Neuropathic symptoms with SARS-CoV-2 vaccination

  1. Farinaz Safavi
  2. Lindsey Gustafson
  3. Brian Walitt
  4. Tanya Lehky
  5. Sara Dehbashi
  6. Amanda Wiebold
  7. Yair Mina
  8. Susan Shin
  9. Baohan Pan
  10. Michael Polydefkis
  11. Anne Louise Oaklander
  12. Avindra Nath

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Abstract

Background and Objectives

Various peripheral neuropathies, particularly those with sensory and autonomic dysfunction may occur during or shortly after acute COVID-19 illnesses. These appear most likely to reflect immune dysregulation. If similar manifestations can occur with the vaccination remains unknown.

Results

In an observational study, we studied 23 patients (92% female; median age 40years) reporting new neuropathic symptoms beginning within 1 month after SARS-CoV-2 vaccination. 100% reported sensory symptoms comprising severe face and/or limb paresthesias, and 61% had orthostasis, heat intolerance and palpitations. Autonomic testing in 12 identified seven with reduced distal sweat production and six with positional orthostatic tachycardia syndrome. Among 16 with lower-leg skin biopsies, 31% had diagnostic/subthreshold epidermal neurite densities (≤5%), 13% were borderline (5.01-10%) and 19% showed abnormal axonal swelling. Biopsies from randomly selected five patients that were evaluated for immune complexes showed deposition of complement C4d in endothelial cells. Electrodiagnostic test results were normal in 94% (16/17). Together, 52% (12/23) of patients had objective evidence of small-fiber peripheral neuropathy. 58% patients (7/12) treated with oral corticosteroids had complete or near-complete improvement after two weeks as compared to 9% (1/11) of patients who did not receive immunotherapy having full recovery at 12 weeks. At 5-9 months post-symptom onset, 3 non-recovering patients received intravenous immunoglobulin with symptom resolution within two weeks.

Conclusions

This observational study suggests that a variety of neuropathic symptoms may manifest after SARS-CoV-2 vaccinations and in some patients might be an immune-mediated process.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.16.22274439: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Twenty-three self-referred patients were evaluated between January to September 2021 for new onset of potential symptoms of polyneuropathy (sensory, motor, or autonomic) within 1 month of SARS-CoV-2 vaccination were enrolled after consent to an IRB approved study at the National Institutes of Health (protocol # 15-N-00125).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    12 Multiplex fluorescence immunohistochemistry was performed by incubating sections with 5% normal donkey serum (Jackson ImmunoResearch, West Grove, PA) for 1 hour, then overnight at room temperature using 0.5-5 μg/ml mixtures of immunocompatible antibodies (anti-human IgG, anti-human IgM and anti-CD31 (Leica Biosystems; NCL-L-IgG; NCL-L-IgM and PA0414); anti-C1q (Dako; A0136); anti-C4d (Biomedica; BIRC4D and anti-NFH (Aves Labs), followed by a 1 µg/ml mixture of appropriately cross-adsorbed secondary antibodies raised in donkey (Thermo Fisher, Waltham, MA; Jackson ImmunoResearch) and conjugated to one of the following spectrally compatible fluorophores: Alexa Fluor 488, Alexa Fluor 546, and Alexa Fluor 647.
    anti-CD31
    suggested: (Bioss Cat# bs-0468R-A488, RRID:AB_2714016)
    PA0414)
    suggested: None
    anti-C1q
    suggested: (Agilent Cat# A0136, RRID:AB_2335698)
    anti-C4d
    suggested: (Biomedica Cat# BI-RC4D, RRID:AB_1944063)
    anti-NFH
    suggested: (Antibodies Incorporated Cat# NFH, RRID:AB_2313552)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2022.05.16.22274439v1 on medRxiv