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1.
Eur J Neurol ; 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1932457

ABSTRACT

BACKGROUND AND PURPOSE: Many single cases and small series of Guillain-Barré syndrome (GBS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported during the coronavirus disease 19 (COVID-19) outbreak worldwide. However, the debate regarding the possible role of infection in causing GBS is still ongoing. This multicenter study aimed to evaluate epidemiological and clinical findings of GBS diagnosed during the COVID-19 pandemic in northeastern Italy in order to further investigate the possible association between GBS and COVID-19. METHODS: Guillain-Barré syndrome cases diagnosed in 14 referral hospitals from northern Italy between March 2020 and March 2021 were collected and divided into COVID-19-positive and COVID-19-negative. As a control population, GBS patients diagnosed in the same hospitals from January 2019 to February 2020 were considered. RESULTS: The estimated incidence of GBS in 2020 was 1.41 cases per 100,000 persons/year (95% confidence interval 1.18-1.68) versus 0.89 cases per 100,000 persons/year (95% confidence interval 0.71-1.11) in 2019. The cumulative incidence of GBS increased by 59% in the period March 2020-March 2021 and, most importantly, COVID-19-positive GBS patients represented about 50% of the total GBS cases with most of them occurring during the two first pandemic waves in spring and autumn 2020. COVID-19-negative GBS cases from March 2020 to March 2021 declined by 22% compared to February 2019-February 2020. CONCLUSIONS: Other than showing an increase of GBS in northern Italy in the "COVID-19 era" compared to the previous year, this study emphasizes how GBS cases related to COVID-19 represent a significant part of the total, thus suggesting a relation between COVID-19 and GBS.

3.
Commun Med (Lond) ; 1: 38, 2021.
Article in English | MEDLINE | ID: covidwho-1860417

ABSTRACT

Background: The antibody response to SARS-CoV-2 mRNA vaccines in individuals with waning immunity generated by a previous SARS-CoV-2 infection, as well as the patterns of IgA and IgM responses in previously infected and in naïve individuals are still poorly understood. Methods: We performed a serology study in a cohort of BTN162b2 mRNA vaccine recipients who were immunologically naïve (N, n = 50) or had been previously infected with SARS-CoV-2 (P.I., n = 51) during the first (n = 25) or second (n = 26) pandemic waves in Italy, respectively. We measured IgG, IgM and IgA antibodies against the SARS-CoV-2 Spike (S) and IgG against the nucleocapsid (N) proteins, as well as the neutralizing activity of sera collected before vaccination, after the first and second dose of vaccine. Results: Most P.I. individuals from the first pandemic wave who showed declining antibody titres responded to the first vaccine dose with IgG-S and pseudovirus neutralization titres that were significantly higher than those observed in N individuals after the second vaccine dose. In all recipients, a single dose of vaccine was sufficient to induce a potent IgA response that was not associated with serum neutralization titres. We observed an unconventional pattern of IgM responses that were elicited in only half of immunologically naïve subjects even after the second vaccine dose. Conclusions: The response to a single dose of vaccine in P.I. individuals is more potent than that observed in N individuals after two doses. Vaccine-induced IgA are not associated with serum neutralization.

4.
Eur J Neurol ; 29(6): 1855-1858, 2022 06.
Article in English | MEDLINE | ID: covidwho-1832044

ABSTRACT

BACKGROUND AND PURPOSE: Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) distinguish a group of inflammatory disorders which can be preceded by specific or non-specific infections. A few single cases have been reported in association with SARS-CoV-2 infection, but a specific study on the correlation between COVID-19 and myelin oligodendrocyte glycoprotein (MOG)-associated disorder (MOGAD) has not yet been performed. The aim of this study was to determine the impact of the pandemic on this condition. METHODS: We analysed SARS-CoV-2 serology in patients newly diagnosed with MOGAD (1 August 2020 to 31 May 2021). MOG-Ab-seronegative age- and time-matched subjects were used as controls. SARS-CoV-2 immunoglobulin G (IgG) levels were analysed using an anti-SARS-CoV-2 US Food and Drug Administration-approved ELISA assay and confirmed with a trimeric anti-SARS-CoV-2 S1/S2 IgG immunochemiluminescent test, concomitantly assaying the anti-receptor binding domain (RBD) of spike protein IgG and anti-RBD total Ig. We actually compared the number of cases referred in each of the last 3 years. RESULTS: Presence of SARS-CoV-2 IgG antibodies was more common (12/30, 40%) in MOGAD patients than in controls (6/30, 20%), although the difference was not significant (p = 0.16; odds ratio 2.67, 95% confidence interval 0.85-9.17). The most common clinical presentations of MOGAD SARS-CoV-2-seropositive patients included optic neuritis (n = 6) and myelitis (n = 3). The number of diagnosed cases increased over the last 3 years, in particular, when including cases referred to us before the COVID-19 pandemic, in the initial phase of the first wave and in the late phase of the second wave (n = 9, rate 10.6% in 2019; n = 13, rate 12.3% in 2020; n = 15, rate 14.7% in 2021). CONCLUSION: Our findings provide preliminary data on SARS-CoV-2 as a potential trigger of MOGAD.


Subject(s)
COVID-19 , Autoantibodies , Humans , Immunoglobulin G , Myelin-Oligodendrocyte Glycoprotein , Pandemics , SARS-CoV-2
5.
Mult Scler Relat Disord ; 63: 103827, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1804910

ABSTRACT

OBJECTIVES: In this retrospective multicenter study, we evaluated the safety of SARS-CoV-2 vaccination in patients harboring autoantibodies targeting neuronal surface and/or synaptic antigens. METHODS: From eight Italian Neurology Units, we included patients with: a) serum and/or CSF positivity for specific neuronal autoantibodies; b) a compatible neurological syndrome; and c) available follow-up ≥6 weeks after vaccination with any of the approved SARS-CoV-2 vaccines. Demographics, clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. Disease relapses were considered "post-infectious" or "post-vaccination" when occurring within 6 weeks from infection/vaccination. RESULTS: We included 66 patients; 7/66 (11%) had a previous history of SARS-CoV-2 infection and 1/7 (14%) had post-infection relapses. BNT162b2-Pfizer-BioNTec was administered in 55 cases (83.3%) and mRNA-1273-Moderna in 11 (16.7%). The median number of doses administered per patient was 2 (1-3) and >50% of patients did not experience side effects. Five patients (8%) had post-vaccination relapses (seizure 3/5); 4/5 improved after immunotherapy, while one did not receive immunotherapy and worsened. Patients with post-vaccination relapses had higher disability scores at vaccination (p = 0.025), a trend favoring Leucine-rich glioma-inactivated protein 1 LGI1 glutamic acid decarboxylase 65 (GAD65) antibodies (p =  0.054) and shorter time from last relapse (p = 0.057). DISCUSSION: Our data support the safety of SARS-CoV-2 vaccines in patients with neurological disorders associated with antibodies to neuronal and synaptic antigens.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , Autoantibodies , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Neoplasm Recurrence, Local , SARS-CoV-2 , Vaccination
6.
PLoS One ; 17(4): e0266740, 2022.
Article in English | MEDLINE | ID: covidwho-1785203

ABSTRACT

The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Biopsy , COVID-19/diagnosis , Humans , Olfactory Mucosa/pathology
7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325484

ABSTRACT

We profiled antibody responses in a cohort of recipients of the BTN162b2 mRNA vaccine who were either immunologically naïve (n=50) or had been previously infected with SARS-CoV-2 (n=51). Of the previously infected, 25 and 26 were infected during the first and second pandemic waves in Italy, respectively;the majority of those from the first wave had corresponding waning immunity with low to undetectable levels of anti-S antibodies and low anti-N antibodies. We observed in recipients who had been previously infected that spike-specific IgG and pseudovirus neutralization titers were rapidly recalled by a single vaccine dose to higher levels than those in naïve recipients after the second vaccine dose, irrespective of waning immunity. In all recipients, a single vaccine dose was sufficient to induce a potent IgA response that was not associated with serum neutralization titers.

8.
Mult Scler Relat Disord ; 58: 103424, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1525909

ABSTRACT

Post-vaccination disease relapses have been reported in patients with MOGAD and AQP4-IgG+NMOSD. In this retrospective multicenter Italian study we assessed the frequency of relapses after SARS-CoV-2 vaccination. We included 56 cases: MOGAD, 30; AQP4-IgG+NMOSD, 26. Vaccines received were BNT162b2-Pfizer-BioNTech in 42 patients and mRNA-1273-Moderna in 14 patients. Six patients had a history of SARS-CoV-2 infection; two of them experienced a post-infection disease relapse (MOGAD). The frequency of relapses within one month of SARS-CoV-2 vaccination was 4% (1/26) in the AQP4-IgG+NMOSD group and 0% in the MOGAD group. In these patients the potential benefits of vaccination overcome the risk of relapses.


Subject(s)
COVID-19 , Neuromyelitis Optica , Aquaporin 4 , Autoantibodies , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , Myelin-Oligodendrocyte Glycoprotein , Recurrence , Retrospective Studies , SARS-CoV-2 , Vaccination
9.
Clin Infect Dis ; 73(9): e3019-e3026, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501050

ABSTRACT

BACKGROUND: Recent findings indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the cerebrospinal fluid (CSF) correlates of SARS-CoV-2 encephalitis. METHODS: Patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC), and healthy controls (HC) underwent an extended panel of CSF neuronal (neurofilament light chain [NfL], T-tau), glial (glial fibrillary acidic protein [GFAP], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], chitinase-3-like protein 1 [YKL-40]) and inflammatory biomarkers (interleukin [IL]-1ß, IL-6, Il-8, tumor necrosis factor [TNF] α, CXCL-13, and ß2-microglobulin). RESULTS: Thirteen COV-Enc, 21 ENC, and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and ß2-microglobulin and glial markers (GFAP, sTREM2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-tau were abnormal only in severe cases. CONCLUSIONS: SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2-related encephalitis.


Subject(s)
COVID-19 , Encephalitis , Cytokine Release Syndrome , Glial Fibrillary Acidic Protein , Humans , SARS-CoV-2
10.
Immunol Res ; 69(6): 553-557, 2021 12.
Article in English | MEDLINE | ID: covidwho-1345196

ABSTRACT

The persistence of neurological symptoms after SARS-CoV-2 infection, as well as the presence of late axonal damage, is still unknown. We performed extensive systemic and neurological follow-up evaluations in 107 out of 193 consecutive patients admitted to the COVID-19 medical unit, University Hospital of Verona, Italy between March and June 2020. We analysed serum neurofilament light chain (NfL) levels in all cases including a subgroup (n = 29) of patients with available onset samples. Comparisons between clinical and biomarker data were then performed. Neurological symptoms were still present in a significant number (n = 49) of patients over the follow-up. The most common reported symptoms were hyposmia (n = 11), fatigue (n = 28), myalgia (n = 14), and impaired memory (n = 11) and were more common in cases with severe acute COVID-19. Follow-up serum NfL values (15.2 pg/mL, range 2.4-62.4) were within normal range in all except 5 patients and did not differentiate patients with vs without persistent neurological symptoms. In patients with available onset and follow-up samples, a significant (p < 0.001) decrease of NfL levels was observed and was more evident in patients with a severe acute disease. Despite the common persistence of neurological symptoms, COVID-19 survivors do not show active axonal damage, which seems a peculiar feature of acute SARS-CoV-2 infection.


Subject(s)
Axons/pathology , COVID-19/pathology , Nervous System Diseases/pathology , Adult , Aged , Aged, 80 and over , Ageusia/pathology , Ageusia/virology , Anosmia/pathology , Anosmia/virology , Axons/virology , Disease Progression , Fatigue/pathology , Fatigue/virology , Female , Humans , Italy , Male , Memory Disorders/pathology , Memory Disorders/virology , Middle Aged , Myalgia/pathology , Myalgia/virology , Nervous System Diseases/virology , Neurofilament Proteins/blood , SARS-CoV-2
11.
J Neurovirol ; 27(4): 631-637, 2021 08.
Article in English | MEDLINE | ID: covidwho-1338291

ABSTRACT

SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We explored (a) ME/CFS-like symptom prevalence and (b) whether axonal, inflammatory, and/or lung changes may contribute to ME/CFS-like symptoms in SARS-CoV-2 survivors through clinical, neuropsychiatric, neuropsychological, lung function assessment, and serum neurofilament light chain, an axonal damage biomarker. ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints, Borg baseline dyspnea of the 6-min walking test vs. those without ME/CFS-like symptoms. These preliminary findings raise concern on a possible future ME/CFS-like pandemic in SARS-CoV-2 survivors.


Subject(s)
COVID-19/complications , Fatigue Syndrome, Chronic/epidemiology , Fatigue Syndrome, Chronic/virology , Adult , Aged , Female , Humans , Male , Middle Aged , Prevalence , SARS-CoV-2
12.
J Neurol Neurosurg Psychiatry ; 92(7): 751-756, 2021 07.
Article in English | MEDLINE | ID: covidwho-1269801

ABSTRACT

OBJECTIVE: Single cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19. METHODS: GBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered. RESULTS: Incidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002). CONCLUSIONS: This study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/epidemiology , Adult , Aged , COVID-19/diagnosis , COVID-19/therapy , Female , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/therapy , Hospitalization , Humans , Incidence , Italy , Male , Middle Aged , Referral and Consultation , Retrospective Studies
13.
J Infect Dis ; 223(7): 1304-1305, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1244882
14.
J Infect Dis ; 223(1): 28-37, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1066338

ABSTRACT

BACKGROUND: Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of encephalitis in coronavirus disease 2019 (COVID-19) disease, but very few data have focused on clinical presentations, clinical course, response to treatment, and outcomes. METHODS: The SARS-CoV-2 related encephalopaties (ENCOVID) multicenter study included patients with encephalitis with full infectious screening, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) data and confirmed SARS-CoV-2 infection recruited from 13 centers in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment, and outcomes were recorded. RESULTS: Twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction resulted negative. Based on MRI, cases were classified as acute demyelinating encephalomyelitis (ADEM; n = 3), limbic encephalitis (LE; n = 2), encephalitis with normal imaging (n = 13), and encephalitis with MRI alterations (n = 7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (P = .001) and were associated with previous, more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to those with other encephalitis. CONCLUSIONS: SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes.


Subject(s)
COVID-19/complications , Encephalitis/diagnosis , Aged , Aged, 80 and over , COVID-19/therapy , Electroencephalography , Encephalitis/classification , Encephalitis/virology , Female , Humans , Italy , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged
15.
J Neurol Neurosurg Psychiatry ; 92(2): 218-220, 2021 02.
Article in English | MEDLINE | ID: covidwho-873577
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