Multicomponent Lipid Nanoparticles for RNA Transfection.

Despite the wide variety of available cationic lipid platforms for the delivery of nucleic acids into cells, the optimization of their composition has not lost its relevance. The purpose of this work was to develop multi-component cationic lipid nanoparticles (LNPs) with or without a hydrophobic core from natural lipids in order to evaluate the efficiency of LNPs with the widely used cationic lipoid DOTAP (1,2-dioleoyloxy-3-[trimethylammonium]-propane) and the previously unstudied oleoylcholine (Ol-Ch), as well as the ability of LNPs containing GM3 gangliosides to transfect cells with mRNA and siRNA. LNPs containing cationic lipids, phospholipids and cholesterol, and surfactants were prepared according to a three-stage procedure. The average size of the resulting LNPs was 176 nm (PDI 0.18). LNPs with DOTAP mesylate were more effective than those with Ol-Ch. Core LNPs demonstrated low transfection activity compared with bilayer LNPs. The type of phospholipid in LNPs was significant for the transfection of MDA-MB-231 and SW 620 cancer cells but not HEK 293T cells. LNPs with GM3 gangliosides were the most efficient for the delivery of mRNA to MDA-MB-231 cells and siRNA to SW620 cells. Thus, we developed a new lipid platform for the efficient delivery of RNA of various sizes to mammalian cells.

Ophthalmoplegia associated with anti-GQ1b antibodies: case report and review.

A 60-year-old man with longstanding bilateral asymmetrical ptosis presented with a partial third nerve palsy. His diplopia improved following an ice pack test. He did not report any symptoms related to the coronavirus disease 2019 (COVID-19), and nasopharyngeal swab was negative. Initial head imaging and blood work-up were normal except for a high titer of anti-GQ1b antibodies. The patient was subsequently diagnosed with acute ophthalmoparesis without ataxia which is part of the anti-GQ1b antibody syndrome spectrum. He made a spontaneous recovery over the following months without the need for immunotherapy. Clinical features, pathophysiology and a review of the literature are discussed herein. It is important to consider anti-GQ1b antibody syndrome in patients with symptoms of diplopia, ptosis or suspected ocular myasthenia.

Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future.

Although very different, in terms of their genomic organization, their enzymatic proteins, and their structural proteins, HIV and SARS-CoV-2 have an extraordinary evolutionary potential in common. Faced with various selection pressures that may be generated by treatments or immune responses, these RNA viruses demonstrate very high adaptive capacities, which result in the continuous emergence of variants and quasi-species. In this retrospective analysis of viral proteins, ensuring the adhesion of these viruses to the plasma membrane of host cells, we highlight many common points that suggest the convergent mechanisms of evolution. HIV and SARS-CoV-2 first recognize a lipid raft microdomain that acts as a landing strip for viral particles on the host cell surface. In the case of mucosal cells, which are the primary targets of both viruses, these microdomains are enriched in anionic glycolipids (gangliosides) forming a global electronegative field. Both viruses use lipid rafts to surf on the cell surface in search of a protein receptor able to trigger the fusion process. This implies that viral envelope proteins are both geometrically and electrically compatible to the biomolecules they select to invade host cells. In the present study, we identify the surface electrostatic potential as a critical parameter controlling the convergent evolution dynamics of HIV-1 and SARS-CoV-2 surface envelope proteins, and we discuss the impact of this parameter on the phenotypic properties of both viruses. The virological data accumulated since the emergence of HIV in the early 1980s should help us to face present and future virus pandemics.

Acute motor and sensory axonal neuropathy in a patient with undiagnosed mixed connective tissue disease

Case Report: Acute motor and sensory axonal neuropathy (AMSAN) syndrome is a rare subtype of Guillain-Barre syndrome (GBS) with poor recovery [1]. While respiratory and gastrointestinal infections may precipitate AMSAN, an underlying autoimmune disorder is seldom reported in literature. We herein report the complex case of a patient with undiagnosed, asymptomatic mixed connective tissue disease (MCTD) who developed AMSAN syndrome. Case: A 44-year-old Asian male without medical history presented with progressively worsening weakness of both upper and lower extremities and inability to perform daily activities. His symptoms started 12 weeks prior with difficulty standing from a seated position. He felt subjectively better for some time until a week prior, when he became bedbound. He had diarrhea 6 months ago, with 5-6 loose bowel movements a day for a few weeks. Vital signs on admission was normal. On neurological examination, he was alert and oriented, with bilateral upper and lower extremity flaccid paralysis, diffuse muscle atrophy, bilateral hand and foot drop, negative Hoover sign, diffuse areflexia, and intact sensation. Cerebrospinal fluid (CSF) analysis showed WBC 0 and protein level 136. MRI cervical, thoracic, and lumbar spine were normal. EMG revealed sensory involvement with positive sharp waves in proximal muscles along with fibrillations. Intravenous immunoglobulin (IVIG) was initiated at 0.4 mg/kg for 5 days. Infectious workup for COVID-19, stool culture, HIV, TB, RPR and campylobacter jejuni antibody (Ab), was negative. ANA was positive in a speckled pattern with titres 1:1280, with a positive RNP Ab, SS-A, and RF IgM, IgG and IgA. Rest of the autoimmune workup (anti-dsDNA, anti-CCP, SS-B, aldolase, anti-Jo-1, anti-Scl-70, p-ANCA, c-ANCA, anti-GM1, anti-GQ1b, and anti-GD1a ganglioside Ab) was negative. The myositis specific 11 Ab panel was negative. Despite IVIG therapy, he developed dysphagia, respiratory distress, with a negative inspiratory force of -0, requiring intubation. He had a tracheostomy and PEG tube placed and remains quadraplegic nearly 120 days later. Discussion(s): The authors report a unique case of a patient who became progressively weak over 3 months, leading to complete quadriplegia. Interestingly, this is more consistent with chronic inflammatory demyelinating poly-neuropathy (CIDP), as AMSAN typically develops over a short period of 2 to 4 weeks [2]. Despite having negative anti-GM1 and anti-GD1a Ab (in which positive Ab are pathognomonic but not always present in AMSAN syndrome), the patient had weakness that began in the lower extremities, progressing to paralysis, along with albuminocytological dissociation on CSF analysis, pointing to a GBS diagnosis [3]. He had sensory involvement in the EMG, thus making the diagnosis as AMSAN. He had an undiagnosed, asymptomatic autoimmune process most consistent with MCTD. Whether the two disease processes are related to each other is a concept that has not yet been investigated. Pediatric Clinical Case Reports Concurrent Session Saturday February 4, 2023 1:00 PM Copyright © 2023 Southern Society for Clinical Investigation.

Electrostatic Surface Potential as a Key Parameter in Virus Transmission and Evolution: How to Manage Future Virus Pandemics in the Post-COVID-19 Era.

Virus-cell interactions involve fundamental parameters that need to be considered in strategies implemented to control viral outbreaks. Among these, the surface electrostatic potential can give valuable information to deal with new epidemics. In this article, we describe the role of this key parameter in the hemagglutination of red blood cells and in the co-evolution of synaptic receptors and neurotransmitters. We then establish the functional link between lipid rafts and the electrostatic potential of viruses, with special emphasis on gangliosides, which are sialic-acid-containing, electronegatively charged plasma membrane components. We describe the common features of ganglioside binding domains, which include a wide variety of structures with little sequence homology but that possess key amino acids controlling ganglioside recognition. We analyze the role of the electrostatic potential in the transmission and intra-individual evolution of HIV-1 infections, including gatekeeper and co-receptor switch mechanisms. We show how to organize the epidemic surveillance of influenza viruses by focusing on mutations affecting the hemagglutinin surface potential. We demonstrate that the electrostatic surface potential, by modulating spike-ganglioside interactions, controls the hemagglutination properties of coronaviruses (SARS-CoV-1, MERS-CoV, and SARS-CoV-2) as well as the structural dynamics of SARS-CoV-2 evolution. We relate the broad-spectrum antiviral activity of repositioned molecules to their ability to disrupt virus-raft interactions, challenging the old concept that an antibiotic or anti-parasitic cannot also be an antiviral. We propose a new concept based on the analysis of the electrostatic surface potential to develop, in real time, therapeutic and vaccine strategies adapted to each new viral epidemic.

Identification of possible binding modes of SARS-CoV-2 spike N-terminal domain for ganglioside GM1.

Coarse-grained molecular dynamics simulations of the lipid bilayer mixture of POPC and cholesterol were carried out in the presence and absence of ganglioside monosialo 1 (GM1) with N - terminal domain (NTD) of SARS-CoV-2 spike glycoprotein. The interactions of GM1 with two different NTD orientations were compared. NTD orientation I compactly bind GM1 predominantly through the sialic acid and the external galactose moieties providing more restriction to GM1 mobility whereas orientation II is more distributed on the lipid surface and due to the relaxed mobility of GM1 there, presumably, the NTD receptor penetrates more through the membrane.

A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L.

The recent outbreak of Monkeypox virus requires the development of a vaccine specifically directed against this virus as quickly as possible. We propose here a new strategy based on a two-step analysis combining (i) the search for binding domains of viral proteins to gangliosides present in lipid rafts of host cells, and (ii) B epitope predictions. Based on previous studies of HIV and SARS-CoV-2 proteins, we show that the Monkeypox virus cell surface-binding protein E8L possesses a ganglioside-binding motif consisting of several subsites forming a ring structure. The binding of the E8L protein to a cluster of gangliosides GM1 mimicking a lipid raft domain is driven by both shape and electrostatic surface potential complementarities. An induced-fit mechanism unmasks selected amino acid side chains of the motif without significantly affecting the secondary structure of the protein. The ganglioside-binding motif overlaps three potential linear B epitopes that are well exposed on the unbound E8L surface that faces the host cell membrane. This situation is ideal for generating neutralizing antibodies. We thus suggest using these three sequences derived from the E8L protein as immunogens in a vaccine formulation (recombinant protein, synthetic peptides or genetically based) specific for Monkeypox virus. This lipid raft/ganglioside-based strategy could be used for developing therapeutic and vaccine responses to future virus outbreaks, in parallel to existing solutions.

2022 EAN/PNS GBS Guideline

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. This is the first systematic clinical guideline, developed by an international task force using formal GRADE methodology. The diagnostic criteria remain primarily clinical, based on history and examination findings of acute progressive limb weakness and areflexia. Variants of GBS may include motor GBS, Miller Fisher Syndrome, and regional variants with weakness predominantly in lower limbs, face, or pharynx/neck/ arms. The differential diagnosis is wide. When uncertain, diagnosis may be assisted by nerve conduction tests, raised cerebrospinal fluid protein, and less often by MRI spine with contrast, or serum antibodies to gangliosides (especially for variants) or nodalparanodal antibodies (especially if not improving). Axonal versus demyelinating subtyping does not affect clinical management. A history of recent gastrointestinal or respiratory infection or of surgery may support the diagnosis. The risk of GBS is only very slightly increased after Covid-19 infection and after the adenovirus-vector vaccines to SARS-CoV2 (AstraZeneca or Johnson & Johnson) but not mRNA vaccines. Immune treatment is recommended with intravenous immunoglobulin or plasma exchange, for most patients except those mildly affected or after four weeks from onset. A repeat course is reasonable after a treatment-related fluctuation. Corticosteroids are not recommended. There is no evidence of benefi t from any other disease-modifying treatment. Respiratory function should be monitored by forced vital capacity and single breath count to assess the risk of needing mechanical ventilation, guided by the mEGRIS scale. Pain is very common. It may be musculoskeletal or neuropathic, and treated with gabapentin, tricyclic antidepressants or carbamazepine. Patients who fail to improve should be reassessed for the correct diagnosis and for axonal degeneration. Around 5% of patients with GBS may later develop CIDP but no test can reliably indicate this within the first eight weeks. Nodal-paranodal antibodies should be tested if CIDP is suspected or if the patient is not recovering well. The long-term outcome is less good in patients of older age, with preceding diarrhoea, or more severe weakness, as quantified by the mEGOS scale, and also in patients with smaller motor potential amplitudes or raised serum neurofilament light chain level.

Case Report: Post-COVID-19 Vaccine Recurrence of Guillain-Barré Syndrome Following an Antecedent Parainfectious COVID-19-Related GBS.

Guillain-Barré syndrome (GBS) is an autoimmune neurological disorder often preceded by viral illnesses or, more rarely, vaccinations. We report on a unique combination of postcoronavirus disease 2019 (COVID-19) vaccine GBS that occurred months after a parainfectious COVID-19-related GBS. Shortly after manifesting COVID-19 symptoms, a 57-year-old man developed diplopia, right-side facial weakness, and gait instability that, together with electrophysiology and cerebrospinal fluid examinations, led to a diagnosis of post-COVID-19 GBS. The involvement of cranial nerves and IgM seropositivity for ganglioside GD1b were noteworthy. COVID-19 pneumonia, flaccid tetraparesis, and autonomic dysfunction prompted his admission to ICU. He recovered after therapy with intravenous immunoglobulins (IVIg). Six months later, GBS recurred shortly after the first dose of the Pfizer/BioNTech vaccine. Again, the GBS diagnosis was confirmed by cerebrospinal fluid and electrophysiology studies. IgM seropositivity extended to multiple gangliosides, namely for GM3/4, GD1a/b, and GT1b IgM. An IVIg course prompted complete recovery. This case adds to other previously reported observations suggesting a possible causal link between SARS-CoV-2 and GBS. Molecular mimicry and anti-idiotype antibodies might be the underlying mechanisms. Future COVID-19 vaccinations/revaccinations in patients with previous para-/post-COVID-19 GBS deserve a reappraisal, especially if they are seropositive for ganglioside antibodies.

Guillain-Barré Syndrome in Mexico: An Updated Review Amid the Coronavirus Disease 2019 ERA.

Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and if not diagnosed and treated timely, a significant cause of long-term disability. Incidence in Latin America ranges from 0.71 to 7.63 cases/100,000 person-years. Historically, GBS has been linked to infections (mainly gastrointestinal by Campylobacter jejuni) and vaccines (including those against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]); however, a trigger cannot be detected in most cases. Regarding SARS-CoV-2, epidemiological studies have found no association with its development. Acute motor axonal neuropathy is the most common electrophysiological variant in Mexico and Asian countries. Intravenous immunoglobulin or plasma exchanges are still the treatment cornerstones. Mortality in Mexico can be as high as 12%. Avances in understanding the drivers of nerve injury in GBS that may provide the basis for developing targeted therapies have been made during the past decade; despite them, accurate criteria for selecting patients requiring acute treatment, prognostic biomarkers, and novel therapies are still needed. The newly-developed vaccines against SARS-CoV-2 have raised concerns regarding the potential risk for developing GBS. In the midst of coronavirus disease 2019 and vaccination campaigns against SARS-CoV-2, this review discusses the epidemiology, clinical presentation, management, and outcomes of GBS in Mexico.

Acute Inflammatory Demyelinating Polyneuropathy as the first presenting feature of COVID 19 infection

Objective: To describe a case of a 58-year-old patient who presented to the hospital with Acute Inflammatory demyelinating Polyneuropathy (AIDP) as the first symptom of SARS COVID-19 infection without other classic manifestations of COVID-19 infection. Background: COVID-19 associated Guillain Barre syndrome is now widely reported. In our literature review, the majority of GBS patients had preceding respiratory symptoms of COVID19 but our patient had no other systemic involvement, and his symptoms started noticeably within a short duration of exposure. Design/Methods: Case report. Results: 58-year-old male patient presented to the hospital with bilateral lower extremity weakness, facial diplegia and dysphagia. Patient was tested positive for COVID-19 infection three days prior to the symptom onset due to a work-related exposure. He denied having any flu-like symptoms except generalized weakness. Patient reported progressive lower leg weakness started three days back with associated numbness and radicular pain up to T4 level. On examination, the patient had facial diplegia, areflexia and bilateral lower limb ataxia with the strength of about 3/5. CSF analysis showed albuminocytological dissociation. MRI brain and spine showed faint enhancement of lower lumbar roots. GQ1b antibody was positive on Ganglioside panel. With the clinical criteria and laboratory evidence, patient was diagnosed with AIDP. Patient was started on IVIG but due to lack of improvement after four doses patient was switched to therapeutic plasma exchange. He underwent a total of 7 sessions of plasmapheresis with improvement of motor and sensory symptoms. Conclusions: Although most cases were symptomatic for COVID-19, patients without respiratory or systemic symptoms raises a significant healthcare concern, namely the importance of SARS COVID-19 testing in all patients with suspected GBS during this global pandemic. Early diagnosis of COVID-19 associated GBS is also essential for rapid case isolation.

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.

Electromyoneurography and laboratory findings in a case of Guillain-Barré syndrome after second dose of Pfizer COVID-19 vaccine.

Guillain-Barre syndrome (GBS) is an acute immune-mediated disease of the peripheral nerves and nerve roots (polyradiculoneuropathy) that is usually elicited by various infections. We present a case of GBS after receiving the second dose of Pfizer-COVID 19 vaccine. Diagnosis was made after performing an accurate clinical examination, electromyoneurography and laboratory tests. In particular, anti-ganglioside antibodies have tested positive. During this pandemic with ongoing worldwide mass vaccination campaign, it is critically important for clinicians to rapidly recognize neurological complications or other side effects associated with COVID-19 vaccination.

(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.

CoViD-19 infection presenting as Guillain Barr syndrome

Background: The Guillain Barr syndrome (GBS) has been linked with several viral infections including CoViD-19. Description of clinical cases: 5 out of 352 patients referring to Department of Medicine for CoViD-19 infection showed neurological symptoms suggesting GBS. All patients were confirmed as SARS-CoV-2 infected by PCR on nasopharyngeal swabs. Mean age was 63.4. One was female and 4 males. In 3 cases the infection was mild, no lung involvement was found and no intensive care was required. Intensive care admission was needed in a case with bilateral interstitial pneumonia and neurological symptoms and in a patient with pulmonary embolism. All patients suffered for diffuse, severe motor and sensory involvement. In 4 cases the ranking score at admission was 4, in one was 5. Neurophysiological investigations were performed in all patients. Two cases showed an acute inflammatory demyelinating neuropathy, in 3 cases an acute axonal neuropathy was observed. An increase in proteins was detected in cerebrospinal fluid. The presence of viral- RNA for SARS-CoV-2 in the CSF resulted negative as well as the antibodies against gangliosides. Two patients were treated with dexamethasone whereas in three patients immunoglobulins were added. Neurological symptoms gradually improved in all cases, in fact, the ranking score was 3 at hospital discharge. Conclusions: Five patients showed neurological symptoms suggesting GBS. These symptoms before treatment resulted severe and improved after therapy. Further studies are needed to confirm whether the CoViD-19 can induce the clinical development of GBS.

Guillain-Barré Syndrome after Novel Coronavirus Disease 2019.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) has affected more than 89 million people worldwide. As the pandemic rages on, more complications of the disease are being recognized, including stroke, cardiovascular disease, thromboembolic events, encephalopathy, seizures, and more. Peripheral nervous system involvement, particularly Guillain-Barré syndrome (GBS), is of special interest, given the increasing reports of cases related to COVID-19. Because of the potentially delayed onset of symptoms of polyradiculoneuropathy and weakness after the traditional COVID-19 symptoms, it is vitally important for emergency physicians to be vigilant and to consider GBS as part of their differential diagnosis. GBS usually occurs after an infectious insult, and a variety of culprit pathogens have been identified in the literature. CASE REPORT: We describe the case of a 35-year-old man who developed GBS after being diagnosed with COVID-19 infection. The patient displayed classic symptoms of neuropathy, areflexia, and lower extremity weakness. Cerebrospinal fluid evaluation demonstrated albuminocytologic dissociation seen in GBS, although anti-ganglioside autoantibodies were negative. These antibodies are often negative and do not exclude the diagnosis. The patient responded clinically to intravenous immunoglobulin therapy and was discharged home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case report contributes further evidence that COVID-19 joins other organisms as causes of GBS. Emergency physicians are the first point of contact for many patients. Increased awareness of this complication of COVID-19 will lead to higher detection. Prompt recognition could lead to speedier and more complete neurologic recovery of affected patients.

Structural dynamics of SARS-CoV-2 variants: A health monitoring strategy for anticipating Covid-19 outbreaks.

OBJECTIVES: the Covid-19 pandemic has been marked by sudden outbreaks of SARS-CoV-2 variants harboring mutations in both the N-terminal (NTD) and receptor binding (RBD) domains of the spike protein. The goal of this study was to predict the transmissibility of SARS-CoV-2 variants from genomic sequence data. METHODS: we used a target-based molecular modeling strategy combined with surface potential analysis of the NTD and RBD. RESULTS: we observed that both domains act synergistically to ensure optimal virus adhesion, which explains why most variants exhibit concomitant mutations in the RBD and in the NTD. Some mutation patterns affect the affinity of the spike protein for ACE-2. However, other patterns increase the electropositive surface of the spike, with determinant effects on the kinetics of virus adhesion to lipid raft gangliosides. Based on this new view of the structural dynamics of SARS-CoV-2 variants, we defined an index of transmissibility (T-index) calculated from kinetic and affinity parameters of coronavirus binding to host cells. The T-index is characteristic of each variant and predictive of its dissemination in animal and human populations. CONCLUSIONS: the T-index can be used as a health monitoring strategy to anticipate future Covid-19 outbreaks due to the emergence of variants of concern.