Acute Flaccid Myelitis in a Pediatric Patient With Coronavirus Disease 2019.

The etiology of acute flaccid myelitis (AFM) has yet to be determined. Viral link has been suggested, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated AFM has not been reported in children. We describe a three-year-old boy, with AFM associated with coronavirus disease 2019 (COVID-19) infection. In the era of COVID-19 pandemic, patients with AFM should be tested for SARS-CoV-2.

Anti-myelin Oligodendrocyte Glycoprotein Antibody-positive Myelitis after Coronavirus Disease 2019.

We herein report a case of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-related myelitis caused by coronavirus disease (COVID-19) infection in 2021. A 22-year-old man with no history of any related illness contracted COVID-19. Eight days later, he developed bladder problems, paraplegia and sensory disturbances. Cervical spinal cord magnetic resonance imaging revealed extensive hyperintensity at T2 and spinal cord lesions extending from C4 to Th1. The patient was diagnosed with transverse myelitis and started on intravenous methylprednisolone, plasma exchange and intravenous immunoglobulin therapy. The symptoms improved only after intravenous methylprednisolone therapy. Anti-MOG antibodies were found in his serum and cerebrospinal fluid during routine screening. As this observation is unusual and could cause serious health problems, we wonder if COVID-19 triggered this autoimmune response.

Evaluation of the safety profile of COVID-19 vaccines in patients with MS, NMOSD, and MOGAD.

INTRODUCTION: Vaccination against the coronavirus disease 2019 (COVID-19) is recommended for patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, vaccine safety in these patients taking immunotherapeutic agents is unclear as they were not included in the vaccine trials. OBJECTIVES: To evaluate the safety of COVID-19 vaccines in patients with MS, NMOSD, and MOGAD. METHODS: We reviewed the medical records of MS, NMOSD, and MOGAD patients at the Keimyung University Dongsan Hospital. Information regarding vaccination schedules and adverse events was collected. RESULTS: A total of 56 patients (19, 22, and 15 patients with MS, NMOSD, and MOGAD, respectively) with a median age of 48.18 ± 15.72 years (range, 16-81 years) were included. Of them, 42 (75.0%) were female. In total, 76.8% (43/56) of all patients were vaccinated, and the vaccination rate was the highest for NMOSD patients (81.8%) and the lowest for MS patients (68.4%). All vaccinated patients were administered mRNA vaccines at least once in single or multiple vaccination doses. Only 3 of 43 (7.0%) vaccinated patients experienced clinical relapse following vaccination. Facial sensory changes with a brainstem lesion developed in an MS patient taking dimethyl fumarate, while myelitis occurred in a MOGAD patient receiving azathioprine maintenance therapy. The first episode of optic neuritis occurred in a patient who was later diagnosed with MOGAD. CONCLUSIONS: Our study demonstrated a favorable safety profile with no serious adverse events associated with COVID-19 vaccines in patients with MS, NMOSD, and MOGAD.

A disproportionality analysis for the association of central nervous system demyelinating diseases with COVID-19 vaccination using the World Health Organization pharmacovigilance database.

BACKGROUND: Limited information is available on associations between COVID-19 vaccines and central nervous system (CNS) demyelinating diseases. OBJECTIVES: We investigated potential safety signals for CNS demyelinating diseases related to COVID-19 vaccines using the World Health Organization pharmacovigilance database. METHODS: Disproportionality analyses of CNS demyelinating disease following COVID-19 vaccination were performed by calculating the information component (IC) or the reporting odds ratio (ROR) compared with those for the entire database and for all other viral vaccines. RESULTS: We identified 715 cases of optic neuritis, 515 of myelitis, 220 of acute disseminated encephalomyelitis (ADEM), and 2840 total CNS demyelinating events adverse drug reactions from July 2020 through February 2022. For mRNA-based and ChAdOx1 nCoV-19 vaccines, there were no potential safety signals of disproportionality for optic neuritis (IC₀₂₅ = -0.93, ROR₀₂₅ = 0.38; IC₀₂₅ = -1.76, ROR₀₂₅ = 0.26), myelitis (IC₀₂₅ = -0.69, ROR₀₂₅ = 0.50; IC₀₂₅ = -0.63, ROR₀₂₅ = 0.53), ADEM (IC₀₂₅ = -1.05, ROR₀₂₅ = 0.33; IC₀₂₅ = -1.76, ROR₀₂₅ = 0.20), or overall CNS demyelinating disease events (IC₀₂₅ = -0.66, ROR₀₂₅ = 0.52; IC₀₂₅ = -1.31, ROR₀₂₅ = 0.34) compared with other viral vaccines. CONCLUSION: As with other viral vaccines, our disproportionality analyses indicate that the risk of COVID-19 vaccine-associated CNS demyelinating disease was low.

Increase in Acute Respiratory Illnesses Among Children and Adolescents Associated with Rhinoviruses and Enteroviruses, Including Enterovirus D68 - United States, July-September 2022.

Increases in severe respiratory illness and acute flaccid myelitis (AFM) among children and adolescents resulting from enterovirus D68 (EV-D68) infections occurred biennially in the United States during 2014, 2016, and 2018, primarily in late summer and fall. Although EV-D68 annual trends are not fully understood, EV-D68 levels were lower than expected in 2020, potentially because of implementation of COVID-19 mitigation measures (e.g., wearing face masks, enhanced hand hygiene, and physical distancing) (1). In August 2022, clinicians in several geographic areas notified CDC of an increase in hospitalizations of pediatric patients with severe respiratory illness and positive rhinovirus/enterovirus (RV/EV) test results.* Surveillance data were analyzed from multiple national data sources to characterize reported trends in acute respiratory illness (ARI), asthma/reactive airway disease (RAD) exacerbations, and the percentage of positive RV/EV and EV-D68 test results during 2022 compared with previous years. These data demonstrated an increase in emergency department (ED) visits by children and adolescents with ARI and asthma/RAD in late summer 2022. The percentage of positive RV/EV test results in national laboratory-based surveillance and the percentage of positive EV-D68 test results in pediatric sentinel surveillance also increased during this time. Previous increases in EV-D68 respiratory illness have led to substantial resource demands in some hospitals and have also coincided with increases in cases of AFM (2), a rare but serious neurologic disease affecting the spinal cord. Therefore, clinicians should consider AFM in patients with acute flaccid limb weakness, especially after respiratory illness or fever, and ensure prompt hospitalization and referral to specialty care for such cases. Clinicians should also test for poliovirus infection in patients suspected of having AFM because of the clinical similarity to acute flaccid paralysis caused by poliovirus. Ongoing surveillance for EV-D68 is critical to ensuring preparedness for possible future increases in ARI and AFM.

SIRT-1 connects autophagy and release of virus-containing vesicles during picornavirus infection (preprint)

ABSTRACT Enterovirus D68 is a re-emerging enterovirus which causes acute respiratory illness in infants. EV-D68 infection has recently been associated with Acute Flaccid Myelitis, a severe polio-like neurological disease that causes limb weakness and loss of muscle tone in infants. There is currently no FDA-approved drug or prophylactic vaccine against EV-D68. Here, we investigated the role of the histone deacetylase, SIRT-1, in autophagy and EV-D68 infection. We show that SIRT-1 plays an important role in both autophagy and EV-D68 infection. siRNA-mediated knockdown of the cellular protein blocks basal and stress-induced autophagy and reduces EV-D68 extracellular viral titers. The proviral activity of SIRT-1 does not require deacetylase activity, since transient expression of both wild-type and deacetylase-inactive SIRT-1 mutant plasmids increased EV-D68 release. In non-lytic conditions, EV-D68 is primarily released in extracellular vesicles, and SIRT-1 is required for this process. Knockdown of SIRT-1 further impedes EV-D68 release in the autophagy-deficient ATG-7 knockout cells. Knockdown of SIRT-1 also decreases titers of poliovirus (PV) and SARS-CoV-2, but not Coxsackievirus-B3 (CVB3). CVB3 is the only tested virus that fails to induce SIRT-1 translocation to the cytosol. Our data suggest a correlation between SIRT-1 translocation during viral infection and extracellular vesicle-mediated non-lytic release of infectious viral particles. SIGNIFICANCE Picornaviruses, including EV-D68, constitute a significant cause of human disease. EV-D68 infection generally causes mild respiratory tract infection in infants but has recently been implicated in a severe polio-like neurological disease, AFM. Given the lack of prophylactic vaccines or antivirals against EV-D68, identifying host factors that modulate EV-D68 infection is crucial. Here, we show that SIRT-1 regulates autophagy and EV-D68 infection. Knockdown of SIRT-1 blocked autophagy and impeded the non-lytic release of EV-D68 in extracellular vesicles. We also show that SIRT-1 modulates the release of SARS-CoV-2 and poliovirus but not Coxsackievirus-B3 virus. Our data suggest that many RNA viruses require SIRT-1 for egress and that targeting SIRT-1 could constitute a broad-spectrum antiviral strategy.

Multisystem inflammatory syndrome in adult with longitudinally extensive transverse myelitis following SARS-CoV-2 vaccination: Case report (preprint)

Introduction: Multisystem inflammatory syndrome in adults (MIS-A) after SARS-CoV-2 infection or vaccination is a known complication. However, longitudinally extensive transverse myelitis (LETM) as a manifestation of MIS-A after SARS-CoV-2 infection or vaccination has not been reported before. Case presentation: 38-year old female, known case of hypothyroidism with history of mild SARS-Cov-2 infection in May 2021 and recent second dose of SARS-CoV-2 vaccination (on 1 st November 2021, COVISHIELD TM Oxford/Astra Zeneca) presented with acute onset progressive flaccid quadriparesis with bowel and bladder involvement since 26 th December 2021. Over next 3 days she developed fever, maculopapular rash , shock, myocarditis, breathlessness, Jaundice, acute kidney injury. Investigations revealed polymorphonuclear leukocytosis, thrombocytopenia, deranged Liver and renal function , severe left ventricular dysfunction. C reactive protein, D-dimer, procalcitonin, Interleukin-6 levels were raised. MRI whole spine revealed LETM from C6 to conus medullaris. Reverse transcriptase polymerase chain reaction for SARS-CoV-2 infection was negative. SARS-CoV-2 antibody titre was raised. Diagnosed as a case of MIS-A with LETM. Managed with ventilatory and ionotropic support, Intravenous Iimmunoglobulin, antibiotics, hemodialysis and intravenous methyl prednisolone and oral steroid. Improved gradually and discharged. Presently patient has grade 5/5 power in both upper limbs and 2/5 power in both lower limbs with improving bowel and bladder control. Conclusions: : This is the first reported case of LETM associated with MIS-A after SARS-CoV-2 infection or vaccination. With wider availability of SARS-CoV-2 vaccination, various side effects are emerging. However as these side effects are rare, SARS-CoV-2 vaccination represents the hope for mankind to overcome this global pandemic.

Antibody-Positive Neuromyelitis Optica Spectrum Disorder After Second COVID-19 Vaccination: A Case Report. (preprint)

Background: We report a case of de novo aquaporin-4 positive neuromyelitis optica spectrum disorder following BNT162b SARS-CoV-2 vaccination. Case Presentation: An 80-year-old South Asian man presented two days following his second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine with progressive left-sided leg weakness and numbness resulting in falls. MRI of the spine revealed a longitudinally extensive transverse myelitis from T3-T4 to T9-T10. Serum antibody testing revealed positive aquaporin-4 (AQP4) antibodies. He was diagnosed with de novo AQP4 positive neuromyelitis optica spectrum disorder (NMOSD) and was treated with high dose intravenous methylprednisolone and plasma exchange with some improvement. He was subsequently treated with mycophenolate mofetil and a slow steroid wean. Conclusions: : Evidence suggests vaccinations may trigger de novo NMOSD or NMOSD relapses in some individuals. Ongoing vaccine surveillance and research are needed to understand the risk of NMOSD post-COVID-19 vaccinations further.

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021.

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.

Varicella Zoster Precipitating a case of Covid-19 Myelitis (preprint)

Covid-19 disease has plethora of clinical manifestations. There have been certain viral coinfection and presence of autoimmunity in Covid-19 disease. The predominant neurological manifestations of Covid-19 disease reported are encephalopathy, anosmia, headache, bell’s palsy, Guillain barre syndrome, acute transverse myelitis, acute demyelinating encephalomyelitis and strokes. In this illustration we presented an 11-year-old girl suffering from Covid-19 illness, presented with acute transverse myelitis along with Varicella-zoster co-infection substantiated by cerebrospinal fluid PCR positivity. There is a scarce literature of coexistence of varicella-zoster co-infection triggering myelitis in Covid-19 illness.

Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance (preprint)

Background: Background incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of nine adverse events of special interest related to COVID-19 vaccines in Ontario, Canada. Methods: We conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bells palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barre syndrome, and transverse myelitis during five pre-pandemic years (2015-2019) and 2020. Results: The average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015-2019 were 43.9 for idiopathic thrombocytopenia, 27.8 for Bells palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.6 for pericarditis, 2.9 for myocarditis, 1.9 for Guillain-Barre syndrome, 1.7 for transverse myelitis, and 1.6 for Kawasaki disease. Females had higher rates of acute disseminated encephalomyelitis and transverse myelitis while males had higher rates of myocarditis, pericarditis, and Guillain-Barre syndrome. Bells palsy, acute disseminated encephalomyelitis, and Guillain-Barre syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12-59 years for myocarditis and 12 years and older for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. Conclusions: Our estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Longitudinally Extensive Transverse Myelitis (LETM) in COVID-19 Infection, A Case-Report (preprint)

Introduction: Since the COVID-19 pandemic, a growing number of central nervous system (CNS) complications in patients with COVID-19 have been reported. Isolated, longitudinally extensive transverse myelitis (LETM), is a unique presentation of CNS involvement. The limited reports, its diverse clinical manifestations and the possible long-term consequences make the reporting crucial to further our understanding of those syndromes occurring in COVID-19 positive patients. Case Presentation A 63-year old male consulted the emergency department after a sudden onset of gait ataxia, a one-week history of paresthesia progressing from the feet to the midsternal area and urinary. He tested positive on a SARS-CoV-2 RNA RT-PCR nasopharyngeal swab two days prior to the onset of his symptoms. Neurological examination showed a sensory level at T7 with symmetrically reduced fine touch, vibration, proprioception and furthermore an ataxic gait was observed. Cerebrospinal fluid on day one of admission showed pleocytosis, predominantly neutrophils, elevated protein count and normal glucose level and IgG. MRI of the spinal cord revealed a diffusely increased signal intensity involving the near-complete spinal cord, from the brainstem to level T12, fitting the diagnosis of LETM. Conclusion: The few cases of transverse myelitis in association with COVID-infection are believed to have an immune-mediated postinfectious mechanism. In this case however, parainfectious direct viral invasion of the spinal cord is far more likely because of a neutrophilic predominance in CSF and a short timespan between infection and symptoms. It could provide more clues that the SARS-CoV-2 is acutally capable of causing direct neurotoxic effects.

Initial clinical manifestation of multiple sclerosis after immunization with the Pfizer-BioNTech COVID-19 vaccine.

Vaccine administration may be involved in the development of some central nervous system demyelinating diseases. The COVID-19 vaccine is being administered to the entire population, but to date, little association between vaccination and the risk of developing multiple sclerosis (MS) has been suggested, and only a few case reports have been published. Here, we present a 40-year-old woman who developed cervical myelitis after receiving the COVID-19 vaccine. Myelitis was considered the initial clinical manifestation of MS. Our case suggests a possible link between the vaccination and the clinical MS attack.

Early effects of the COVID-19 pandemic on the acute flaccid paralysis surveillance in East and Southern African countries.

INTRODUCTION: the World health organisation (WHO) African Region reported the first confirmed COVID-19 case caused by the SARS-CoV-2 on 25th February 2020, and the first case for the East Southern Africa (ESA) sub-region was on 5th March 2020. Almost all countries in the ESA sub region implemented the WHO-recommended preventive measures variably after the notification of community transmission of the COVID-19 disease. This resulted in the disruption of the outpatient, immunization surveillance, and the related supply chain activities. METHODS: a comparative analysis study design of secondary acute flaccid paralysis (AFP) surveillance data received from the East and Southern Africa sub-region countries to evaluate the effect of the COVID-19 pandemic in the AFP field surveillance for the same time period of March to December 2019 and 2020. RESULTS: we observed that 52.4% of second stool samples were received in the laboratory within 72 hours from March to December 2019, and only 48.1% in the same period of 2020. A 4.3% decline with a p-value of <0.0001 (95% CI, ranges from 2.326% to 6.269%). Similarly, we noted a 4.7% decline in the number of reported AFP cases in the ESA sub-region for March to December 2020 compared to the same period in 2019, a p-value of less than 0.001 (95% CI ranges from 2.785 to 6.614). For the percentage of stool adequacy, we observed a 3.37% decline for April in 2020 compared to April 2019 with a p-value of less than 0.001 (95% CI ranges from 2.059 to 4.690). CONCLUSION: we observed a decline in the core AFP surveillance (non polio) NP-AFP rate, and percentage of stool adequacy in countries severely affected by the COVID-19 disease. These countries implemented stringent transmission prevention measures such as lock-down and international transportation restrictions.

COVID-19-Associated Myelitis Involving the Dorsal and Lateral White Matter Tracts: A Case Series and Review of the Literature.

Coronavirus disease 2019 (COVID-19) myelitis is a rare condition, most commonly presenting with nonenhancing central expansile cord T2 signal changes. A single case report has also described longitudinal involvement of the dorsal columns. We present 5 cases of COVID-19-associated myelitis with tract-specific involvement of the dorsal and lateral columns and discuss potential pathophysiologic pathways for this unique pattern.