculty of Medicine, HUN-REN-SE Cerebrovascular and Neurocognitive Disease Research Group, Semmelweis University, 1094 Budapest, Hungary
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Panagea E, Messinis L, Patrikelis P, Malefaki S, Petri MC, Nasios G, Liontos A, Biros D, Kosmidis MH, Milionis H. Persistent neuropsychological deficits in recovered COVID-19 patients: Correlations with disease biomarkers. APPLIED NEUROPSYCHOLOGY. ADULT 2025:1-13. [PMID: 40353707 DOI: 10.1080/23279095.2025.2502871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
OBJECTIVE Cognitive impairment, including deficits in attention, memory, executive function, and processing speed, is common in post-COVID-19 conditions, though language performance remains less studied. The present study examined the long-term effects of COVID-19 condition on cognition and language - communication, and its associations with disease severity, Body Mass Index (BMI), inflammatory markers, and quality of life. METHOD Nighty eight Greek participants under 65 years of age were recruited for this study. Forty-seven participants were allocated in the COVID-19 group and 51 served as cognitively healthy controls. The COVID-19 group was categorized by disease severity and long COVID status. Assessments occurred 12 weeks post-infection, with 12 patients reevaluated after another 12 weeks. Neurocognitive tests included ABCD-II, verbal fluency, CCT, SDMT, and Euro QoL EQ-5D. Blood samples were analyzed for inflammatory markers. RESULTS Covid-19 survivors experienced significant cognitive deficits compared to healthy controls, particularly in processing speed, memory, and verbal fluency. Long COVID patients showed notably lower scores in processing speed and QoL, compared to those without Long COVID. However, no significant differences were observed between groups on episodic memory and executive functions tasks. Cognitive deficits were associated with biomarkers such as d-dimers and C-Reactive protein, with elevated d-dimers linked to poorer performance on generative drawing and cognitive flexibility. Higher education served as a protective factor, and was associated with higher scores in tasks such as story retelling, confrontation naming, generative drawing and reading comprehension. Older age and higher Body Mass Index were associated with poorer cognitive performance, especially on processing speed. Sex appears to influence language comprehension outcomes, with males exhibiting enhanced performance on the reading comprehension-sentence task. Disease severity negatively affected performance on the Symbol Digit Modalities Test and generative naming, indicating that greater severity was linked to poorer outcomes in these domains. Follow-up evaluations of recovered COVID-19 patients revealed significant improvements in processing speed and recall, suggesting partial recovery in these areas, although some deficits persisted over time. CONCLUSION The study supports findings that the prolonged effects of COVID-19 markedly impaired neurocognitive functions in recovering patients, especially those with severe or long COVID syndrome. Moreover, while several cognitive domains may improve over time, many other domains remain impaired and vulnerable.
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Affiliation(s)
- Evgenia Panagea
- Laboratory of Neuropsychology and Behavioral Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Department of Speech and Language Therapy, University Hospital of Patras, Patras, Greece
| | - Lambros Messinis
- Laboratory of Neuropsychology and Behavioral Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Panayiotis Patrikelis
- Laboratory of Neuropsychology and Behavioral Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Sonia Malefaki
- Department of Mechanical Engineering and Aeronautics, University of Patras, Patras, Greece
| | - Maria Christina Petri
- Laboratory of Neuropsychology and Behavioral Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Grigorios Nasios
- Department of Speech and Language Therapy, University of Ioannina, Ioannina, Greece
| | - Angelos Liontos
- First Department of Internal Medicine, Faculty of Medicine, University Hospital of Ioannina, University of Ioannina, Ioannina, Greece
| | - Dimitris Biros
- First Department of Internal Medicine, Faculty of Medicine, University Hospital of Ioannina, University of Ioannina, Ioannina, Greece
| | - Mary H Kosmidis
- Laboratory of Neuropsychology and Behavioral Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Haralampos Milionis
- First Department of Internal Medicine, Faculty of Medicine, University Hospital of Ioannina, University of Ioannina, Ioannina, Greece
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Wöhrstein S, Matuz T, Rötzer L, Karnath H. Post-COVID-Syndrome Patients Might Overestimate Own Cognitive Impairment. Eur J Neurol 2025; 32:e70195. [PMID: 40371967 PMCID: PMC12079761 DOI: 10.1111/ene.70195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 04/11/2025] [Accepted: 04/30/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND After a COVID-19 infection, some patients experience long-term consequences known as Post-Covid Syndrome, which often includes cognitive impairment. We investigated the congruence between subjectively experienced and objectively measured cognitive deficits after a COVID-19 infection in an unselected, successively admitted cohort of 46 patients reporting subjective cognitive complaints (SCC). METHODS We employed a comprehensive neuropsychological test battery to assess objective cognitive impairment across various cognitive domains. Three different cut-off criteria were applied, commonly used in the literature to define objective neurocognitive disorder (NCD). RESULTS We observed a notably low congruence between SCC and NCD in Post-Covid Syndrome, regardless of the cut-off criterion. Depending on the cognitive domain, only 4% to maximally 40% of the SCC could be objectified. CONCLUSIONS One possible explanation for this discrepancy could be the high rate of depressive symptoms observed in the group of patients studied, which may negatively influence the perception of one's cognitive abilities. These findings emphasize the need for careful evaluation of SCC in Post-Covid Syndrome and suggest that treating depressive symptoms may also alleviate some of the perceived cognitive deficits.
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Affiliation(s)
- Sofia Wöhrstein
- Center of Neurology, Division of NeuropsychologyHertie Institute for Clinical Brain Research, University of TübingenTübingenGermany
| | - Tamara Matuz
- Center of Neurology, Division of NeuropsychologyHertie Institute for Clinical Brain Research, University of TübingenTübingenGermany
| | - Lilli Rötzer
- Center of Neurology, Division of NeuropsychologyHertie Institute for Clinical Brain Research, University of TübingenTübingenGermany
| | - Hans‐Otto Karnath
- Center of Neurology, Division of NeuropsychologyHertie Institute for Clinical Brain Research, University of TübingenTübingenGermany
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6
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Adibi A, Motahharynia A, Adibi I, Sanayei M. Long-term consequences of COVID-19 on sleep, mental health, fatigue, and cognition: a preliminary study. DISCOVER MENTAL HEALTH 2025; 5:66. [PMID: 40312523 PMCID: PMC12045894 DOI: 10.1007/s44192-025-00193-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 04/14/2025] [Indexed: 05/03/2025]
Abstract
INTRODUCTION Post-COVID-19 Syndrome (PCS) is defined as symptoms persisting beyond 12 weeks from the onset of symptoms. Notably, COVID-19 has been associated with long-term effects on the brain and mental health. This cross-sectional study aims to investigate depression, fatigue, sleep quality, and cognitive dysfunction, particularly working memory, in individuals with PCS compared to a healthy control group. MATERIAL AND METHODS Between April and December 2021, 45 COVID-19 individuals and 60 healthy individuals met the eligibility criteria. Demographic information and the Montreal Cognitive Assessment were collected. Two visual working memory tasks, Delayed Match-to-Sample (DMS) and n-back, were performed, along with self-report questionnaires: Beck Depression Inventory, Modified Fatigue Impact Scale, and Pittsburgh Sleep Quality Index. RESULTS A total of 105 participants were enrolled. Findings reveal that the PCS group exhibited notably higher levels of cognitive impairment (13.3% vs. 1.6%, p = 0.04), depression (53.9% vs. 25.9%, p = 0.03), and sleep disturbances (53.9% vs. 18.6%, p = 0.01) compared to the healthy control group. Sleep latency and sleep duration were particularly affected. No significant differences in working memory function were observed between the two groups (p = 0.90 for DMS and p = 0.98 for n-back). CONCLUSION The study highlights the higher prevalence of sleep disturbance, depression, and cognitive impairment in the PCS phase, with inflammation likely playing a significant role. Moreover, the study suggests that untreated depression and sleep disturbances may pose long-term risks for dementia. Understanding the underlying mechanisms is crucial for developing effective interventions and support for individuals recovering from the infection. Prospective longitudinal studies with larger and more diverse samples are warranted to confirm and expand upon these findings.
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Affiliation(s)
- Armin Adibi
- Center for Translational Neuroscience (CTN), Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Neuroscience Research Center, Isfahan University of Medical Science, Isfahan, 8183983434, Iran
| | - Ali Motahharynia
- Center for Translational Neuroscience (CTN), Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Neuroscience Research Center, Isfahan University of Medical Science, Isfahan, 8183983434, Iran
| | - Iman Adibi
- Center for Translational Neuroscience (CTN), Isfahan University of Medical Sciences, Isfahan, Iran.
- Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran.
- Isfahan Neuroscience Research Center, Isfahan University of Medical Science, Isfahan, 8183983434, Iran.
| | - Mehdi Sanayei
- Center for Translational Neuroscience (CTN), Isfahan University of Medical Sciences, Isfahan, Iran.
- School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.
- Isfahan Neuroscience Research Center, Isfahan University of Medical Science, Isfahan, 8183983434, Iran.
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7
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Denno P, Zhao S, Husain M, Hampshire A. Defining brain fog across medical conditions. Trends Neurosci 2025; 48:330-348. [PMID: 40011078 DOI: 10.1016/j.tins.2025.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 01/05/2025] [Accepted: 01/19/2025] [Indexed: 02/28/2025]
Abstract
'Brain fog' is commonly reported in more than a dozen chronic diseases, but what is it? We review research across conditions which has characterised brain fog and evaluate its definitions and objective correlates. Brain fog has been used to refer to a variable set of overlapping symptoms implicating cognition, fatigue, and affect. It has been defined as a distinct symptom, a syndrome, or a nonspecific term. We consider the evidence that brain fog is a transdiagnostic entity with a common phenomenology and profile of objective cognitive deficits. We discuss where these commonalities arise and argue that linguistic ambiguity, shared cognitive impairments, and noncognitive factors are more likely than shared neurobiology. We suggest how future research might apply existing tools to disambiguate the phenomena that brain fog conflates.
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Affiliation(s)
- Peter Denno
- Department of Brain Sciences, Imperial College London, London W12 0NN, UK; Institute of Psychiatry, Psychology, and Neuroscience, Kings College London, London WC2R 2LS, UK.
| | - Sijia Zhao
- Department of Experimental Psychology, University of Oxford, Oxford OX2 6GG, UK
| | - Masud Husain
- Department of Experimental Psychology, University of Oxford, Oxford OX2 6GG, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK
| | - Adam Hampshire
- Department of Brain Sciences, Imperial College London, London W12 0NN, UK; Institute of Psychiatry, Psychology, and Neuroscience, Kings College London, London WC2R 2LS, UK
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Koterba CH, Considine CM, Becker JH, Hoskinson KR, Ng R, Vargas G, Basso MR, Puente AE, Lippa SM, Whiteside DM. Neuropsychology practice guidance for the neuropsychiatric aspects of Long COVID. Clin Neuropsychol 2025; 39:870-898. [PMID: 39177216 DOI: 10.1080/13854046.2024.2392943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 08/12/2024] [Indexed: 08/24/2024]
Abstract
Objective: The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has had a profound global impact on individual health and well-being in adults and children. While most fully recover from COVID-19, a relatively large subgroup continues to experience persistent physical, cognitive, and emotional/behavioral symptoms beyond the initial infection period. The World Health Organization has termed this phenomenon "Post-COVID-19 Condition" (PCC), better known as "Long COVID." Due to the cognitive and psychosocial symptoms, neuropsychologists often assess and recommend treatment for individuals with Long COVID. However, guidance for neuropsychologists' involvement in clinical care, policy-making, and research has not yet been developed. The authors of this manuscript convened to address this critical gap and develop guidance for clinical neuropsychologists working with patients presenting with Long COVID. Method: Authors include pediatric and adult neuropsychologists with expertise in Long COVID and behavioral health. All authors have been engaged in clinical and research efforts examining the impact of COVID-19. Authors summarized the literature-to-date pertinent to the neuropsychiatric sequelae of Long COVID and developed guidance for neuropsychologists working with individuals with Long COVID. Conclusions: Research findings regarding neuropsychiatric symptoms associated with Long COVID are mixed and limited by methodological differences. As they practice and conduct research, neuropsychologists should remain mindful of the evolving and tenuous nature of the literature.
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Affiliation(s)
- Christine H Koterba
- Department of Neuropsychology, Nationwide Children's Hospital, Columbus, OH, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Ciaran M Considine
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jacqueline H Becker
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kristen R Hoskinson
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
- Center for Biobehavioral Health, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
| | - Rowena Ng
- Department of Neuropsychology, Kennedy Krieger Institute, Baltimore, MD, USA
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Gray Vargas
- Department of Neuropsychology, Kennedy Krieger Institute, Baltimore, MD, USA
| | - Michael R Basso
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
| | | | - Sara M Lippa
- National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, USA
- Department of Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Douglas M Whiteside
- Department of Rehabilitation Medicine, University of Minnesota, Minneapolis, MN, USA
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Mishra SS, Gupta H, Gandhi TK, Biswal BB. Psychological symptoms and risk factors associated with long COVID: a study on the Indian cohort. PSYCHOL HEALTH MED 2025:1-16. [PMID: 40272079 DOI: 10.1080/13548506.2025.2496831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 04/17/2025] [Indexed: 04/25/2025]
Abstract
The long-term neurological effects of COVID-19, such as lack of concentration, loss of memory, and anxiety, present major concerns for COVID-19 Recovered Individuals (CRIs). Our study aims at understanding these long-term COVID-19 symptoms (LCS) and associated risk factors among the Indian cohort. In this two-part study, we analyze self-reported symptom information such as fatigue in different life spheres, symptoms experienced in past months, hospitalization status, and sex of Healthy Controls (HCs) and CRIs. In Study 1, we compare the symptoms of 62 CRIs (16 Females; 30.60 ± 10.34 years) with 36 hCs (11 Females; 27.53 ± 7.3 years). Chi-square analysis revealed that both the groups differ significantly from each other in terms of self-reported major symptoms experienced (MSEs) (p < 0.001) and major life spheres being affected by fatigue (MLSA) (p = 0.008). Further, in Study 2, we explore predictive models for these symptoms as reported by 57 of the CRIs (15 Females; 31.28 ± 10.50 years) using logistic regression and receiver operator characteristic (ROCs) information, with unrefreshing sleep, hospitalization status, and sex as the predictors for LCS. Statistical analysis reveals unrefreshing sleep as an important predictor of attention issues (odds ratio (OR) = 6.25, p = 0.003), anxiety issues (OR = 7.75, p = 0.018), and fatigue (OR = 5.83, p = 0.018) but was found non-significant for memory issues (OR = 1.86, p = 0.513) among CRIs. Hospitalization status and sex were not found to significantly affect these reported symptoms.
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Affiliation(s)
- Sapna S Mishra
- Department of Electrical Engineering, Indian Institute of Technology, Delhi, India
| | - Hritik Gupta
- Department of Humanities and Social Sciences, Indian Institute of Technology, Delhi, India
| | - Tapan K Gandhi
- Department of Electrical Engineering, Indian Institute of Technology, Delhi, India
| | - Bharat B Biswal
- Department of Biomedical Engineering, New Jersey Institute of Technology (NJIT), Newark, NJ, USA
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Liu Y, Peng B, Qin H, Zhou K, Lin S, Lai Y, Liang L, Duan G, Li X, Zhou X, Wei Y, Zhang Q, Huang J, Zhang Y, Huang J, Sun R, Tuo S, Chen Y, Deng D. Longitudinal alterations in morphological brain networks and cognitive function in common-type COVID-19: a 3-month follow-up study. Front Neurol 2025; 16:1549195. [PMID: 40303891 PMCID: PMC12037390 DOI: 10.3389/fneur.2025.1549195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 03/27/2025] [Indexed: 05/02/2025] Open
Abstract
Purpose To investigate the morphological network and cognitive function of patients with common-type coronavirus disease 2019 (COVID-19) during the acute phase, and examine dynamic changes at 3-month follow-up. Methods At baseline, high-resolution T1-weighted imaging was conducted in 35 patients with COVID-19 and 40 healthy controls; 22 patients were reassessed at 3 months. All patients underwent cognitive assessments. Individual morphological brain networks were constructed using grey matter volume similarity, and topological properties were analyzed using graph theory. We used an independent sample t-test at baseline and a paired sample t-test to compare the 3-month follow-up with the acute phase, with false discovery rate corrections (p < 0.05). Results In the acute phase, patients exhibited increased subcortical network (SCN) connectivity, and reduced connectivity between the frontoparietal network (FPN) and limbic network (LN), the SCN and dorsal/ventral attention network (DAN/VAN), and the LN and DAN. At follow-up, SCN connectivity remained elevated, with partial recovery in SCN-DAN/VAN and LN-DAN connectivity, and significant FPN-LN improvements. Enhanced global efficiency and reduced path length indicated improved network integration. Additionally, digit symbol substitution test and verbal fluency test scores improved over time. Conclusion COVID-19 induces short-term disruptions in cognition-related morphological subnetworks, with subcortical networks compensating for these changes. Significant recovery in FPN-LN connectivity and partial restoration of other networks highlight the plasticity of the brain and suggest that FPN-LN connectivity is a potential neuroimaging marker for cognitive recovery.
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Affiliation(s)
- Ying Liu
- Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Bei Peng
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Haixia Qin
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Kaixuan Zhou
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Shihuan Lin
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Yinqi Lai
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Lingyan Liang
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Gaoxiong Duan
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Xiaocheng Li
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Xiaoyan Zhou
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Yichen Wei
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Qingping Zhang
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Jinli Huang
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Yan Zhang
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Jiazhu Huang
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Ruijing Sun
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Sijing Tuo
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Yuxin Chen
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
| | - Demao Deng
- Department of Radiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China
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11
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Madden D, Stephens TM, Scott J, O’Neal Swann C, Prather K, Hoffmeister J, Ding L, Dunn IF, Conner AK, Yuan H. Functional connectivity of default mode network in non-hospitalized patients with post-COVID cognitive complaints. Front Neurosci 2025; 19:1576393. [PMID: 40276574 PMCID: PMC12018477 DOI: 10.3389/fnins.2025.1576393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Accepted: 03/26/2025] [Indexed: 04/26/2025] Open
Abstract
Introduction Neurologic impairment is common in patients with acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. While patients with severe COVID have a higher prevalence of neurologic symptoms, as many as one in five patients with mild COVID may also be affected, exhibiting impaired memory as well as other cognitive dysfunctions. Methods To characterize the effect of COVID on the brain, the current study recruited a group of adults with post-COVID cognitive complaints but with mild, non-hospitalized cases. They were then evaluated through formal neuropsychological testing and underwent functional MRI of the brain. The participants in our study performed nearly as expected for cognitively intact individuals. Additionally, we characterized the functional connectivity of the default mode network (DMN), which is known for cognitive functions including memory as well as the attention functions involved in normal aging and degenerative diseases. Results Along with the retention of functional connectivity in the DMN, our results found the DMN to be associated with neurocognitive performance through region-of-interest and whole-brain analyses. The connectivity between key nodes of the DMN was positively correlated with cognitive scores (r = 0.51, p = 0.02), with higher performers exhibiting higher DMN connectivity. Discussion Our findings provide neuroimaging evidence of the functional connectivity of brain networks among individuals experiencing cognitive deficits beyond the recovery of mild COVID. These imaging outcomes indicate expected functional trends in the brain, furthering understanding and guidance of the DMN and neurocognitive deficits in patients recovering from COVID.
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Affiliation(s)
- Derek Madden
- Stephenson School of Biomedical Engineering, Gallogly College of Engineering, The University of Oklahoma, Norman, OK, United States
| | - Tressie M. Stephens
- Department of Neurosurgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Jim Scott
- Department of Psychiatry and Behavioral Sciences, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Christen O’Neal Swann
- Department of Neurosurgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Kiana Prather
- Department of Neurosurgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Jordan Hoffmeister
- Department of Psychiatry and Behavioral Sciences, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Lei Ding
- Stephenson School of Biomedical Engineering, Gallogly College of Engineering, The University of Oklahoma, Norman, OK, United States
- Institute for Biomedical Engineering, Science, and Technology, University of Oklahoma, Norman, OK, United States
| | - Ian F. Dunn
- Department of Neurosurgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Andrew K. Conner
- Department of Neurosurgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Han Yuan
- Stephenson School of Biomedical Engineering, Gallogly College of Engineering, The University of Oklahoma, Norman, OK, United States
- Department of Neurosurgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- Institute for Biomedical Engineering, Science, and Technology, University of Oklahoma, Norman, OK, United States
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12
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Foreman L, Child B, Saywell I, Collins-Praino L, Baetu I. Cognitive reserve moderates the effect of COVID-19 on cognition: A systematic review and meta-analysis of individual participant data. Neurosci Biobehav Rev 2025; 171:106067. [PMID: 39965723 DOI: 10.1016/j.neubiorev.2025.106067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 11/11/2024] [Accepted: 02/11/2025] [Indexed: 02/20/2025]
Abstract
Elucidating the factors that mitigate the effects of COVID-19 on cognitive function offers important insights for public health policy and intervention. This systematic review and individual participant data (IPD) meta-analysis assesses cognitive reserve (CR) as a potential moderator of post-COVID-19 cognitive dysfunction (PCCD). Under PRISMA-IPD guidelines, data searches were conducted via PubMed, PsycINFO, Scopus, and Embase, up to January 2023. Eligible studies included at least one cognitive assessment, CR proxy, and disease severity indicator. Of 5604 studies, 87 were eligible (10,950 COVID-19 cases; 78,305 controls), and IPD was obtained for 29 datasets (3919 COVID-19 cases; 8267 controls). Three-level random-effects meta-analyses indicated that CR had a moderate positive association (rsp =.29), and COVID-19 severity had a small negative association (rsp = -.07) with cognitive outcomes. These effects were moderated by a significant within-study interaction. Cognitive deficits following COVID-19 were 33 % smaller among high CR individuals, and 33 % greater among low CR individuals, relative to those with average CR. Population-based initiatives promoting reserve-building behaviors may alleviate the PCCD-related public health burden. REVIEW REGISTRATION: PROSPERO registration number: CRD42022360670.
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Affiliation(s)
- Lauren Foreman
- School of Psychology, University of Adelaide, South Australia 5005, Australia.
| | - Brittany Child
- School of Psychology, University of Adelaide, South Australia 5005, Australia
| | - Isaac Saywell
- School of Psychology, University of Adelaide, South Australia 5005, Australia
| | | | - Irina Baetu
- School of Psychology, University of Adelaide, South Australia 5005, Australia.
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13
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Wang S, Menor A, Chibnik LB, Kang JH, Vyas CM, Blacker DL, Kubzansky LD, Koenen KC, Roberts AL. COVID-19 Pandemic-Related Exposures and Cognitive Function in Middle-Aged Women. JAMA Netw Open 2025; 8:e255532. [PMID: 40244583 PMCID: PMC12006873 DOI: 10.1001/jamanetworkopen.2025.5532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 01/22/2025] [Indexed: 04/18/2025] Open
Abstract
Importance The COVID-19 pandemic has been associated with risk factors for cognitive decline, such as bereavement and SARS-CoV-2 infection. Objective To examine whether the COVID-19 pandemic and pandemic-related exposures are associated with cognitive function among middle-aged women. Design, Setting, and Participants This cohort study analyzed data from the Nurses' Health Study II, an ongoing study of registered nurses in the US. The present study focused on women aged 51 to 76 years who completed 2 to 8 objective cognitive assessments both prior to (October 1, 2014, to February 29, 2020) and during the COVID-19 pandemic (March 1, 2020, to September 30, 2022). Statistical analyses were performed from January 2023 to January 2025. Exposure COVID-19 pandemic. Main Outcomes and Measures Two standardized (ie, z-scored) composite cognitive scores (psychomotor speed and attention, learning and working memory) and a global score constituted the primary outcomes. Higher scores indicated better cognitive function. Cognitive function was assessed using the Cogstate Brief Battery, a computer-administered cognitive test battery. Participants completed cognitive assessments every 6 to 12 months. Results A total of 5191 women (mean [SD] age at first cognitive assessment, 63.0 [4.8] years) completed both prepandemic and during-pandemic measures, contributing 23 678 cognitive assessments. After adjustment for age at cognitive assessment, educational level for both participants and their parents, cognitive test practice effects, and comorbidities (eg, diabetes, hypertension), no difference in cognitive function was observed between assessments taken during vs before the pandemic (psychomotor speed and attention: β = -0.01 SD [95% CI, -0.05 to 0.02 SD]; learning and working memory: β = 0.00 SD [95% CI, -0.03 to 0.03 SD]; global score: β = 0.00 SD [95% CI, -0.03 to 0.02 SD]). Among 4456 participants who responded to the COVID-19 substudy (ie, surveys about pandemic-related events), those with a history of SARS-CoV-2 infection (164 [3.7%]) or post-COVID-19 conditions (PCC; 62 [1.4%]), at a median (IQR) 20.0 (18.5-22.1) months after initial infection, had reduced cognitive function compared with women without infection or PCC; however, these differences did not reach statistical significance, and the wide CIs suggested considerable uncertainty. Conclusions and Relevance This cohort study of middle-aged women found that the COVID-19 pandemic and pandemic-related events were not associated with cognitive decline up to 2.5 years after the onset of the pandemic. Future studies are needed to examine the long-term implications of SARS-CoV-2 infection and PCC for cognitive function.
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Affiliation(s)
- Siwen Wang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Anthony Menor
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Lori B. Chibnik
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Psychiatry, Massachusetts General Hospital, Boston
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
- Department of Neurology, Massachusetts General Hospital, Boston
- Department of Neurology, Harvard Medical School, Boston, Massachusetts
| | - Jae H. Kang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
| | - Chirag M. Vyas
- Department of Psychiatry, Massachusetts General Hospital, Boston
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
- Department of Neurology, Massachusetts General Hospital, Boston
- Department of Neurology, Harvard Medical School, Boston, Massachusetts
| | - Deborah L. Blacker
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Psychiatry, Massachusetts General Hospital, Boston
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
- Department of Neurology, Massachusetts General Hospital, Boston
- Department of Neurology, Harvard Medical School, Boston, Massachusetts
| | - Laura D. Kubzansky
- Department of Social and Behavioral Science, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Karestan C. Koenen
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Social and Behavioral Science, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Andrea L. Roberts
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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14
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Xu SS, Li Y, Li W, Capio CM, Tso WWY, Chan DKC. The Impact of Long COVID on Language Proficiency Across Different School Levels in Hong Kong. Behav Sci (Basel) 2025; 15:432. [PMID: 40282054 PMCID: PMC12023945 DOI: 10.3390/bs15040432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 03/16/2025] [Accepted: 03/25/2025] [Indexed: 04/29/2025] Open
Abstract
Long COVID, where symptoms persist after recovering from COVID-19, can affect cognitive functions like language. However, little is known about its impact on children's language skills, especially across different school levels. This study investigated the impact of long COVID on language proficiency among 1244 children (Asian; 53.5% boys) from kindergartens (N = 408, Mage = 4.42 ± 1.26 years), primary schools (N = 547, Mage = 9.69 ± 1.96 years), and secondary schools (N = 289, Mage = 14.97 ± 1.85 years) in Hong Kong. Language proficiency was assessed using the Language Experience and Proficiency Questionnaire (LEAP-Q), which measured speaking, listening, reading, and writing in both Chinese and English. Participants were categorized into three groups: long COVID, recovered from COVID-19, and no history of COVID-19. One-way and two-way ANOVAs were used to analyze the differences in language proficiency across these groups and school levels. Children with long COVID symptoms exhibited significantly lower overall language proficiency, particularly in speaking and listening, compared to those in the recovered and no-COVID groups. The effect was more pronounced among primary and secondary students, with secondary school students showing the most substantial deficits. No significant differences were found between the recovered and no-COVID groups. The results suggest that long COVID might have detrimental effects on children's linguistic proficiency. The language development of older students who suffered from long COVID could benefit from receiving targeted educational and therapeutic interventions.
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Affiliation(s)
- Shebe S. Xu
- Department of Early Childhood Education, Faculty of Education and Human Development, The Education University of Hong Kong, 10 Lo Ping Road, Tai Po, New Territories, Hong Kong; (S.S.X.); (Y.L.)
| | - Yixun Li
- Department of Early Childhood Education, Faculty of Education and Human Development, The Education University of Hong Kong, 10 Lo Ping Road, Tai Po, New Territories, Hong Kong; (S.S.X.); (Y.L.)
| | - Wanyi Li
- Department of Curriculum and Instruction, The Chinese University of Hong Kong, Hong Kong;
| | - Catherine M. Capio
- Department of Physiotherapy, Hong Kong Metropolitan University, Hong Kong;
- Health Science Department, Ateneo de Manila University, Quezon City 1108, Philippines
| | - Winnie W. Y. Tso
- Department of Pediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong;
| | - Derwin K. C. Chan
- Department of Early Childhood Education, Faculty of Education and Human Development, The Education University of Hong Kong, 10 Lo Ping Road, Tai Po, New Territories, Hong Kong; (S.S.X.); (Y.L.)
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15
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Kotozaki Y, Nibbio G, Chen C. Editorial: Cognitive and mental health improvement under- and post-COVID-19, volume III. Front Psychol 2025; 16:1588477. [PMID: 40177043 PMCID: PMC11962722 DOI: 10.3389/fpsyg.2025.1588477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 04/05/2025] Open
Affiliation(s)
- Yuka Kotozaki
- Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Morioka, Iwate, Japan
| | - Gabriele Nibbio
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Chong Chen
- Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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16
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McNeill R, Marshall R, Fernando SA, Harrison O, Machado L. COVID-19 may Enduringly Impact Cognitive Performance and Brain Haemodynamics in Undergraduate Students. Brain Behav Immun 2025; 125:58-67. [PMID: 39709062 DOI: 10.1016/j.bbi.2024.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 11/19/2024] [Accepted: 12/09/2024] [Indexed: 12/23/2024] Open
Abstract
To date, 770 million people worldwide have contracted COVID-19, with many reporting long-term "brain fog". Concerningly, young adults are both overrepresented in COVID-19 infection rates and may be especially vulnerable to prolonged cognitive impairments following infection. This calls for focused research on this population to better understand the mechanisms underlying cognitive impairment post-COVID-19. Addressing gaps in the literature, the current study investigated differences in neuropsychological performance and cerebral haemodynamic activity following COVID-19 infection in undergraduate students. 94 undergraduates (age in years: M = 20.58, SD = 3.33, range = 18 to 46; 89 % female) at the University of Otago reported their COVID-19 infection history before completing a neuropsychological battery while wearing a multichannel near-infrared spectroscopy (NIRS) device to record prefrontal haemodynamics. We observed that 40 % retrospectively self-reported cognitive impairment (brain fog) due to COVID-19 and 37 % exhibited objective evidence of cognitive impairment (assessed via computerised testing), with some suggestion that executive functioning may have been particularly affected; however, group-level analyses indicated preserved cognitive performance post COVID-19, which may in part reflect varying compensatory abilities. The NIRS data revealed novel evidence that previously infected students exhibited distinct prefrontal haemodynamic patterns during cognitive engagement, reminiscent of those observed in adults four decades older, and this appeared to be especially true if they reported experiencing brain fog due to COVID-19. These results provide new insights into the potential neuropathogenic mechanisms influencing cognitive impairment following COVID-19.
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Affiliation(s)
- Ronan McNeill
- Department of Psychology, and Brain Health Research Centre, University of Otago, William James Building, 275 Leith Walk, Dunedin 9054, New Zealand
| | - Rebekah Marshall
- Department of Psychology, and Brain Health Research Centre, University of Otago, William James Building, 275 Leith Walk, Dunedin 9054, New Zealand
| | - Shenelle Anne Fernando
- Department of Psychology, and Brain Health Research Centre, University of Otago, William James Building, 275 Leith Walk, Dunedin 9054, New Zealand
| | - Olivia Harrison
- Department of Psychology, and Brain Health Research Centre, University of Otago, William James Building, 275 Leith Walk, Dunedin 9054, New Zealand; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Translational Neuromodeling Unit, University of Zurich and ETHZ Zurich, Zurich, Switzerland
| | - Liana Machado
- Department of Psychology, and Brain Health Research Centre, University of Otago, William James Building, 275 Leith Walk, Dunedin 9054, New Zealand.
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17
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Tas A, Bayhan MI, Yildiz M, Alan Y, Atay Z, Sezer F, Kitapli C, Tas IK, Umman S, Sezer M. Alterations in cerebral artery flow velocity acceleration pattern correlate with cognitive impairment in diabetes mellitus. APPLIED NEUROPSYCHOLOGY. ADULT 2025:1-10. [PMID: 39992094 DOI: 10.1080/23279095.2025.2469261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
INTRODUCTION Flow velocity acceleration pattern is related to shear stress, pressure changes, cardiovascular risk factors, diabetes mellitus, hypertension, endothelial dysfunction and arterial stiffness. Considering the hemodynamic alterations in cognitive impairment, perturbations in cerebral artery flow acceleration pattern may correlate with cognitive impairment, which could enhance our understanding of how cardiovascular risk factors drive cognitive decline from a mechanistic point of view. METHOD The first derivative of middle cerebral artery flow velocity waveforms obtained via transcranial Doppler were computed to visualize acceleration/deceleration waves (a,b,c,d,e) in ensemble-averaged signals. Vascular Aging Index was calculated per its definition (VAI:(b-c-d-e)/a). Relationship between multiple cognitive domains and VAI was evaluated with standard statistical tests. RESULTS VAI was significantly correlated with HVLT total recall (Hopkins Verbal Learning Test-revised) (r: -0.310 p: 0.046, n: 42), delayed recall (r: -0.396 p: 0.009), % Retention (r: -0.305 p: 0.050) and components of RCFT(Rey-Osterrieth Complex Figure Test), namely raw copy score (r: -0.524 p < 0.001), immediate recall (r: -0.323 p: 0.037). Controlling for age, body mass index, gray matter volume and diabetes duration yielded stronger correlations but lower group numbers due to missing data. Correlation coefficients for VAI with HVLT delayed recall and % Retention were -0.439 (p: 0.012) and -0.444(p: 0.011 n: 36) respectively. Likewise the adjusted correlations of VAI with RCFT components were improved (Raw Copy r: -0.557 p < 0.001, Immediate Recall r: -0.440 p: 0.012, Delayed Recall (r: -0.358 p: 0.044). CONCLUSION In patients with diabetes, cerebral artery flow velocity acceleration pattern correlates with cognitive performance in visuo-constructional and verbal cognitive domains. Computational fluid dynamics may aid developing a better mechanistic understanding of arterial hemodynamics-cortical function coupling.
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Affiliation(s)
- Ahmet Tas
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
- Goslar Asklepios Hospital, Goslar, Germany
| | | | - Mehlika Yildiz
- Department of Sociology, Bogazici University, Istanbul, Turkey
- Faculty of Medicine, Bahcesehir University, Istanbul, Turkey
| | - Yaren Alan
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Zeynep Atay
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Fatih Sezer
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Cagla Kitapli
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ilke Kara Tas
- Goslar Asklepios Hospital, Goslar, Germany
- Faculty of Medicine, Bahcesehir University, Istanbul, Turkey
| | - Sabahattin Umman
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
- Department of Cardiology, Istanbul Faculty of Medicine, Istanbul University, Turkey
| | - Murat Sezer
- Acibadem International Hospital, Istanbul, Turkey
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18
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Lopes-Santos LE, de Lacerda Ferreira D, de Angelis G, Foss MP, Trevisan AC, de Lacerda KJCC, Tumas V, Bellissimo-Rodrigues F, Wichert-Ana L. How Mild Is the Mild Long COVID? A Comprehensive Neuropsychological Assessment of Patients with Cognitive Complaints. Arch Clin Neuropsychol 2025; 40:302-309. [PMID: 39244203 DOI: 10.1093/arclin/acae071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 08/08/2024] [Accepted: 08/22/2024] [Indexed: 09/09/2024] Open
Abstract
The global impact of the Coronavirus Disease (COVID-19) pandemic has extended beyond physical health, leading to widespread mental health issues. Beyond respiratory symptoms, there is a growing concern about long-term cognitive effects, particularly in individuals who experienced mild cases of the infection. We aimed to investigate the neuropsychological aspects of long-term COVID-19 in non-hospitalized adults compared with a control group. This cross-sectional study included 42 participants, 22 individuals with a history of mild COVID, and 20 healthy controls. The participants were recruited from the community and underwent a comprehensive neuropsychological assessment. Participants from the mild COVID group reported cognitive symptoms persisting for an average of 203.86 days and presented a higher frequency of psychological treatment history (81.8%) compared with the control group (25.0%). History of anxiety disorders was more prevalent in the mild COVID group (63.6%) than in the control group (20.0%). Significant reductions in verbal working memory were observed in the mild COVID group. Levels of anxiety were found to have a significant impact on difficulties with visual recognition memory. This study reveals important neuropsychological alterations in individuals following mild COVID-19, emphasizing executive functions deficits. Our findings underscore the persistence of these deficits even in non-hospitalized cases, suggesting potential inflammatory mechanisms in the central nervous system. The study highlights the need for comprehensive assessments and targeted interventions to address the diverse cognitive impacts on individuals recovering from COVID-19.
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Affiliation(s)
- Lucas Emmanuel Lopes-Santos
- Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Diego de Lacerda Ferreira
- Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Geisa de Angelis
- Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Maria Paula Foss
- Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Ana Carolina Trevisan
- Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
| | | | - Vitor Tumas
- Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | | | - Lauro Wichert-Ana
- Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
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19
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Li H, Yang Y, Ding P, Xu R. Causal association of long COVID with brain structure changes: Findings from a 2-sample Mendelian randomization study. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.02.12.25322170. [PMID: 39990549 PMCID: PMC11844608 DOI: 10.1101/2025.02.12.25322170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
Nearly 7.5% U.S. adults have long COVID. Recent epidemiological studies indicated that long COVID, is significantly associated with subsequent brain structure changes. However, it remains unknown if long COVID is causally associated with brain structure change. Here we applied two Mendelian Randomization (MR) methods - Inverse Variance Weighting MR method (IVW) for correlated instrument variables and Component analysis-based Generalized Method of Moments (PC-GMM) - to examine the potential causal relationships from long COVID to brain structure changes. The MR study was based on an instrumental variable analysis of data from a recent long COVID genome-wide association study (GWAS) (3,018 cases and 994,582 controls), the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) (Global and regional cortical measures, N = 33,709; combined hemispheric subcortical volumes, N = 38,851), and UK Biobank (left/right subcortical volumes, N = 19,629). We found no significant causal relationship between long COVID and brain structure changes. As we gain more insights into long COVID and its long-term health outcomes, future works are necessary to validate our findings and understand the mechanisms underlying the observed associations, though not causal, of long COVID with subsequent brain structure changes.
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20
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Mancilla-Corona CO, Sanchez-Alavez M, Pineda-García G, Islas-Limon JY, Zazueta OE, Lopez-Baena JV, Rodríguez-Vásquez JI, Serafin-Higuera IR. The influence of physical fatigue on telephone-based neuropsychological test performance in COVID-19 survivors. Eur Arch Psychiatry Clin Neurosci 2025; 275:75-88. [PMID: 37336825 DOI: 10.1007/s00406-023-01638-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 06/03/2023] [Indexed: 06/21/2023]
Abstract
Fatigue has been characterized as a post COVID-19 condition known to persist months after SARS-CoV-2 infection. COVID-19 has been reported to be associated with impaired cognitive function, including disorders in attention, memory, information processing, and executive functions. The objective of this study was to determine if post-COVID fatigue, manifested as tiredness while performing low-intensity physical activity, has a detrimental effect on neuropsychological performance, to achieve this, we randomly selected 20 participants with post-COVID fatigue and 20 SARS-CoV-2 negative age-matched controls from a database of 360 residents of Tijuana, Baja California in a cross-sectional study design. All 40 participants responded to a health survey, along with a neuropsychological assessment test via telephone call. Statistical analysis was performed using a multiple linear regression model including the following independent variables: study condition (post-COVID fatigue or negative control), sex, age, years of education, hypertension, asthma, administration of supplemental oxygen during COVID-19 recovery, and the hour at which the evaluation started. Significant regression analysis was obtained for all global parameters of the assessment, including BANFE-2 score (p = 0.021, R2 Adj. = 0.263), NEUROPSI score (p = 0.008, R2 Adj. = 0.319), and total errors (p = 0.021, R2 Adj. = 0.263), with significant regression coefficients for study condition on two global parameters, BANFE-2 score (p = 0.028, β = - 0.371) and NEUROPSI score (p = 0.010, β = -0.428). These findings suggest that the presence of post-COVID fatigue is a factor associated with a decrease in neuropsychological performance.
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Affiliation(s)
- Cristian O Mancilla-Corona
- Centro de Diagnóstico COVID-19, Facultad de Medicina y Psicología, Calzada Tecnológico y Universidad S/N Delegación Mesa de Otay, 22390, Tijuana, BC, Mexico.
| | - Manuel Sanchez-Alavez
- Centro de Diagnóstico COVID-19, Facultad de Medicina y Psicología, Calzada Tecnológico y Universidad S/N Delegación Mesa de Otay, 22390, Tijuana, BC, Mexico
- Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA
| | - Gisela Pineda-García
- Centro de Diagnóstico COVID-19, Facultad de Medicina y Psicología, Calzada Tecnológico y Universidad S/N Delegación Mesa de Otay, 22390, Tijuana, BC, Mexico
| | - Julieta Y Islas-Limon
- Centro de Diagnóstico COVID-19, Facultad de Medicina y Psicología, Calzada Tecnológico y Universidad S/N Delegación Mesa de Otay, 22390, Tijuana, BC, Mexico
| | - Oscar E Zazueta
- Baja California Ministry of Health, Pioneros No. 1005 Centro, 21000, Mexicali, BC, Mexico
| | - Jonathan V Lopez-Baena
- Centro de Diagnóstico COVID-19, Facultad de Medicina y Psicología, Calzada Tecnológico y Universidad S/N Delegación Mesa de Otay, 22390, Tijuana, BC, Mexico
| | - Jesús I Rodríguez-Vásquez
- Centro de Diagnóstico COVID-19, Facultad de Medicina y Psicología, Calzada Tecnológico y Universidad S/N Delegación Mesa de Otay, 22390, Tijuana, BC, Mexico
| | - Idanya R Serafin-Higuera
- Centro de Diagnóstico COVID-19, Facultad de Medicina y Psicología, Calzada Tecnológico y Universidad S/N Delegación Mesa de Otay, 22390, Tijuana, BC, Mexico.
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21
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Bonner-Jackson A, Vangal R, Li Y, Thompson N, Chakrabarti S, Krishnan K. Factors Associated with Cognitive Impairment in Patients with Persisting Sequelae of COVID-19. Am J Med 2025; 138:337-345. [PMID: 38331138 DOI: 10.1016/j.amjmed.2024.01.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 01/26/2024] [Accepted: 01/30/2024] [Indexed: 02/10/2024]
Abstract
OBJECTIVE Quantify cognitive deficits in patients with postacute sequelae of COVID-19 (PASC) and identify key variables related to cognitive impairment in PASC. METHOD Patients with polymerase chain reaction-confirmed COVID-19 underwent a comprehensive neuropsychological evaluation. The comparison group included patients without neurological disorders determined by the neuropsychologist to be cognitively intact. Cognitive impairment was defined as impairment (Composite T ≤35) in 1 of 6 cognitive domains. The PASC group was split into impaired or intact based on the above criteria. Multivariable logistic regression models assessed predictors including demographics, COVID-19 severity, clinical characteristics, and mood. RESULTS There were 210 patients with PASC, predominantly female (73.3%, P < .001), without other demographic differences when compared with 369 normal controls. Patients with PASC were more likely to have cognitive impairment (odds ratio 3.61; 95% confidence interval, 2.36-5.54; P < .001) compared with controls, with significantly lower scores in domains of memory, language, processing speed, visuospatial function, executive function (P < .001), and higher depressive (P = .004) and anxiety symptoms (P = .003). Patients with PASC who demonstrated cognitive impairment (n = 93) had higher body mass index compared with those with PASC without cognitive impairment (n = 117), without differences in other predictors. CONCLUSION Patients with PASC are almost 4 times more likely to evidence cognitive dysfunction compared with normal controls. Forty-four percent of patients with PASC demonstrated cognitive deficits about 7 months from infection. Estimated premorbid intelligence significantly correlated with impairment. Higher body mass index was the only metric shown to differentiate those with PASC and cognitive impairment from those with PASC who were cognitively intact.
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Affiliation(s)
- Aaron Bonner-Jackson
- Neurological Institute, Section of Neuropsychology; Lou Ruvo Center for Brain Health, Cleveland Clinic, Ohio
| | - Rohun Vangal
- University of Toledo College of Medicine and Life Sciences, Ohio
| | - Yadi Li
- Center for Outcomes Research & Evaluation, Neurological Institute, Cleveland Clinic, Ohio
| | - Nicolas Thompson
- Center for Outcomes Research & Evaluation, Neurological Institute, Cleveland Clinic, Ohio
| | | | - Kamini Krishnan
- Neurological Institute, Section of Neuropsychology; Lou Ruvo Center for Brain Health, Cleveland Clinic, Ohio.
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22
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Calabrese LH, Calabrese C. Long COVID for the Rheumatologist: Current Understanding and Approach to Management. Rheum Dis Clin North Am 2025; 51:29-43. [PMID: 39550105 DOI: 10.1016/j.rdc.2024.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2024]
Abstract
There are estimated tens of millions of individuals throughout the world suffering from a variety of postinfectious sequela following infection with severe acute respiratory syndrome coronavirus 2 also commonly referred to as long coronavirus disease (COVID). Long COVID is providing an opportunity for the field of rheumatology to explore the relationship between similar syndromes including fibromyalgia seen in patients with underlying inflammatory and noninflammatory rheumatic diseases, as well as other postacute infectious sequela and bring our field's traditional skill sets to bear on improving our understanding of these disorders and the care of such patients.
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Affiliation(s)
- Leonard H Calabrese
- Department of Immunologic and Rheumatic Diseases, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA.
| | - Cassandra Calabrese
- Department of Immunologic and Rheumatic Diseases, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA. https://twitter.com/CCalabreseDO
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23
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Nagy B, Protzner AB, Czigler B, Gaál ZA. Resting-state neural dynamics changes in older adults with post-COVID syndrome and the modulatory effect of cognitive training and sex. GeroScience 2025; 47:1277-1301. [PMID: 39210163 PMCID: PMC11872858 DOI: 10.1007/s11357-024-01324-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024] Open
Abstract
Post-COVID syndrome manifests with numerous neurological and cognitive symptoms, the precise origins of which are still not fully understood. As females and older adults are more susceptible to developing this condition, our study aimed to investigate how post-COVID syndrome alters intrinsic brain dynamics in older adults and whether biological sex and cognitive training might modulate these effects, with a specific focus on older females. The participants, aged between 60 and 75 years, were divided into three experimental groups: healthy old female, post-COVID old female and post-COVID old male. They underwent an adaptive task-switching training protocol. We analysed multiscale entropy and spectral power density of resting-state EEG data collected before and after the training to assess neural signal complexity and oscillatory power, respectively. We found no difference between post-COVID females and males before training, indicating that post-COVID similarly affected both sexes. However, cognitive training was effective only in post-COVID females and not in males, by modulating local neural processing capacity. This improvement was further evidenced by comparing healthy and post-COVID females, wherein the latter group showed increased finer timescale entropy (1-30 ms) and higher frequency band power (11-40 Hz) before training, but these differences disappeared following cognitive training. Our results suggest that in older adults with post-COVID syndrome, there is a pronounced shift from more global to local neural processing, potentially contributing to accelerated neural aging in this condition. However, cognitive training seems to offer a promising intervention method for modulating these changes in brain dynamics, especially among females.
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Affiliation(s)
- Boglárka Nagy
- Institute of Cognitive Neuroscience and Psychology, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.
| | - Andrea B Protzner
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
- Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, Alberta, Canada
| | | | - Zsófia Anna Gaál
- Institute of Cognitive Neuroscience and Psychology, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary
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24
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Ewing AG, Salamon S, Pretorius E, Joffe D, Fox G, Bilodeau S, Bar-Yam Y. Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology. MEDICAL REVIEW (2021) 2025; 5:66-75. [PMID: 39974559 PMCID: PMC11834749 DOI: 10.1515/mr-2024-0030] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 06/11/2024] [Indexed: 02/21/2025]
Abstract
Long COVID, as currently defined by the World Health Organization (WHO) and other authorities, is a symptomatic condition that has been shown to affect an estimated 10 %-30 % of non-hospitalized patients after one infection. However, COVID-19 can also cause organ damage in individuals without symptoms, who would not fall under the current definition of Long COVID. This organ damage, whether symptomatic or not, can lead to various health impacts such as heart attacks and strokes. Given these observations, it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections. It is important to consider that many known adverse health outcomes, including heart conditions and cancers, can be asymptomatic until harm thresholds are reached. Many more medical conditions can be identified by testing than those that are recognized through reported symptoms. It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage, there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.
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Affiliation(s)
- Andrew G. Ewing
- Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
- World Health Network, Cambridge, MA, USA
| | | | - Etheresia Pretorius
- World Health Network, Cambridge, MA, USA
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, WC, South Africa
- Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
| | - David Joffe
- World Health Network, Cambridge, MA, USA
- Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Greta Fox
- World Health Network, Cambridge, MA, USA
| | - Stephane Bilodeau
- World Health Network, Cambridge, MA, USA
- Department of Bioengineering, McGill University, Montreal, QC, Canada
| | - Yaneer Bar-Yam
- World Health Network, Cambridge, MA, USA
- New England Complex Systems Institute, Cambridge, MA, USA
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25
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Wu DJ, Liu N. Association of cognitive deficits with sociodemographic characteristics among adults with post-COVID conditions: Findings from the United States household pulse survey. Biol Methods Protoc 2025; 10:bpaf006. [PMID: 39896706 PMCID: PMC11785365 DOI: 10.1093/biomethods/bpaf006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 01/07/2025] [Accepted: 01/17/2025] [Indexed: 02/04/2025] Open
Abstract
People infected with coronavirus disease-19 (COVID-19) may continue to experience symptoms for several weeks or even months after acute infection, a condition known as long COVID. Cognitive problems such as memory loss are among the most commonly reported symptoms of long COVID. However, a comprehensive evaluation of the risks of cognitive decline following COVID-19 infection among different sociodemographic groups has not been undertaken at the national level in the USA. We conducted a secondary analysis on the datasets from the U.S. Census Bureau Household Pulse Survey, encompassing data collected from 1 June 2022 to 19 December 2022. Based on a cohort of 385 370 individuals aged 18 years or older, we employed logistic regression analysis to examine the association between self-reported cognitive deficits and different sociodemographic factors among individuals with long COVID conditions. We have demonstrated that individuals with long COVID had a significantly higher risk of cognitive deficits compared to those with no history of COVID infection. Cognitive deficits vary across sociodemographic groups. In individuals without long COVID, men, older adults, and those with higher education reported fewer cognitive deficits, while Hispanics and residents of the South reported more. Long COVID had similar impacts across genders and regions but appeared to have the smallest impact on Hispanics compared to other racial groups. Conversely, the effects of long COVID were most significant in older adults and individuals with higher education. The state-level analysis further suggests potential variation in long COVID's effects across different states. The risks of cognitive deficits among adults with post-COVID conditions are substantial. Various sociodemographic groups can have different risks of developing cognitive deficits after experiencing long COVID. The findings of this large-scale study can help identify sociodemographic groups at higher risk of cognitive deficits, facilitate medical interventions, and guide resource allocation to target populations at risk and prioritize areas with a high rate of cognitive decline.
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Affiliation(s)
- Daniel J Wu
- Statistics & Data Sciences, College of Natural Sciences, University of Texas at Austin, Austin, TX 78712, United States
| | - Nianjun Liu
- Department of Epidemiology and Biostatistics, Indiana University School of Public Health, Bloomington, IN 47405, United States
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26
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Onisiforou A, Charalambous EG, Zanos P. Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer's Disease Pathogenesis-From Gut Microbiota and Viruses to Brain Biofilms. Microorganisms 2025; 13:90. [PMID: 39858858 PMCID: PMC11767882 DOI: 10.3390/microorganisms13010090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 12/18/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut-brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut-brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide's antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions.
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Affiliation(s)
- Anna Onisiforou
- Translational Neuropharmacology Laboratory, Department of Psychology, University of Cyprus, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus;
- Center of Applied Neuroscience, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus
| | - Eleftheria G. Charalambous
- Translational Neuropharmacology Laboratory, Department of Psychology, University of Cyprus, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus;
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 1–2, Ellernholzstr., 17489 Greifswald, Germany
| | - Panos Zanos
- Translational Neuropharmacology Laboratory, Department of Psychology, University of Cyprus, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus;
- Center of Applied Neuroscience, 75 Kallipoleos Avenue, 1678 Nicosia, Cyprus
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27
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Franco-Rocha OY, Lewis KA, Kesler SR, Henneghan AM. An Exploratory Analysis of Contributors to Cognitive Functioning Among Sexual and Gender Minority Individuals Who Had COVID-19. JOURNAL OF HOMOSEXUALITY 2025; 72:129-144. [PMID: 38305820 PMCID: PMC11294494 DOI: 10.1080/00918369.2024.2309497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Sexual and gender minority (SGM) individuals face mental health disparities. However, research analyzing SGM people's mental health after a COVID-19 diagnosis is scarce. In this secondary analysis of a remote study, we 1) examined associations between cognitive and psychosocial health and 2) explored differences between these health outcomes among SGM (n = 14) and heterosexual cisgender (n = 64) U.S. adults who had COVID-19. We used the Patient Reported Outcome Measures Information System (PROMIS) v2.0 to assess subjective cognition and the BrainCheck cognitive test to analyze objective cognition. We administered the Perceived Stress Scale and PROMIS 57 Profile V.2.0 to measure psychosocial health. SGM COVID-19 survivors had worse scores in depression, anxiety, sleep disturbance, pain, stress, and objective cognition than heterosexual cisgender participants (p-values < .05). Objective cognition was associated with age, SGM classification, racial or ethnic minority classification, income, comorbidities, COVID-19 severity, number of symptoms, and pain (|0.137| < r < |0.373|, p-values < .05). Subjective cognition was associated with comorbidities, number of symptoms, depression, anxiety, sleep disturbance, pain, and stress (|0.158| < r < |0.537|, p-values < .05). Additional studies are needed to expand what is known about post-COVID-19 health disparities and to guide policies and interventions that promote cognitive functioning.
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Affiliation(s)
- Oscar Y. Franco-Rocha
- School of Nursing, University of Texas at Austin. 1710 Red River St. Austin, TX, 78712. U.S
| | - Kimberly A. Lewis
- School of Nursing, University of Texas at Austin. 1710 Red River St. Austin, TX, 78712. U.S
- Postdoctoral Scholar, Department of Physiological Nursing, School of Nursing, University of California, San Francisco. San Francisco, CA, U.S
| | - Shelli R. Kesler
- School of Nursing, University of Texas at Austin. 1710 Red River St. Austin, TX, 78712. U.S
- Department of Diagnostic Medicine, Dell Medical School, The University of Texas at Austin. 1501 Red River St. Austin, TX, 78712. U.S
| | - Ashley M. Henneghan
- School of Nursing, University of Texas at Austin. 1710 Red River St. Austin, TX, 78712. U.S
- Department of Oncology, Dell Medical School, The University of Texas at Austin. 1501 Red River St. Austin, TX, 78712. U.S
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28
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Peter RS, Nieters A, Göpel S, Merle U, Steinacker JM, Deibert P, Friedmann-Bette B, Nieß A, Müller B, Schilling C, Erz G, Giesen R, Götz V, Keller K, Maier P, Matits L, Parthé S, Rehm M, Schellenberg J, Schempf U, Zhu M, Kräusslich HG, Rothenbacher D, Kern WV, on behalf of the EPILOC Phase 2 Study Group. Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study. PLoS Med 2025; 22:e1004511. [PMID: 39847575 PMCID: PMC12005676 DOI: 10.1371/journal.pmed.1004511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 12/17/2024] [Indexed: 01/25/2025] Open
Abstract
BACKGROUND Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for >1 year and assessed risk factors for PCS persistence versus improvement. METHODS AND FINDINGS This nested population-based case-control study included subjects with PCS aged 18-65 years with (n = 982) and age- and sex-matched control subjects without PCS (n = 576) according to an earlier population-based questionnaire study (6-12 months after acute infection, phase 1) consenting to provide follow-up information and to undergo comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, and laboratory testing in four university health centres in southwestern Germany (phase 2, another 8.5 months [median, range 3-14 months] after phase 1). The mean age of the participants was 48 years, and 65% were female. At phase 2, 67.6% of the patients with PCS at phase 1 developed persistent PCS, whereas 78.5% of the recovered participants remained free of health problems related to PCS. Improvement among patients with earlier PCS was associated with mild acute index infection, previous full-time employment, educational status, and no specialist consultation and not attending a rehabilitation programme. The development of new symptoms related to PCS among participants initially recovered was associated with an intercurrent secondary SARS-CoV-2 infection and educational status. Patients with persistent PCS were less frequently never smokers (61.2% versus 75.7%), more often obese (30.2% versus 12.4%) with higher mean values for body mass index (BMI) and body fat, and had lower educational status (university entrance qualification 38.7% versus 61.5%) than participants with continued recovery. Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness and anxiety/depression/sleep problems remained the predominant symptom clusters. Exercise intolerance with post-exertional malaise (PEM) for >14 h and symptoms compatible with myalgic encephalomyelitis/chronic fatigue syndrome were reported by 35.6% and 11.6% of participants with persistent PCS patients, respectively. In analyses adjusted for sex-age class combinations, study centre and university entrance qualification, significant differences between participants with persistent PCS versus those with continued recovery were observed for performance in three different neurocognitive tests, scores for perceived stress, subjective cognitive disturbances, dysautonomia, depression and anxiety, sleep quality, fatigue and quality of life. In persistent PCS, handgrip strength (40.2 [95% confidence interval (CI) [39.4, 41.1]] versus 42.5 [95% CI [41.5, 43.6]] kg), maximal oxygen consumption (27.9 [95% CI [27.3, 28.4]] versus 31.0 [95% CI [30.3, 31.6]] ml/min/kg body weight) and ventilatory efficiency (minute ventilation/carbon dioxide production slope, 28.8 [95% CI [28.3, 29.2]] versus 27.1 [95% CI [26.6, 27.7]]) were significantly reduced relative to the control group of participants with continued recovery after adjustment for sex-age class combinations, study centre, education, BMI, smoking status and use of beta blocking agents. There were no differences in measures of systolic and diastolic cardiac function at rest, in the level of N-terminal brain natriuretic peptide blood levels or other laboratory measurements (including complement activity, markers of Epstein-Barr virus [EBV] reactivation, inflammatory and coagulation markers, serum levels of cortisol, adrenocorticotropic hormone and dehydroepiandrosterone sulfate). Screening for viral persistence (PCR in stool samples and SARS-CoV-2 spike antigen levels in plasma) in a subgroup of the patients with persistent PCS was negative. Sensitivity analyses (pre-existing illness/comorbidity, obesity, medical care of the index acute infection) revealed similar findings. Patients with persistent PCS and PEM reported more pain symptoms and had worse results in almost all tests. A limitation was that we had no objective information on exercise capacity and cognition before acute infection. In addition, we did not include patients unable to attend the outpatient clinic for whatever reason including severe illness, immobility or social deprivation or exclusion. CONCLUSIONS In this study, we observed that the majority of working age patients with PCS did not recover in the second year of their illness. Patterns of reported symptoms remained essentially similar, non-specific and dominated by fatigue, exercise intolerance and cognitive complaints. Despite objective signs of cognitive deficits and reduced exercise capacity, there was no major pathology in laboratory investigations, and our findings do not support viral persistence, EBV reactivation, adrenal insufficiency or increased complement turnover as pathophysiologically relevant for persistent PCS. A history of PEM was associated with more severe symptoms and more objective signs of disease and might help stratify cases for disease severity.
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Affiliation(s)
- Raphael S. Peter
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
| | - Alexandra Nieters
- Institute for Immunodeficiency, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany
| | - Siri Göpel
- Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany
| | - Uta Merle
- Department of Internal Medicine IV, Heidelberg University Faculty of Medicine and Heidelberg University Hospital, Heidelberg, Germany
| | - Jürgen M. Steinacker
- Division of Sports and Rehabilitation Medicine, Department of Medicine, Ulm University Hospital, Ulm, Germany
| | - Peter Deibert
- Institute for Exercise and Occupational Medicine, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany
| | - Birgit Friedmann-Bette
- Department of Sports Medicine, Heidelberg University Faculty of Medicine and Heidelberg University Hospital, Heidelberg, Germany
| | - Andreas Nieß
- Department of Sports Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Barbara Müller
- Department of Infectious Diseases—Virology, Heidelberg University Faculty of Medicine, and Heidelberg University Hospital, Heidelberg, Germany
| | - Claudia Schilling
- Department of Psychiatry and Psychotherapy, Sleep Laboratory, Medical Faculty Mannheim, Central Institute of Mental Health (ZI), University of Heidelberg, Heidelberg, Germany
| | - Gunnar Erz
- Department of Sports Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Roland Giesen
- Division of Infectious Diseases, Department of Medicine II, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany
| | - Veronika Götz
- Division of Infectious Diseases, Department of Medicine II, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany
| | - Karsten Keller
- Department of Sports Medicine, Heidelberg University Faculty of Medicine and Heidelberg University Hospital, Heidelberg, Germany
| | - Philipp Maier
- Institute for Exercise and Occupational Medicine, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany
| | - Lynn Matits
- Division of Sports and Rehabilitation Medicine, Department of Medicine, Ulm University Hospital, Ulm, Germany
| | - Sylvia Parthé
- Department of Infectious Diseases—Virology, Heidelberg University Faculty of Medicine, and Heidelberg University Hospital, Heidelberg, Germany
| | - Martin Rehm
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
| | - Jana Schellenberg
- Division of Sports and Rehabilitation Medicine, Department of Medicine, Ulm University Hospital, Ulm, Germany
| | - Ulrike Schempf
- Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany
| | - Mengyu Zhu
- Department of Internal Medicine IV, Heidelberg University Faculty of Medicine and Heidelberg University Hospital, Heidelberg, Germany
- Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
| | - Hans-Georg Kräusslich
- Department of Infectious Diseases—Virology, Heidelberg University Faculty of Medicine, and Heidelberg University Hospital, Heidelberg, Germany
- German Centre for Infection Research (DZIF) Partner Site Heidelberg, Heidelberg, Germany
| | | | - Winfried V. Kern
- Division of Infectious Diseases, Department of Medicine II, Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany
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29
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Wood GK, Sargent BF, Ahmad ZUA, Tharmaratnam K, Dunai C, Egbe FN, Martin NH, Facer B, Pendered SL, Rogers HC, Hübel C, van Wamelen DJ, Bethlehem RAI, Giunchiglia V, Hellyer PJ, Trender W, Kalsi G, Needham E, Easton A, Jackson TA, Cunningham C, Upthegrove R, Pollak TA, Hotopf M, Solomon T, Pett SL, Shaw PJ, Wood N, Harrison NA, Miller KL, Jezzard P, Williams G, Duff EP, Williams S, Zelaya F, Smith SM, Keller S, Broome M, Kingston N, Husain M, Vincent A, Bradley J, Chinnery P, Menon DK, Aggleton JP, Nicholson TR, Taylor JP, David AS, Carson A, Bullmore E, Breen G, Hampshire A, Michael BD, Paddick SM, Leek EC. Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction. Nat Med 2025; 31:245-257. [PMID: 39312956 PMCID: PMC11750706 DOI: 10.1038/s41591-024-03309-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 09/18/2024] [Indexed: 09/25/2024]
Abstract
The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19. Severity of the initial infective insult, postacute psychiatric symptoms and a history of encephalopathy were associated with the greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies.
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Affiliation(s)
- Greta K Wood
- Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Brendan F Sargent
- Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK
- Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK
| | - Zain-Ul-Abideen Ahmad
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Kukatharmini Tharmaratnam
- Department of Health Data Science, Institute of Population Health, University of Liverpool, Liverpool, UK
| | - Cordelia Dunai
- Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
| | - Franklyn N Egbe
- Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
| | - Naomi H Martin
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Bethany Facer
- Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Sophie L Pendered
- Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
| | - Henry C Rogers
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Christopher Hübel
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- National Centre for Register-based Research, Aarhus Business and Social Sciences, Aarhus University, Aarhus, Denmark
- Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Daniel J van Wamelen
- Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- Parkinson's Foundation Center of Excellence, King's College Hospital, London, UK
- Department of Neurology; Centre of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands
| | | | | | - Peter J Hellyer
- Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - William Trender
- Department of Brain Sciences, Imperial College London, London, UK
| | - Gursharan Kalsi
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Edward Needham
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Ava Easton
- Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- Encephalitis International, Malton, UK
| | - Thomas A Jackson
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Colm Cunningham
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
| | - Rachel Upthegrove
- Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, UK
| | - Thomas A Pollak
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- South London and Maudsley NHS Foundation Trust, London, UK
| | - Matthew Hotopf
- Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Tom Solomon
- Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- The Pandemic Institute, University of Liverpool, Liverpool, UK
- Department of Neurology, Walton Centre Foundation Trust, Liverpool, UK
| | - Sarah L Pett
- MRC Clinical Trials Unit, UCL, London, UK
- Institute of Clinical Trials and Methodology, UCL, London, UK
- Institute for Global Health, UCL, London, UK
| | - Pamela J Shaw
- Division of Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
- Sheffield Institute for Translational Neuroscience, NIHR Biomedical Research Centre, University of Sheffield, Sheffield, UK
| | - Nicholas Wood
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, UCL, London, UK
- UCL Genetics Institute, Division of Biosciences, UCL, London, UK
| | - Neil A Harrison
- Cardiff University Brain Research Imaging Centre, School of Medicine, Cardiff University, Cardiff, UK
| | - Karla L Miller
- Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK
| | - Peter Jezzard
- Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK
| | - Guy Williams
- Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
| | - Eugene P Duff
- UK Dementia Research Institute, Department of Brain Sciences, Imperial College London, London, UK
| | - Steven Williams
- Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Fernando Zelaya
- Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- NIHR Maudsley Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust, London, UK
| | - Stephen M Smith
- Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK
| | - Simon Keller
- Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Matthew Broome
- Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, UK
- Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Nathalie Kingston
- NIHR Bioresource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Department of Haematology, School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Masud Husain
- Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital, University of Oxford, Oxford, UK
- Department of Experimental Psychology, University of Oxford, Oxford, UK
| | - Angela Vincent
- Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | - John Bradley
- NIHR Bioresource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Patrick Chinnery
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK
| | - David K Menon
- Section of Perioperative, Acute, Critical Care and Emergency Medicine, Department of Medicine, University of Cambridge, Cambridge, UK
| | | | - Timothy R Nicholson
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- South London and Maudsley NHS Foundation Trust, London, UK
- Neuropsychiatry Research and Education Group, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - John-Paul Taylor
- Translational and Clinical Research Institute, Newcastle University, Newcastle, UK
- Old Age Psychiatry, Tyne and Wear NHS Trust, Newcastle, UK
| | - Anthony S David
- Department of Psychiatry, Institute of Mental Health, UCL, London, UK
| | - Alan Carson
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
| | - Ed Bullmore
- Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Department of Psychiatry, Institute of Behavioural and Clinical Neuroscience, University of Cambridge, Cambridge, UK
| | - Gerome Breen
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- NIHR Maudsley Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust, London, UK
| | - Adam Hampshire
- Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- Department of Brain Sciences, Imperial College London, London, UK
| | - Benedict D Michael
- Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
- NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
- Department of Neurology, Walton Centre Foundation Trust, Liverpool, UK.
| | - Stella-Maria Paddick
- Translational and Clinical Research Institute, Newcastle University, Newcastle, UK
- Department of Old Age Psychiatry, Gateshead Health NHS Foundation Trust, Gateshead, UK
- Millenium Institute for Care Research (MICARE), Santiago, Chile
| | - E Charles Leek
- Department of Psychology, Institute of Population Health, Institute of Life and Human Sciences, University of Liverpool, Liverpool, UK
- School of Psychology, University of Southampton, Southampton, UK
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30
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Fanshawe JB, Sargent BF, Badenoch JB, Saini A, Watson CJ, Pokrovskaya A, Aniwattanapong D, Conti I, Nye C, Burchill E, Hussain ZU, Said K, Kuhoga E, Tharmaratnam K, Pendered S, Mbwele B, Taquet M, Wood GK, Rogers JP, Hampshire A, Carson A, David AS, Michael BD, Nicholson TR, Paddick S, Leek CE. Cognitive domains affected post-COVID-19; a systematic review and meta-analysis. Eur J Neurol 2025; 32:e16181. [PMID: 38375608 PMCID: PMC11618111 DOI: 10.1111/ene.16181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 10/23/2023] [Accepted: 11/29/2023] [Indexed: 02/21/2024]
Abstract
BACKGROUND AND PURPOSE This review aims to characterize the pattern of post-COVID-19 cognitive impairment, allowing better prediction of impact on daily function to inform clinical management and rehabilitation. METHODS A systematic review and meta-analysis of neurocognitive sequelae following COVID-19 was conducted, following PRISMA-S guidelines. Studies were included if they reported domain-specific cognitive assessment in patients with COVID-19 at >4 weeks post-infection. Studies were deemed high-quality if they had >40 participants, utilized healthy controls, had low attrition rates and mitigated for confounders. RESULTS Five of the seven primary Diagnostic and Statistical Manual of Mental Disorders (DSM-5) cognitive domains were assessed by enough high-quality studies to facilitate meta-analysis. Medium effect sizes indicating impairment in patients post-COVID-19 versus controls were seen across executive function (standardised mean difference (SMD) -0.45), learning and memory (SMD -0.55), complex attention (SMD -0.54) and language (SMD -0.54), with perceptual motor function appearing to be impacted to a greater degree (SMD -0.70). A narrative synthesis of the 56 low-quality studies also suggested no obvious pattern of impairment. CONCLUSIONS This review found moderate impairments across multiple domains of cognition in patients post-COVID-19, with no specific pattern. The reported literature was significantly heterogeneous, with a wide variety of cognitive tasks, small sample sizes and disparate initial disease severities limiting interpretability. The finding of consistent impairment across a range of cognitive tasks suggests broad, as opposed to domain-specific, brain dysfunction. Future studies should utilize a harmonized test battery to facilitate inter-study comparisons, whilst also accounting for the interactions between COVID-19, neurological sequelae and mental health, the interplay between which might explain cognitive impairment.
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Affiliation(s)
- Jack B. Fanshawe
- Department of PsychiatryUniversity of OxfordOxfordUK
- Oxford Health NHS Foundation TrustOxfordUK
| | - Brendan F. Sargent
- Department of PsychiatryUniversity of OxfordOxfordUK
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological SciencesUniversity of LiverpoolLiverpoolUK
| | - James B. Badenoch
- Barts Health NHS TrustLondonUK
- Preventive Neurology UnitQueen Mary University of LondonLondonUK
| | - Aman Saini
- School of Life and Medical SciencesUniversity College LondonLondonUK
| | - Cameron J. Watson
- Institute of Psychiatry, Psychology and NeuroscienceKing's College LondonLondonUK
- South London and Maudsley NHS Foundation TrustLondonUK
| | | | - Daruj Aniwattanapong
- Institute of Psychiatry, Psychology and NeuroscienceKing's College LondonLondonUK
- Department of PsychiatryKing Chulalongkorn Memorial HospitalBangkokThailand
| | - Isabella Conti
- Institute of Psychiatry, Psychology and NeuroscienceKing's College LondonLondonUK
| | - Charles Nye
- Gloucestershire Hospitals NHS Foundation TrustGloucesterUK
| | - Ella Burchill
- Division of PsychiatryUniversity College LondonLondonUK
| | - Zain U. Hussain
- NHS Greater Glasgow and ClydeGlasgowUK
- Edinburgh Medical SchoolUniversity of EdinburghEdinburghUK
| | - Khanafi Said
- Mbeya College of Health and Allied SciencesUniversity of Dar es SalaamMbeyaTanzania
| | - Elinda Kuhoga
- Mbeya College of Health and Allied SciencesUniversity of Dar es SalaamMbeyaTanzania
| | - Kukatharmini Tharmaratnam
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological SciencesUniversity of LiverpoolLiverpoolUK
| | - Sophie Pendered
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological SciencesUniversity of LiverpoolLiverpoolUK
| | - Bernard Mbwele
- Mbeya College of Health and Allied SciencesUniversity of Dar es SalaamMbeyaTanzania
| | - Maxime Taquet
- Department of PsychiatryUniversity of OxfordOxfordUK
- Oxford Health NHS Foundation TrustOxfordUK
| | - Greta K. Wood
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological SciencesUniversity of LiverpoolLiverpoolUK
| | | | - Adam Hampshire
- Department of Brain SciencesImperial College LondonLondonUK
| | - Alan Carson
- Centre for Clinical Brain SciencesUniversity of EdinburghEdinburghUK
| | | | - Benedict D. Michael
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological SciencesUniversity of LiverpoolLiverpoolUK
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of LiverpoolLiverpoolUK
- Walton Centre NHS Foundation TrustLiverpoolUK
| | - Timothy R. Nicholson
- Institute of Psychiatry, Psychology and NeuroscienceKing's College LondonLondonUK
| | - Stella‐Maria Paddick
- Translational and Clinical Research InstituteNewcastle UniversityNewcastle upon TyneUK
- Gateshead Health NHS Foundation TrustGatesheadUK
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31
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Hasbun R, George M. SARS-CoV-2 and nervous system: From pathogenesis of disease to clinical manifestations. NEUROBIOLOGY OF INFECTIOUS DISEASES 2025:363-370. [DOI: 10.1016/b978-0-443-19130-5.00022-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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32
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Bremner JD, Russo SJ, Gallagher R, Simon NM. Acute and long-term effects of COVID-19 on brain and mental health: A narrative review. Brain Behav Immun 2025; 123:928-945. [PMID: 39500417 PMCID: PMC11974614 DOI: 10.1016/j.bbi.2024.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/16/2024] [Accepted: 11/02/2024] [Indexed: 11/09/2024] Open
Abstract
BACKGROUND COVID infection has been associated with long term sequalae (Long COVID) which include neurological and behavioral effects in thousands of patients, but the etiology and scope of symptoms is not well understood. This paper reviews long term sequelae of COVID on brain and mental health in patients with the Long COVID syndrome. METHODS This was a literature review which queried databases for Pubmed, Psychinfo, and Medline for the following topics for January 1, 2020-July 15, 2023: Long COVID, PASC, brain, brain imaging, neurological, neurobiology, mental health, anxiety, depression. RESULTS Tens of thousands of patients have developed Long COVID, with the most common neurobehavioral symptoms anosmia (loss of smell) and fatigue. Anxiety and mood disorders are elevated and seen in about 25% of Long COVID patients. Neuropsychological testing studies show a correlation between symptom severity and cognitive dysfunction, while brain imaging studies show global decreases in gray matter and alterations in olfactory and other brain areas. CONCLUSIONS Studies to date show an increase in neurobehavioral disturbances in patients with Long COVID. Future research is needed to determine mechanisms.
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Affiliation(s)
- J Douglas Bremner
- Departments of Psychiatry & Behavioral Sciences and Radiology, Emory University School of Medicine, Atlanta Georgia, and the Atlanta VA Medical Center, Decatur, GA, USA; Nash Family Department Neuroscience and Brain-Body Research Center, Icahn School of Medicine at Mt. Sinai, New York, NY, USA; Department of Child and Adolescent Psychiatry, New York University (NYU) Langone Health, New York, NY, USA.
| | - Scott J Russo
- Nash Family Department Neuroscience and Brain-Body Research Center, Icahn School of Medicine at Mt. Sinai, New York, NY, USA
| | - Richard Gallagher
- Department of Child and Adolescent Psychiatry, New York University (NYU) Langone Health, New York, NY, USA; Department of Psychiatry, New York University (NYU) Langone Health, New York, NY, USA
| | - Naomi M Simon
- Department of Psychiatry, New York University (NYU) Langone Health, New York, NY, USA
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Latifi A, Flegr J. Persistent Health and Cognitive Impairments up to Four Years Post-COVID-19 in Young Students: The Impact of Virus Variants and Vaccination Timing. Biomedicines 2024; 13:69. [PMID: 39857653 PMCID: PMC11760454 DOI: 10.3390/biomedicines13010069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 12/27/2024] [Accepted: 12/28/2024] [Indexed: 01/27/2025] Open
Abstract
Background: The long-term consequences of COVID-19 infection are becoming increasingly evident in recent studies. This repeated cross-sectional study aimed to explore the long-term health and cognitive effects of COVID-19, focusing on how virus variants, vaccination, illness severity, and time since infection impact post-COVID-19 outcomes. Methods: We examined three cohorts of university students (N = 584) and used non-parametric methods to assess correlations of various health and cognitive variables with SARS-CoV-2 infection, COVID-19 severity, vaccination status, time since infection, time since vaccination, and virus variants. Results: Our results suggest that some health and cognitive impairments may persist, with some even appearing to progressively worsen-particularly fatigue in women and memory in men-up to four years post-infection. The data further indicate that the ancestral SARS-CoV-2 variant may have the most significant long-term impact, while the Omicron variant appears to have the least. Interestingly, the severity of the acute illness was not correlated with the variant of SARS-CoV-2. The analysis also revealed that individuals who contracted COVID-19 after vaccination had better health and cognitive outcomes compared to those infected before vaccination. Conclusions: Overall, our results indicate that even in young individuals who predominantly experienced only mild forms of the infection, a gradual decline in health and fitness can occur over a span of four years post-infection. Notably, some negative trends-at least in men-only began to stabilize or even reverse during the fourth year, whereas in women, these trends showed no such improvement. These findings suggest that the long-term public health impacts of COVID-19 may be more severe and affect a much broader population than is commonly assumed.
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Affiliation(s)
| | - Jaroslav Flegr
- Laboratory of Evolutionary Biology, Department of Philosophy and History of Sciences, Faculty of Science, Charles University, Viničná 7, 128 00 Prague, Czech Republic;
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Jebrini T, Thomas A, Sachenbacher S, Heimkes F, Karch S, Goerigk S, Ruzicka M, Fonseca GJI, Wunderlich N, Benesch C, Pernpruner A, Heindl B, Stubbe HC, Uebleis AO, Grosse-Wentrup F, Adorjan K. Effects of cognitive training and group psychotherapy on cognitive performance of post COVID-19 patients: an exploratory and non-randomized clinical trial. Eur Arch Psychiatry Clin Neurosci 2024; 274:1969-1982. [PMID: 39356325 PMCID: PMC11579059 DOI: 10.1007/s00406-024-01904-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 09/07/2024] [Indexed: 10/03/2024]
Abstract
Cognitive complaints are common signs of the Post COVID-19 (PC) condition, but the extent and type of cognitive impairment may be heterogeneous. Little is known about neuropsychological treatment options. Preliminary evidence suggests cognitive symptoms may improve with cognitive training and naturally over time. In this clinical trial, we examined whether participation in a weekly group consisting of cognitive training and group psychotherapy is feasible and would exert beneficial effects on cognitive performance in PC and whether improvements were associated with intervention group participation or represented a temporal improvement effect during syndrome progression. 15 PC patients underwent an 8-week intervention. Cognitive performance was assessed before and after each intervention group participation. A control group of 15 PC patients with subjective neurocognitive or psychiatric complaints underwent two cognitive assessments with comparable time intervals without group participation. To attribute changes to the intervention group participation, interaction effects of group participation and time were checked for significance. This is an exploratory, non-randomized, non-blinded controlled clinical trial. Within the intervention group, significant improvements were found for most cognitive measures. However, significant time x group interactions were only detected in some dimensions of verbal memory and visuo-spatial construction skills. Significant time effects were observed for attention, concentration, memory, executive functions, and processing speed. The intervention setting was feasible and rated as helpful and relevant by the patients. Our results suggest that cognitive symptoms of PC patients may improve over time. Patients affected by both neurocognitive impairments and mental disorders benefit from group psychotherapy and neurocognitive training. The present study provides evidence for a better understanding of the dynamic symptomatology of PC and might help to develop further studies addressing possible therapy designs. The main limitations of this exploratory feasibility trial are the small sample size as well as the non-randomized design due to the clinical setting.
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Affiliation(s)
- Tarek Jebrini
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany.
| | - Anabel Thomas
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany
| | - Simone Sachenbacher
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany
| | - Fides Heimkes
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany
| | - Susanne Karch
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany
| | - Stephan Goerigk
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany
- Charlotte Fresenius Hochschule, University of Psychology, Munich, Germany
| | - Michael Ruzicka
- Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
| | | | - Nora Wunderlich
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany
| | | | - Anna Pernpruner
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Bernhard Heindl
- Stabstelle Strategische Unternehmenssteuerung, LMU Munich, Munich, Germany
| | | | - Aline Olivia Uebleis
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany
| | - Fabienne Grosse-Wentrup
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstraße 7, 80336, Munich, Germany
| | - Kristina Adorjan
- Department of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
- Institute of Psychiatric Phenomics and Genomics, LMU University Hospital, Munich, Germany
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Schild AK, Scharfenberg D, Regorius A, Klein K, Kirchner L, Yasemin G, Lülling J, Meiberth D, Schweitzer F, Fink GR, Jessen F, Franke C, Onur OA, Jost ST, Warnke C, Maier F. Six-month follow-up of multidomain cognitive impairment in non-hospitalized individuals with post-COVID-19 syndrome. Eur Arch Psychiatry Clin Neurosci 2024; 274:1945-1957. [PMID: 39048833 PMCID: PMC11579205 DOI: 10.1007/s00406-024-01863-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 07/03/2024] [Indexed: 07/27/2024]
Abstract
Some people infected with SARS-CoV-2 report persisting symptoms following acute infection. If these persist for over three months, they are classified as post-COVID-19 syndrome (PCS). Although PCS is frequently reported, detailed longitudinal neuropsychological characterization remains scarce. We aimed to describe the trajectory of cognitive and neuropsychiatric PCS symptoms. 42 individuals with persisting cognitive deficits after asymptomatic to mild/moderate acute COVID-19 at study inclusion received neuropsychological assessment at baseline (BL) and follow-up (FU; six months after BL). Assessments included comprehensive testing of five neurocognitive domains, two cognitive screening tests, and questionnaires on depression, anxiety, sleep, fatigue, and health-related quality of life. Results showed high rates of subjective cognitive complaints at BL and FU (95.2% versus 88.1%) without significant change over time. However, objectively measured neurocognitive disorder (NCD) decreased (61.9% versus 42.9%). All cognitive domains were affected, yet most deficits were found in learning and memory, followed by executive functions, complex attention, language, and perceptual motor functions. In individuals with NCD, the first three domains mentioned improved significantly over time, while the last two domains remained unchanged. Cognitive screening tests did not prove valuable in detecting impairment. Neuropsychiatric symptoms remained constant except for quality of life, which improved. This study emphasizes the importance of comprehensive neuropsychological assessment in longitudinal research and provides valuable insights into the trajectory of long-term neuropsychological impairments in PCS. While cognitive performance significantly improved in many domains, neuropsychiatric symptoms remained unchanged.
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Affiliation(s)
- Ann-Katrin Schild
- Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
| | - Daniel Scharfenberg
- Department of Medical Psychology ǀ Neuropsychology and Gender Studies and Center for Neuropsychological Diagnostics and Intervention (CeNDI), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Anton Regorius
- Department of Psychology, Clinical Psychology, Experimental Psychopathology, and Psychotherapy, Philipps University Marburg, Marburg, Germany
| | - Kim Klein
- Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Lukas Kirchner
- Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Goereci Yasemin
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Joachim Lülling
- Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Dix Meiberth
- Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
| | - Finja Schweitzer
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Gereon R Fink
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Jülich, Jülich, Germany
| | - Frank Jessen
- Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
| | - Christiana Franke
- Department of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Oezguer A Onur
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Jülich, Jülich, Germany
| | - Stefanie Theresa Jost
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Clemens Warnke
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Franziska Maier
- Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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Zhang S, Yuan M, He D, Dang W, Zhang W. Long-term follow-up of brain regional changes and the association with cognitive impairment in quarantined COVID-19 survivors. Eur Arch Psychiatry Clin Neurosci 2024; 274:1911-1922. [PMID: 38319396 DOI: 10.1007/s00406-023-01741-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 12/11/2023] [Indexed: 02/07/2024]
Abstract
OBJECTIVE This study aimed to evaluate the neuropsychiatric symptoms of quarantined COVID-19 survivors 15 months after discharge and explore its potential association with structural and functional brain changes and inflammation. METHODS A total of 51 quarantined COVID-19 survivors and 74 healthy controls were included in this study. Cognitive function was assessed using the THINC-integrated tool. Structural brain changes were examined through both surface- and volume-based analyses, and functional changes were assessed using resting-state amplitude low-frequency fluctuation (ALFF). Serum inflammatory markers were measured by a multiplexed flow cytometric assay. RESULTS COVID-19 survivors exhibited subjective cognitive decline compared to healthy controls, despite no significant differences in objective cognitive tasks. Structural analysis revealed significantly increased gray matter volume and cortical surface area in the left transverse temporal gyrus (Heschl's gyrus) in quarantined COVID-19 survivors. This enlargement was negatively correlated with cognitive impairment. The ALFF analysis showed decreased neural activity in multiple brain regions. Elevated levels of serum inflammatory markers were also found in COVID-19 survivors, including MIP-1a, MIP-1b, TNF-a, and IL-8, which correlated with functional abnormalities. CONCLUSIONS Our findings indicate a subjective cognitive decline in quarantined COVID-19 survivors 15 months after discharge, which is associated with brain structural alterations in the left Heschl's gyrus. The observed elevation of inflammatory markers suggests a potential mechanism involving inflammation-induced neurogenesis. These results contribute to our understanding of the possible mechanisms underlying long-term neuropsychiatric consequences of COVID-19 and highlight the need for further research to develop targeted interventions.
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Affiliation(s)
- Simai Zhang
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, No. 37 Guoxue Street, Chengdu, 610041, China
- Med-X Center for Informatics, Sichuan University, Chengdu, 610041, China
| | - Minlan Yuan
- Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Danmei He
- Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wen Dang
- Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wei Zhang
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, No. 37 Guoxue Street, Chengdu, 610041, China.
- Med-X Center for Informatics, Sichuan University, Chengdu, 610041, China.
- Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Ellingjord-Dale M, Nygaard AB, Støer NC, Bø R, Landrø NI, Brunvoll SH, Istre M, Kalleberg KT, Dahl JA, Geng L, Tsilidis K, Riboli E, Ursin G, Søraas A. Temporal trajectories of long-COVID symptoms in adults with 22 months follow-up in a prospective cohort study in Norway. Int J Infect Dis 2024; 149:107263. [PMID: 39419167 DOI: 10.1016/j.ijid.2024.107263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/29/2024] [Accepted: 10/05/2024] [Indexed: 10/19/2024] Open
Abstract
OBJECTIVES There is a lack of large studies on long-COVID symptoms with symptoms measurements before the onset of COVID-19. Therefore, long-COVID is still poorly defined. METHODS The Norwegian COVID-19 Cohort Study is a population-based, open cohort of adult participants (aged 18-96 years) from Norway. From March 27, 2020, participants were recruited through social media, invitations, and nationwide media coverage. Fourteen somatic and cognitive symptoms were assessed at baseline and four follow-ups for up to 22 months. SARS-CoV-2 test status was obtained from a mandatory national registry or from self-report. RESULTS After follow-up, 15 737 participants had a SARS-CoV-2-positive test, 67 305 had a negative test, and 37 563 were still untested. Persistent symptoms reported more frequently by positive compared with negative participants one month after infection, were memory problems (3-6 months: adjusted odds ratio (aOR) = 6.8, CI = 5.7-8.1; >18 months: aOR = 9.4, CI = 4.1-22), and concentration problems (3-6 months: aOR = 4.1, CI = 3.5-4.7; >18 months: aOR = 4.4, CI = 2.0-9.7) as well fatigue, dyspnea, anosmia and dysgeusia. CONCLUSIONS COVID-19 was associated with cognitive symptoms, anosmia, dysgeusia, dyspnea, and fatigue as well as worsening of overall health up to 22 months after a SARS-CoV-2 test, even when correcting for symptoms before the onset of COVID-19.
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Affiliation(s)
| | | | | | - Ragnhild Bø
- Department of Psychology, University of Oslo, Oslo, Norway
| | | | | | - Mette Istre
- Department of Microbiology, Oslo University Hospital, Nydalen, Oslo, Norway
| | | | - John Arne Dahl
- Department of Microbiology, Oslo University Hospital, Nydalen, Oslo, Norway
| | - Linda Geng
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Kostas Tsilidis
- Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, UK; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, UK
| | - Giske Ursin
- Cancer Registry of Norway, University of Oslo, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, Oslo, Norway; Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
| | - Arne Søraas
- Department of Microbiology, Oslo University Hospital, Nydalen, Oslo, Norway
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di Filippo L, Franzese V, Santoro S, Doga M, Giustina A. Long COVID and pituitary dysfunctions: a bidirectional relationship? Pituitary 2024; 27:955-969. [PMID: 39240511 DOI: 10.1007/s11102-024-01442-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/02/2024] [Indexed: 09/07/2024]
Abstract
Long COVID is a novel emerging syndrome known to affect multiple health areas in patients previously infected by SARS-CoV-2 markedly impairing their quality of life. The pathophysiology of Long COVID is still largely poorly understood and multiple mechanisms were proposed to underlie its occurrence, including alterations in the hormonal hypothalamic-pituitary axes. Aim of this review is to present and discuss the potential negative implications of these hormonal dysfunctions in promoting and influencing the Long COVID syndrome. To date, the hypothalamic-pituitary-adrenal axis is the mostly investigated and several studies have reported a prolonged impairment leading to mild and subclinical forms of central adrenal insufficiency. Few data are also available regarding central hypogonadism, central hypothyroidism and growth hormone (GH) deficiency. A high prevalence of central hypogonadism in COVID-19 survivors several months after recovery was consistently reported in different cohorts. Conversely, very few data are available on the hypothalamic-pituitary-thyroid axis function that was mainly shown to be preserved in COVID-19 survivors. Finally, a potential impairment of the hypothalamic-GH axis in Long COVID has also been reported. These data altogether may suggest a novel possible pituitary-centred pathophysiological view of Long COVID syndrome which if confirmed by large clinical studies may have relevant implication for the diagnostic and therapeutic approach at least in a subset of patients with the syndrome.
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Affiliation(s)
- Luigi di Filippo
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS San Raffaele Hospital, Via Olgettina 60, Milan, 20132, Italy.
| | - Vincenzo Franzese
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS San Raffaele Hospital, Via Olgettina 60, Milan, 20132, Italy
| | - Simona Santoro
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS San Raffaele Hospital, Via Olgettina 60, Milan, 20132, Italy
| | - Mauro Doga
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS San Raffaele Hospital, Via Olgettina 60, Milan, 20132, Italy
| | - Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS San Raffaele Hospital, Via Olgettina 60, Milan, 20132, Italy
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von Etzdorf A, Harzen M, Heinrichs H, Seifert H, Groiß SJ, Balloff C, Feldt T, Jensen BEO, Lüdde T, Bernhard M, Schnitzler A, Goebels K, Kraus J, Meuth SG, Elben S, Albrecht P. The population based cognitive testing in subjects with SARS-CoV-2 (POPCOV2) study: longitudinal investigation of remote cognitive and fatigue screening in PCR-positive cases and negative controls. Front Hum Neurosci 2024; 18:1468204. [PMID: 39677403 PMCID: PMC11638161 DOI: 10.3389/fnhum.2024.1468204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 10/25/2024] [Indexed: 12/17/2024] Open
Abstract
Background The majority of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) only show mild respiratory symptoms. However, some patients with SARS-CoV-2 display neurological symptoms. Data on the exact prevalence and course of cognitive symptoms are often limited to patient reported outcomes or studies recruited at specialized centers. Methods For this prospective, non-interventional population based POPCOV2 study, 156 subjects who performed SARS-CoV-2 testing in the Düsseldorf metropolitan area at public test centers between December 2020 and February 2022 were recruited by handouts. SARS-CoV-2-positive and negatively tested subjects were included within the first seven days after the PCR test results. Cognitive testing was performed at baseline during home quarantine and after 4-6 as well as 12-14 weeks of follow-up. Individuals were examined remotely by videocalls using the Symbol Digit Modalities Test (SDMT) and the Montreal Cognitive Assessment (MoCA) in addition to the Brief Fatigue Inventory (BFI) and the Beck Depression Inventory-Fast Screen (BDI-FS). Results At baseline, the SARS-CoV-2-positive group presented with higher levels of fatigue in the BFI. In both the SARS-CoV-2-positive and SARS-CoV-2-negative groups, some subjects presented attention and memory deficits, defined as a z-score < -1,65 on the SDMT or < 26 points on the MoCA (SDMT: 22.9% in the positive and 8.8% in the negative group, p = 0.024; MoCA: 35.6% in the positive and 27.3% in the negative group, p = 0.313). MoCA and SDMT improved over time in both groups. For MoCA scores, a significant difference between the two groups was only seen at the first follow-up. SDMT z-scores did not differ at any time between the groups. Conclusion These results support previous evidence that mild SARS-CoV-2 infections are associated with increased fatigue. However, we found relevant rates of cognitive impairment not only in the infected but also in the control group. This underlines the importance of including a control group in such investigations.
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Affiliation(s)
- Alina von Etzdorf
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Maja Harzen
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Hannah Heinrichs
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Henning Seifert
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Stefan J. Groiß
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Carolin Balloff
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Neurology, Maria-Hilf-Clinics Mönchengladbach, Mönchengladbach, Germany
| | - Torsten Feldt
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Björn-Erik Ole Jensen
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Tom Lüdde
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michael Bernhard
- Emergency Department, Faculty of Medicine, Heinrich Heine University, Düsseldorf, Germany
| | - Alfons Schnitzler
- Institute for Clinical Neuroscience and Medical Psychology, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | | | - Jörg Kraus
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Laboratory Medicine, Paracelsus Medical University and Salzburger Landeskliniken, Salzburg, Austria
| | - Sven G. Meuth
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Saskia Elben
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Philipp Albrecht
- Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Neurology, Maria-Hilf-Clinics Mönchengladbach, Mönchengladbach, Germany
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Giunchiglia V, Gruia DC, Lerede A, Trender W, Hellyer P, Hampshire A. An iterative approach for estimating domain-specific cognitive abilities from large scale online cognitive data. NPJ Digit Med 2024; 7:328. [PMID: 39562825 DOI: 10.1038/s41746-024-01327-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 11/05/2024] [Indexed: 11/21/2024] Open
Abstract
Online cognitive tasks are gaining traction as scalable and cost-effective alternatives to traditional supervised assessments. However, variability in peoples' home devices, visual and motor abilities, and speed-accuracy biases confound the specificity with which online tasks can measure cognitive abilities. To address these limitations, we developed IDoCT (Iterative Decomposition of Cognitive Tasks), a method for estimating domain-specific cognitive abilities and trial-difficulty scales from task performance timecourses in a data-driven manner while accounting for device and visuomotor latencies, unspecific cognitive processes and speed-accuracy trade-offs. IDoCT can operate with any computerised task where cognitive difficulty varies across trials. Using data from 388,757 adults, we show that IDoCT successfully dissociates cognitive abilities from these confounding factors. The resultant cognitive scores exhibit stronger dissociation of psychometric factors, improved cross-participants distributions, and meaningful demographic's associations. We propose that IDoCT can enhance the precision of online cognitive assessments, especially in large scale clinical and research applications.
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Affiliation(s)
- Valentina Giunchiglia
- Department of Brain Sciences, Imperial College London, London, UK.
- Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
- Department of Biomedical Informatics, Harvard University, Boston, USA.
| | | | - Annalaura Lerede
- Department of Brain Sciences, Imperial College London, London, UK
- Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - William Trender
- Department of Brain Sciences, Imperial College London, London, UK
| | - Peter Hellyer
- Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Adam Hampshire
- Department of Brain Sciences, Imperial College London, London, UK
- Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
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Szewczyk W, Fitzpatrick AL, Fossou H, Gentile NL, Sotoodehnia N, Vora SB, West TE, Bertolli J, Cope JR, Lin JMS, Unger ER, Vu QM. Long COVID and recovery from Long COVID: quality of life impairments and subjective cognitive decline at a median of 2 years after initial infection. BMC Infect Dis 2024; 24:1241. [PMID: 39497076 PMCID: PMC11536968 DOI: 10.1186/s12879-024-10158-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 10/30/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Recovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support. METHODS We characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12. RESULTS Nearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p < 0.05). The Recovered Long COVID group (n = 34) had significantly lower prevalence of fatigue, pain, depression, and physical and social function impairment compared to those with Current Long COVID (n = 181; all p < 0.05). However, compared to patients Without Long COVID, the Recovered Long COVID group had greater prevalences of fatigue, pain (p ≤ 0.06) and subjective cognitive decline (61.8% vs 29.1%; p < 0.01). Multivariate relative risk (RR) regression indicated Long COVID risk was greater for older age groups (RR range 1.46-1.52; all p ≤ 0.05), those without a bachelor's degree (RR = 1.33; 95% CI = 1.03-1.71; p = 0.03), and those with 3 or more comorbidities prior to SARS-CoV-2 infection (RR = 1.45; 95% CI = 1.11-1.90; p < 0.01). CONCLUSIONS Long COVID is associated with long-term subjective cognitive decline and diminished quality of life. Clinically significant cognitive complaints, fatigue, and pain were present even in those who reported they had recovered from Long COVID. These findings have implications for the sustainability of participation in work, education, and social activities.
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Affiliation(s)
- Warren Szewczyk
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
| | - Annette L Fitzpatrick
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - Herve Fossou
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - Nicole L Gentile
- Department of Family Medicine, School of Medicine, University of Washington, Seattle, WA, USA
| | - Nona Sotoodehnia
- Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA
| | - Surabhi B Vora
- Division of Infectious Diseases, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA
| | - T Eoin West
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Jeanne Bertolli
- Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Jennifer R Cope
- Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Jin-Mann S Lin
- Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | - Quan M Vu
- Centers for Disease Control and Prevention, Atlanta, GA, USA
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Shrestha A, Chen R, Kunasekaran M, Honeyman D, Notaras A, Sutton B, Quigley A, MacIntyre CR. The risk of cognitive decline and dementia in older adults diagnosed with COVID-19: A systematic review and meta-analysis. Ageing Res Rev 2024; 101:102448. [PMID: 39127446 DOI: 10.1016/j.arr.2024.102448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 07/30/2024] [Accepted: 08/03/2024] [Indexed: 08/12/2024]
Abstract
BACKGROUND Cognitive impairment can be caused by infections with various pathogens, including SARS-CoV-2. Research has yet to determine the true incidence and course of cognitive impairment in older adults following COVID-19. Furthermore, research has theorised that COVID-19 is associated with dementia progression and diagnosis but this association has yet to be fully described. METHODS A systematic review was registered in Prospero and conducted on the databases PubMed, Embase, Ovid, CENTRAL and Cochrane Library. Studies reporting cognitive impairment and dementia outcomes in post-acute and post-COVID-19 patients aged ≥65 years, and which included control data, were included in this review. RESULTS 15,124 articles were identified by the search strategy. After eliminating duplicate titles and completing title, abstracts and full-text review, 18 studies were included comprising of 412,957 patients with COVID-19 (46.63 % male) and 411,929 patients without COVID-19 (46.59 % male). The overall mean Montreal Cognitive Assessment (MoCA) score in COVID-19 patients was 23.34 out of 30 (95 % CI [22.24, 24.43]). indicating cognitive impairment. The overall proportion of patients identified as having new onset cognitive impairment was 65 % (95 % CI [44,81]). Subgroup analyses indicated that time since infection significantly improves overall MoCA score and reduces proportion of patients with cognitive impairment. CONCLUSION This study indicates that cognitive impairment may be an important sequela of COVID-19. Further research with adequate sample sizes is warranted regarding COVID-19's association with new-onset dementia and dementia progression, and the effect of repeat infections. There is a need for development of diagnostic and management protocols for COVID-19 patients with cognitive impairment.
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Affiliation(s)
- A Shrestha
- Infections West, Hollywood Private Hospital, Suite 37, Monash Avenue, Western Australia, Australia
| | - R Chen
- The Biosecurity Program, The Kirby Institute, The University of New South Wales, Sydney, Australia
| | - M Kunasekaran
- The Biosecurity Program, The Kirby Institute, The University of New South Wales, Sydney, Australia.
| | - D Honeyman
- The Biosecurity Program, The Kirby Institute, The University of New South Wales, Sydney, Australia
| | - A Notaras
- The Biosecurity Program, The Kirby Institute, The University of New South Wales, Sydney, Australia
| | - B Sutton
- The Biosecurity Program, The Kirby Institute, The University of New South Wales, Sydney, Australia
| | - A Quigley
- The Biosecurity Program, The Kirby Institute, The University of New South Wales, Sydney, Australia
| | - C Raina MacIntyre
- The Biosecurity Program, The Kirby Institute, The University of New South Wales, Sydney, Australia; Watts College of Public Service and Community Solutions, Arizona State University, Phoenix, AZ, United States
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Leuzy A, Heeman F, Bosch I, Lenér F, Dottori M, Quitz K, Moscoso A, Kern S, Zetterberg H, Blennow K, Schöll M. REAL AD-Validation of a realistic screening approach for early Alzheimer's disease. Alzheimers Dement 2024; 20:8172-8182. [PMID: 39311530 PMCID: PMC11567841 DOI: 10.1002/alz.14219] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 07/31/2024] [Accepted: 08/02/2024] [Indexed: 11/17/2024]
Abstract
Early diagnosis is crucial to treatment success. This is especially relevant for Alzheimer's disease (AD), with its protracted preclinical phase. Most health care systems do not have the resources to conduct large-scale AD screenings in middle-aged individuals in need of novel AD treatment options and early, accurate diagnosis. Recent developments in blood-based biomarkers and remote cognitive testing offer novel, cost-effective, and scalable methods to detect cognitive and biomarker changes that may indicate early AD. In research cohorts, promising results have been reported, but these modalities have not been validated in population-based settings. The validation of a realistic screening approach for early Alzheimer's disease (REAL AD) study aims to validate the diagnostic and prognostic performance of the combined use of blood-based biomarkers and remote cognitive testing as a screening approach for early AD employing an existing health care infrastructure (the Swedish Västra Götaland Region Primary Healthcare). REAL AD aims to provide a concrete, individualized diagnostic framework, which could significantly improve AD prognosis. HIGHLIGHTS: In Sweden, most Alzheimer's disease (AD) diagnoses are made in primary care, where access to AD biomarkers is almost non-existent. Most health care systems have limited resources for the screening of middle-aged adults for early evidence of AD pathology. Blood-based biomarkers and remote cognitive testing offer novel, cost-effective, and scalable methods for detecting cognitive and biomarker changes that may indicate early AD. The REAL AD study aims to validate the diagnostic and prognostic performance of blood-based biomarkers and remote cognitive testing as a screening approach for early AD in an existing primary health care infrastructure in the Västra Götaland Region in Sweden. Studies such as REAL AD will play a vital role in helping to move the field toward concrete implementation of biomarkers in AD diagnostic workup at all care levels, eventually providing more comprehensive treatments options for the large and growing AD population, and for those at risk.
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Affiliation(s)
- Antoine Leuzy
- Wallenberg Centre for Molecular and Translational MedicineUniversity of GothenburgGothenburgSweden
- Department of Psychiatry and NeurochemistryUniversity of GothenburgMölndalSweden
- Department of NeuropsychiatryRegion Västra GötalandSahlgrenska University HospitalGötalandSweden
| | - Fiona Heeman
- Wallenberg Centre for Molecular and Translational MedicineUniversity of GothenburgGothenburgSweden
- Department of Psychiatry and NeurochemistryUniversity of GothenburgMölndalSweden
| | - Iris Bosch
- Department of Psychiatry and NeurochemistryUniversity of GothenburgMölndalSweden
- Department of NeuropsychiatryRegion Västra GötalandSahlgrenska University HospitalGötalandSweden
| | - Frida Lenér
- Centre for REDI FyrbodalPrimary Health Care, Region VästraGötalandSweden
- Department of Public Health and Community MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Maria Dottori
- Region Västra Götaland, Research, Education, Development & Innovation (REDI)Primary Health CareGothenburgSweden
| | - Kajsa Quitz
- Department of Public Health and Community MedicineUniversity of GothenburgGothenburgSweden
| | - Alexis Moscoso
- Wallenberg Centre for Molecular and Translational MedicineUniversity of GothenburgGothenburgSweden
- Department of Psychiatry and NeurochemistryUniversity of GothenburgMölndalSweden
| | - Silke Kern
- Department of Psychiatry and NeurochemistryUniversity of GothenburgMölndalSweden
- Department of NeuropsychiatryRegion Västra GötalandSahlgrenska University HospitalGötalandSweden
| | - Henrik Zetterberg
- Department of Psychiatry and NeurochemistryUniversity of GothenburgMölndalSweden
- Department of Public Health and Community MedicineUniversity of GothenburgGothenburgSweden
- Clinical Neurochemistry LaboratorySahlgrenska University HospitalGothenburgSweden
- UK Dementia Research Institute, UCL Institute of NeurologyUniversity College LondonLondonUK
- Department of Neurodegenerative Disease, UCL Queen Square Institute of NeurologyUniversity College LondonLondonUK
- Hong Kong Center for Neurodegenerative DiseasesHong KongChina
- Wisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin School of Medicine and Public HealthUniversity of Wisconsin‐MadisonMadisonUSA
| | - Kaj Blennow
- Department of Psychiatry and NeurochemistryUniversity of GothenburgMölndalSweden
- Clinical Neurochemistry LaboratorySahlgrenska University HospitalGothenburgSweden
| | - Michael Schöll
- Wallenberg Centre for Molecular and Translational MedicineUniversity of GothenburgGothenburgSweden
- Department of Psychiatry and NeurochemistryUniversity of GothenburgMölndalSweden
- Department of NeuropsychiatryRegion Västra GötalandSahlgrenska University HospitalGötalandSweden
- Department of Neurodegenerative Disease, UCL Queen Square Institute of NeurologyUniversity College LondonLondonUK
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44
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Gaudry C, Dhersin R, Dubée V. [Mechanisms of prolonged symptoms following acute COVID-19: Some pathophysiological pathways]. Rev Mal Respir 2024; 41:660-668. [PMID: 39426876 DOI: 10.1016/j.rmr.2024.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 07/30/2024] [Indexed: 10/21/2024]
Abstract
INTRODUCTION Following the Omicron wave in early 2022, an estimated 60-70% of the French population was infected with the SARS-CoV-2 virus. One out of ten infected subjects could have persistent symptoms three months after infection, representing a public health challenge. CURRENT STATE OF KNOWLEDGE The persistent symptoms may be secondary to diverse entities with distinct mechanisms. While organic infection sequelae occur mainly after severe COVID-19, some symptoms appear to be essentially psychological in origin; in addition, many subjects present stereotyped symptoms of fluctuating intensity with no identified anatomical or psychic substratum, often in the aftermath of a benign infection. The most frequent complaints are fatigue, pain, dyspnea and difficulty concentrating. PERSPECTIVES The hypotheses explored to explain these symptoms include: persistent immune dysfunction, inducted autoimmunity, and microbiome disturbances. Persistent viral antigens may lie at the crossroads of these mechanisms. To date, these different etiological avenues have yet to lead to the development of diagnostic tests or specific therapeutic strategies. CONCLUSION Prolonged symptoms after COVID-19 correspond to heterogeneous nosological entities with poorly understood mechanisms.
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Affiliation(s)
- C Gaudry
- Service des maladies infectieuses et tropicales, CHU d'Angers, 4, rue Larrey, 49100 Angers, France
| | - R Dhersin
- Service des maladies infectieuses et tropicales, CHU d'Angers, 4, rue Larrey, 49100 Angers, France
| | - V Dubée
- Service des maladies infectieuses et tropicales, CHU d'Angers, 4, rue Larrey, 49100 Angers, France.
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45
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Buer S, Hagen B, Søraas A, White R, Bø R, Ellingjord-Dale M, Istre M, Brunvoll S, Lerdal A, Landrø N, Nygaard A, Stubberud J. Executive deficits after SARS-CoV-2 infection: A cross-sectional population study. Brain Behav Immun Health 2024; 41:100857. [PMID: 39314761 PMCID: PMC11418142 DOI: 10.1016/j.bbih.2024.100857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/20/2024] [Accepted: 09/07/2024] [Indexed: 09/25/2024] Open
Abstract
Importance Despite the major implications of executive deficits in day-to-day functioning, few studies have investigated this in post-acute sequelae of SARS-CoV-2 infection using standardized measures that differentiate between aspects of executive function. Objective Examine whether SARS-CoV-2 infection is associated with deficits in executive functions and if so, investigate the duration of this association. Design Setting and Participants The present research has a cross-sectional design and uses data from the Norwegian Covid-19 Cohort study. The current cohort (n = 8102) completed the Behavior Rating Inventory of Executive Function- Adult Version (BRIEF-A) electronically between April 2021 and September 2021. During the assessment, 4183 of the included participants had a prior positive polymerase chain reaction test (PCR) for SARS-CoV-2 and 3919 were untested or had a confirmed negative PCR test. Exposure Laboratory-confirmed SARS-CoV-2 infection. Main outcomes and measures Executive functions were measured using the BRIEF-A, a self-report questionnaire comprising 75 items within nine theoretically and empirically distinct clinical scales. All participants self-reported on demographical variables and comorbidity. Information on sex and age was derived from the personal identification number, and vaccination status was obtained from the Norwegian Immunization Registry (SYSVAK). Results Participants with a positive SARS-CoV-2 status reported executive deficits in everyday life above the clinical threshold (T-score ≥65) more often than non-infected controls (383 vs. 225). Specifically, the SARS-CoV-2 positive status group indicated significantly more deficits related to metacognition, with the greatest difference demonstrated for working memory. This difference remained when adjusting for various demographic factors and comorbidities, with significantly greater odds of reporting above the clinical threshold following SARS-CoV-2 infection, as observed on the global executive composite score 6-12 months after infection (OR 1.97; 95% CI 1.51 to 2.55). Conclusions Our study confirms more perceived executive deficits following SARS-CoV-2 infection compared to non-infected controls, with metacognitive aspects being the most affected. These findings shed light on the potential functional difficulties that individuals may encounter during the post-acute phase of SARS-CoV-2 infection and may guide further development of targeted interventions addressing metacognitive domains of executive functioning.
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Affiliation(s)
- S. Buer
- Department of Research, Lovisenberg Diaconal Hospital, Oslo, Norway
- Department of Psychology, University of Oslo, Oslo, Norway
| | - B.I. Hagen
- Department of Research, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - A. Søraas
- Department of Microbiology, Oslo University Hospital, Oslo, Norway
| | - R.A. White
- Department of Infection Control and Vaccines, Norwegian Institute of Public Health, Oslo, Norway
| | - R. Bø
- Department of Psychology, University of Oslo, Oslo, Norway
| | | | - M.S. Istre
- Department of Microbiology, Oslo University Hospital, Oslo, Norway
| | - S.H. Brunvoll
- Department of Microbiology, Oslo University Hospital, Oslo, Norway
| | - A. Lerdal
- Department of Research, Lovisenberg Diaconal Hospital, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
| | - N.I. Landrø
- Department of Psychology, University of Oslo, Oslo, Norway
| | - A.B. Nygaard
- Department of Microbiology, Oslo University Hospital, Oslo, Norway
| | - J. Stubberud
- Department of Research, Lovisenberg Diaconal Hospital, Oslo, Norway
- Department of Psychology, University of Oslo, Oslo, Norway
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46
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Vanova M, Patel AMR, Scott I, Gilpin G, Manning EN, Ash C, Wittenberg P, Lim J, Hoare Z, Evans R, Bray N, Kipps CM, Devine C, Ahmed S, Dunne R, Koniotes A, Warren C, Chan D, Suarez-Gonzalez A. Telehealth-delivered cognitive rehabilitation for people with cognitive impairment as part of the post-COVID syndrome: protocol for a randomised controlled trial as part of the CICERO (Cognitive Impairment in Long COVID: Phenotyping and Rehabilitation) study. Trials 2024; 25:704. [PMID: 39434179 PMCID: PMC11494741 DOI: 10.1186/s13063-024-08554-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 10/14/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND Between 25 and 75% of people with persistent post-acute sequelae of SARS-CoV-2 infection (PASC) experience cognitive difficulties, compromising functional ability, quality of life, and activities of daily living, including work. Despite this significant morbidity, there is a paucity of interventions for this disorder that have undergone evaluation within a formal trial setting. Therefore, we have developed a cognitive rehabilitation programme, specifically designed to address the cognitive symptoms of PASC, notably impaired attention and processing speed, while also accounting for other PASC symptoms (fatigue, post-exertional malaise) that may aggravate the cognitive impairment. This study protocol outlines a randomised controlled trial (RCT) designed to evaluate the effectiveness of this programme compared to standard clinical care. METHODS This is a multi-centre, parallel-group, individually randomised controlled trial, comparing standard clinical care with and without cognitive rehabilitation. We will recruit 120 non-hospitalised adults (aged 30-60 years) from three NHS sites in England with a history of COVID-19 infection and cognitive impairment persisting more than 3 months after the acute infection. Participants will be randomised (1:1) to the intervention or control groups, with the latter represented as a provision of standard clinical care without cognitive rehabilitation. The cognitive rehabilitation programme consists of ten 1-hour sessions, delivered weekly. Outcomes will be collected at baseline, 3, and 6 months, with participant-defined goal-attainment scores, relating to functional goals, at 3 months as the primary outcome measure. Secondary outcomes will be cognitive function, measures of quality of life, social functioning, mental health, fatigue, sleep, post-exertional malaise, and social and health care service use. We will also evaluate the health-economic benefits of cognitive rehabilitation in this population. DISCUSSION Cognitive impairment in PASC is a major cause of functional disability with no effective treatment. Accordingly, we will undertake an RCT of cognitive rehabilitation, the protocol of which is published here. If this trial is successful in delivering improvements in trial outcomes, it will address a major unmet need relating to this emergent disorder, with a significant impact on affected individuals and the wider health economy. TRIAL REGISTRATION ClinicalTrials.gov NCT05731570. Registered on February 16, 2023.
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Affiliation(s)
- Martina Vanova
- Dementia Research Centre, Faculty of Brain Sciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
| | | | - Iona Scott
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Gina Gilpin
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Emily N Manning
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Charlotte Ash
- Institute of Cognitive Neuroscience, University College London, London, UK
| | | | - Jason Lim
- School of Applied Sciences, University of Brighton, Brighton, UK
| | - Zoe Hoare
- North Wales Medical School, Bangor University, Bangor, UK
| | - Rachel Evans
- North Wales Medical School, Bangor University, Bangor, UK
| | - Nathan Bray
- School of Health Sciences, Bangor University, Bangor, UK
| | - Christopher M Kipps
- Department of Neurology, University Hospitals Southampton NHS Trust, Southampton, UK
| | - Ciara Devine
- Department of Neurology, University Hospitals Southampton NHS Trust, Southampton, UK
| | - Saliha Ahmed
- GM Dementia Research Centre, Greater Manchester Mental Health NHS Trust, Manchester, UK
| | - Ross Dunne
- GM Dementia Research Centre, Greater Manchester Mental Health NHS Trust, Manchester, UK
- Geoffery Jefferson Brain Research Centre, University of Manchester, Manchester, UK
| | - Anna Koniotes
- Department of Neurology, University Hospitals Sussex NHS Trust, Brighton, UK
| | - Catherine Warren
- Department of Neurology, University Hospitals Sussex NHS Trust, Brighton, UK
| | - Dennis Chan
- Institute of Cognitive Neuroscience, University College London, London, UK
- Department of Neurology, University Hospitals Sussex NHS Trust, Brighton, UK
| | - Aida Suarez-Gonzalez
- Dementia Research Centre, Faculty of Brain Sciences, UCL Queen Square Institute of Neurology, University College London, London, UK
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47
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Serrano Del Pueblo VM, Serrano-Heras G, Romero Sánchez CM, Landete PP, Rojas-Bartolome L, Feria I, Morris RGM, Strange B, Mansilla F, Zhang L, Castro-Robles B, Arias-Salazar L, López-López S, Payá M, Segura T, Muñoz-López M. Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects. Brain 2024; 147:3611-3623. [PMID: 38562097 DOI: 10.1093/brain/awae101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 02/15/2024] [Accepted: 04/01/2024] [Indexed: 04/04/2024] Open
Abstract
Between 2.5% and 28% of people infected with SARS-CoV-2 suffer long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy control subjects chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with long COVID assessed by Addenbrooke's Cognitive Examination-III screening test [overall cognitive level (OCLz) = -0.39 ± 0.12] was significantly below the infection recovered-controls (OCLz = +0.32 ± 0.16, P < 0.01). We observed that 48% of patients with long COVID had episodic memory deficit, with 27% also with impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy and higher radial diffusivity were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.
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Affiliation(s)
| | - Gemma Serrano-Heras
- Research Unit, University General Hospital of Albacete, 02008 Albacete, Spain
| | | | | | | | - Inmaculada Feria
- Neurology Service, University General Hospital of Albacete, 02008 Albacete, Spain
| | | | - Bryan Strange
- The Laboratory for Clinical Neuroscience, Centre for Biomedical Technology, Madrid Polytechnic University, IdISSC, 28223 Madrid, Spain
- Reina Sofia Centre for Alzheimer's Research, 28031 Madrid, Spain
| | - Francisco Mansilla
- Radiology Service, University Hospital Complex of Albacete and Mansilla Diagnostic Imaging Clinic, 02008 Albacete, Spain
| | - Linda Zhang
- The Laboratory for Clinical Neuroscience, Centre for Biomedical Technology, Madrid Polytechnic University, IdISSC, 28223 Madrid, Spain
- Reina Sofia Centre for Alzheimer's Research, 28031 Madrid, Spain
| | | | | | - Susana López-López
- Research Unit, University General Hospital of Albacete, 02008 Albacete, Spain
| | - María Payá
- Neurology Service, University General Hospital of Albacete, 02008 Albacete, Spain
| | - Tomás Segura
- Faculty of Medicine, Albacete, University of Castilla-La Mancha, 02008 Albacete, Spain
- Neurology Service, University General Hospital of Albacete, 02008 Albacete, Spain
- Institute for Research in Neurological Disabilities (IDINE), 02008 Albacete, Spain
| | - Mónica Muñoz-López
- Faculty of Medicine, Albacete, University of Castilla-La Mancha, 02008 Albacete, Spain
- Regional Centre for Biomedical Research (CRIB), 02008 Albacete, Spain
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48
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Invernizzi A, Renzetti S, van Thriel C, Rechtman E, Patrono A, Ambrosi C, Mascaro L, Corbo D, Cagna G, Gasparotti R, Reichenberg A, Tang CY, Lucchini RG, Wright RO, Placidi D, Horton MK. COVID-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study. Transl Psychiatry 2024; 14:402. [PMID: 39358346 PMCID: PMC11447249 DOI: 10.1038/s41398-024-03108-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 09/18/2024] [Accepted: 09/20/2024] [Indexed: 10/04/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdelta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdelta between groups (p = 0.041). The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.
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Affiliation(s)
- Azzurra Invernizzi
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Stefano Renzetti
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Christoph van Thriel
- Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany
| | - Elza Rechtman
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alessandra Patrono
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Claudia Ambrosi
- Department of Neuroscience, Neuroradiology Unit, ASST Cremona, Cremona, Italy
| | | | - Daniele Corbo
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Giuseppa Cagna
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Roberto Gasparotti
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Abraham Reichenberg
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Cheuk Y Tang
- Department of Diagnostic, Molecular, and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Roberto G Lucchini
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
- Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA
| | - Robert O Wright
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Donatella Placidi
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Megan K Horton
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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49
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Hayes A, Kasner SE, Favilla CG, Rothstein A, Witsch J, Hamilton RH, Sloane KL. Not So Transient?: A Narrative Review on Cognitive Impairment After Transient Ischemic Attack. Stroke 2024; 55:2558-2566. [PMID: 39212043 PMCID: PMC11421974 DOI: 10.1161/strokeaha.124.046821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Transient ischemic attack (TIA) is traditionally viewed as a self-resolving episode of neurological change without persistent impairments and without evidence of acute brain injury on neuroimaging. However, emerging evidence suggests that TIA may be associated with lingering cognitive dysfunction. Cognitive impairment is a prevalent and disabling sequela of ischemic stroke, but the clinical relevance of this phenomenon after TIA is less commonly recognized. We performed a literature search of observational studies of cognitive function after TIA. There is a consistent body of literature suggesting that rates of cognitive impairment following TIA are higher than healthy controls, but the studies included here are limited by heterogeneity in design and analysis methods. We go on to summarize recent literature on proposed pathophysiological mechanisms underlying the development of cognitive impairment following TIA and finally suggest future directions for further research in this field.
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Affiliation(s)
| | - Scott E. Kasner
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Christopher G. Favilla
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Aaron Rothstein
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jens Witsch
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Roy H. Hamilton
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Kelly L. Sloane
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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50
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Gutman EG, Salvio AL, Fernandes RA, Duarte LA, Raposo-Vedovi JV, Alcaraz HF, Teixeira MA, Passos GF, de Medeiros KQM, Hammerle MB, Pires KL, Vasconcelos CCF, Leon LAA, Figueiredo CP, Alves-Leon SV. Long COVID: plasma levels of neurofilament light chain in mild COVID-19 patients with neurocognitive symptoms. Mol Psychiatry 2024; 29:3106-3116. [PMID: 38678084 PMCID: PMC11449780 DOI: 10.1038/s41380-024-02554-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 04/02/2024] [Accepted: 04/05/2024] [Indexed: 04/29/2024]
Abstract
It is well known the potential of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection to induce post-acute sequelae, a condition called Long COVID. This syndrome includes several symptoms, but the central nervous system (CNS) main one is neurocognitive dysfunction. Recently it has been demonstrated the relevance of plasma levels of neurofilament light chain (pNfL), as a biomarker of early involvement of the CNS in COVID-19. The aim of this study was to investigate the relationship between pNfL in patients with post-acute neurocognitive symptoms and the potential of NfL as a prognostic biomarker in these cases. A group of 63 long COVID patients ranging from 18 to 59 years-old were evaluated, submitted to a neurocognitive battery assessment, and subdivided in different groups, according to results. Plasma samples were collected during the long COVID assessment and used for measurement of pNfL with the Single molecule array (SIMOA) assays. Levels of pNfL were significantly higher in long COVID patients with neurocognitive symptoms when compared to HC (p = 0.0031). Long COVID patients with cognitive impairment and fatigue symptoms presented higher pNfL levels when compared to long COVID patients without these symptoms, individually and combined (p = 0.0263, p = 0.0480, and 0.0142, respectively). Correlation analysis showed that levels of cognitive lost and exacerbation of fatigue in the neurocognitive evaluation had a significative correlation with higher pNfL levels (p = 0.0219 and 0.0255, respectively). Previous reports suggested that pNfL levels are related with higher risk of severity and predict lethality of COVID-19. Our findings demonstrate that SARS-CoV-2 infection seems to have a long-term impact on the brain, even in patients who presented mild acute disease. NfL measurements might be useful to identify CNS involvement in long COVID associated with neurocognitive symptoms and to identify who will need continuous monitoring and treatment support.
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Affiliation(s)
- Elisa Gouvea Gutman
- Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, ZIP CODE 20211-040, Brazil
- Clinical Medicine post-graduation program, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Andreza Lemos Salvio
- Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, ZIP CODE 20211-040, Brazil
| | - Renan Amphilophio Fernandes
- Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, ZIP CODE 20211-040, Brazil
| | - Larissa Araujo Duarte
- Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, ZIP CODE 20211-040, Brazil
- Clinical Medicine post-graduation program, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Jessica Vasques Raposo-Vedovi
- Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, ZIP CODE 20211-040, Brazil
| | - Helena França Alcaraz
- Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, ZIP CODE 20211-040, Brazil
| | - Milene Ataíde Teixeira
- Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, ZIP CODE 20211-040, Brazil
| | | | | | - Mariana Beiral Hammerle
- Division of Neurology, Gaffrée and Guinle University Hospital, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, Brazil
| | - Karina Lebeis Pires
- Division of Neurology, Gaffrée and Guinle University Hospital, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, Brazil
| | | | | | | | - Soniza Vieira Alves-Leon
- Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro/UNIRIO, Rio de Janeiro, RJ, ZIP CODE 20211-040, Brazil.
- Department of Neurology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
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