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1.
Neurological Sciences ; 43(Supplement 1):S332, 2022.
Article in English | EMBASE | ID: covidwho-2174357

ABSTRACT

Aims: Growing evidence indicates that neurological manifestations become evident and may persist over a long time in patients with COVID-19. A number of studies have provided a detailed characterization of the clinical neurological involvement occurring during SARS-Cov-2 infection. While this bulk of data are definitely in favour of a particular tropism of SARS-Cov-2 for the central and peripheral nervous system leading to overt clinical manifestations, it is interesting to know, however, whether the SARS-Cov 2 infection may damage the nervous system, specifically neurons and glia cells, even without signs of clear clinical involvement. Material(s) and Method(s): To provide consistent evidence whether SARS-Cov 2 infection can cause damage of nervous system even when signs of clear clinical involvement are absent, we studied the serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAp) in 149 hospitalized COVID-19 patients without clinical neurological manifestations and compared them to a group of 108 healthy controls (HCs) and to a group of 53 patients with interstitial lung diseases (ILD) different from COVID-19. Result(s): sNfL levels where higher in COVID-19 patients (median log10 sNfL 1,40;IQR 1,04-1,82) than ILDs (median log10 sNfL 1,18;IQR 0,98-1,38;p < .001) and HCs (median log10 sNfL 0,89;IQR 0,72- 1,14;p < .001) (Fig. 1A). sGFAP levels where higher in COVID-19 patients (median log10 sGFAP 2,25;IQR 2,02-2,52) in comparison to ILDs (median log10 sGFAP 2,15;IQR 1,94-2,30;p < .001) and HCs (median log10 sGFAP 1,87;IQR 0,64-2,09;p < .001) (Fig. 1B). No significant difference was found comparing HCs and ILD patients (p= .388 for sNfL and p= .251 for sGFAp). Interestingly, there was no significant difference in sNfL and sGFAP levels between COVID-19 patients when they were grouped accordingly with disease severity (median log10 sNfL 1,39;IQR 1,11-1,70 in moderate and median log10 sNfL 1,42;IQR 1,10-1,98 in severe COVID-19 patients;p = ,191). Discussion and conclusions: The results of our study suggest neuronal and glial degeneration occur in COVID-19 patients regardless of clinical neurologicalmanifestations. The long term consequences of the subclinical neuronal and glial damage revealed by the elevation of these biomarkers in COVID-19 patients is currently unknown and warrants further investigations.

2.
J Med Virol ; 2022 Oct 19.
Article in English | MEDLINE | ID: covidwho-2075084

ABSTRACT

A wide spectrum of neurological symptoms (NS) has been described in patients with COVID-19. We examined the plasma levels of neuron-specific enolase (NSE) and neurofilament light chain (NFL) together, as neuronal damage markers, and their relationships with clinical severity in patients with NS at acute COVID-19. A total of 20 healthy controls and 59 patients with confirmed COVID-19 were enrolled in this pilot prospective study. Serum NSE and NFL levels were measured by using the enzyme-linked immunoassay method from serum samples. Serum NSE levels were found to be significantly higher in the severe group than in the nonsevere group (p = 0.034). However, serum NFL levels were similar between the control and disease groups (p > 0.05). For the mild group, serum NFL levels were significantly higher in patients with the sampling time ≥5 days than in those with the sampling time <5 days (p = 0.019). However, no significant results for NSE and NFL were obtained in patients with either single or multiple NS across the groups (p > 0.05). Increased serum NSE levels were associated with disease severity regardless of accompanied NS in patients with acute COVID-19 infection. However, serum NFL levels may have a role at the subacute phase of COVID-19.

3.
Journal of Neuromuscular Diseases ; 9:S8-S9, 2022.
Article in English | EMBASE | ID: covidwho-2043385

ABSTRACT

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. This is the first systematic clinical guideline, developed by an international task force using formal GRADE methodology. The diagnostic criteria remain primarily clinical, based on history and examination findings of acute progressive limb weakness and areflexia. Variants of GBS may include motor GBS, Miller Fisher Syndrome, and regional variants with weakness predominantly in lower limbs, face, or pharynx/neck/ arms. The differential diagnosis is wide. When uncertain, diagnosis may be assisted by nerve conduction tests, raised cerebrospinal fluid protein, and less often by MRI spine with contrast, or serum antibodies to gangliosides (especially for variants) or nodalparanodal antibodies (especially if not improving). Axonal versus demyelinating subtyping does not affect clinical management. A history of recent gastrointestinal or respiratory infection or of surgery may support the diagnosis. The risk of GBS is only very slightly increased after Covid-19 infection and after the adenovirus-vector vaccines to SARS-CoV2 (AstraZeneca or Johnson & Johnson) but not mRNA vaccines. Immune treatment is recommended with intravenous immunoglobulin or plasma exchange, for most patients except those mildly affected or after four weeks from onset. A repeat course is reasonable after a treatment-related fluctuation. Corticosteroids are not recommended. There is no evidence of benefi t from any other disease-modifying treatment. Respiratory function should be monitored by forced vital capacity and single breath count to assess the risk of needing mechanical ventilation, guided by the mEGRIS scale. Pain is very common. It may be musculoskeletal or neuropathic, and treated with gabapentin, tricyclic antidepressants or carbamazepine. Patients who fail to improve should be reassessed for the correct diagnosis and for axonal degeneration. Around 5% of patients with GBS may later develop CIDP but no test can reliably indicate this within the first eight weeks. Nodal-paranodal antibodies should be tested if CIDP is suspected or if the patient is not recovering well. The long-term outcome is less good in patients of older age, with preceding diarrhoea, or more severe weakness, as quantified by the mEGOS scale, and also in patients with smaller motor potential amplitudes or raised serum neurofilament light chain level.

4.
Cells ; 11(16)2022 08 10.
Article in English | MEDLINE | ID: covidwho-2032864

ABSTRACT

Neurofilament light chain (NfL) is a specific biomarker of neuro-axonal damage. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in blood-brain barrier (BBB) integrity. We explored neuro-axonal damage, alteration of BBB integrity and SARS-CoV-2 RNA presence in COVID-19 patients with severe neurological symptoms (neuro-COVID) as well as neuro-axonal damage in COVID-19 patients without severe neurological symptoms according to disease severity and after recovery, comparing the obtained findings with healthy donors (HD). Overall, COVID-19 patients (n = 55) showed higher plasma NfL levels compared to HD (n = 31) (p < 0.0001), especially those who developed ARDS (n = 28) (p = 0.0005). After recovery, plasma NfL levels were still higher in ARDS patients compared to HD (p = 0.0037). In neuro-COVID patients (n = 12), higher CSF and plasma NfL, and CSF MMP-2 levels in ARDS than non-ARDS group were observed (p = 0.0357, p = 0.0346 and p = 0.0303, respectively). SARS-CoV-2 RNA was detected in four CSF and two plasma samples. SARS-CoV-2 RNA detection was not associated to increased CSF NfL and MMP levels. During COVID-19, ARDS could be associated to CNS damage and alteration of BBB integrity in the absence of SARS-CoV-2 RNA detection in CSF or blood. CNS damage was still detectable after discharge in blood of COVID-19 patients who developed ARDS during hospitalization.


Subject(s)
Blood-Brain Barrier , COVID-19 , Axons , Humans , RNA, Viral , SARS-CoV-2
5.
Brain ; 2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2017744

ABSTRACT

The advancing validation and exploitation of cerebrospinal fluid and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current diagnostic and prognostic approach to neurological diseases. Further, recent studies have provided evidence of potential new applications of this biomarker also in non-primary neurological diseases. In the present review we summarise the current evidence, future perspectives, but also limitations, of neurofilament light chain protein as a cerebrospinal fluid and blood biomarker in several medical fields, including intensive care, surgery, internal medicine and psychiatry. In particular, neurofilament light chain protein is associated with the degree of neurologic impairment and outcome in patients admitted to intensive care units or in the perioperative phase and it seems to be highly interconnected with cardiovascular risk factors. Beyond that, interesting diagnostic and prognostic insights have been provided by the investigation of neurofilament light chain protein in psychiatric disorders as well as in the current coronavirus disease 19 (COVID-19) pandemic and in normal aging. Altogether, current data outline a multifaceted applicability of cerebrospinal fluid and blood neurofilament light chain protein ranging from the critical clinical setting to the development of precision medicine models suggesting a strict interplay between the nervous system pathophysiology and the health-illness continuum.

6.
Brain Commun ; 4(4): fcac195, 2022.
Article in English | MEDLINE | ID: covidwho-1985044

ABSTRACT

Neurological monitoring in sedated Intensive Care Unit patients is constrained by the lack of reliable blood-based biomarkers. Neurofilament light is a cross-disease biomarker for neuronal damage with potential clinical applicability for monitoring Intensive Care Unit patients. We studied the trajectory of neurofilament light over a month in Intensive Care Unit patients diagnosed with severe COVID-19 and explored its relation to clinical outcomes and pathophysiological predictors. Data were collected over a month in 31 Intensive Care Unit patients (166 plasma samples) diagnosed with severe COVID-19 at Amsterdam University Medical Centre, and in the first week after emergency department admission in 297 patients with COVID-19 (635 plasma samples) admitted to Massachusetts General hospital. We observed that Neurofilament light increased in a non-linear fashion in the first month of Intensive Care Unit admission and increases faster in the first week of Intensive Care Unit admission when compared with mild-moderate COVID-19 cases. We observed that baseline Neurofilament light did not predict mortality when corrected for age and renal function. Peak neurofilament light levels were associated with a longer duration of delirium after extubation in Intensive Care Unit patients. Disease severity, as measured by the sequential organ failure score, was associated to higher neurofilament light values, and tumour necrosis factor alpha levels at baseline were associated with higher levels of neurofilament light at baseline and a faster increase during admission. These data illustrate the dynamics of Neurofilament light in a critical care setting and show associations to delirium, disease severity and markers for inflammation. Our study contributes to determine the clinical utility and interpretation of neurofilament light levels in Intensive Care Unit patients.

7.
J Neurol ; 269(11): 5691-5701, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1971703

ABSTRACT

BACKGROUND: Increased serum levels of neurofilament light chain (sNFL), a biomarker of neuroaxonal damage, have been reported in patients with Covid-19. We aimed at investigating whether sNFL is increased in Covid-19 patients without major neurological manifestations, is associated with disease severity, respiratory and routine blood parameters, and changes longitudinally in the short term. METHODS: sNFL levels were measured with single molecule array (Simoa) technology in 57 hospitalized Covid-19 patients without major neurological manifestations and in 30 neurologically healthy controls. Patients were evaluated for PaO2/FiO2 ratio on arterial blood gas, Brescia Respiratory Covid Severity Scale (BRCSS), white blood cell counts, serum C-reactive protein (CRP), plasma D-dimer, plasma fibrinogen, and serum creatinine at admission. In 20 patients, NFL was also measured on serum samples obtained at a later timepoint during the hospital stay. RESULTS: Covid-19 patients had higher baseline sNFL levels compared to controls, regardless of disease severity. Baseline sNFL correlated with serum CRP and plasma D-dimer in patients with mild disease, but was not associated with measures of respiratory impairment. Longitudinal sNFL levels tended to be higher than baseline ones, albeit not significantly, and correlated with serum CRP and plasma D-dimer. The PaO2/FiO2 ratio was not associated with longitudinal sNFL, whereas BRCSS only correlated with longitudinal sNFL variation. CONCLUSIONS: We provide neurochemical evidence of subclinical axonal damage in Covid-19 also in the absence of major neurological manifestations. This is apparently not fully explained by hypoxic injury; rather, systemic inflammation might promote this damage. However, a direct neurotoxic effect of SARS-CoV-2 cannot be excluded.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Biomarkers , C-Reactive Protein , COVID-19/complications , Creatinine , Fibrinogen , Humans , Intermediate Filaments , Neurofilament Proteins , SARS-CoV-2
8.
Front Neurol ; 13: 915712, 2022.
Article in English | MEDLINE | ID: covidwho-1933730

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) is prevalent among young people, and neurological involvement has been reported. We investigated neurological symptoms, cognitive test results, and biomarkers of brain injury, as well as associations between these variables in non-hospitalized adolescents and young adults with COVID-19. Methods: This study reports baseline findings from an ongoing observational cohort study of COVID-19 cases and non-COVID controls aged 12-25 years (Clinical Trials ID: NCT04686734). Symptoms were charted using a standardized questionnaire. Cognitive performance was evaluated by applying tests of working memory, verbal learning, delayed recall, and recognition. The brain injury biomarkers, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp), were assayed in serum samples using ultrasensitive immunoassays. Results: A total of 405 COVID-19 cases and 111 non-COVID cases were prospectively included. Serum Nfl and GFAp concentrations were significantly elevated in COVID-19 cases as compared with non-COVID controls (p = 0.050 and p = 0.014, respectively). The COVID-19 cases reported more fatigue (p < 0.001) and post-exertional malaise (PEM) (p = 0.001) compared to non-COVID-19 controls. Cognitive test performance and clinical neurological examination did not differ across the two groups. Within the COVID-19 group, there were no associations between symptoms, cognitive test results, and NfL or GFAp levels. However, fatigue and PEM were strongly associated with older age and female sex. Conclusions: Non-hospitalized adolescents and young adults with COVID-19 reported more fatigue and PEM and had slightly elevated levels of brain injury markers, but showed normal cognitive performance. No associations were found between symptoms, brain injury markers, and cognitive test results, but fatigue and PEM were strongly related to female sex and older age.

9.
Topics in Antiviral Medicine ; 30(1 SUPPL):49, 2022.
Article in English | EMBASE | ID: covidwho-1880191

ABSTRACT

Background: The underlying CNS pathogenesis in COVID-19 is not clear and viral RNA is rarely detected in cerebrospinal fluid (CSF). We measured viral antigen and biomarker profiles in CSF in relation to neurological symptoms and disease severity. Methods: We included 44 (32% female) hospitalized patients (26 moderate, 18 severe COVID-19) and 10 healthy controls (HC). 21 patients were neuroasymptomatic (NA), 23 neurosymptomatic (NS;encephalopathy=21, encephalitis=1, GBS=1). For antigen and cytokine analyses, a patient control (PC;n=41) group (COVID-negative with no sign of CNS infection in clinical CSF samples) was used. CSF nucleocapsid antigen (N-Ag) was analyzed using an ultrasensitive antigen capture immunoassay platform, S-PLEX direct detection assay, S-PLEX SARS-CoV-2 N Kit (MesoScale Diagnostics, LLC. Rockville, MD). Additional analyses included CSF neopterin, β2-microglobulin, cytokines and neurofilament light (NfL). Results: CSF N-Ag was detected in 31/35 patients (0/41 controls) while viral RNA was negative in all. CSF N-Ag was significantly correlated with CSF neopterin (r=0.38;p=0.03) and IFN-γ (r=0.42;p=0.01) adjusted for sampling day. No differences in CSF N-Ag concentrations were found between patient groups. All patient groups had markedly increased CSF neopterin, β2M, IL-6, IL-10 and TNF-α compared to controls, while IL-2, IL-1β and IFN-γ were significantly increased only in the NS group. CSF biomarkers were associated with time from symptom onset to CSF sampling. After adjusting for time of sampling, the NS group had significantly higher CSF IFN-γ (p=0.03), and showed a statistical trend towards significantly higher CSF neopterin, IL-6 and TNF-α (p=0.056-0.06) than the NA group. Additionally, age-adjusted CSF NfL was higher in the NS compared to the HC (p=0.01) group. No differences were seen in any CSF biomarkers in moderate compared to severe disease. Conclusion: Viral antigen is detectable in CSF in a majority of patients with COVID-19 despite the absence of detectable viral RNA, and is correlated to CNS immune activation markers. Patients with neurological symptoms had a more marked immune activation profile compared to NA patients, as well as signs of neuroaxonal injury compared to controls. These observations could not be attributed to a difference in COVID-19 severity. Our results highlight the importance of neurological symptoms and indicate that the CNS immune response and CNS pathogenesis can be initiated by viral components without direct viral invasion of the CNS.

10.
Mult Scler ; 28(7): 1121-1125, 2022 06.
Article in English | MEDLINE | ID: covidwho-1861984

ABSTRACT

In this observational study, 159 patients with multiple sclerosis received personalized dosing of ocrelizumab incentivized by the COVID-19 pandemic. Re-dosing was scheduled when CD19 B-cell count was ⩾10 cells/µL (starting 24 weeks after the previous dose, repeated 4-weekly). Median interval until re-dosing or last B-cell count was 34 [30-38] weeks. No clinical relapses were reported and a minority of patients showed Expanded Disability Status Scale (EDSS) progression. Monthly serum neurofilament light levels remained stable during extended intervals. Two (1.9%) of 107 patients with a follow-up magnetic resonance imaging (MRI) scan showed radiological disease activity. Personalized dosing of ocrelizumab could significantly extend intervals with low short-term disease activity incidence, encouraging future research on long-term safety and efficacy.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , Humans , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Pandemics
11.
Ther Adv Neurol Disord ; 15: 17562864221080528, 2022.
Article in English | MEDLINE | ID: covidwho-1799140

ABSTRACT

Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild-moderate (n = 39) and severe (n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild-moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild-moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.

12.
Infectious Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1699267

ABSTRACT

Background The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in late 2019. More recently, there have been sporadic case reports on development of Miller-Fisher Syndrome (MFS), a rare variant of Guillain-Barré Syndrome (GBS) in COVID-19 patients. Case report We reported herein the case of a French young women presenting with ophtalmoplegia, cerebellar ataxia and universal areflexia following a bariatric surgery (sleeve gastrectomy). A concomitant COVID-19 diagnosis was retained based on microbiological testing. The patient was successfully treated after high-dose intravenous thiamine, but areflexia persisted. Underlying COVID-19 related MFS was established on physical examination and confirmed by pathologic neurophysiological findings and elevated level of phosphorylated neurofilament heavy chain protein (pNfH) in cerebrospinal fluid analysis. Conclusion GBS and its variants after SARS-CoV-2 infection are extremely rare. The measurement of pNfH should be considered as an easy tool to detect an early affection of the peripheral nervous system.

13.
Alzheimers Dement (Amst) ; 13(1): e12145, 2021.
Article in English | MEDLINE | ID: covidwho-1680307

ABSTRACT

INTRODUCTION: This study investigated alternative pre-analytical handling of blood for neurofilament light (NfL) analysis where resources are limited. METHOD: Plasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48-hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n = 10) and a confirmatory cohort (n = 21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters. RESULTS: Delayed centrifugation (R2 = 0.991) and DPS (discovery cohort, R2 = 0.954; confirmatory cohort, DPS: R2 = 0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R2 = 0.995) and shaking (R2 = 0.975) did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS. DISCUSSION: DPS or delayed centrifugation are viable pre-analytical procedures for the accurate quantification of plasma NfL.

14.
Cell Rep Med ; 3(1): 100490, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1665525

ABSTRACT

Neurofilament light (NFL) is a promising circulating biomarker in preeclampsia and COVID-19, even without evident neurological complications. Several pathways might contribute to the elevated serum NFL levels seen in both pathologies. Future studies will determine whether NFL is a long COVID marker and delineate NFL's role in COVID-19-associated preeclampsia.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , Neurofilament Proteins/blood , Pre-Eclampsia/blood , Pre-Eclampsia/epidemiology , SARS-CoV-2 , Biomarkers/blood , COVID-19/virology , Comorbidity , Female , Humans , Incidence , Pregnancy
15.
Alzheimers Dement ; 18(5): 899-910, 2022 05.
Article in English | MEDLINE | ID: covidwho-1620097

ABSTRACT

INTRODUCTION: Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS: Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aß40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS: Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION: Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.


Subject(s)
Alzheimer Disease , COVID-19 , Cognitive Dysfunction , Amyloid beta-Peptides , Biomarkers , COVID-19/complications , Cognition , Hospital Mortality , Humans , tau Proteins
16.
Pain Med ; 23(4): 774-781, 2022 04 08.
Article in English | MEDLINE | ID: covidwho-1595614

ABSTRACT

OBJECTIVES: To assess risk factors for persistent neuropathic pain in subjects recovered from coronavirus disease 2019 (COVID-19) and to study the serum level of neurofilament light chain (NFL) in those patients. DESIGN: Case-control study. SETTING: Persistent post-COVID-19 pain. SUBJECTS: In total, 45 patients with post-COVID-19 pain and another 45 age and sex-matched healthcare workers who recovered from COVID-19 without pain. METHODS: The included participants were subjected to medical history taking, screening for depressive disorders, comprehensive neurological examination, and pain evaluation using the Douleur Neuropathique en 4 questions (DN4). All patients who had a score at least 4/10 on DN4 were included. The serum NFL level was measured for both groups at the time of patients' enrollment. RESULTS: The frequency of depression, moderate and severe COVID-19 cases, disease duration and serum ferritin were significantly higher in the cases with post-COVID-19 pain than controls. Binary logistic regression revealed that depression, azithromycin use, moderate and severe COVID-19 increased the odds of post-COVID-19 pain by 4.462, 5.444, 4.901, and 6.276 times, respectively. Cases with post-COVID-19 pain had significantly higher NFL (11.34 ± 9.7, 95% confidence interval [CI]: 8.42-14.25) than control group (7.64 ± 5.40, 95% CI: 6.02-9.27), (P value = .029). Patients with allodynia had significantly higher NFL (14.96 ± 12.41, 95% CI: 8.58-21.35) compared to those without (9.14 ± 6.99, 95% CI: 6.43-11.85) (P value = .05). DISCUSSION: Depression, azithromycin, and moderate and severe COVID-19 are independent predictors of persistent post-COVID-19 pain. Serum NFL may serve as a potential biomarker for persistent neuropathic pain after COVID-19.


Subject(s)
COVID-19 , Neuralgia , Azithromycin , COVID-19/complications , Case-Control Studies , Humans , Neuralgia/diagnosis , Neuralgia/epidemiology , Neuralgia/etiology , Risk Factors
17.
Cardiol Cardiovasc Med ; 5(5): 551-565, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1498306

ABSTRACT

In critically ill COVID-19 patients, the risk of long-term neurological consequences is just beginning to be appreciated. While recent studies have identified that there is an increase in structural injury to the nervous system in critically ill COVID-19 patients, there is little known about the relationship of COVID-19 neurological damage to the systemic inflammatory diseases also observed in COVID-19 patients. The purpose of this pilot observational study was to examine the relationships between serum neurofilament light protein (NfL, a measure of neuronal injury) and co-morbid cardiovascular disease (CVD) and neurological complications in COVID-19 positive patients admitted to the intensive care unit (ICU). In this observational study of one-hundred patients who were admitted to the ICU in Tucson, Arizona between April and August 2020, 89 were positive for COVID-19 (COVID-pos) and 11 was COVID-negative (COVID-neg). A healthy control group (n=8) was examined for comparison. The primary outcomes and measures were subject demographics, serum NfL, presence and extent of CVD, diabetes, sequential organ failure assessment score (SOFA), presence of neurological complications, and blood chemistry panel data. COVID-pos patients in the ICU had significantly higher mean levels of Nfl (229.6 ± 163 pg/ml) compared to COVID-neg ICU patients (19.3 ± 5.6 pg/ml), Welch's t-test, p =.01 and healthy controls (12.3 ± 3.1 pg/ml), Welch's t-test p =.005. Levels of Nfl in COVID-pos ICU patients were significantly higher in patients with concomitant CVD and diabetes (n=35, log Nfl 1.6±.09), and correlated with higher SOFA scores (r=.5, p =.001). These findings suggest that in severe COVID-19 disease, the central neuronal and axonal damage in these patients may be driven, in part, by the level of systemic cardiovascular disease and peripheral inflammation. Understanding the contributions of systemic inflammatory disease to central neurological degeneration in these COVID-19 survivors will be important to the design of interventional therapies to prevent long-term neurological and cognitive dysfunction.

18.
Mult Scler Relat Disord ; 57: 103364, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1487906

ABSTRACT

BACKGROUND: Patients with multiple sclerosis (MS) who are treated with monoclonal antibodies frequently report an increase of MS-related symptoms prior to the next dose known as the wearing-off phenomenon. The objective of this study was to assess the prevalence and predicting factors of the wearing-off phenomenon in patients with MS using ocrelizumab. METHODS: This was a prospective cohort study in patients with MS receiving ocrelizumab ≥1 year. Most participants received B-cell guided personalized extended interval dosing to limit ocrelizumab exposure and hospital visits during the COVID-19 pandemic (cut-off ≥ 10 cells/µL). Participants completed questionnaires during ocrelizumab infusion and 2 weeks thereafter. Demographics, clinical and radiological characteristics, CD19 B-cell counts, and serum neurofilament light (sNfL) levels were collected. Data were analyzed using logistic regression analyses. RESULTS: Seventy-one (61%) out of 117 participants reported the wearing-off phenomenon during ocrelizumab treatment. The most frequently reported symptoms were fatigue, cognitive disability and sensory symptoms. Wearing-off symptoms started < 1 week (11%), 1-4 weeks (49%) or more than 4 weeks (37%) before ocrelizumab infusion. Fifty participants (43%) reported a current wearing-off phenomenon at the first questionnaire. Higher body mass index (threshold BMI ≥ 25) increased the odds of reporting a current wearing-off phenomenon (OR 2.70, 95% CI 1.26 to 5.80, p = .011). Infusion interval, EDSS score, MRI disease activity, clinical relapses, CD19 B-cell counts, and sNfL levels were no predictors. Disappearance of the wearing-off phenomenon occurred in the first week after ocrelizumab infusion in most participants. Participants with a current wearing-off phenomenon significantly improved in self-reported physical and psychological functioning after ocrelizumab infusion. Reporting the wearing-off phenomenon did not influence treatment satisfaction. Forty of 109 participants (37%) reported post-infusion symptoms, such as fatigue, flu-like symptoms or walking difficulties. These post-infusion symptoms started directly or in the first week after ocrelizumab infusion and disappeared within 2 weeks. CONCLUSIONS: The wearing-off phenomenon is reported by more than half of patients with MS using ocrelizumab. Only BMI was identified as a predicting factor. The wearing-off phenomenon was not elicited by extending infusion intervals or higher B-cell counts. The wearing-off phenomenon of ocrelizumab therefore does not seem to reflect suboptimal control of MS disease activity.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , Humans , Immunologic Factors/adverse effects , Multiple Sclerosis/drug therapy , Pandemics , Prospective Studies , SARS-CoV-2
19.
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
20.
J Clin Med ; 10(9)2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1238901

ABSTRACT

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid ß peptides (Aß1-40, Aß1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

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