Deep Phenotyping of Neurologic Postacute Sequelae of SARS-CoV-2 Infection.

Female Male Humans CD8-Positive T-Lymphocytes COVID-19 / complications SARS-CoV-2 Brain Catecholamines

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
07 2023
Historique:
received: 29 08 2022
accepted: 04 01 2023
medline: 8 5 2023
pubmed: 6 5 2023
entrez: 5 5 2023
Statut: epublish

Résumé

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). 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. 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 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.

Sections du résumé

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
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.

Identifiants

DOI: 10.1212/NXI.0000000000200097 PMID: 37147136 PMC: PMC10162706
pubmed: 37147136
pii: 10/4/e200097
doi: 10.1212/NXI.0000000000200097
pmc: PMC10162706
pii:
doi:

Substances chimiques

Catecholamines 0

Types de publication

Observational Study Journal Article Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.

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Auteurs

Yair Mina (Y)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
ORCID: 0000-0003-2311-6623

Yoshimi Enose-Akahata (Y)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
ORCID: 0000-0002-7102-9703

Dima A Hammoud (DA)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
ORCID: 0000-0001-7406-7871

Anthony J Videckis (AJ)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Sandeep R Narpala (SR)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Sarah E O'Connell (SE)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Robin Carroll (R)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Bob C Lin (BC)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Cynthia Chen McMahan (CC)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Govind Nair (G)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
ORCID: 0000-0003-3725-615X

Lauren B Reoma (LB)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
ORCID: 0000-0001-6305-7723

Adrian B McDermott (AB)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Brian Walitt (B)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Steven Jacobson (S)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

David S Goldstein (DS)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Bryan R Smith (BR)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
ORCID: 0000-0001-9850-5944

Avindra Nath (A)

From the National Institute of Neurological Disorders and Stroke (Y.M., Y.E.-A., A.J.V., C.C.M., G.N., L.B.R., B.W., S.J., D.S.G., B.R.S., A.N.), National Institutes of Health, Bethesda, MD; Sackler Faculty of Medicine (Y.M.), Tel-Aviv University, Israel; Center for Infectious Disease Imaging (D.A.H.), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health; and Vaccine Immunology Program (S.R.N., S.E.O.C., R.C., B.C.L., A.B.M.), Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. natha@ninds.nih.gov.
ORCID: 0000-0003-0927-5855

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Deep Phenotyping of Neurologic Postacute...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Deep Phenotyping of Neurologic Postacute...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Deep Phenotyping of Neurologic Postacute...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Deep Phenotyping of Neurologic Postacute...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Deep Phenotyping of Neurologic Postacute...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Phénols › Catéchols › Catécholamines › Deep Phenotyping of Neurologic Postacute...