Tag: long covid neurology

Neurological post-acute sequelae of SARS-CoV-2 infection (PASC)

Abstract:

The novel corona virus infectious disease, COVID-19, caused by SARS-CoV-2, can have two phases: acute (generally 4 weeks after onset) and chronic (> 4 weeks after onset). Both phases include a wide variety of signs and symptoms including neurological and psychiatric symptoms. The signs and symptoms that are considered sequelae of COVID-19 are termed post-COVID condition, long COVID-19, and post-acute sequelae of SARS-CoV-2 infection (PASC).

PASC symptoms include fatigue, dyspnea, palpitation, dysosmia, sub-fever, hypertension, alopecia, sleep problems, loss of concentration, amnesia, numbness, pain, gastrointestinal symptoms, depression, and anxiety. Because the specific pathophysiology of PASC has not yet been clarified, there are no definite criteria of the condition, hence the World Health Organization’s definition is quite broad. Consequently, it is difficult to correctly diagnose PASC.

Approximately 50% of patients may show at least one PASC symptom up to 12 months after COVID-19 infection; however, the exact prevalence of PASC has not been determined. Despite extensive research in progress worldwide, there are currently no clear diagnostic methodologies or treatments for PASC.

In this review, we discuss the currently available information on PASC and highlight the neurological sequelae of COVID-19 infection. Furthermore, we provide clinical suggestions for diagnosing and caring for PASC patients based on our outpatient clinic experience.

Source: Takao M, Ohira M. Neurological post-acute sequelae of SARS-CoV-2 infection (PASC). Psychiatry Clin Neurosci. 2022 Sep 23. doi: 10.1111/pcn.13481. Epub ahead of print. PMID: 36148558. https://pubmed.ncbi.nlm.nih.gov/36148558/

Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity

Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR).

In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups.

We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients.

Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.

Source: Franziska Sotzny, Igor Salerno Filgueiras, Claudia Kedor, Helma Freitag, Kirsten Wittke, Sandra Bauer, Nuno Sepúlveda, Dennyson Leandro Mathias da Fonseca, Gabriela Crispim Baiocchi, Alexandre H. C. Marques, Myungjin Kim, Tanja Lange, Desirée Rodrigues Plaça, Finn Luebber, Frieder M. Paulus, Roberta De Vito, Igor Jurisica, Kai Schulze-Forster, Friedemann Paul, Judith Bellmann-Strobl, Rebekka Rust, Uta Hoppmann, Yehuda Shoenfeld, Gabriela Riemekasten, Harald Heidecke, Otavio Cabral-Marques, Carmen Scheibenbogen. Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity. Front. Immunol., 27 September 2022
Sec. Autoimmune and Autoinflammatory Disorders https://doi.org/10.3389/fimmu.2022.981532 (Full text)

Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance

Abstract:

Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups.

Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention.

Results: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests.

Conclusion: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.

Source: O’Connor EE, Rednam N, O’Brien R, O’Brien S, Rock P, Levine A, Zeffiro TA. Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance. medRxiv [Preprint]. 2022 Sep 23:2022.09.22.22280222. doi: 10.1101/2022.09.22.22280222. PMID: 36172134; PMCID: PMC9516858. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516858/ (Full text)

Differential diagnosis and pathogenesis of the neurological signs and symptoms in COVID-19 and long-COVID syndrome

Abstract:

Neurological features have now been reported very frequently in the ongoing COVID-19 pandemic caused by SARS-CoV-2. The neurological deficits associated features are observed in both acute and chronic stages of COVID-19 and they appear to overlap with wide-ranging symptoms that can be attributed to being of non-neural origins, thus obscuring the definitive diagnosis of neuro-COVID.

The pathogenetic factors acting in concert to cause neuronal injury are now emerging, with SARS-CoV-2 directly affecting the brain coupled with the neuroinflammatory factors have been implicated in the causation of disabilities in acute COVID-19 and patients with Long-COVID syndrome. As the differentiation between a neural origin and other organ-based causation of a particular neurological feature is of prognostic significance, it implores a course of action to this covert, yet important neurological challenge.

Source: Baig AM. Differential diagnosis and pathogenesis of the neurological signs and symptoms in COVID-19 and long-COVID syndrome. CNS Neurosci Ther. 2022 Sep 19. doi: 10.1111/cns.13957. Epub ahead of print. PMID: 36117492. https://onlinelibrary.wiley.com/doi/10.1111/cns.13957 (Full text)

Memory alterations after COVID-19 infection: a systematic review

Abstract:

SARS-CoV-2 infection has a wide range of both acute and long-term symptoms. Memory alterations have been frequently reported in studies that explore cognition. The main objective of the systematic review is to update and further analyze the existing evidence of objective memory impairments in long-COVID-19 considering sample and study design characteristics, as well as to explore associations between memory performance and their epidemiological, clinical, and pathological features.

A total of 13 studies were identified by searching in PubMed, Web of Science, and PsycInfo databases up to May 6, 2022. Most studies evaluated verbal component of memory in the short-term and long-term recall up to 30 min and mainly performed a single assessment completed at 4-6 months after the infection. The samples mainly consisted of middle-aged adults that required hospitalization. Samples were not stratified by sex, age, and severity.

Poor verbal learning was reported in most cases (6-58%), followed by deficits in long-term (4-58%) and short-term (4-37%) verbal memory. Visuospatial component of memory was studied less than verbal component, showing impairment of long-term retention of visual items (10-49%). COVID-19 severity in the acute stage was not systematically associated with poor memory performance. Verbal memory deficits were associated with anxiety and depression.

The existing literature on objective memory assessment in long-COVID suggests further research is warranted to confirm memory dysfunction in association with epidemiological, pathological, and clinical factors, using both verbal and visuospatial tests, and exploring in deep long-term memory deficits.

Source: Llana T, Zorzo C, Mendez-Lopez M, Mendez M. Memory alterations after COVID-19 infection: a systematic review. Appl Neuropsychol Adult. 2022 Sep 15:1-14. doi: 10.1080/23279095.2022.2123739. Epub ahead of print. PMID: 36108666.  https://pubmed.ncbi.nlm.nih.gov/36108666/

Long-term neurologic outcomes of COVID-19

Abstract:

The neurologic manifestations of acute COVID-19 are well characterized, but a comprehensive evaluation of postacute neurologic sequelae at 1 year has not been undertaken. Here we use the national healthcare databases of the US Department of Veterans Affairs to build a cohort of 154,068 individuals with COVID-19, 5,638,795 contemporary controls and 5,859,621 historical controls; we use inverse probability weighting to balance the cohorts, and estimate risks and burdens of incident neurologic disorders at 12 months following acute SARS-CoV-2 infection.

Our results show that in the postacute phase of COVID-19, there was increased risk of an array of incident neurologic sequelae including ischemic and hemorrhagic stroke, cognition and memory disorders, peripheral nervous system disorders, episodic disorders (for example, migraine and seizures), extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain–Barré syndrome, and encephalitis or encephalopathy.

We estimated that the hazard ratio of any neurologic sequela was 1.42 (95% confidence intervals 1.38, 1.47) and burden 70.69 (95% confidence intervals 63.54, 78.01) per 1,000 persons at 12 months. The risks and burdens were elevated even in people who did not require hospitalization during acute COVID-19. Limitations include a cohort comprising mostly White males. Taken together, our results provide evidence of increased risk of long-term neurologic disorders in people who had COVID-19.

Source: Xu, E., Xie, Y. & Al-Aly, Z. Long-term neurologic outcomes of COVID-19. Nat Med (2022). https://doi.org/10.1038/s41591-022-02001-z https://www.nature.com/articles/s41591-022-02001-z (Full text)

Larger gray matter volumes in neuropsychiatric long-COVID syndrome

Abstract:

Neuropsychiatric symptoms are the most common sequelae of long-COVID. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it is necessary to further investigate brain structural changes in relation to course and neuropsychiatric symptom burden in long-COVID. To this end, the present study investigated 3T-MRI scans from long-COVID patients suffering from neuropsychiatric symptoms (n = 30), and healthy controls (n = 20). Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry.

To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and/or initial severity of symptoms of COVID-19 and time since onset of COVID-19 stepwise linear regression analysis was performed. Significantly enlarged GMV in long-COVID patients was present in several clusters (spanning fronto-temporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres) when compared to controls. Time since onset of COVID-19 was a significant regressor in four of these clusters with an inverse relationship. No associations with clinical symptom burden were found.

GMV alterations in limbic and secondary olfactory areas are present in long-COVID patients and might be dynamic over time. Larger samples and longitudinal data in long-COVID patients are required to further clarify the mediating mechanisms between COVID-19, GMV and neuropsychiatric symptoms.

Source: Besteher B, Machnik M, Troll M, Toepffer A, Zerekidze A, Rocktäschel T, Heller C, Kikinis Z, Brodoehl S, Finke K, Reuken PA, Opel N, Stallmach A, Gaser C, Walter M. Larger gray matter volumes in neuropsychiatric long-COVID syndrome. Psychiatry Res. 2022 Sep 6;317:114836. doi: 10.1016/j.psychres.2022.114836. Epub ahead of print. PMID: 36087363; PMCID: PMC9444315. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444315/ (Full text)

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial

Abstract:

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection.

Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = – 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001).

Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate.

These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT’s beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

Source: Zilberman-Itskovich S, Catalogna M, Sasson E, Elman-Shina K, Hadanny A, Lang E, Finci S, Polak N, Fishlev G, Korin C, Shorer R, Parag Y, Sova M, Efrati S. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Sci Rep. 2022 Jul 12;12(1):11252. doi: 10.1038/s41598-022-15565-0. PMID: 35821512; PMCID: PMC9276805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276805/ (Full text)

Autonomic and neuropathic complaints of long-COVID objectified: an investigation from electrophysiological perspective

Abstract:

Purpose: Here , we aimed to assess the frequency and phenomenology of autonomic and neuropathic complaints of long-COVID and to evaluate them by means of electrophysiology.

Methods: Step 1. Patients with prior COVID-19 infection were screened by COMPASS-31 and mTORONTO to create the target population for further evaluation. Step 2. Patients with high scores were invited for a detailed history of their complaints and electrophysiological analysis, which included nerve conduction studies, cutaneous silent period (CSP), and sympathetic skin response (SSR). We also constituted a control group composed of healthy subjects of similar age and sex for electrophysiological analysis.

Results: There were 106 patients, who matched the study criteria. Among them, thirty-eight patients (%35.8) had neuropathic or autonomic complaints or both. Fatigue and headache were significantly more frequent in patients with autonomic and neuropathic complaints. Detailed examination and electrophysiological evaluation were performed in 14 of 38 patients. Neuropathic complaints were patchy and proximally located in the majority. The entire CSP suppression index was higher in the patients (p = 0.002). There was no difference in palmar and plantar SSR between patients and healthy subjects. mTORONTO scores were negatively correlated with palmar and plantar SSR amplitudes, and the correlation was moderate.

Conclusion: Neuropathic or autonomic complaints were seen in more than one-third of patients with long-COVID. Neuropathic complaints were generally patchy, proximally predominant, asymmetric, or diffuse. The CSP suppression index was abnormal whereas SSRs were normal.

Source: Ser MH, Çalıkuşu FZ, Tanrıverdi U, Abbaszade H, Hakyemez S, Balkan İİ, Karaali R, Gündüz A. Autonomic and neuropathic complaints of long-COVID objectified: an investigation from electrophysiological perspective. Neurol Sci. 2022 Aug 22:1–11. doi: 10.1007/s10072-022-06350-y. Epub ahead of print. PMID: 35994135; PMCID: PMC9395948. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395948/ (Full text)

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)