Dear Sirs,

In terms of epidemiology, Guillain-Barré syndrome (GBS) accounts for 1–2 new cases/100.000 inhabitants per year [1, 2]. During the last two weeks, in coincidence with the descending slope of the pandemic peak in our region (Friuli Venezia-Giulia, Italy), we noted an unusual cluster of patients affected by GBS. The Neurology of the Udine University Hospital is the only Neurology Unit for the entire territory of the province, making unlikely the possibility of missing new cases, since this is the only facility for neurophysiological investigation and cerebrospinal fluid (CSF) examination in an area of 4,969.3 km2. Solicited by this observation and by a recent paper reporting the association of GBS with COVID-19 infection [3], we decided to re-examine the frequency of GBS cases during the March–April months of the last three years and to compare it with the admissions for GBS during the same months of the current year (up to April 16th).

After having the possibility to perform a quick test (Cellex™ q rapid test [4]) for the presence of IgM and IgG against SARS-CoV-2 nucleocapsid protein (N-protein), we tested the four patients still present in our ward and two more patients already discharged who accepted to come back to the hospital. Furthermore, we briefly described clinical, laboratory and neuro-physiological data of patients admitted this year in Table 1. Data dealing with COVID-19 are reported in Table 2.

Table 1 Demographic, clinical, CSF and neurophysiological findings in the observed population with GBS
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Table 2 Data dealing with COVID-19 in the population with GBS
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The total number of GBS in the March–April interval of the previous three years is four. In 2020, from March 1st to April 15th, we observed instead seven new cases diagnosed as GBS, in addition to a relapse in one more patient. This means 0.67 cases/month of observation (four cases in six months) in the previous three years, compared to 3.5 cases/month (seven cases in two months) during the current year, which increases to 4 cases/month (eight cases in two months), if we consider also the patient with relapse. Considering a population of 535,516 inhabitants in the province of Udine (2017 census), the monthly incidence in March–April period of previous years was 0.12 new cases/100.000 inhabitants per month (in line with the epidemiological literature [1, 2]) versus 0.65 cases/100.000 inhabitants per month during the ongoing pandemic. Accordingly, compared to years 2017–2019, the increase of GBS cases in 2020 is 5.41-fold.

The suspicion that this striking difference could be due to the pandemic curve in our region is, therefore, legitimate. In fact, it is well known that GBS and related syndromes are often post-infectious (as for the influenza epidemics and more recently for Zika virus [5]), with an usual latency of 10–14 days after infection [2]. However, in our series, only one patient (twice negative at swab test) had positive serology and thorax CT scan. Despite the serologic and swab negativity of the others, we think that the association with the descending slope of SARS-CoV-2 infection should still be evaluated, since the specificity and sensitivity of these tests are not yet completely assessed and the exact slope of the humoral immune response curve to this new virus is still unknown. It could also be possible that asymptomatic or paucisymptomatic infections may not develop an antibody response sufficient enough to be detected, especially considering that the available test is only qualitative.

We wonder if similar clusters have been observed elsewhere.