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Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions
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  • Published on:
    Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions; response to Keddie et al.
    • Massimiliano Filosto, Neurologist Department of Clinical and Experimental Sciences, University of Brescia, Italy
    • Other Contributors:
      • Stefano Cotti Piccinelli, MD
      • Stefano Gazzina, Neurologist
      • Alessandro Padovani, Neurologist
      • Antonino Uncini, Neurologist

    We read with interest the comments of Keddie and Colleagues who suggested caution in accepting a causation link between SARS-CoV-2 infection and Guillain-Barré syndrome (GBS) and in interpreting results from our study “Guillain-Barrè syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions" (1).
    We believe they have misinterpreted the message of our paper and have drawn conclusions that was not our intention to draw.
    Their first consideration is that our paper cannot demonstrate a causation link between COVID-19 and GBS. Of course, we agree. In fact, we did not talk about any causal nexus. It is well known that, in statistics, “causation” indicates a relationship between two events where one event is affected by the other. In order to demonstrate “causation”, prospective studies are needed. Our study is based on retrospective findings and identified an increased rate of GBS cases concomitantly with the COVID-19 spread in our regions. On this basis, we could not (and indeed we did not) conclude for a definite causative relationship but we suggested a pathogenic link for which COVID-19 could represent a trigger for GBS, as already suggested by other authors (2).
    Keddie et al. claimed some possible methodological biases. Part of them is obviously related to the retrospective nature of the study and have been listed as limitations of the study at the end of our paper. They calculated the 95% confidence intervals of the...

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    Conflict of Interest:
    None declared.
  • Published on:
    Further research required to support a causative association between GBS and COVID-19
    • Stephen Keddie, Neurology SpR and Clinical Research Fellow Centre for neuromuscular disease, National Hospital for Neurology and Neurosurgery, UCLH, London.
    • Other Contributors:
      • Julia Pakpoor, Neurology SpR
      • Aisling Carr, Neurology Consultant
      • Michael P Lunn, Neurology consultant

    To the Editor

    We were interested to read the study of Filosto et al [1] concluding a significant link between Guillain-Barre Syndrome (GBS) and COVID-19 infection in Northern Italy at the peak of the 1st wave SARS-CoV2 pandemic. We urge caution in accepting such a causative conclusion using a retrospective observational study; causation is not conclusively proven and is drawn from potentially biased data and small case numbers of a rare condition, and a rate calculation without confidence intervals to infer uncertainty.

    Only 34 cases of GBS, of whom 30 were COVID-19 positive, are reported over a 2-month period, with a denominator population of 8,400,107. We calculated the 95% confidence intervals of the incidence rates as 0.08 per 100,000 per month (95% C.I.: 0.04-0.15) in 2019 and 0.2 per 100,000 per month (95% C.I.: 0.14-0.28) in 2020. The overlapping confidence intervals do not support a statistically significant increase in GBS rates from 2019 to 2020. Furthermore, the simple multiplication of the monthly rate by 12 to create an approximate annualised incidence potentially amplifies the inaccuracy. We suggest that the 2.6-fold difference in GBS incidence from 2019 to 2019 is prone to meaningful statistical error.

    During the initial stages of the pandemic the denominator of COVID-19 positive cases will have been under-reported because testing was limited to the symptomatic and presenting populations. We are told that 62,679 inhabitants of the regi...

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    Conflict of Interest:
    We have a similar paper due to be published with larger numbers and have found opposing conclusions.