Findings from an epidemiological and cohort study published in Brain do not support any significant causal link between coronavirus disease 2019 (COVID-19) and Guillain-Barré syndrome (GBS).
“To date we know of no homology between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface epitopes and peripheral nerve tissue. Reports of varied anti-ganglioside antibodies in association with COVID-19 GBS suggest that a uniform cytomegalovirus-like immune-mediated hypothesis is unsupported,” wrote Stephen Keddie, University College London, London, United Kingdom, and colleagues. “More comprehensive epidemiological characterization is crucial to understanding any causal link.”
Researchers retrospectively ascertained Incident hospitalized cases of GBS from the UK Immunoglobulin Database for GBS cases from January 1 to May 31 each year from 2016 to 2019 and compared with those reported during the same time period in 2020. In parallel to the epidemiological study, researchers conducted a prospective cohort study to compare the demographic, phenotypic and infective associations of COVID-19 associated GBS (definite and probable) to COVID-19-negative GBS cases reported from March 1 to May 31, 2020. Reports of GBS were submitted by members of the British Peripheral Nerve Society, who cover 81 different UK sites.
The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65–1.88 per 100 000 individuals per year. Meanwhile, in 2020, GBS and COVID-19 incidences 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 addition, there were “significantly fewer” GBS cases reported in March, April and May 2020 (93, 70 and 56, respectively) compared to mean cases for the same months (132, 116 and 113, respectively) from 2016 to 2019.
In an independent cohort study, 47 GBS cases were reported over the 12-week collection period. Of the cases, 13 had definite COVID-19 infection, 12 had probable infection, and 22 had GBS with no evidence of COVID-19. There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. For patients with COVID-19 infection, the median time between onset of infective symptoms and neurological weakness was 12 days for definite COVID-19 and 5 days for probable cases; however, the range of time intervals was very broad, ranging from 0 to 37 days in definite cases and −14 to 52 days in probable cases, with only one case in which GBS developed over 6 weeks following COVID-19 onset.
Moreover, the researchers found no significant homology between any SARS-CoV-2 genetic or linear protein structure and human linear protein structures, making a molecular mimicry, causation “less likely”. Molecular mimicry, noted the authors, is the only fully proven pathogenic GBS mechanism.
“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,” the authors wrote. “This epidemiological and cohort study contradicts a growing number of reports postulating causation between SARS-CoV-2 and GBS, and indeed demonstrates a reduction of GBS cases.”
“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,” the authors added.
Nonetheless, the authors cautioned that this study alone cannot be considered definitive in ruling out SARS-CoV-2 as a cause of GBS, but said that further prospective data collection of COVID-19 associated GBS cases and laboratory research are required.