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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318998

ABSTRACT

Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making –especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted –resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.

2.
Infect Dis Now ; 52(1): 23-30, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1661845

ABSTRACT

OBJECTIVES: Strasbourg University Hospital faced an important COVID-19 first wave from early March 2020. We performed a longitudinal prospective cohort study to describe clinical and virological data, exposure history to COVID-19, and adherence to strict hygiene standards during the first pandemic wave in 1497 workers undergoing a SARS-CoV-2 serological test at our hospital, with a follow up of serology result three months later. PATIENTS AND METHODS: A total of 1497 patients were enrolled from April 6 to May 7, 2020. Antibody response to SARS-CoV-2 was measured, and COVID-19 exposure routes were analyzed according to SARS-CoV-2 serological status. RESULTS: A total of 515 patients (34.4%) were seropositive, mainly medical students (13.2%) and assistant nurses (12.0%). A history of COVID-19 exposure in a professional and/or private setting was mentioned by 83.1% of seropositive subjects (P<0.05; odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.8-3.4). COVID-19 exposure factors associated with seropositive status were non-professional exposure (OR: 1.9, 95% CI: 1.3-2.7), especially outside the immediate family circle (OR: 2.2, 95% CI: 1.2-3.9) and contact with a COVID-19 patient (OR: 1.6; 95% CI: 1.1-2.2). Among professionally exposed workers, systematic adherence to strict hygiene standards was well observed, except for the use of a surgical mask (P<0.05, OR: 1.9, 95% CI: 1.3-2.8). Of those who reported occasionally or never wearing a surgical mask, nurses (25.7%), assistant nurses (16.2%), and medical students (11.7%) were predominant. CONCLUSION: Infection of staff members during the first pandemic wave in our hospital occurred after both professional and private COVID-19 exposure, underlining the importance of continuous training in strict hygiene standards.


Subject(s)
COVID-19 , SARS-CoV-2 , Hospitals, University , Humans , Pandemics , Personnel, Hospital , Prospective Studies
3.
Eur J Neurol ; 28(10): 3461-3466, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1606253

ABSTRACT

BACKGROUND: Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. METHODS: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). RESULTS: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]). CONCLUSIONS: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population.


Subject(s)
COVID-19 , Neuromyelitis Optica , Adult , Aquaporin 4 , Female , Humans , Neuromyelitis Optica/drug therapy , Neuromyelitis Optica/epidemiology , Retrospective Studies , Rituximab , SARS-CoV-2 , Young Adult
4.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294752

ABSTRACT

Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting protection against reinfection and durability of vaccine protection. Here, we longitudinally measured Spike (S) and Nucleocapsid (N)-specific antibodies in 1,309 healthcare workers (HCWs), including 916 COVID-19 negative HCWs and 393 convalescent COVID-19 for up to 422 days post-symptom. From month (M)1 to M7-9 post-infection, SARS-CoV-2 antibodies decreased moderately in convalescent HCWs in a biphasic model, with men showing a slower decay of anti-N (p=0.02), and a faster decay of anti-S (p=0.0008) than women. At M11-13, anti-N dramatically decreased (half-life: 283 days) while anti-S stabilized (half-life: 725 days) at a median of 2.39 log Arbitrary Units (AU)/mL (Interquartile Range (IQR): 2.10 -2.75). Overall, 69 SARS-CoV-2 infections developed in the COVID-19 negative group (incidence of 12.22 per 100 person-years) versus one in the COVID-19 positive group (incidence of 0.40 per 100 person-years), indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7% (p<0.0001). Correlation with live-virus neutralization assay revealed that variants D614G and B.1.1.7, but not B.1.351, were sensitive to anti-S antibodies at 2.3 log AU/mL, while IgG ≥ 3 log AU/mL neutralized all three variants. After SARS-CoV-2 vaccination, anti-S levels reached at least 3 logs regardless of pre-vaccination IgG levels, type of vaccine, and number of doses. Our study demonstrates a long-term persistence of anti-S IgG antibodies that may protect against reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against escape mutants.

5.
EBioMedicine ; 71: 103561, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1372964

ABSTRACT

BACKGROUND: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. METHODS: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. FINDINGS: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11-13 of 283 days (95% CI 231-349) for anti-N and 725 days (95% CI 623-921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42-1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. INTERPRETATION: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. FUN1DING: None.


Subject(s)
COVID-19/pathology , Immunity, Humoral , Reinfection/pathology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Kinetics , Longitudinal Studies , Male , Middle Aged , Phosphoproteins/immunology , Prospective Studies , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Time Factors
6.
Neurol Neuroimmunol Neuroinflamm ; 8(5)2021 09.
Article in English | MEDLINE | ID: covidwho-1331974

ABSTRACT

OBJECTIVE: To compare the humoral response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with multiple sclerosis (MS) receiving different disease-modifying treatments (DMTs). METHODS: Patients with MS with coronavirus disease 2019 (COVID-19) and available anti-SARS-CoV-2 serology were included. The primary endpoint was the anti-SARS-CoV-2 immunoglobulin G (IgG) index. The multivariate analysis was adjusted for COVID-19 severity, SARS-CoV-2 PCR result, and the time between COVID-19 onset and the serology. RESULTS: We included 61 patients with available IgG index. The IgG index was lower in patients with fingolimod or anti-CD20 monoclonal antibodies compared with patients without treatment (p < 0.01), patients with interferon ß-1a or glatiramer (p < 0.01), and patients with another DMT (p = 0.01). The IgG index was correlated with the time between COVID-19 onset and serology (r = -0.296 [-0.510; -0.0477], p = 0.02). CONCLUSIONS: Humoral response after COVID-19 was lower in patients with MS with fingolimod or anti-CD20 mAb. These patients could therefore be at risk of recurrent infection and could benefit from anti-SARS-CoV-2 vaccination. The humoral response after vaccination and the delay before vaccination need to be evaluated. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that patients treated with fingolimod or anti-CD20 monoclonal antibodies for MS have a lower humoral response after COVID-19 compared with patients without DMTs or with another DMTs.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Adult , Antibodies, Viral/drug effects , Female , Humans , Male , Middle Aged , SARS-CoV-2/immunology
7.
Eur J Neurol ; 28(10): 3461-3466, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-889737

ABSTRACT

BACKGROUND: Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. METHODS: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). RESULTS: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]). CONCLUSIONS: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population.


Subject(s)
COVID-19 , Neuromyelitis Optica , Adult , Aquaporin 4 , Female , Humans , Neuromyelitis Optica/drug therapy , Neuromyelitis Optica/epidemiology , Retrospective Studies , Rituximab , SARS-CoV-2 , Young Adult
8.
EBioMedicine ; 59: 102915, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-691414

ABSTRACT

BACKGROUND: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized. METHODS: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% specificity). The neutralizing activity of the sera was tested with a pseudovirus-based assay. FINDINGS: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV-2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P = 0.02). INTERPRETATION: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients. FUNDINGS: The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.


Subject(s)
Antibodies, Viral/blood , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Adult , Antibodies, Neutralizing/blood , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Female , France , Health Personnel , Hospitals , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Serologic Tests , Severity of Illness Index
9.
JAMA Neurol ; 77(9): 1079-1088, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-616243

ABSTRACT

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity. Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020. Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms. Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes. Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01). Conclusions and Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis/therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Adult , COVID-19 , Cohort Studies , Female , France/epidemiology , Humans , Male , Middle Aged , Pandemics , Registries , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
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