Going Remote: A Revised Study Protocol for a Pilot Randomized Controlled Trial for Biofeedback Treatment of Anxiety Associated With Chronic Spinal Cord Injury.

Background: The incidence of anxiety in adults with spinal cord injury/disorder (SCI/D) exceeds that of the general population. Heart rate variability (HRV) biofeedback training is a potential treatment associated with a reduction in stress and anxiety, however HRV training has not been explored in the SCI/D population. Objectives: To describe a modified protocol piloting HRV training to reduce anxiety associated with SCI/D and detail the COVID-19-related modifications. Methods: To test the feasibility of the biofeedback treatment, 30 adults with SCI/D will complete this pilot randomized controlled trial. Enrollment started in January 2020, halted in March 2020 due to the COVID-19 pandemic, and resumed in March 2021 with a modified protocol. Protocol modifications are documented using the Framework for Reporting Adaptations and Modifications (FRAME). Participants are allocated to the treatment or control arm and undergo eight sessions of physiological monitoring at home using a commercially available HRV sensor and mobile application, which also delivers biofeedback training for those in the treatment arm. Surveys are administered following each session to capture self-reported stress, anxiety, and mood. The study is approved by the HCA-HealthONE institutional review board and is registered with clinicaltrials.gov (NCT# 03975075). Conclusion: COVID-19 has changed the research landscape, forcing scientists to rethink their study designs to address patient and staff safety in this new context. Our modified protocol accomplished this by moving the treatment setting and delivery out of the clinic and into the home. In doing so, we address patient and staff safety, increase external validity, and reduce participant burden.

SARS-CoV-2 Vaccine Booster Elicits Robust Prolonged Maternal Antibody Responses and Passive Transfer Via The Placenta And Breastmilk (preprint)

Background: Infection during pregnancy can result in adverse outcomes for both pregnant persons and offspring. Maternal vaccination is an effective mechanism to protect both mother and neonate into post-partum. However, our understanding of passive transfer of antibodies elicited by maternal SARS-CoV-2 mRNA vaccination during pregnancy remains incomplete. Objective: We aimed to evaluate the antibody responses engendered by maternal SARS-CoV-2 vaccination following initial and booster doses in maternal circulation and breastmilk to better understand passive immunization of the newborn. Study Design: We collected longitudinal blood samples from 121 pregnant women who received SARS-CoV-2 mRNA vaccines spanning from early gestation to delivery followed by collection of blood samples and breastmilk between delivery and 12 months post-partum. During the study, 70% of the participants also received a booster post-partum. Paired maternal plasma, breastmilk, umbilical cord plasma, and newborn plasma samples were tested via enzyme-linked immunosorbent assays (ELISA) to evaluate SARS-CoV-2 specific IgG antibody levels. Results: Vaccine-elicited maternal antibodies were detected in both cord blood and newborn blood, albeit at lower levels than maternal circulation, demonstrating transplacental passive immunization. Booster vaccination significantly increased spike specific IgG antibody titers in maternal plasma and breastmilk. Finally, SARS-CoV-2 specific IgG antibodies in newborn blood correlated negatively with days post initial maternal vaccine dose. Conclusion: Vaccine-induced maternal SARS-CoV-2 antibodies were passively transferred to the offspring in utero via the placenta and after birth via breastfeeding. Maternal booster vaccination, regardless of gestational age at maternal vaccination, significantly increased antibody levels in breastmilk and maternal plasma, indicating the importance of this additional dose to maximize passive protection against SARS-CoV-2 infection for neonates and infants until vaccination eligibility. Keywords: Antibody, Booster, Breastmilk, COVID-19 vaccine, Newborn, Passive transfer

Comprehensive Serological Profile and Specificity of Maternal and Neonatal Cord Blood SARS CoV-2 Antibodies (preprint)

ObjectiveTo describe the profile and specificity of maternal and neonatal cord-blood antibody profile in response SARS-CoV-2 virus exposure MethodsThis is a Prospective cohort study of delivering patients at Thomas Jefferson University Hospital from April 2020-February 2021. Primary objective was to describe unique maternal and fetal antibody epitope titers and specificity in those patients with COVID-19 history. Serologic profile assessed with a multiplex platform. Antigens used were: HA-trimer Influenza A (Hong Kong H3), spike trimers for SARS-CoV-2, SARS-CoV-1, MERS-CoV, and betacoronaviruses HKU-1 and OC43, as well as the spike N-terminal domain (NTD), spike receptor binding domain (RBD), and nucleocapsid protein (N; full length) for SARS-CoV-2. Results112 maternal samples and 101 maternal and cord blood pairs were analyzed. Thirty-seven had a known history of COVID-19 (positive PCR test) in the pregnancy and of those, 17 (47%) were diagnosed with COVID-19 within 30 days of delivery. Fifteen of remaining seventy-six (20%) without a known diagnosis had positive maternal serology. For those with history of COVID-19 we identified robust IgG response in maternal blood to CoV2 nucleocapsid (N), spike (S) full-length and S (RBD) antigens with more modest responses to the S (NTD) antigen. By contrast, the maternal blood IgM response appeared more specific to S (full-length), than N, S (RBD) or S (NTD) epitopes. There were significantly higher maternal and cord blood IgG response not just to CoV2 spike (p < 10-18), but also CoV1 spike (p < 10-9) and MERS spike (p < 10-8). By contrast, maternal IgM responses were more specific to CoV2 (p < 10-19), but to a lesser degree for CoV1 (p < 10-5), and no significant differences for MERS. Maternal and cord-blood IgG were highly correlated for both S and N (R2 = 0.96 and 0.94). ConclusionsPlacental transfer is efficient, with robust N and S responses. Both nucleocapsid and spike antibody responses should be studied for a better understanding of COVID-19 immunity. IgG antibodies are cross reactive with related CoV-1 and MERS spike epitopes while IgM, which cannot cross placenta to provide neonatal passive immunity, is more SARS CoV-2 specific. Neonatal cord blood may have significantly different fine-specificity than maternal blood, despite the high efficiency of IgG transfer.

Nosocomial COVID-19 infection mortality following surgery for severe progressive cervical myelopathy: a case report.

INTRODUCTION: We present the unique case of a nosocomial COVID infection acquired after urgent surgical intervention for cervical myelopathy, as well as the sequelae that followed in the postoperative period. CASE PRESENTATION: An initially COVID-negative patient underwent urgent surgical intervention for cervical myelopathy with significant neurological deterioration. She underwent an uncomplicated staged anterior cervical discectomy and fusion with corpectomy, as well as a subsequent posterior cervical instrumented fusion within the same hospitalization. The patient would refuse to adhere to standard COVID precautions during her admission and demonstrated rapid decompensation following her particularly uneventful surgeries, ultimately leading to her expiration. A laboratory test confirmed that she had contracted COVID at the time of the patient's death. DISCUSSION: This report highlights the repercussions of COVID-19 infection during the perioperative period and its implications on surgical outcomes. The stresses of surgery and the body's immunosuppressive responses during this time place patients at particular risk for the contraction of this virus. The standard precautions should be followed and vaccination should be considered for surgical candidates prior to their operations, as they become more readily accessible.

Clinical Features, Laboratory, and Radiological Findings of Patients With Acute Inflammatory Myelopathy After COVID-19 Infection: A Narrative Review.

ABSTRACT: The objective of this review was to analyze the existing data on acute inflammatory myelopathies associated with coronavirus disease 2019 infection, which were reported globally in 2020. PubMed, CENTRAL, MEDLINE, and online publication databases were searched. Thirty-three acute inflammatory myelopathy cases (among them, seven cases had associated brain lesions) associated with coronavirus disease 2019 infection were reported. Demyelinating change was seen in cervical and thoracic regions (27.3% each, separately). Simultaneous involvement of both regions, cervical and thoracic, was seen in 45.4% of the patients. Most acute inflammatory myelopathy disorders reported sensory motor and bowel bladder dysfunctions. On cerebrospinal fluid analysis, pleocytosis and increased protein were reported in 56.7% and 76.7% of the patients, respectively. Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction was positive in five patients. On T2-weighted imaging, longitudinally extensive transverse myelitis and short-segment demyelinating lesions were reported in 76% and 21%, respectively. Among the patients with longitudinally extensive transverse myelitis, 61% reported "moderate to significant" improvement and 26% demonstrated "no improvement" in the motor function of lower limbs. Demyelinating changes in the entire spinal cord were observed in three patients. Most of the patients with acute inflammatory myelopathy (including brain lesions) were treated with methylprednisolone (81.8%) and plasma-exchange therapy (42.4%). An early treatment, especially with intravenous methylprednisolone with or without immunoglobulin and plasma-exchange therapy, helped improve motor recovery in the patients with acute inflammatory myelopathy associated with coronavirus disease 2019.

Infectious Myelopathies.

PURPOSE OF REVIEW: This article reviews infectious etiologies of spinal cord dysfunction, emphasizing the importance of recognizing common clinicoradiographic syndromes and interpreting them in the context of exposure risk and individual host susceptibilities. RECENT FINDINGS: This article discusses the shifting spectrum of neurologic infectious diseases, the growing population of patients who are immunocompromised, and the emergence of effective antiretroviral therapies. In addition, it discusses new molecular and serologic tests that have the potential to enhance our ability to rapidly and accurately diagnose infectious diseases of the spine. SUMMARY: When evaluating patients with suspected infectious myelopathies, it is imperative to narrow the range of pathogens under consideration. The geography, seasonality, and clinicoradiographic presentation and immunocompetence status of the patient define the range of potential pathogens and should guide testing and initial management.

MRI negative myelopathy post mild SARS-CoV-2 infection: vasculopathy or inflammatory myelitis?

Since the onset of the COVID-19 pandemic, there have been rare reports of spinal cord pathology diagnosed as inflammatory myelopathy and suspected spinal cord ischemia after SARS-CoV-2 infection. Herein, we report five cases of clinical myelopathy and myeloradiculopathy in the setting of post-COVID-19 disease, which were all radiographically negative. Unlike prior reports which typically characterized hospitalized patients with severe COVID-19 disease and critical illness, these patients typically had asymptomatic or mild-moderate COVID-19 disease and lacked radiologic evidence of structural spinal cord abnormality. This case series highlights that COVID-19 associated myelopathy is not rare, requires a high degree of clinical suspicion as imaging markers may be negative, and raises several possible pathophysiologic mechanisms.

Myelopathy associated with SARS-COV-2 infection. A systematic review.

Background׃COVID-19 (CoranaVirus disease 2019) is an ongoing infectious disease caused by the RNA SARS-CoV-2 virus (Severe Acute Respiratory Syndrome CoronaVirus-2). More than one-third of COVID-19 patients report neurological symptoms and cases of neurological diseases are increasingly accumulating. The aim of this systematic review was to characterize all - to date - reported cases with COVID-19 related myelopathy. Methods׃Eighteen papers were included in this review. Patients of all ages could be affected, although there is a predilection for middle-aged people. Results׃There were no significant co-morbidities or immunodeficiencies in the affected patients. COVID-19 related myelopathy started roughly within the first month after COVID-19 onset, either concomitantly with COVID-19 symptoms or within 10 days after their remission. The vast majority of cases fulfilled our criteria for postinfectious transverse myelitis. However, some cases were considered to have had parainfectious or infectious myelitis or, in one case, vascular myelopathy. Motor, sensory and bowel and/or bladder symptoms predominated the clinical presentation of myelopathies, explained mainly by centrally localized and longitudinally extensive lesions within the cervical and/or thoracic segments of the spinal cord. Occasionally lesions were complicated by necrosis and hemorrhages. Treatment with corticosteroids, intravenous immunoglobulin or plasma exchange was offered mostly a mild to marked improvement within a period of some weeks. Conclusions׃ Considering the imminent arrival of new vaccines against COVID-19 pandemic, and their potential risk for postvaccination transverse myelitis, this characterization of COVID-19 related myelopathy is of utmost importance.

Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals.

BACKGROUND: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals. MATERIALS AND METHODS: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated. RESULTS: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection. CONCLUSION: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.

Virtual Care in the Veterans Affairs Spinal Cord Injuries and Disorders System of Care During the COVID-19 National Public Health Emergency.

Telehealth reduces disparities that result from physical disabilities, difficulties with transportation, geographic barriers, and scarcity of specialists, which are commonly experienced by individuals with spinal cord injuries and disorders (SCI/D). The Department of Veterans Affairs (VA) has been an international leader in the use of virtual health. The VA's SCI/D System of Care is the nation's largest coordinated system of lifelong care for people with SCI/D and has implemented the use of telehealth to ensure that Veterans with SCI/D have convenient access to their health care, particularly during the restrictions that were imposed by the COVID-19 pandemic.

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

OBJECTIVE: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes. METHODS: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders. RESULTS: Of 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17-1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, p < 0.001). CONCLUSIONS: Neurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Spinal cord dysfunction after COVID-19 infection.

INTRODUCTION: We observed individuals affected by spinal cord dysfunction (SCD) after coronavirus disease 2019 (COVID-19). The aim of our report is to provide our initial experience with individuals experiencing SCD after COVID-19 in a referral center in Northern Italy, from February 21 to July 15, 2020. CASE PRESENTATION: We report on three men with SCD after COVID-19. Case 1, aged 69 years, experienced T10 AIS B paraplegia upon awakening due to spinal cord ischemia from T8 to conus medullaris, besides diffuse thromboses, 27 days after the onset of COVID-19 symptoms. Case 2, aged 56 years, reported progressive cervicalgia 29 days after COVID-19 onset associated with C3 AIS C tetraplegia. Magnetic resonance imaging (MRI) revealed a C4-C6 spinal epidural abscess (SEA) requiring a C3-C4 left hemilaminectomy. Case 3, aged 48 years, reported backache together with lower limb muscle weakness on day 16 after being diagnosed with COVID-19. Exam revealed T2 AIS A paraplegia and an MRI showed a T1-T7 SEA. He underwent a T3-T4 laminectomy. Prior to SCD, all three individuals suffered from respiratory failure due to COVID-19, required mechanical ventilation, had cardiovascular risk factors, experienced lymphopenia, and received tocilizumab (TCZ). DISCUSSION: To our knowledge, this is the first report of SCD after COVID-19. Based on our experience, we did not observe a direct viral infection, but there were two different etiologies. In Case 1, the individual developed spinal cord ischemia, whereas in Cases 2 and 3 SEAs were likely related to the use of TCZ used to treat COVID-19.

Acute transverse myelitis in a HIV-positive patient with COVID-19 (preprint)

Immunocompromised status keeps on being a challenge for a neurologist, especially in the context of the coronavirus disease – 19 (COVID-19) pandemic. We report a clinical case of a human-immunodeficiency virus (HIV) - positive patient who developed an acute transverse myelitis. Magnetic Resonance Imaging (MRI) examination showed longitudinally extensive spinal cord abnormality, and laboratory tests confirmed SARS-CoV-2 infection. The patient responded to methylprednisolone pulse therapy and therapeutic plasma exchange. No cases of HIV-positive patients with myelitis and COVID-19 has been reported yet.

Need for ensuring care for neuro-emergencies-lessons learned from the COVID-19 pandemic.

BACKGROUND: To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic. METHODS: In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms. RESULTS: During the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years. CONCLUSIONS: Despite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.

Clinical characteristics of 106 patients with neurological diseases and co-morbid coronavirus disease 2019: a retrospective study (preprint)

Objectives:To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with co-morbid neurological symptoms. Design:Retrospective case series. Setting:Huoshenshan Hospital in Wuhan, China. Participants:From 4 February to 14 April 2020, 106 patients with neurological diseases were enrolled from all patients in the hospital with confirmed COVID-19 and divided into a severe group and a nonsevere group according to their COVID-19 diagnosis. Main outcome measures:Clinical characteristics, laboratory results, imaging findings, and treatment methods were all retrieved through an electronic medical records system and recorded in spreadsheets. Results:The mean (standard deviation, SD) age of patients was 72.7 (11.8) years, and 64 patients were male (60.4%). Among patients with co-morbid neurological diseases, 81 had a previous cerebral infarction (76.4%), 20 had dementia (18.9%), 10 had acute cerebral infarction (9.4%), 5 had sequelae of cerebral haemorrhage (4.7%), 4 had intracranial mass lesions (3.8%), 3 had epilepsy (2.8%), 2 had Parkinsons disease (1.9%), and 1 had myelopathy (0.9%). Fever (n = 62, 58.5%) was the most common symptom. The most common neurological symptoms were myalgia (n = 26, 24.5%), followed by extremity paralysis (n = 20, 18.9%), impaired consciousness (n = 17, 16%), and positive focal neurological signs (n = 42, 39.6%). Eight patients (7.5%) died. There were more patients with altered mental status in the severe group than in the non-severe group (6 [10.2%] vs. 0, P = 0.033). The inflammatory response in the severe group was more significant than that in the non-severe group. There were more patients taking anticoagulant drugs (25 [42.4%] vs. 4 [8.5%], P < 0.001) and sedative drugs (22 [37.3%] vs. 9 [19.1%], P = 0.041) in the severe group than in the non-severe group. Amid all 93 patients with cerebrovascular diseases, only 32 (34.4%) were taking aspirin, 13 (14%) taking clopidogrel, and 33 (35.5%) taking statins. Conclusions:Patients with COVID-19 with co-morbid neurological diseases had an advanced age, a high rate of severe illness, and a high mortality rate. Among the neurological symptoms, altered mental status was more common in patients with severe COVID-19 with co-morbid neurological diseases.

Evolution of CT Manifestations of 105 novel coronavirus pneumonia patients in Wuhan, China (preprint)

Objectives: The purpose of this study was to observe the chest HRCT manifestation evolution of the 105 patients with pneumonia caused by SARS-CoV-2.Methods: 105 confirmed patients were enrolled from January 11, 2020 to February 9, 2020. Chest HRCT were performed. The number of affected lung lobes, lesion shape, density, range, and dynamic changes of various lesions in each CT examination of each patient were recorded to comprehensively evaluate whether it is improved. Results: CT images of 105 confirmed patients were collected. The patients underwent 2-7 chest CT examinations. M/F ratio: 49/56. The age range was 23-72 y, and the mean age was 48.6±13.1 y. The patients' chest CT examinations were divided into 5 groups according to the re-examination interval, group A (25 cases): ≤3 days, group B (70 cases): 4-7 days, group C (75 cases): 8-14 days, group D (29 cases): 15-21 days, group E (4 cases):> 21 days. There was significant difference in the improvement and progress rates between group B and C. Furthermore, the changes of ground glass nodules (GGO), consolidation and cord lesions in each group were recorded.Conclusions: The chest CT manifestations of the patients changed rapidly, and the re-examination of 7-14 days was of great significance in evaluating the prognosis of patients while minimizing the radiation dose.