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May 2022; 9 (3) Clinical/Scientific NoteOpen Access

Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID

View ORCID ProfileAnne Louise Oaklander, Alexander J. Mills, Mary Kelley, Lisa S. Toran, Bryan Smith, Marinos C. Dalakas, Avindra Nath
First published March 1, 2022, DOI: https://doi.org/10.1212/NXI.0000000000001146
Anne Louise Oaklander
From the Nerve Unit (A.L.O., A.J.M.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Pathology (Neuropathology) (A.L.O.), Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology (M.K.), Dell Medical School, The University of Texas, Austin, Texas; Department of Neurology (L.S.T.), Confluence Health, Wenatchee; Section of Infections of the Nervous System (B.S., A.N.), National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH), Bethesda, Maryland; and Neuromuscular Division (M.C.D.), Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, and National and Kapodistrian University of Athens Medical School, Greece.
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  • ORCID record for Anne Louise Oaklander
Alexander J. Mills
From the Nerve Unit (A.L.O., A.J.M.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Pathology (Neuropathology) (A.L.O.), Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology (M.K.), Dell Medical School, The University of Texas, Austin, Texas; Department of Neurology (L.S.T.), Confluence Health, Wenatchee; Section of Infections of the Nervous System (B.S., A.N.), National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH), Bethesda, Maryland; and Neuromuscular Division (M.C.D.), Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, and National and Kapodistrian University of Athens Medical School, Greece.
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  • For correspondence: amills8@mgh.harvard.edu
Mary Kelley
From the Nerve Unit (A.L.O., A.J.M.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Pathology (Neuropathology) (A.L.O.), Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology (M.K.), Dell Medical School, The University of Texas, Austin, Texas; Department of Neurology (L.S.T.), Confluence Health, Wenatchee; Section of Infections of the Nervous System (B.S., A.N.), National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH), Bethesda, Maryland; and Neuromuscular Division (M.C.D.), Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, and National and Kapodistrian University of Athens Medical School, Greece.
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  • For correspondence: mary.kelley@ascension.org
Lisa S. Toran
From the Nerve Unit (A.L.O., A.J.M.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Pathology (Neuropathology) (A.L.O.), Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology (M.K.), Dell Medical School, The University of Texas, Austin, Texas; Department of Neurology (L.S.T.), Confluence Health, Wenatchee; Section of Infections of the Nervous System (B.S., A.N.), National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH), Bethesda, Maryland; and Neuromuscular Division (M.C.D.), Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, and National and Kapodistrian University of Athens Medical School, Greece.
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  • For correspondence: ltoranca@gmail.com
Bryan Smith
From the Nerve Unit (A.L.O., A.J.M.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Pathology (Neuropathology) (A.L.O.), Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology (M.K.), Dell Medical School, The University of Texas, Austin, Texas; Department of Neurology (L.S.T.), Confluence Health, Wenatchee; Section of Infections of the Nervous System (B.S., A.N.), National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH), Bethesda, Maryland; and Neuromuscular Division (M.C.D.), Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, and National and Kapodistrian University of Athens Medical School, Greece.
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  • For correspondence: bryan.smith2@nih.gov
Marinos C. Dalakas
From the Nerve Unit (A.L.O., A.J.M.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Pathology (Neuropathology) (A.L.O.), Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology (M.K.), Dell Medical School, The University of Texas, Austin, Texas; Department of Neurology (L.S.T.), Confluence Health, Wenatchee; Section of Infections of the Nervous System (B.S., A.N.), National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH), Bethesda, Maryland; and Neuromuscular Division (M.C.D.), Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, and National and Kapodistrian University of Athens Medical School, Greece.
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  • For correspondence: marinos.dalakas@jefferson.edu
Avindra Nath
From the Nerve Unit (A.L.O., A.J.M.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Pathology (Neuropathology) (A.L.O.), Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology (M.K.), Dell Medical School, The University of Texas, Austin, Texas; Department of Neurology (L.S.T.), Confluence Health, Wenatchee; Section of Infections of the Nervous System (B.S., A.N.), National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH), Bethesda, Maryland; and Neuromuscular Division (M.C.D.), Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, and National and Kapodistrian University of Athens Medical School, Greece.
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  • For correspondence: natha@ninds.nih.gov
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Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID
Anne Louise Oaklander, Alexander J. Mills, Mary Kelley, Lisa S. Toran, Bryan Smith, Marinos C. Dalakas, Avindra Nath
Neurol Neuroimmunol Neuroinflamm May 2022, 9 (3) e1146; DOI: 10.1212/NXI.0000000000001146

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Abstract

Background and Objectives Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

Methods We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.

Results Among 17 patients (mean age 43.3 years, 69% female, 94% Caucasian, and 19% Latino), 59% had ≥1 test interpretation confirming neuropathy. These included 63% (10/16) of skin biopsies, 17% (2/12) of electrodiagnostic tests and 50% (4/8) of autonomic function tests. One patient was diagnosed with critical illness axonal neuropathy and another with multifocal demyelinating neuropathy 3 weeks after mild COVID, and ≥10 received small-fiber neuropathy diagnoses. Longitudinal improvement averaged 52%, although none reported complete resolution. For treatment, 65% (11/17) received immunotherapies (corticosteroids and/or IV immunoglobulins).

Discussion Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset. Various evidence suggested infection-triggered immune dysregulation as a common mechanism.

Footnotes

  • ↵* Co–senior authors.

  • The Article Processing Charge was funded by the NIH.

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • Received November 22, 2021.
  • Accepted in final form January 14, 2022.
  • Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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