To the Editor:

From February 28 through March 21, 2020, in three hospitals in northern Italy, we examined five patients who had Guillain–Barré syndrome after the onset of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During that period, an estimated 1000 to 1200 patients with Covid-19 were admitted to these hospitals. Four of the patients in this series had a positive nasopharyngeal swab for SARS-CoV-2 at the onset of the neurologic syndrome, and one had a negative nasopharyngeal swab and negative bronchoalveolar lavage but subsequently had a positive serologic test for the virus. Detailed case reports are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.

Table 1. Table 1. Characteristics of Five Patients with Guillain–Barré Syndrome after the Onset of Covid-19.

The first symptoms of Guillain–Barré syndrome were lower-limb weakness and paresthesia in four patients and facial diplegia followed by ataxia and paresthesia in one patient (Table 1). Generalized, flaccid tetraparesis or tetraplegia evolved over a period of 36 hours to 4 days in four patients; three received mechanical ventilation. The interval between the onset of symptoms of Covid-19 and the first symptoms of Guillain–Barré syndrome ranged from 5 to 10 days (Table 1 and Fig. S1 in the Supplementary Appendix). None of the patients had dysautonomic features.

On analysis of the cerebrospinal fluid (CSF), two patients had a normal protein level and all the patients had a white-cell count of less than 5 per cubic millimeter. Antiganglioside antibodies were absent in the three patients who were tested. In all the patients, a real-time polymerase-chain-reaction assay of the CSF was negative for SARS-CoV-2. Results of electrophysiological studies are shown in Table S1. Compound muscle action potential amplitudes were low but could be obtained; two patients had prolonged motor distal latencies. On electromyography, fibrillation potentials were present in three patients initially; in another patient, they were absent initially but were present at 12 days. The findings were generally consistent with an axonal variant of Guillain–Barré syndrome in three patients and with a demyelinating process in two patients.1 Magnetic resonance imaging, performed with the administration of gadolinium, showed enhancement of the caudal nerve roots in two patients, enhancement of the facial nerve in one patient, and no signal changes in nerves in two patients. Additional laboratory findings are shown in Table S2.

All the patients were treated with intravenous immune globulin (IVIG); two received a second course of IVIG and one started plasma exchange. At 4 weeks after treatment, two patients remained in the intensive care unit and were receiving mechanical ventilation, two were undergoing physical therapy because of flaccid paraplegia and had minimal upper-limb movement, and one had been discharged and was able to walk independently.

The interval of 5 to 10 days between the onset of viral illness and the first symptoms of Guillain–Barré syndrome is similar to the interval seen with Guillain–Barré syndrome that occurs during or after other infections.2 Although many infectious agents have been associated with Guillain–Barré syndrome, there may be a propensity for preceding infection with Campylobacter jejuni, Epstein–Barr virus, cytomegalovirus, and Zika virus. There have been reports of an association between Guillain–Barré syndrome and coronavirus infections.3,4

On the basis of this observational series involving five patients, it is not possible to determine whether severe deficits and axonal involvement are typical features of Covid-19–associated Guillain–Barré syndrome. We could not determine the effect of reduced vital capacity due to neuromuscular failure from Guillain–Barré syndrome in these patients, but such an effect might be considered if findings on chest imaging are not commensurate with the severity of respiratory insufficiency. Guillain–Barré syndrome with Covid-19 should be distinguished from critical illness neuropathy and myopathy, which tend to appear later in the course of critical illness than Guillain–Barré syndrome.

Gianpaolo Toscano, M.D.

IRCCS C. Mondino Foundation, Pavia, Italy

Francesco Palmerini, M.D.

Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy

Sabrina Ravaglia, M.D., Ph.D.

IRCCS C. Mondino Foundation, Pavia, Italy

[email protected]

Luigi Ruiz, M.D.

Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

Paolo Invernizzi, M.D.

Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy

M. Giovanna Cuzzoni, M.D.

Diego Franciotta, M.D.

IRCCS C. Mondino Foundation, Pavia, Italy

Fausto Baldanti, M.D.

Rossana Daturi, M.D.

IRCCS Policlinico San Matteo, Pavia, Italy

Paolo Postorino, M.D.

Anna Cavallini, M.D.

Giuseppe Micieli, M.D.

IRCCS C. Mondino Foundation, Pavia, Italy

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was published on April 17, 2020, at NEJM.org.

This letter is dedicated to the loving memory of Dr. Arrigo Moglia.