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1.
Alzheimer's & Dementia ; 17(S5):e057841, 2021.
Article in English | Wiley | ID: covidwho-1589190

ABSTRACT

Background COVID-19 is a respiratory disease where neurological sequelae are frequently reported. Neurofilament light (NfL) in plasma is a validated biomarker for neuronal damage. We assessed the trajectory of NfL levels in intensive care unit (ICU) patients diagnosed with COVID-19, and studied its relationship to clinical outcomes and markers of hypothesized pathophysiological mechanisms. Method As part of the Art-Deco study and Amsterdam UMC COVID-biobank, longitudinal samples and clinical data were collected weekly from a cohort of 31 prospectively admitted ICU patients with a minimum of 7 days of ventilation. The mean±sd age was 63±11 years. Admission duration ranged from 14-35 days and 156 samples were collected. We evaluated the NfL trajectory over time, and whether this trajectory differed by 90-day mortality outcome. Due to the non-linear trajectory of NfL, we applied linear mixed models including cubic splines for the time variable. Secondly, we tested whether baseline or peak NfL levels predicted mortality (n=7/31), delirium incidence after detubation (n=18/22), and duration of delirium (6±6 days). Third, we assessed if disease severity (day 7 Sequential Organ Failure Assessment [SOFA] score) and baseline hypoxemia (pAO2 before intubation), inflammation (IL1-b, IL-6, IL-8, TNF-α), and coagulopathy (d-dimer, presence of pulmonary embolism) were predictive of the NfL trajectory. For the latter models, we included an interaction term for the pathophysiological markers in the linear mixed models. All models were adjusted for age. Result NfL increased during ICU admission (p<001), and persisted longer in the non-survivors (p<0.05;Figure 1). Baseline or maximum NfL was not predictive of mortality or delirium incidence. However, maximum NfL correlated to the duration of delirium (r=0.5;p=0.02). From the pathophysiological markers, SOFA scores (p<0.05) and baseline TNF-α (p<0.05) were related to a stronger increase of NfL over time. Conclusion NfL levels increased over time and plateaued after 2-3 weeks in most COVID-19 patients at the ICU. Peak levels of NfL were predictive of delirium persistence. Repeated NfL levels may provide a future method for monitoring neurological outcomes in sedated ICU patients. Disease severity and specific inflammatory components appear important predictors of the NfL trajectory reflecting axonal damage in severe COVID-19 patients.

2.
Biomark Med ; 15(12): 987-997, 2021 08.
Article in English | MEDLINE | ID: covidwho-1320567

ABSTRACT

Aim: We investigated the effect of pre-analytical sample handling variations on coronavirus disease 2019-relevant circulating cytokine levels IFN-γ, IL-10, IL-12p70, IL-17A, IL-6 and TNF-α. Materials & methods: We collected blood in different collection tubes (ethylenediaminetetraacetic acid, sodium citrate, lithium heparin, serum), and subjected ethylenediaminetetraacetic acid plasma to among others increasing delays in centrifugation or -80°C storage. Six subjects were included in each experimental condition. Cytokine levels were measured in these samples using the Simoa Cytokine 6-plex kit. Results: Different tube types resulted in different blood cytokine levels. IL-17A and IL-6 levels declined with 3 h centrifugation delay. IFN-γ levels declined with 24 h postcentrifugation storage delay. IL-17A levels declined with 2-week storage delay. Conclusion: It is recommended to centrifuge tubes quickly following collection, for accurate cytokine measurement.


Subject(s)
Biological Specimen Banks/standards , COVID-19/blood , Cytokines/blood , Quality Control , SARS-CoV-2/metabolism , Specimen Handling/standards , Adult , Female , Humans , Male , Middle Aged
3.
Mult Scler ; : 13524585211028833, 2021 Jul 09.
Article in English | MEDLINE | ID: covidwho-1304376

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.

4.
EBioMedicine ; 67: 103378, 2021 May.
Article in English | MEDLINE | ID: covidwho-1230442

ABSTRACT

BACKGROUND: Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies. METHODS: We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality. FINDINGS: A total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest-specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids. INTERPRETATION: Clinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19. FUNDING: Amsterdam UMC, Amsterdam UMC Corona Fund, and Dr. C.J. Vaillant Fonds.


Subject(s)
Biomarkers/blood , COVID-19/mortality , Patient Admission/statistics & numerical data , Aged , COVID-19/blood , Chemotaxis , Female , Humans , Intensive Care Units , Interleukins/blood , Male , Middle Aged , Prognosis , Prospective Studies
5.
J Clin Virol ; 139: 104821, 2021 06.
Article in English | MEDLINE | ID: covidwho-1188731

ABSTRACT

BACKGROUND: Detecting SARS-CoV-2 antibodies may help to diagnose COVID-19. Head-to-head validation of different types of immunoassays in well-characterized cohorts of hospitalized patients remains needed. METHODS: We validated three chemiluminescence immunoassays (CLIAs) (Liaison, Elecsys, and Abbott) and one single molecule array assay (SIMOA) (Quanterix) for automated analyzers, one rapid immunoassay RIA (AllTest), and one ELISA (Wantai) in parallel in first samples from 126 PCR confirmed COVID-19 hospitalized patients and 158 pre-COVID-19 patients. Specificity of the AllTest was also tested in 106 patients with confirmed parasitic and dengue virus infections. Specificity of the Wantai assay was not tested due to limitations in sample volumes. RESULTS: Overall sensitivity in first samples was 70.6 % for the Liaison, 71.4 % for the Elecsys, 75.4 % for the Abbott, 70.6 % for the Quanterix, 77.8 % for the AllTest, and 88.9 % for the Wantai assay, respectively. Sensitivity was between 77.4 % (Liaison) and 94.0 % (Wantai) after 10 dpso. No false positive results were observed for the Elecsys and Abbott assays. Specificity was 91.1 % for the Quanterix, 96.2 % for the Liaison, and 98.1 % for the AllTest assay, respectively. CONCLUSION: We conclude that low sensitivity of all immunoassays limits their use early after onset of illness in diagnosing COVID-19 in hospitalized patients. After 10 dpso, the Wantai ELISA has a relatively high sensitivity, followed by the point-of-care AllTest RIA that compares favorably with automated analyzer immunoassays.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Immunoassay/methods , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19 Serological Testing , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Sensitivity and Specificity
6.
J Alzheimers Dis ; 76(1): 27-31, 2020.
Article in English | MEDLINE | ID: covidwho-637281

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic led to an abrupt halt of many Alzheimer's disease (AD) research studies at sites spanning the world. This is especially true for studies requiring in-person contact, such as studies collecting biofluids. Since COVID-19 is likely to remain a threat for an extended period, the resumption of fluid biomarker studies requires the development and implementation of procedures that minimize the risk of in-person visits to participants, staff, and individuals handling the biofluid samples. Some issues to consider include structuring the visit workflow to minimize contacts and promote social distancing; screening and/or testing participants and staff for COVID-19; wearing masks and performing hand hygiene; and precautions for handling, storing, and analyzing biofluids. AD fluid biomarker research remains a vitally important public health priority and resuming studies requires appropriate safety procedures to protect research participants and staff.


Subject(s)
Alzheimer Disease/metabolism , Betacoronavirus , Coronavirus Infections/metabolism , Health Personnel/trends , Patient Safety , Personal Protective Equipment , Pneumonia, Viral/metabolism , Alzheimer Disease/diagnosis , Biomarkers/metabolism , Body Fluids/metabolism , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Humans , Pandemics , Personal Protective Equipment/trends , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , SARS-CoV-2
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