Guillain-Barré Syndrome in the Placebo and Active Arms of a COVID-19 Vaccine Clinical Trial: Temporal Associations Do Not Imply Causality

Abstract

There are reports of Guillain-Barré syndrome (GBS) and cranial neuropathies occurring during or shortly after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.1,2 Some recent infections are known to trigger GBS. A recent epidemiologic cohort study found no evidence for causality between coronavirus disease 2019 (COVID-19) and GBS.3 There is a modest risk of GBS attributed to any vaccination (about 1 to 3 additional cases per million people vaccinated for seasonal influenza),4 and this has raised the possibility that the worldwide COVID-19 vaccination campaign may lead to some people developing GBS.5 Documents submitted to the Food and Drug Administration for Emergency Use Authorization of the Johnson Johnson COVID-19 vaccine, d26.COV2.S, a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein, however, include reports of 2 patients, 1 in the placebo and 1 in the active arm of the trial, developing GBS within 2 weeks of receiving an injection.6,7 Here we report the clinical features of the participant who received the vaccine (5 × 1010 viral particles) at the intended dose for clinical practice and discuss why this case cannot be used to establish a causal association between vaccination and the onset of GBS.