Tag: neurocognitive functioning

Deep Dive into the Long Haul: Analysis of Symptom Clusters and Risk Factors for Post-Acute Sequelae of COVID-19 to Inform Clinical Care

Abstract:

Long COVID is a chronic condition characterized by symptoms such as fatigue, dyspnea, and cognitive impairment that persist or relapse months after an acute infection with the SARS-CoV-2 virus. Many distinct symptoms have been attributed to Long COVID; however, little is known about the potential clustering of these symptoms and risk factors that may predispose patients to certain clusters. In this study, an electronic survey was sent to patients in the UC San Diego Health (UCSDH) system who tested positive for COVID-19, querying if patients were experiencing symptoms consistent with Long COVID.

Based on survey results, along with patient demographics reported in the electronic health record (EHR), linear and logistic regression models were used to examine putative risk factors, and exploratory factor analysis was performed to determine symptom clusters. Among 999 survey respondents, increased odds of Long COVID (n = 421; 42%) and greater Long COVID symptom burden were associated with female sex (OR = 1.73, 99% CI: 1.16-2.58; β = 0.48, 0.22-0.75), COVID-19 hospitalization (OR = 4.51, 2.50-8.43; β = 0.48, 0.17-0.78), and poorer pre-COVID self-rated health (OR = 0.75, 0.57-0.97; β = -0.19, -0.32–0.07).

Over one-fifth of Long COVID patients screened positive for depression and/or anxiety, the latter of which was associated with younger age (OR = 0.96, 0.94-0.99). Factor analysis of 16 self-reported symptoms suggested five symptom clusters-gastrointestinal (GI), musculoskeletal (MSK), neurocognitive (NC), airway (AW), and cardiopulmonary (CP), with older age (β = 0.21, 0.11-0.30) and mixed race (β = 0.27, 0.04-0.51) being associated with greater MSK symptom burden. Greater NC symptom burden was associated with increased odds of depression (OR = 5.86, 2.71-13.8) and anxiety (OR = 2.83, 1.36-6.14).

These results can inform clinicians in identifying patients at increased risk for Long COVID-related medical issues, particularly neurocognitive symptoms and symptom clusters, as well as informing health systems to manage operational expectations on a population-health level.

Source: Goldhaber NH, Kohn JN, Ogan WS, Sitapati A, Longhurst CA, Wang A, Lee S, Hong S, Horton LE. Deep Dive into the Long Haul: Analysis of Symptom Clusters and Risk Factors for Post-Acute Sequelae of COVID-19 to Inform Clinical Care. Int J Environ Res Public Health. 2022 Dec 15;19(24):16841. doi: 10.3390/ijerph192416841. PMID: 36554723; PMCID: PMC9778884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778884/ (Full text)

Association between long COVID symptoms and employment status

Abstract:

Background: Symptoms of Coronavirus-19 (COVID-19) infection persist beyond 2 months in a subset of individuals, a phenomenon referred to as long COVID, but little is known about its functional correlates and in particular the relevance of neurocognitive symptoms.

Method: We analyzed a previously-reported cohort derived from 8 waves of a nonprobability-sample internet survey called the COVID States Project, conducted every 4-8 weeks between February 2021 and July 2022. Primary analyses examined associations between long COVID and lack of full employment or unemployment, adjusted for age, sex, race and ethnicity, education, urbanicity, and region, using multiple logistic regression with interlocking survey weights.

Results: The cohort included 15,307 survey respondents ages 18-69 with test-confirmed COVID-19 at least 2 months prior, of whom 2,236 (14.6%) reported long COVID symptoms, including 1,027/2,236 (45.9%) reporting either ‘brain fog’ or impaired memory. Overall, 1,418/15,307 (9.3%) reported being unemployed, including 276/2,236 (12.3%) of those with long COVID and 1,142/13,071 (8.7%) of those without; 8,228 (53.8%) worked full-time, including 1,017 (45.5%) of those with long COVID and 7,211 (55.2%) without. In survey-weighted regression models, presence of long COVID was associated with being unemployed (crude OR 1.44, 95% CI 1.20-1.72; adjusted OR 1.23, 95% CI 1.02-1.48), and with lower likelihood of working full-time (crude OR 0.73, 95% CI 0.64-0.82; adjusted OR 0.79, 95% CI 0.70 -0.90). Among individuals with long COVID, the presence of cognitive symptoms — either brain fog or impaired memory — was associated with lower likelihood of working full time (crude OR 0.71, 95% CI 0.57-0.89, adjusted OR 0.77, 95% CI 0.61-0.97).

Conclusion: Long COVID was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. Presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to respond to long COVID, and particularly the associated neurocognitive symptoms.

Source: Kristin Lunz Trujillo, Roy H Perlis, Alauna Safarpour, Mauricio Santillana, Katherine Ognyanova, James Druckman, David Lazer. Association between long COVID symptoms and employment status. medRxiv 2022.11.17.22282452; doi: https://doi.org/10.1101/2022.11.17.22282452 (Full text available as PDF file)

Orthostatic intolerance and neurocognitive impairment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Objectives: The Institute of Medicine (IOM 2015. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington: The National Academies Press) suggested new criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), which requires an endorsement of either neurocognitive impairment or orthostatic intolerance (OI) in addition to other core symptoms. While some research supports the inclusion of OI as a core symptom, others argue that overlap with neurocognitive impairment does not justify the either/or option. The current study assessed methods of operationalizing OI using items from the DePaul Symptom Questionnaire (DSQ-1 and -2) as a part of the IOM criteria. Evaluating the relationship between OI and neurocognitive symptoms may lead to a better understanding of diagnostic criteria for ME/CFS.

Methods: Two-hundred and forty-two participants completed the DSQ. We examined how many participants met the IOM criteria while endorsing different frequencies and severities of various OI symptoms.

Results: Neurocognitive impairment was reported by 93.4% of respondents. OI without concurrent neurocognitive symptoms only allowed for an additional 1.7–4.5% of participants to meet IOM criteria.

Conclusions: Neurocognitive symptoms and OI overlap in ME/CFS, and our results do not support the IOM’s inclusion of neurocognitive impairment and OI as interchangeable symptoms. Furthermore, our findings highlight the need for a uniform method of defining and measuring OI via self-report in order to accurately study OI as a symptom of ME/CFS.

Source: Gaglio, Caroline L., Islam, Mohammed F., Cotler, Joseph and Jason, Leonard A.. “Orthostatic intolerance and neurocognitive impairment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)” Epidemiologic Methods, vol. 11, no. 1, 2022, pp. 20210033. https://doi.org/10.1515/em-2021-0033

NeuroCOVID-19: a critical review

Abstract:

Background: The COVID-19 pandemic has challenged neurologists since its early days. Neurology consultation services were then overloaded by emergency department and intensive-care patients with acute neurological syndromes. These complications are better explained today, but the growing number of patients with reported longstanding neurological symptoms constitute an emerging, complex, and still poorly understood phenomenon.

Objective: This review summarizes data on relevant neurological manifestations of acute SARS-CoV-2 infection and lasting post-infectious disease, also known as Long COVID. The complex history of Long COVID is examined to illustrate the upsides and challenges imposed by the active participation of patient communities in the production of medical knowledge.

Methods: Narrative review.

Results: Infection with the severe acute respiratory syndrome coronavirus 2 is associated with encephalopathy/delirium, cerebrovascular disease, headache, and peripheral nervous system involvement. Long COVID is a living concept jointly defined by patient communities, physicians and scientists, including neurologists.

Conclusion: Co-production of Long COVID knowledge between scientists and patients has initiated an era of patient-led research and evidence-based activism that acts as a two-edged sword – putting patient’s suffering in the spotlight, but with a tradeoff in methodological consistency.

Source: Guedes BF. NeuroCOVID-19: a critical review. Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):281-289. doi: 10.1590/0004-282X-ANP-2022-S136. PMID: 35976326. https://www.scielo.br/j/anp/a/v6c3Xcvq4PkkD3HvKtT7DJN/?lang=en  (Full tex)

Cognitive Complications of COVID-19 Infection

Abstract:

SARS-CoV-2 is associated with a post-infectious neurocognitive syndrome characterized by fatigue and deficits in attention, memory, and executive function. As screening cognitive testing generally remains normal, the pathophysiologic basis of these symptoms remains controversial and there is no standardized treatment paradigm.

We present a clinical case demonstrative of typical neurocognitive sequelae of SARS-CoV-2 infection, highlighting medical and social factors that may have contributed to the severity of symptoms. We discuss the pathophysiologic evidence for cognitive “brain fog” following COVID-19 infection as well as lifestyle changes and rehabilitation strategies that may improve recovery. As the benefits of pharmacologic therapy remain unproven, we close with a brief discussion of medication options that might be appropriate targets for future clinical trials in the context of rehabilitative treatment.

Source: Warren S, Drake J, Wu CK. Cognitive Complications of COVID-19 Infection. R I Med J (2013). 2022 Sep 1;105(7):27-30. PMID: 35930487. https://pubmed.ncbi.nlm.nih.gov/35930487/ http://rimed.org/rimedicaljournal/2022/09/2022-09-27-covid-warren.pdf  (Full text available as PDF file)

Orbito-Frontal Cortex Hypometabolism in Children With Post-COVID Condition (Long COVID): A Preliminary Experience

Abstract:

We describe 3 children with new-onset neurocognitive problems after coronavirus disease 2019 (COVID-19), that showed, at the brain [18F]-fluorodeoxyglucose positron emission tomography/computed tomography, hypometabolism in the left orbito-frontal region. The voxel-wise analysis confirmed a cluster of hypometabolic voxels in this region with a peak at -18/46/-4mm (179 voxels, T-Score 8.1). These findings may explain neurocognitive symptoms that some children develop after COVID-19 and require further investigations.

Source: Cocciolillo F, Di Giuda D, Morello R, De Rose C, Valentini P, Buonsenso D. Orbito-Frontal Cortex Hypometabolism in Children With Post-COVID Condition (Long COVID): A Preliminary Experience. Pediatr Infect Dis J. 2022 Aug 1;41(8):663-665. doi: 10.1097/INF.0000000000003578. Epub 2022 Jul 13. PMID: 35839175.  https://pubmed.ncbi.nlm.nih.gov/35839175/

‘I can’t cope with multiple inputs’: a qualitative study of the lived experience of ‘brain fog’ after COVID-19

Abstract:

Objective: To explore the lived experience of ‘brain fog’-the wide variety of neurocognitive symptoms that can follow COVID-19.

Design and setting: A UK-wide longitudinal qualitative study comprising online focus groups with email follow-up.

Method: 50 participants were recruited from a previous qualitative study of the lived experience of long COVID-19 (n=23) and online support groups for people with persistent neurocognitive symptoms following COVID-19 (n=27). In remotely held focus groups, participants were invited to describe their neurocognitive symptoms and comment on others’ accounts. Individuals were followed up by email 4-6 months later. Data were audiotaped, transcribed, anonymised and coded in NVIVO. They were analysed by an interdisciplinary team with expertise in general practice, clinical neuroscience, the sociology of chronic illness and service delivery, and checked by people with lived experience of brain fog.

Results: Of the 50 participants, 42 were female and 32 white British. Most had never been hospitalised for COVID-19. Qualitative analysis revealed the following themes: mixed views on the appropriateness of the term ‘brain fog’; rich descriptions of the experience of neurocognitive symptoms (especially executive function, attention, memory and language), accounts of how the illness fluctuated-and progressed over time; the profound psychosocial impact of the condition on relationships, personal and professional identity; self-perceptions of guilt, shame and stigma; strategies used for self-management; challenges accessing and navigating the healthcare system; and participants’ search for physical mechanisms to explain their symptoms.

Conclusion: These qualitative findings complement research into the epidemiology and mechanisms of neurocognitive symptoms after COVID-19. Services for such patients should include: an ongoing therapeutic relationship with a clinician who engages with their experience of neurocognitive symptoms in its personal, social and occupational context as well as specialist services that include provision for neurocognitive symptoms, are accessible, easily navigable, comprehensive and interdisciplinary.

Source: Callan C, Ladds E, Husain L, Pattinson K, Greenhalgh T. ‘I can’t cope with multiple inputs’: a qualitative study of the lived experience of ‘brain fog’ after COVID-19. BMJ Open. 2022 Feb 11;12(2):e056366. doi: 10.1136/bmjopen-2021-056366. PMID: 35149572; PMCID: PMC8844964. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844964/ (Full text)

Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19

Abstract:

Objective: A subset of individuals with coronavirus disease 2019 (COVID-19) appears to develop persisting cognitive and medical symptoms. Research in the acute stages of illness, generally utilizing cognitive screening measures or case reports, suggests presence of deficits in attention and executive function. This observational study investigated cognitive functioning among individuals with persistent cognitive complaints about 5.5 months after COVID-19 infection.

Methods: Patients with polymerase chain reaction confirmed COVID-19 and persistent cognitive complaints underwent comprehensive in-person neuropsychological evaluations. Patients with prior neurological disorders were excluded. When diagnosed, 40% required hospitalization, 15% were in an intensive care unit, 10% needed mechanical ventilation, and 10% experienced delirium.

Results: This sample was predominately women (90%), White non-Hispanic (70%), with average education of 15 years. Mild cognitive deficits were seen on tests involving attention and processing speed or executive function. Seventy percent of patients were diagnosed with a mood disorder prior to COVID-19 infection. At the time of testing, 35%-40% endorsed moderate to severe mood symptoms and 85% noted significant fatigue as measured by the Fatigue Severity Scale.

Conclusions: The pattern of cognitive deficits, although mild, is consistent with prior research at the acute stage of the illness. These findings suggest that psychological factors and other persisting symptoms (e.g., sleep, fatigue) may play a significant role in subjective cognitive complaints in patients with persisting complaints post COVID-19 who did not require intensive treatment. These patients would likely benefit from resources to manage persisting or new mood symptoms and compensatory strategies for the cognitive inefficiencies they experience.

Source: Krishnan K, Miller AK, Reiter K, Bonner-Jackson A. Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19. Arch Clin Neuropsychol. 2022 Feb 5:acac004. doi: 10.1093/arclin/acac004. Epub ahead of print. PMID: 35136912. https://academic.oup.com/acn/advance-article/doi/10.1093/arclin/acac004/6522998 (Full text)

Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging

Abstract:

INTRODUCTION: Studies of neurocognition suggest that abnormalities in cognitive control contribute to the pathophysiology of chronic fatigue syndrome (CFS) in adolescents, yet these abnormalities remain poorly understood at the neurobiological level. Reports indicate that adolescents with CFS are significantly impaired in conflict processing, a primary element of cognitive control.

METHOD: In this study, we examine whether emotional conflict processing is altered on behavioral and neural levels in adolescents with CFS and a healthy comparison group. Fifteen adolescent patients with CFS and 24 healthy adolescent participants underwent functional magnetic resonance imaging (fMRI) while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect labeled words.

RESULTS: Adolescent CFS patients were less able to engage the left amygdala and left midposterior insula (mpINS) in response to conflict than the healthy comparison group. An association between accuracy interference and conflict-related reactivity in the amygdala was observed in CFS patients. A relationship between response time interference and conflict-related reactivity in the mpINS was also reported. Neural responses in the amygdala and mpINS were specific to fatigue severity.

CONCLUSIONS: These data demonstrate that adolescent CFS patients displayed deficits in emotional conflict processing. Our results suggest abnormalities in affective and cognitive functioning of the salience network, which might underlie the pathophysiology of adolescent CFS.

 

Source: Wortinger LA, Endestad T, Melinder AM, Øie MG, Sulheim D, Fagermoen E, Wyller VB. Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging. J Clin Exp Neuropsychol. 2016 Sep 20:1-14. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27647312

 

Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence

Abstract:

Cognitive difficulties represent a common and debilitating feature of the enigmatic chronic fatigue syndrome (CFS). These difficulties manifest as self-reported problems with attention, memory, and concentration and present objectively as slowed information processing speed particularly on complex tasks requiring sustained attention. The mechanisms underlying cognitive dysfunction remain to be established; however, alterations in autonomic nervous system activity and cerebral blood flow have been proposed as possibilities.

Heterogeneity in the experience of cognitive impairment, as well as differences in the methods utilised to quantify dysfunction, may contribute to the difficulties in establishing plausible biological underpinnings. The development of a brief neurocognitive battery specifically tailored to CFS and adoption by the international research community would be beneficial in establishing a profile of cognitive dysfunction. This could also provide better insights into the underlying biological mechanisms of cognitive dysfunction in CFS and enhance the development of targeted treatments.

 

Source: Cvejic E, Birch RC, Vollmer-Conna U. Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence. Curr Rheumatol Rep. 2016 May;18(5):24. doi: 10.1007/s11926-016-0577-9. https://www.ncbi.nlm.nih.gov/pubmed/27032787