Humoral and Cellular Responses to SARS-CoV-2 in Convalescent COVID-19 Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Information about humoral and cellular responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antibody persistence in convalescent (COVID-19) patients with multiple sclerosis (PwMS) is scarce. The objectives of this study were to investigate factors influencing humoral and cellular responses to SARS-CoV-2 and its persistence in convalescent COVID-19 PwMS. METHODS: This is a retrospective study of confirmed COVID-19 convalescent PwMS identified between February 2020 and May 2021 by SARS-CoV-2 antibody testing. We examined relationships between demographics, MS characteristics, disease-modifying therapy (DMT), and humoral (immunoglobulin G against spike and nucleocapsid proteins) and cellular (interferon-gamma [IFN-γ]) responses to SARS-CoV-2. RESULTS: A total of 121 (83.45%) of 145 PwMS were seropositive, and 25/42 (59.5%) presented a cellular response up to 13.1 months after COVID-19. Anti-CD20-treated patients had lower antibody titers than those under other DMTs (p < 0.001), but severe COVID-19 and a longer time from last infusion increased the likelihood of producing a humoral response. IFN-γ levels did not differ among DMT. Five of 7 (71.4%) anti--CD20-treated seronegative patients had a cellular response. The humoral response persisted for more than 6 months in 41/56(81.13%) PwMS. In multivariate analysis, seropositivity decreased due to anti-CD20 therapy (OR 0.08 [95% CI 0.01-0.55]) and increased in males (OR 3.59 [1.02-12.68]), whereas the cellular response decreased in those with progressive disease (OR 0.04 [0.001-0.88]). No factors were associated with antibody persistence. DISCUSSION: Humoral and cellular responses to SARS-CoV-2 are present in COVID-19 convalescent PwMS up to 13.10 months after COVID-19. The humoral response decreases under anti-CD20 treatment, although the cellular response can be detected in anti-CD20-treated patients, even in the absence of antibodies.

Neurological complications of COVID-19 in hospitalized patients: The registry of a neurology department in the first wave of the pandemic.

OBJECTIVE: To describe the spectrum of neurological complications observed in a hospital-based cohort of COVID-19 patients who required a neurological assessment. METHODS: We conducted an observational, monocentric, prospective study of patients with a COVID-19 diagnosis hospitalized during the 3-month period of the first wave of the COVID-19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID-19 symptoms. These diagnoses could be divided into different groups. RESULTS: Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID-19 pandemic compared to neuromuscular disorders, which usually appeared later on (p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). CONCLUSIONS: The prevalence of neurological complications is low in patients hospitalized for COVID-19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID-19, as they occurred at different times following the onset of COVID-19 symptoms.

Plasma exchange in acute attacks of demyelinating diseases of the central nervous system: clinical outcomes and predictors of response.

BACKGROUND: Plasma exchange (PLEX) is a therapeutic option in the treatment of acute attacks of Demyelinating Diseases of the Central Nervous System (DDCNS). Factors related with PLEX response are not well established. METHODS: Descriptive and retrospective study. We included patients treated with PLEX for acute attacks of DDCNS between 2008 and 2017. We recorded demographics, clinical and treatment-related data, and Expanded Disability Status Scale (EDSS) score at admission, at discharge, and at 6 months. RESULTS: We included 64 patients. Forty-eight (75%) were female with a mean age of 48.28 ± 11.5 years. Half of our patients were diagnosed with multiple sclerosis. Clinical improvement was achieved in 51.6% at discharge and 62.5% at 6 months. The logistic regression model showed that EDSS score > 3 at admission (p = 0.04) and early clinical improvement with PLEX (p = 0.00) were predictors of good response to PLEX at discharge and at 6 months, respectively. No serious adverse effects were identified. CONCLUSIONS: PLEX is a safe and effective treatment for acute attacks of DDCNS. EDSS score at admission and early clinical improvement with PLEX were factors associated with good response to PLEX.

Patterned Vascularization of Embryonic Mouse Forebrain, and Neuromeric Topology of Major Human Subarachnoidal Arterial Branches: A Prosomeric Mapping.

The prosomeric brain model contemplates progressive regionalization of the central nervous system (CNS) from a molecular and morphological ontogenetic perspective. It defines the forebrain axis relative to the notochord, and contemplates intersecting longitudinal (zonal, columnar) and transversal (neuromeric) patterning mechanisms. A checkboard pattern of histogenetic units of the neural wall results, where each unit is differentially fated by an unique profile of active genes. These natural neural units later expand their radial dimension during neurogenesis, histogenesis, and correlative differential morphogenesis. This fundamental topologic framework is shared by all vertebrates, as a Bauplan, each lineage varying in some subtle aspects. So far the prosomeric model has been applied only to neural structures, but we attempt here a prosomeric analysis of the hypothesis that major vessels invade the brain wall in patterns that are congruent with its intrinsic natural developmental units, as postulated in the prosomeric model. Anatomic and embryologic studies of brain blood vessels have classically recorded a conserved pattern of branches (thus the conventional terminology), and clinical experience has discovered a standard topography of many brain arterial terminal fields. Such results were described under assumptions of the columnar model of the forebrain, prevalent during the last century, but this is found insufficient in depth and explanatory power in the modern molecular scenario. We have thus explored the possibility that brain vascularization in rodents and humans may relate systematically to genoarchitectonic forebrain subdivisions contemplated in the prosomeric model. Specifically, we examined first whether early vascular invasion of some molecularly characterized prosomeric domains shows heterochrony. We indeed found a heterochronic pattern of vascular invasion that distinguishes between adjacent brain areas with differential molecular profiles. We next mapped topologically on the prosomeric model the major arterial branches serving the human brain. The results of this approach bear on the possibility of a developmentally-based modern arterial terminology.