Guillain-Barré syndrome after SARS-CoV-2 infection in an international prospective cohort study

Author:

Luijten Linda W G12ORCID,Leonhard Sonja E1,van der Eijk Annemiek A3,Doets Alex Y1,Appeltshauser Luise4,Arends Samuel15,Attarian Shahram6,Benedetti Luana7,Briani Chiara8,Casasnovas Carlos9,Castellani Francesca8,Dardiotis Efthimios10,Echaniz-Laguna Andoni11,Garssen Marcel P J12,Harbo Thomas13,Huizinga Ruth14,Humm Andrea M15,Jellema Korné16,van der Kooi Anneke J17,Kuitwaard Krista118,Kuntzer Thierry19,Kusunoki Susumu20,Lascano Agustina M21,Martinez-Hernandez Eugenia22,Rinaldi Simon23,Samijn Johnny P A24,Scheidegger Olivier25,Tsouni Pinelopi1926,Vicino Alex19,Visser Leo H2,Walgaard Christa124,Wang Yuzhong27,Wirtz Paul W5,Ripellino Paolo28,Jacobs Bart C114ORCID,Jacobs Bart CORCID,Hughes Richard A C,Cornblath David R,Gorson Kenneth C,Hartung Hans-Peter,Kusunoki Susumu,van Doorn Pieter A,Willison Hugh J,van den Berg Bianca,Verboon Christine,Roodbol Joyce,Doets Alex Y,Leonhard Sonja E,Luijten Linda W GORCID,de Koning Laura C,Mandarakas Melissa,van Woerkom Marieke,Arends Samuel,Reisin Ricardo C,Reddel Stephen W,Islam Zhahirul,Mohammad Quazi Deen,van den Bergh Peter,Feasby Tom E,Wang Yuzhong,Harbo Thomas,Péréon Yann,Lehmann Helmar C,Dardiotis Efthimios,Nobile-Orazio Eduardo,Shahrizaila Nortina,Bateman Kathleen,Illa Isabel,Querol Luis,Ripellino Paolo,Hsieh Sung-Tsang,Chavada Govindsinh,Davidson Amy,Addington James M,Andersen Henning,Antonini Giovanni,Ajroud-Driss Senda,Attarian Shahram,Badrising Umesh A,Balducci Claudia,Barroso Fabio A,Bella Isabelita R,Benedetti Luana,Bertorini Tulio E,Bhavaraju-Sanka Ratna,Brannagan Thomas H,Briani Chiara,Bürmann Jan,Busby Mark,Butterworth Stephen,Casasnovas Carlos,Castellani Francesca,Cavaletti Guido,Chao Chi-Chao,Chen Shan,Claeys Kristl G,Conti Maria Eugenia,Cosgrove Jeremy S,Dalakas Marinos C,Derejko Miroslawa A,Dimachkie Mazen M,de la Cour Charlotte Dornonville,Echaniz-Laguna Andoni,Eftimov Filip,Faber Karin G,Fazio Raffaella,Fokke Chris,Fujioka Toshiki,Fulgenzi Ernesto A,Galassi Giuliana,García-Sobrino Tania,Garssen Marcel P J,Gentile Francesco,Gijsbers Cees J,Gilchrist James M,Job Gilhuis H,Goldstein Jonathan M,Goyal Namita A,Granit Volkan,Grapperon Aude-Marie,Grisanti Stefano,Gutiérrez-Gutiérrez Gerardo,Gutmann Lauri,Hadden Robert D M,Holbech Jakob V,Holt James K L,Htut Min,Humm Andrea,Hundsberger Thomas,Jellema Korné,Pascual Ivonne Jericó,Jimeno Montero Maria C,Kaida Kenichi,Karafiath Summer,Katzberg Hans D,Khoshnoodi Mohammad,Kiers Lynette,Kimpinski Kurt,Kleyweg Ruud P,Kokubun Norito,Kolb Noah,Kuitwaard Krista,Kuntzer Thierry,Kuwabara Satoshi,Kuwahara Motoi,Kwan Justin Y,Ladha Shafeeq S,Lassen Lisbeth Landschoff,Lascano Agustina M,Lawson Victoria,Pan Edward Lee,Cejas Luciana León,Magot Armelle,Manji Hadi,Marfia Gerola A,Márquez-Infante Celedonio,Aguilar Lorena Martin,Hernandez Eugenia Martinez,Sanchez Pilar Massaro,Mataluni Giorgia,Mattiazzi Marcelo G,McDermott Chris J,Meekins Gregg D,Miller James A L,Monges Maria Soledad,de la Tassa Germán Morís,Nascimbene Caterina,Nedkova-Hristova Velina,Nowak Richard J,Osei-Bonsu Michael,Pardo Julio,Pascuzzi Robert M,Pritchard Jane,Pulley Michael,Rinaldi Simon,Roberts Rhys C,Rojas-Marcos Iñigo,Rudnicki Stacy A,Sachs George M,Samijn Johnny P A,Santoro Lucio,Scheidegger Olivier,Schenone Angelo,Schwindling Lenka,Sedano Tous Maria J,Sheikh Kazim A,Silvestri Nicholas J,Sindrup Soren H,Sommer Claudia L,Song Yan,Stein Beth,Stino Amro M,Tan Cheng-Yin,Tankisi Hatice,Tsouni Pinelopi,Twydell Paul T,Van Damme Philip,van der Kooi Anneke J,van der Meulen Willem,van der Ree Taco C,van Dijk Gert W,van Koningsveld Rinske,Varrato Jay D,Vermeij Frederique H,Verschuuren Jan J G M,Vicino Alex,Visser Leo H,Vytopil Michal,Waheed Waqar,Walgaard Christa,Wirtz Paul W,Xing Chunye,Yamagishi Yuko,Zhou Lan,Zivkovic Sasha,

Affiliation:

1. Department of Neurology, Erasmus MC, University Medical Center Rotterdam, 3015 GD, Rotterdam, The Netherlands

2. Department of Neurology, St. Elisabeth-TweeSteden Hospital, 5022 GC, Tilburg, The Netherlands

3. Department of Viroscience, Unit Clinical Virology, Erasmus MC, University Medical Center Rotterdam, 3015 CN, Rotterdam, The Netherlands

4. Department of Neurology, University of Würzburg, 97080 Würzburg, Germany

5. Department of Neurology, Haga Hospital, 2545 AA Den Haag, The Netherlands

6. Reference Center for Neuromuscular Disorders and ALS, Hôpital de La Timone, 13005 Marseille, France

7. Department of Neurology, IRCCS Ospedale Policlinico, San Martino, Genova, Italy

8. Neurology Unit, Department of Neuroscience, University of Padova, 35128 Padova, Italy

9. Neuromuscular Unit, Department of Neurology, Bellvitge University Hospital, Neurometabolic Diseases Group, IDIBELL and CIBERER, Barcelona, Spain

10. Department of Neurology, University Hospital of Larissa, 41110 Larissa, Greece

11. Department of Neurology, APHP, CHU de Bicêtre, 94270 Le Kremlin Bicêtre, France

12. Department of Neurology, Jeroen Bosch Hospital, 5223 GZ ‘s-Hertogenbosch, The Netherlands

13. Department of Neurology, Aarhus University Hospital, 8200 Aarhus N, Denmark

14. Department of Immunology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands

15. Unit of Neurology, Department of Internal Medicine, HFR Fribourg—Hôpital Cantonal, CH-1708 Fribourg, Switzerland

16. Department of Neurology, Haaglanden Medical Center, 2512 VA, Den Haag, The Netherlands

17. Department of Neurology, Amsterdam University Medical Center, Location AMC, University of Amsterdam, Neuroscience institute, 1105 AZ Amsterdam, The Netherlands

18. Department of Neurology, Albert Schweitzer Hospital, 3318 AT Dordrecht, The Netherlands

19. Nerve-muscle Unit, Department of Clinical Neurosciences, Lausanne University Hospital CHUV and University of Lausanne, CH-1011 Lausanne, Switzerland

20. Department of Neurology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589-8511, Japan

21. Department of Neurology, Geneva University Hospitals and University of Geneva, 1205 Geneva, Switzerland

22. Department of Neurology, Hospital Clinic, 08036 Barcelona, Spain

23. Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, UK

24. Department of Neurology, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands

25. Department of Neurology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland

26. Department of Neurology, Hôpital du Valais, 1950 Sion, Switzerland

27. Department of Neurology, Affiliated Hospital of Jining Medical University, 272029 Jining, China

28. Department of Neurology, Neurocenter of Southern Switzerland, 6903 Lugano, Switzerland

Abstract

Abstract 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.

Funder

GBS-CIDP Foundation International

Erasmus MC University Medical Center Rotterdam

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

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