Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome

  1. Stephen Keddie
  2. Julia Pakpoor
  3. Christina Mousele
  4. Menelaos Pipis
  5. Pedro M Machado
  6. Mark Foster
  7. Christopher J Record
  8. Ryan Y S Keh
  9. Janev Fehmi
  10. Ross W Paterson
  11. Viraj Bharambe
  12. Lisa M Clayton
  13. Claire Allen
  14. Olivia Price
  15. Jasmine Wall
  16. Annamaria Kiss-Csenki
  17. Devi Priya Rathnasabapathi
  18. Ruth Geraldes
  19. Tatyana Yermakova
  20. Joshua King-Robson
  21. Maya Zosmer
  22. Sanjeev Rajakulendran
  23. Sheetal Sumaria
  24. Simon F Farmer
  25. Ross Nortley
  26. Charles R Marshall
  27. Edward J Newman
  28. Niranjanan Nirmalananthan
  29. Guru Kumar
  30. Ashwin A Pinto
  31. James Holt
  32. Tim M Lavin
  33. Kathryn M Brennan
  34. Michael S Zandi
  35. Dipa L Jayaseelan
  36. Jane Pritchard
  37. Robert D M Hadden
  38. Hadi Manji
  39. Hugh J Willison
  40. Simon Rinaldi
  41. Aisling S Carr
  42. Michael P Lunn

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Abstract

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65–1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016–19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: −0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.

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  1. Version published to 10.1093/brain/awaa433
  2. ScreenIT

    SciScore for 10.1101/2020.07.24.20161471: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics: The UK Health Research Authority was consulted and advised the study did not require review by an NHS Research Ethics Committee as an analysis of previously collected non-identifiable information.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We searched for human homologs of proteins encoded by the SARS CoV-2 genome using the National Centre for Biotechnology Information (NCBI’s) Basic Local Alignment Search Tool (BLAST) to identify common amino acid sequences in the human Reference Sequence Database (refseq_protein).
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)
    R (4.0.0) and GraphPad prism (8.1.2) were used for analysis and figures.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: We detected the following sentences addressing limitations in the study:
    Under reporting of COVID-19 cases poses limitations to true estimates of incidence, resulting in a potential over-reporting of a COVID-19 GBS association. Whilst at an epidemiological level we found no increase in GBS linked to the COVID-19 epidemic, our data do not exclude the possibility that SARS-Cov-2 might be a driver of GBS in very rare cases, or that a significant reduction in non-COVID-19 GBS could mask a smaller spike of COVID GBS cases. Early series of COVID-19 associated GBS reported specific disease characteristics suggesting differences from typical AIDP.7 This larger cohort revealed no differences in the clinical and neurophysiological features, disease severity and outcomes of COVID-19 and non-COVID-19 associated GBS. A larger proportion of COVID-19 PCR positive GBS cases required mechanical intervention compared to all other groups. The similar rate of neurological recovery across all groups suggests ventilation was related to COVID-19 associated pulmonary involvement rather than neuromuscular deficit at nadir. Guillain-Barré Syndrome is an acute immune mediated inflammatory polyneuropathy which can result in severe disability and death. Epidemiological and laboratory research have revealed a number of infective pathogens that precede autoimmune peripheral nerve damage thought to represent molecular mimicry. Experiential evidence from previous coronaviruses alerted physicians to the possibilities of links between SARS-CoV-2 and neurological diseases, of which ...

    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.

    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.

  3. Version published to 10.1101/2020.07.24.20161471v1 on medRxiv