Coronavirus disease that first appeared in China in December 2019 is currently a pandemic with over two hundred million cases and over four million deaths (1). SARS-CoV-2 infection is a multi-systemic disorder that manifests primarily at the respiratory level causing respiratory failure in severe cases and triggering aa multisystem response (2–4). Currently, many neurological manifestations associated with SARS-CoV-2 infection have been reported, including Guillain-Barre syndrome (GBS) (4–6).

GBS is an immune mediated acute inflammatory polyneuropathy, preceded by a respiratory or gastrointestinal infection in 70% of cases which typically manifests as a progressive, areflexic, ascending quadriparesis. However, other variants have also been described. Based on electrophysiological and pathological characteristics, GBS has been classified as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute sensory motor axonal neuropathy (AMSAN) (7–10).

Previous epidemics have been associated with outbreaks of GBS, describing its association with several agents such as Campylobacter jejuni, Haemophilus influenzae, Epstein–barr, Cytomegalovirus, Zika, among others (11, 12). GBS is one of the most frequently associated diseases of the peripheral nervous system with SARS-CoV-2 infection (13). This study described demographic characteristics, clinical and neurophysiological manifestations of patients with GBS and SARS-CoV-2, and factors associated with disability at hospital discharge.

We performed a retrospective analytical observational study approved by the Institutional Review Board of the National Institute of Neurological Sciences (INCN), Lima, Peru. We included patients with the diagnosis of GBS, admitted at the INCN, between 2019 and 2021. The INCN is the national reference center for neurological diseases in Peru where only moderate to severe cases of GBS are hospitalized.

During the COVID-19 pandemic, patients with GBS continued to be admitted to our center. However, those with severe respiratory symptoms were referred to general hospitals where COVID-19 cases were treated. The study included patients above 18 years of age, diagnosed with GBS according to the Brighton criteria. COVID-19 was diagnosed using the polymerase chain reaction (PCR) test for SARS-CoV-2 based on nasopharyngeal swab detection or by detecting the anti-SARS-CoV-2 antibodies.

Conditions that mimic GBS such as acute muscle or peripheral nerve diseases were excluded from the study. Medical records were used to collect epidemiological, clinical, and laboratory data including age, sex, duration of the disease, cerebrospinal fluid (CSF) characteristics, electromyography, medical history and management.

The patients underwent one electromyography after the first week of symptoms, and the neurophysiological diagnosis was obtained according to the Uncini’s criteria (14).

Disability was measured using the Hughes functional grading scale as follows: 0, healthy; 1, minor symptoms, able to run; 2, able to walk 10 meters to more without support, unable to run; 3, able to walk 10 meters with help; 4, bedridden or wheelchair; 5, requires assisted ventilation; 6: dead (15). Disability was measured at admission, nadir (the day the highest score was reached) and at discharge, defined as a score ≥ 3 on the Hughes Scale. Also, the treatment response was defined as the decrease by at least one point on the Hughes Discharge Scale. Sample size was not considered in the study since all patients diagnosed with GBS during the reported period were included.

The mean or median, standard deviation, interquartile range (IQR) were used for continuous variables, and the categorical variables were expressed with frequencies and percentages. Normal assessment was performed using Shapiro Wilk test and the analysis between the groups was performed using a t-test in cases of quantitative variables with normal distribution or using Mann–Whitney U test. Additionally, chi-2 test, and Fisher’s exact test were used for categorical variables. The statistical significance was set at 0.05. The groups were compared based on COVID-19 diagnosis, pre- and post-pandemic periods, and disability at discharge. Likewise, a generalized linear regression model was constructed, with the presence of disability at discharge as a dependent variable. The analysis was performed using STATA (v.17.0, Texas, USA). Approval for this study was granted by the Institutional Research Ethics Committee of the INCN, Lima, Peru.

We found that there were no differences in the age, according to COVID-19 infection, which was unique when compared to the previously reported studies which had described a higher mean age for the group of patients with COVID-19 (3). Our patients were predominantly males, with a higher proportion in the COVID-19 group, possibly due to male predominance in patients with COVID-19 (16), which could predispose them to an increased risk of developing GBS.

Unlike other studies, we did not observe a significant increase in the frequency of GBS cases during the pandemic (17), due to the measures established by the Ministry of Health of Peru that led to a decrease in the flow of patients in all health facilities in the country.

Patients with GBS and COVID-19 had longer admission durations when compared to those without COVID-19, this delay in care may have been related to the longer time of isolation of patients with respiratory symptoms by COVID-19. Likewise, the time between SARS-CoV-2 infection and the onset of GBS symptoms was 9 days, which is consistent with the hypothesis of a postinfectious mechanism associated with COVID-19, rather than direct neuronal damage or a para-infectious mechanism (10). The average duration has previously been reported to be 2 weeks, like other infections associated with GBS (3, 10, 18).

According to the results of our study in patients with COVID-19, the clinical manifestations and distribution of clinical variants were like those of classical GBS, characterized by sensory-motor predominance and a neurophysiological AIDP pattern, similar to previous reports (18–20). Likewise, cerebrospinal fluid protein levels were higher in patients with COVID-19, as described previously (19, 21) which attributes more to an immune response than to an inflammatory or infectious (19).

Independent of the concomitant infection with COVID-19, participants with GBS had a disease of similar severity both at admission and nadir; this differs from the studies reported previously, where differences have been found in the severity evaluated at admission (22), during hospitalization and at hospital discharge (18, 23). However, in the multivariate analysis that resulted in disability at hospital discharge, it was determined that infection with SARS-CoV-2 is associated with greater disability, although patients admitted to our center presented with COVID-19 of mild to moderate severity. The progression of disability was found to be slower in patients with COVID-19 compared to patients without COVID-19. One reason attributed for this difference could be that most patients with COVID-19 had an electromyographic pattern corresponding to AIDP, a pattern associated with slower progression (16, 24).

Although patients admitted to our center had moderate to severe GBS, none had a fatal outcome, as reported in other countries, in which no changes in mortality associated with COVID-19 were evidenced (25).

The limitations of our study included selection bias as patients with severe respiratory symptoms from COVID-19 were referred to the general hospitals for multidisciplinary management, which can influence disability-related outcomes and severity. This situation, however, was due to the restrictions on health care and hospital admission introduced during the start of the pandemic. Despite having a significant number of cases, there was no balanced ratio between the groups with and without COVID-19. The uniformity in the diagnostic criteria for SARS-CoV-2 infection was also affected because of its modification by the Peruvian Ministry of Health in the very beginning of the pandemic. Other limitation is that on our resource limited settings, we were not able to perform serial EMGs and this could introduce wrong classifications, however, we followed Uncini criteria for the diagnosis.

It was concluded that patients with COVID-19 presented more frequently with the neurophysiological subtype AIDP, an increase in the concentration of proteins in CSF. Greater disability at discharge was associated with SARS-CoV-2 infection, despite evidence of slower progression in this group. We believe that these findings can not only be useful in the diagnostic approach aimed toward patients with a recent history of COVID-19, but also as a guide to the immediate prognosis of patients in this group.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Instituto Nacional de Ciencias Neurologicas. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

SS-B and DS-C contributed to conception and design of the study. SS-B and JT-C organized the database. SS-B, AS-B, and WA-Q performed the statistical analysis and wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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