Guillain-Barré Syndrome After SARS-CoV-2 Infection in an International Prospective Cohort Study

Linda W. G. Luijten; Sonja E. Leonhard; Annemiek A. van der Eijk; Alex Y. Doets; Luise Appeltshauser; Samuel Arends; Shahram Attarian; Luana Benedetti; Chiara Briani; Carlos Casasnovas; Francesca Castellani; Efthimios Dardiotis; Andoni Echaniz-Laguna; Marcel P. J. Garssen; Thomas Harbo; Ruth Huizinga; Andrea M. Humm; Korné Jellema; Anneke J. van der Kooi; Krista Kuitwaard; Thierry Kuntzer; Susumu Kusunoki; Agustina M. Lascano; Eugenia Martinez-Hernandez; Simon Rinaldi; Johnny P. A. Samijn; Olivier Scheidegger; Pinelopi Tsouni; Alex Vicino; Leo H. Visser; Christa Walgaard; Yuzhong Wang; Paul W. Wirtz; Paolo Ripellino; Bart C. Jacobs


Brain. 2021;144(11):3392-3404. 

In This Article

Abstract and Introduction


In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies.

The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization.

Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12–22).

Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not.


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected the entire world population, either by direct infection or through its social and economic consequences. The severity and impact of this outbreak prompted the World Health Organization (WHO) to declare SARS-CoV-2 a Public Health Emergency of International Concern on 30 January 2020.[1] Besides the well known severe respiratory signs, both central and peripheral neurological complications have been reported.[2–4] Potential pathophysiological mechanisms for these complications may be either direct viral invasion, indirect damage as a result of the inflammatory response (para-infectious, post-infectious), or hypercoagulability in cases of cardiovascular complications.[5] One of the reported neurological disorders is Guillain-Barré syndrome (GBS), an inflammatory polyradiculoneuropathy characterized by rapidly progressive weakness and sensory signs, usually preceded by an infectious trigger.[6] Several pathogens have previously been associated with GBS and outbreaks of these infections may lead to an increased incidence of GBS as seen during the Zika virus pandemic in 2015–16.[7–9] The clinical phenotype, electrophysiological subtype and disease course of GBS are heterogeneous and may be influenced by the type of preceding infection as a result of differences in antigenic targets. In some of these clinical variants specific antibody responses against gangliosides could be found. For example, a preceding infection with Campylobacter jejuni is associated with antibodies against GM1 and GD1a, and a pure motor axonal variant with a more severe disease course and poor outcome.[10]

Since the beginning of the recent pandemic, over 90 GBS patients with a possible relation to SARS-CoV-2 have been reported.[11–14] However, whether SARS-CoV-2 is another potential infectious trigger or whether the reported cases are coincidental is still unclear. In the current study, we identified GBS cases with a preceding SARS-CoV-2 infection, based on clinical and laboratory features, during the first months of the pandemic within the framework of the International GBS Outcome Study (IGOS), an ongoing prospective observational cohort study which began in 2012.[15] We describe in detail the clinical phenotype, electrophysiological subtype, and disease course of these patients.