sharon sanders
Editor-in-Chief & President
July 2023; 10 (4) RESEARCH ARTICLE
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Deep Phenotyping of Neurologic Postacute Sequelae of SARS-CoV-2 Infection
View ORCID ProfileYair Mina, View ORCID ProfileYoshimi Enose-Akahata, View ORCID ProfileDima A. Hammoud, Anthony J. Videckis, Sandeep R. Narpala, Sarah E. O'Connell, Robin Carroll, Bob C. Lin, Cynthia Chen McMahan, View ORCID ProfileGovind Nair, View ORCID ProfileLauren B. Reoma, Adrian B. McDermott, Brian Walitt, Steven Jacobson, David S. Goldstein, View ORCID ProfileBryan R. Smith, View ORCID ProfileAvindra Nath
First published May 5, 2023, DOI: https://doi.org/10.1212/NXI.0000000000200097
Abstract
Background and Objectives SARS-CoV-2 infection has been associated with a syndrome of long-term neurologic sequelae that is poorly characterized. We aimed to describe and characterize in-depth features of neurologic postacute sequelae of SARS-CoV-2 infection (neuro-PASC).
Methods Between October 2020 and April 2021, 12 participants were seen at the NIH Clinical Center under an observational study to characterize ongoing neurologic abnormalities after SARS-CoV-2 infection. Autonomic function and CSF immunophenotypic analysis were compared with healthy volunteers (HVs) without prior SARS-CoV-2 infection tested using the same methodology.
Results Participants were mostly female (83%), with a mean age of 45 ± 11 years. The median time of evaluation was 9 months after COVID-19 (range 3–12 months), and most (11/12, 92%) had a history of only a mild infection. The most common neuro-PASC symptoms were cognitive difficulties and fatigue, and there was evidence for mild cognitive impairment in half of the patients (MoCA score <26). The majority (83%) had a very disabling disease, with Karnofsky Performance Status ≤80. Smell testing demonstrated different degrees of microsmia in 8 participants (66%). Brain MRI scans were normal, except 1 patient with bilateral olfactory bulb hypoplasia that was likely congenital. CSF analysis showed evidence of unique intrathecal oligoclonal bands in 3 cases (25%). Immunophenotyping of CSF compared with HVs showed that patients with neuro-PASC had lower frequencies of effector memory phenotype both for CD4[SUP]+[/SUP] T cells (p < 0.0001) and for CD8[SUP]+[/SUP] T cells (p = 0.002), an increased frequency of antibody-secreting B cells (p = 0.009), and increased frequency of cells expressing immune checkpoint molecules. On autonomic testing, there was evidence for decreased baroreflex-cardiovagal gain (p = 0.009) and an increased peripheral resistance during tilt-table testing (p < 0.0001) compared with HVs, without excessive plasma catecholamine responses.
Discussion CSF immune dysregulation and neurocirculatory abnormalities after SARS-CoV-2 infection in the setting of disabling neuro-PASC call for further evaluation to confirm these changes and explore immunomodulatory treatments in the context of clinical trials.
source: https://nn.neurology.org/content/10/4/e200097
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Neurologic Long COVID Patients Show Immune Dysregulation
— Autonomic dysfunction also emerges, NIH study shows
by Judy George, Deputy Managing Editor, MedPage Today May 8, 2023
Broad immune dysregulation was seen in the cerebrospinal fluid (CSF) of a small cohort of people with long COVID neurologic symptoms, a deep phenotype analysisopens in a new tab or window showed.
People with persistent neurologic symptoms after SARS-CoV-2 infection had lower levels of CD4+ and CD8+ T cells compared with healthy controls, reported Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke (NINDS) of the NIH in Bethesda, Maryland, and co-authors.
snip
Compared with healthy controls, long COVID participants had lower frequencies of effector memory phenotype both for CD4 + T cells (P<0.0001) and for CD8 + T cells (P=0.002). They also had an increased frequency of antibody-secreting B cells (P=0.009) and some increase in immune checkpoint molecules.
"The persistence of these immune abnormalities several months after a mild infection suggests the possibility of either a persistent infection or an aberrant immune response to the infection," Nath and co-authors observed.
more....https://www.medpagetoday.com/neurology/longcovid/104395
OPEN ACCESS
Deep Phenotyping of Neurologic Postacute Sequelae of SARS-CoV-2 Infection
View ORCID ProfileYair Mina, View ORCID ProfileYoshimi Enose-Akahata, View ORCID ProfileDima A. Hammoud, Anthony J. Videckis, Sandeep R. Narpala, Sarah E. O'Connell, Robin Carroll, Bob C. Lin, Cynthia Chen McMahan, View ORCID ProfileGovind Nair, View ORCID ProfileLauren B. Reoma, Adrian B. McDermott, Brian Walitt, Steven Jacobson, David S. Goldstein, View ORCID ProfileBryan R. Smith, View ORCID ProfileAvindra Nath
First published May 5, 2023, DOI: https://doi.org/10.1212/NXI.0000000000200097
Abstract
Background and Objectives SARS-CoV-2 infection has been associated with a syndrome of long-term neurologic sequelae that is poorly characterized. We aimed to describe and characterize in-depth features of neurologic postacute sequelae of SARS-CoV-2 infection (neuro-PASC).
Methods Between October 2020 and April 2021, 12 participants were seen at the NIH Clinical Center under an observational study to characterize ongoing neurologic abnormalities after SARS-CoV-2 infection. Autonomic function and CSF immunophenotypic analysis were compared with healthy volunteers (HVs) without prior SARS-CoV-2 infection tested using the same methodology.
Results Participants were mostly female (83%), with a mean age of 45 ± 11 years. The median time of evaluation was 9 months after COVID-19 (range 3–12 months), and most (11/12, 92%) had a history of only a mild infection. The most common neuro-PASC symptoms were cognitive difficulties and fatigue, and there was evidence for mild cognitive impairment in half of the patients (MoCA score <26). The majority (83%) had a very disabling disease, with Karnofsky Performance Status ≤80. Smell testing demonstrated different degrees of microsmia in 8 participants (66%). Brain MRI scans were normal, except 1 patient with bilateral olfactory bulb hypoplasia that was likely congenital. CSF analysis showed evidence of unique intrathecal oligoclonal bands in 3 cases (25%). Immunophenotyping of CSF compared with HVs showed that patients with neuro-PASC had lower frequencies of effector memory phenotype both for CD4[SUP]+[/SUP] T cells (p < 0.0001) and for CD8[SUP]+[/SUP] T cells (p = 0.002), an increased frequency of antibody-secreting B cells (p = 0.009), and increased frequency of cells expressing immune checkpoint molecules. On autonomic testing, there was evidence for decreased baroreflex-cardiovagal gain (p = 0.009) and an increased peripheral resistance during tilt-table testing (p < 0.0001) compared with HVs, without excessive plasma catecholamine responses.
Discussion CSF immune dysregulation and neurocirculatory abnormalities after SARS-CoV-2 infection in the setting of disabling neuro-PASC call for further evaluation to confirm these changes and explore immunomodulatory treatments in the context of clinical trials.
source: https://nn.neurology.org/content/10/4/e200097
-----------------------------------------------------------------------------------------
Neurologic Long COVID Patients Show Immune Dysregulation
— Autonomic dysfunction also emerges, NIH study shows
by Judy George, Deputy Managing Editor, MedPage Today May 8, 2023
Broad immune dysregulation was seen in the cerebrospinal fluid (CSF) of a small cohort of people with long COVID neurologic symptoms, a deep phenotype analysisopens in a new tab or window showed.
People with persistent neurologic symptoms after SARS-CoV-2 infection had lower levels of CD4+ and CD8+ T cells compared with healthy controls, reported Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke (NINDS) of the NIH in Bethesda, Maryland, and co-authors.
snip
Compared with healthy controls, long COVID participants had lower frequencies of effector memory phenotype both for CD4 + T cells (P<0.0001) and for CD8 + T cells (P=0.002). They also had an increased frequency of antibody-secreting B cells (P=0.009) and some increase in immune checkpoint molecules.
"The persistence of these immune abnormalities several months after a mild infection suggests the possibility of either a persistent infection or an aberrant immune response to the infection," Nath and co-authors observed.
more....https://www.medpagetoday.com/neurology/longcovid/104395