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Initial reports from the first months of the COVID-19 pandemic suggested that Guillain-Barré syndrome (GBS) was associated with SARS-CoV-2 infection (NEJM JW Neurol Jul 2020 and N Engl J Med 2020; 382:2574). Researchers in the U.K. conducted three studies to investigate whether this association is causal or coincidental.
First, they retrospectively reviewed national immunoglobulin, public health, and SARS-CoV-2 seroprevalence databases to study the national and regional epidemiology of GBS and COVID-19 during the initial months of the pandemic. Nationally, there were fewer GBS cases in March (93), April (70), and May (56) of 2020 than in the same months of 2016 through 2019 (mean, 132, 116, and 113, respectively). GBS and COVID-19 incidences varied across U.K. regions but had no temporal association at the regional level. The estimated rate of GBS was 1.6 cases per 100,000 COVID-19 cases, comparable to rates observed in the general populations of the U.K., Europe, and North America before the pandemic.
Second, they prospectively compared clinical characteristics and paraclinical findings for U.K. GBS patients with and without COVID-19 hospitalized over a 3-month period. Forty-seven patients with GBS were identified, 13 of these with definite polymerase chain reaction–confirmed SARS-CoV-2 infection, 12 with probable COVID-19 based on clinical presentation, and 22 without COVID-19. The GBS patients with definite or probable COVID-19 were indistinguishable from those without COVID-19 in terms of clinical presentation, time to nadir, cerebrospinal fluid and electrophysiologic findings, and GBS disability score at 4 weeks.
Finally, the researchers found no genomic similarities upon searching for homology between the SARS-CoV-2 and human genomes. The lone protein match was a viral replicase polyprotein with a human enzyme that is involved in histone modification during DNA damage (32% identical).
Keddie S et al. Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome. Brain 2020 Dec 14; [e-pub]. (https://doi.org/10.1093/brain/awaa433)
Comment
Although initial reports suggested an association between GBS and COVID-19, GBS incidence in the U.K. decreased during the first months of the pandemic compared with the same months in preceding years. As the authors note, the lockdown measures to prevent SARS-CoV-2 transmission may also have reduced the transmission of commonly associated infective GBS triggers. The absence of distinguishing clinical and paraclinical features and the paucity of genomic and protein similarities to support a molecular mimicry model speak against a causal association of SARS-CoV-2 infection with GBS.