Changes in Guillain-Barre Syndrome-Associated Ganglioside Antibody Test Results at a National Clinical Laboratory During the COVID-19 Pandemic

Objective: To assess changes in test positivity rates for Guillain-Barre syndrome (GBS)-associated ganglioside antibodies during the COVID-19 pandemic at a national clinical laboratory. Background: Case reports have suggested a temporal association between SARS-CoV-2 infection and subsequent occurrence of GBS, but subsequent studies produced conflicting results regarding the incidence trends of GBS during the COVID-19 pandemic. More than half of reported GBS cases have identifiable antibodies present to various gangliosides. This high frequency allows for the examination of the potential association of the COVID-19 pandemic with different forms of GBS-associated antibodies. Design/Methods: This cross-sectional observational study assessed quarterly test volume and positivity rates for GQ1b, GM-1, GD1a, and GD1b for tests performed January 2016, through March 2021, at Quest Diagnostics. Pandemic period was defined as March 2020 through March 2021. Results: Positivity rates on ganglioside antibody tests during the study period were 2.6% (660 positive/25,006 tested) for GQ1b;17.2% (7734/45,040) for GM-1;7.1% (1390/19,711) for GD1a;and 2.9% (556/18,959) for GD1b. Relative to pre-pandemic levels, positivity rates during the pandemic declined by 61% for GQ1b (3.1%, 95% CI 2.9-3.4% pre-pandemic;1.2%, 95% CI 0.9- 1.4% during the pandemic, p<0.001) and 24% for GM-1 (18.2%, 95% CI 17.8-18.6% vs 13.8%, 95% CI 13.2-14.5%;p<0.001);however, GM-1 positivity rates also declined significantly in each of the prior two years. There was no significant change in positivity rates during the pandemic for GD1a (compared to entire pre-pandemic period) or GD1b (compared to the prior two years). Conclusions: These findings from a national clinical laboratory suggest heterogeneity in the association of the COVID-19 pandemic with positivity rates of GBS-associated ganglioside antibodies. Mitigation strategies taken during the pandemic may have reduced the frequency of certain forms of GBS, such as those mediated by GQ1b and GM-1.

Immune Mediated Bulbar Myasthenia Gravis Incited by SARS-CoV2 mRNA Vaccination

Objective: NA Background: A 32 year-old man with no medical history and no prior documented SARS-CoV2 infection developed malaise, dyspnea, and exercise intolerance in the days following first dose SARS-CoV2 vaccine administration (Pzifer-BioNTECH mRNA). Dysarthria and dysphagia manifested within hours of the second vaccine dose administration, and progressed to severe bifacial weakness with reduced eyelid and mouth closures within one week's time. Design/Methods: NA Results: Severe dysphagia prompted hospitalization and neurology consultation. At an outside hospital, IVIG (2 gm/kg) and pyridostigmine were initiated for empiric treatment of suspected myasthenia gravis. The patient's facial strength, dysphagia and dysarthria improved. Anti-AChR and anti-MuSK serologic studies were non-reactive. A thymoma was not identified. MR brain, cerebrospinal fluid, and ganglioside antibody serologic studies were without explanatory pathological findings. A nerve conduction study, obtained in the outpatient setting, demonstrated decrement in facial nerve-nasalis CMAPs with low frequency repetitive stimulation, consistent with a post-synaptic neuromuscular disorder. Monthly IVIG infusions and pyridostigmine were prescribed. The patient's symptoms worsened and he was rehospitalized. A repeat nerve conduction study revealed post-exercise and repetitive stimulation-induced decrements in median-abductor policus brevis and spinal accessorytrapezius CMAPs, confirming a systemic post-synaptic neuromuscular disorder. AChR binding and blocking antibodies were ultimately detected through repeat serologic testing, consistent with autoimmune myasthenia gravis. Plasma exchange and prednisone therapies engendered near full symptom resolution. Conclusions: While myasthenia gravis symptom exacerbation and crisis in the setting of vaccination are well described, no cases of new-onset myasthenia gravis following vaccination are reported to date. Further, the patient's bifacial weakness with impaired eyelid closure was atypical in contrast to ptosis and diploia typically observed in oculo-bulbar forms of myasthenia gravis. The immune-mediated mechanism and clinical phenotype of SARS-CoV2 vaccinationassociated myasthenia gravis require further investigation.

Atypical Pharyngo-Cervico-Brachial Variant of GBS Associated with Covid-19 Antibodies

Objective: Neurological manifestations are common with Covid-19 illness. Many unusual neurological manifestations have been described and we herewith report one such case. Background: COVID-19 is predominantly a respiratory pathogen but can cause multi system involvement. Many studies have shown significant neurological manifestations associated with Covid-19 infection. Some of these neurological manifestations are quite specific like GuillainBarre syndrome. But, many uncommon manifestations have been described like the following case. Design/Methods: A 35-year old woman with no prior history of fever or any other illness presented with insidious onset, gradually progressive weakness of bulbar and bilateral facial weakness along with asymmetrical weakness of both upper limbs of one and half months duration. She was evaluated and investigated accordingly. Results: On neurological examination, the patient had dysphonia, dysphagia, bilateral lower motor neuron facial palsy. Along with weakness of neck flexors and grossly asymmetrical weakness of upper limbs. The motor power on right is MRC 2/5 and MRC 4/5 in left upper limb with diffuse hypotonia. Motor power was normal in lower limbs. There was diffuse hyporeflexia in all the four limbs. Nerve conduction studies showed absent SNAPS with decreased motor nerve conduction velocities and increased CMAP latencies in both upper and lower limbs. CSF examination showed albumin-cytological dissociation. MRI Brain and Cervical Spine were normal. Serum ANA and Serum Ganglioside antibodies were negative. She was tested for total Covid-19 antibodies which was significantly positive with 55.25 COI. Patient was treated initially with IV Methylprednisolone with no significant response. So, followed with intravenous immunoglobulins and showed some improvement. Conclusions: Atypical Pharyngo-cervico-brachial variant of GB Syndrome with gross asymmetrical upper limb weakness and progressed over six weeks associated with positive SARS Cov-2 antibodies. During the pandemic, unusual neurological manifestations should be evaluated for possibility of SARS-CoV-2 associated antibodies as neuropathogenesis has shown both vascular and post infectious demyelinating disorders.

(Auto)immune manifestations in COVID-19

Introduction: It is well established that many types of infections can lead to autoimmunity or autoimmune disease. Since the emergence of coronavirus disease 2019 (COVID-19), a number of confirmed cases reported autoimmune manifestations. Objectives: To evaluate occurence of (auto)immune manifestations in pediatric patients with evidence of recent infection with severe acute respiratory syndrome (SARS) associated coronavirus 2 (SARSCoV- 2). Methods: A single small center study was performed. Included were patients with (auto)immune manifestations and evidence of concomitant or recent SARS-CoV-2 infection seen at our pediatric clinic from December 2020 till April 2021. Infections with other microorganisms were excluded. Data was collected from patients' medical records. Results: A total of 12 patients were enrolled. The results are presented in Table 1. The mean age of all patients was 9.5 years (range 4-18 years). Interestingly, there was a slight male predominance (7 patients, 58%). Among immune diseases related to COVID-19, MIS-C/PIMS-TS was the most common (7 patients, 58%). It has been suggested that the syndrome results from an abnormal immune response to the virus and it is not considered an autoimmune disease. 2 boys with MIS-C/ PIMS-TS, aged 4 and 5 years, also fulfilled diagnostic criteria for Kawasaki disease. Autoantibodies were detected in 2 patients, in a 15 years old boy with Miller Fisher syndrome (anti GQ1b antiganglioside antibodies) and in a 13 years old girl with Henoch- Schonlein purpura (antinuclear antibodies, ANA). Most of our patients had positive COVID-19 serology (10 patients, 83.3%), negative PCR swab for COVID-19 (9 patients, 75%) and had a family history of COVID-19 (9 patients, 75%). Conclusion: So far, some patients have been reported to develop (auto)immune diseases after COVID-19. It is speculated that SARSCoV- 2 can disturb self- tolerance and trigger autoimmune responses through cross- reactivity with host cells. Overall, more data are needed to further understand the relationship between COVID-19 and autoimmunity.