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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329893

ABSTRACT

Growing evidence suggests that coronavirus disease 2019 (COVID-19) is associated with acute and long-term neurological sequelae. However, the underlying pathophysiological mechanisms resulting in central nervous system (CNS) derogation remain unclear, posing both diagnostic and therapeutic challenges. Here, we performed a cross-sectional study (NCT04472013) and multidimensional characterization of cerebrospinal fluid (CSF) and plasma-targeted proteomics in different Neuro-COVID severity classes with corresponding clinical and imaging data. COVID-19 patients displayed a plasma cytokine storm but a non-inflammatory CSF profile. Severely affected patients displayed signs of blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self- and non-self antigens. Also, COVID-19 patients had decreased regional brain volumes associated with specific CSF and plasma parameters. We provide a multiparametric framework of Neuro-COVID severity classifiers. Collectively, this data identified several potentially actionable targets that may be addressed to prevent COVID-19-related neurological sequelae.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329760

ABSTRACT

Importance Growing evidence suggests that coronavirus disease 2019 (COVID-19) is associated with neurological sequelae. However, the underlying pathophysiological mechanisms resulting in central nervous system (CNS) derogation remain unclear. Objective To identify severity-dependent immune mechanisms in the cerebrospinal fluid (CSF) and plasma of COVID-19 patients and their association with brain imaging alterations. Design Prospective cross-sectional cohort study. Setting This study was performed from August 2020 to April 2021. Participants were enrolled in the outpatient clinics, hospital wards and intensive care units (ICU) of two clinical sites in Basel and Zurich, Switzerland. Participants Age >18 years and a positive SARS-CoV-2 test result were inclusion criteria. Potentially matching individuals were identified (n=310), of which 269 declined to participate and 1 did not match inclusion criteria. Paired CSF and plasma samples, as well as brain images, were acquired. The COVID-19 cohort (n=40;mean [SD] age, 54 [20] years;17 women (42%)) was prospectively assorted by neurological symptom severity (classes I, II and III). Age/sex-matched inflammatory (n=25) and healthy (n=25) CSF and plasma control samples were obtained. For volumetric brain analysis, a healthy age/sex-matched control cohort (n=36) was established. Exposures Lumbar puncture, blood sampling and cranial MRI and/or CT. Main outcomes and measures Proteomics, standard parameters and antibody profiling of paired CSF and plasma samples in COVID-19 patients and controls. Brain imaging and gray matter volumetric analysis in association with biomarker profiles. Follow-up after 10-months. Results COVID-19 patients displayed a plasma cytokine storm but a non-inflammatory CSF profile. Class III patients displayed signs of blood-brain barrier (BBB) impairment and a polyclonal B cell response targeting self- and non-self antigens. Decreased regional brain volumes were present in COVID-19 patients and associated with specific CSF and plasma parameters. Conclusion and relevance Neuro-COVID class III patients had a strong, peripheral immune response resulting in (1) BBB impairment (2) ingress of (auto-)antibodies, (3) microglia activation and neuronal damage signatures. Our data point towards several potentially actionable targets that may be addressed to prevent COVID-19-related neurological sequelae. Trial registration The trial ( NCT04472013 ) was registered on clinicaltrials.gov. Key points Question Does a severity-dependent pattern of immune mechanisms exist in the cerebrospinal fluid (CSF) and plasma of COVID-19 patients and are these associated with clinical and brain imaging findings? Findings Neuro-COVID patients display a robust class III-specific peripheral immune response resulting in (1) blood-brain barrier (BBB) impairment, (2) ingress of (auto-)antibodies, (3) microglia activation and neuronal damage signatures. Integration of MRIs, brain volumetry and proteomics identified biomarkers associated with regional brain volume loss in severe Neuro-COVID. Meaning We provide a multidimensional framework of mechanisms associated with severe Neuro-COVID and present possible targets to prevent COVID-19-related neurological sequelae.

3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327654

ABSTRACT

Increasing evidence shows that the brain is a target of SARS-CoV-2. However, the consequences of the virus on the cortical regions of hospitalized patients are currently unknown. The purpose of this study was to assess brain cortical gray matter volume (GMV), thickness (Th), and surface area (SA) characteristics in SARS-CoV-2 hospitalized patients with a wide range of neurological symptoms and their association with clinical indicators of inflammatory processes. A total of 33 patients were selected from a prospective, multicenter, cross-sectional study during the ongoing pandemic (August 2020-April 2021) at Basel University Hospital. Retrospectively biobank healthy controls with the same image protocol served as controls group. For each anatomical T1w MPRAGE image, the Th and GMV segmentation were performed with the FreeSurfer-5.0. Cortical measures were compared between groups using a linear regression model. The covariates were age, gender, age*gender, MRI magnetic field strength, and total intracranial volume/mean Th/Total SA. The association between cortical features and laboratory variables was assessed using partial correlation adjusting for the same covariates. P-values were adjusted using false discovery rate (FDR). Our findings revealed a lower cortical gray matter volume in orbitofrontal and cingulate regions in patients compared to controls. The orbitofrontal grey matter volume was negatively associated with protein levels, CSF-blood/albumin ratio and CSF EN-RAGE level. CSF EN-RAGE and CSF/Blood-albumin ratio, which are neuroinflammatory biomarkers, were associated with cortical alterations in gray matter volume and thickness in frontal, orbitofrontal, and temporal regions. Our data suggest that viral-triggered inflammation leads to increased neurotoxic damage in some cortical areas.

4.
Int J Stroke ; 16(5): 573-584, 2021 07.
Article in English | MEDLINE | ID: covidwho-1156042

ABSTRACT

BACKGROUND: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. AIMS: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). METHODS: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. RESULTS: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. CONCLUSION: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.


Subject(s)
COVID-19 , Global Health , Hospitalization/trends , Intracranial Hemorrhages/therapy , Stroke/therapy , Thrombectomy/trends , Cross-Sectional Studies , Hospitals, High-Volume/trends , Hospitals, Low-Volume/trends , Humans , Intracranial Hemorrhages/diagnosis , Intracranial Hemorrhages/epidemiology , Registries , Retrospective Studies , Stroke/diagnosis , Stroke/epidemiology , Time Factors
5.
J Neurointerv Surg ; 13(4): 304-307, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1013062

ABSTRACT

BACKGROUND: The coronavirus disease (COVID-19) pandemic has affected stroke care globally. In this study, we aim to evaluate the impact of the current pandemic on racial disparities among stroke patients receiving mechanical thrombectomy (MT). METHODS: We used the prospectively collected data in the Stroke Thrombectomy and Aneurysm Registry from 12 thrombectomy-capable stroke centers in the US and Europe. We included acute stroke patients who underwent MT between January 2017 and May 2020. We compared baseline features, vascular risk factors, location of occlusion, procedural metrics, complications, and discharge outcomes between patients presenting before (before February 2020) and those who presented during the pandemic (February to May 2020). RESULTS: We identified 2083 stroke patients: of those 235 (11.3%) underwent MT during the COVID-19 pandemic. Compared with pre-pandemic, stroke patients who received MT during the pandemic had longer procedure duration (44 vs 38 min, P=0.006), longer length of hospitalization (6 vs 4 days, P<0.001), and higher in-hospital mortality (18.7% vs 11%, P<0.001). Importantly, there was a lower number of African American patients undergoing MT during the COVID-19 pandemic (609 (32.9%) vs 56 (23.8%); P=0.004). CONCLUSION: The COVID-19 pandemic has affected the care process for stroke patients receiving MT globally. There is a significant decline in the number of African American patients receiving MT, which mandates further investigation.


Subject(s)
African Americans/ethnology , COVID-19/ethnology , Healthcare Disparities/trends , Pandemics , Stroke/ethnology , Thrombectomy/trends , Aged , Aged, 80 and over , COVID-19/therapy , Female , Hospital Mortality/trends , Hospitalization/trends , Humans , Internationality , Male , Middle Aged , Prospective Studies , Registries , Risk Factors , Stroke/therapy , Thrombectomy/methods , Treatment Outcome
7.
J Neurointerv Surg ; 12(11): 1039-1044, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-742246

ABSTRACT

BACKGROUND: In response to the COVID-19 pandemic, many centers altered stroke triage protocols for the protection of their providers. However, the effect of workflow changes on stroke patients receiving mechanical thrombectomy (MT) has not been systematically studied. METHODS: A prospective international study was launched at the initiation of the COVID-19 pandemic. All included centers participated in the Stroke Thrombectomy and Aneurysm Registry (STAR) and Endovascular Neurosurgery Research Group (ENRG). Data was collected during the peak months of the COVID-19 surge at each site. Collected data included patient and disease characteristics. A generalized linear model with logit link function was used to estimate the effect of general anesthesia (GA) on in-hospital mortality and discharge outcome controlling for confounders. RESULTS: 458 patients and 28 centers were included from North America, South America, and Europe. Five centers were in high-COVID burden counties (HCC) in which 9/104 (8.7%) of patients were positive for COVID-19 compared with 4/354 (1.1%) in low-COVID burden counties (LCC) (P<0.001). 241 patients underwent pre-procedure GA. Compared with patients treated awake, GA patients had longer door to reperfusion time (138 vs 100 min, P=<0.001). On multivariate analysis, GA was associated with higher probability of in-hospital mortality (RR 1.871, P=0.029) and lower probability of functional independence at discharge (RR 0.53, P=0.015). CONCLUSION: We observed a low rate of COVID-19 infection among stroke patients undergoing MT in LCC. Overall, more than half of the patients underwent intubation prior to MT, leading to prolonged door to reperfusion time, higher in-hospital mortality, and lower likelihood of functional independence at discharge.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , Stroke/therapy , Thrombectomy/statistics & numerical data , Aged , Aged, 80 and over , Anesthesia, General , COVID-19 , Endovascular Procedures , Female , Hospital Mortality , Humans , Independent Living , Linear Models , Male , Middle Aged , Prospective Studies , Reperfusion , Thrombectomy/methods , Treatment Outcome , Workflow
8.
J Clin Med ; 9(8)2020 Aug 06.
Article in English | MEDLINE | ID: covidwho-711365

ABSTRACT

BACKGROUND AND PURPOSE: Intracranial hemorrhage has been observed in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19), but the clinical, imaging, and pathophysiological features of intracranial bleeding during COVID-19 infection remain poorly characterized. This study describes clinical and imaging characteristics of patients with COVID-19 infection who presented with intracranial bleeding in a European multicenter cohort. METHODS: This is a multicenter retrospective, observational case series including 18 consecutive patients with COVID-19 infection and intracranial hemorrhage. Data were collected from February to May 2020 at five designated European special care centers for COVID-19. The diagnosis of COVID-19 was based on laboratory-confirmed diagnosis of SARS-CoV-2. Intracranial bleeding was diagnosed on computed tomography (CT) of the brain within one month of the date of COVID-19 diagnosis. The clinical, laboratory, radiologic, and pathologic findings, therapy and outcomes in COVID-19 patients presenting with intracranial bleeding were analyzed. RESULTS: Eighteen patients had evidence of acute intracranial bleeding within 11 days (IQR 9-29) of admission. Six patients had parenchymal hemorrhage (33.3%), 11 had subarachnoid hemorrhage (SAH) (61.1%), and one patient had subdural hemorrhage (5.6%). Three patients presented with intraventricular hemorrhage (IVH) (16.7%). CONCLUSION: This study represents the largest case series of patients with intracranial hemorrhage diagnosed with COVID-19 based on key European countries with geospatial hotspots of SARS-CoV-2. Isolated SAH along the convexity may be a predominant bleeding manifestation and may occur in a late temporal course of severe COVID-19.

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