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1.
Zh Nevrol Psikhiatr Im S S Korsakova ; 121(11): 81-87, 2021.
Article in Russian | MEDLINE | ID: covidwho-1599964

ABSTRACT

Present two clinical cases of cerebral circulation disorders in COVID-19. Cerebrovascular disorders in patients have been associated with COVID-19. Despite the similarity of symptoms, the pathogenesis of neurological damage in these patients was different due to damage to the arterial system in the first case and the venous system in the second case. It is concluded that during the COVID-19 pandemic, doctors need to be alert to all patients with new-onset neurological symptoms.


Subject(s)
COVID-19 , Cerebrovascular Disorders , Nervous System Diseases , Cerebrovascular Circulation , Cerebrovascular Disorders/epidemiology , Humans , Nervous System Diseases/epidemiology , Pandemics , SARS-CoV-2
2.
Biol Res ; 54(1): 39, 2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1577124

ABSTRACT

BACKGROUND: The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO2), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO2 from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m2, age 30.8 ± 13.4 years). RESULTS: We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema. CONCLUSIONS: Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO2 and SAS width monitoring might be beneficial for patients with acute lung disease.


Subject(s)
Cerebrovascular Circulation , Lung Diseases , Adolescent , Adult , Female , Hemoglobins , Humans , Hypoxia , Male , Prefrontal Cortex , Spectroscopy, Near-Infrared , Young Adult
3.
J Stroke Cerebrovasc Dis ; 30(12): 106118, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1415616

ABSTRACT

BACKGROUND AND OBJECTIVES: RCVS (Reversible Cerebral Vasoconstrictive Syndrome) is a condition associated with vasoactive agents that alter endothelial function. There is growing evidence that endothelial inflammation contributes to cerebrovascular disease in patients with coronavirus disease 2019 (COVID-19). In our study, we describe the clinical features, risk factors, and outcomes of RCVS in a multicenter case series of patients with COVID-19. MATERIALS AND METHODS: Multicenter retrospective case series. We collected clinical characteristics, imaging, and outcomes of patients with RCVS and COVID-19 identified at each participating site. RESULTS: Ten patients were identified, 7 women, ages 21 - 62 years. Risk factors included use of vasoconstrictive agents in 7 and history of migraine in 2. Presenting symptoms included thunderclap headache in 5 patients with recurrent headaches in 4. Eight were hypertensive on arrival to the hospital. Symptoms of COVID-19 included fever in 2, respiratory symptoms in 8, and gastrointestinal symptoms in 1. One patient did not have systemic COVID-19 symptoms. MRI showed subarachnoid hemorrhage in 3 cases, intraparenchymal hemorrhage in 2, acute ischemic stroke in 4, FLAIR hyperintensities in 2, and no abnormalities in 1 case. Neurovascular imaging showed focal segment irregularity and narrowing concerning for vasospasm of the left MCA in 4 cases and diffuse, multifocal narrowing of the intracranial vasculature in 6 cases. Outcomes varied, with 2 deaths, 2 remaining in the ICU, and 6 surviving to discharge with modified Rankin scale (mRS) scores of 0 (n=3), 2 (n=2), and 3 (n=1). CONCLUSIONS: Our series suggests that patients with COVID-19 may be at risk for RCVS, particularly in the setting of additional risk factors such as exposure to vasoactive agents. There was variability in the symptoms and severity of COVID-19, clinical characteristics, abnormalities on imaging, and mRS scores. However, a larger study is needed to validate a causal relationship between RCVS and COVID-19.


Subject(s)
COVID-19/complications , Cerebral Arteries/physiopathology , Cerebrovascular Circulation , Vasoconstriction , Vasospasm, Intracranial/etiology , Adult , COVID-19/diagnosis , COVID-19/therapy , Cerebral Arteries/diagnostic imaging , Female , Humans , Male , Middle Aged , Neuroimaging , Retrospective Studies , Risk Factors , Severity of Illness Index , Syndrome , Time Factors , Treatment Outcome , United States , Vasospasm, Intracranial/diagnostic imaging , Vasospasm, Intracranial/physiopathology , Vasospasm, Intracranial/therapy , Young Adult
5.
Am J Physiol Heart Circ Physiol ; 321(3): H479-H484, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1322856

ABSTRACT

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, to our knowledge, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral [brachial artery flow-mediated dilation (FMD) and reactive hyperemia] and cerebral vasodilator function (cerebral vasomotor reactivity to hypercapnia; CVMR) and increased central arterial stiffness. Sixteen young adults who were at least 4 wk past a COVID-19 diagnosis and 12 controls who never had COVID-19 were studied. Eight subjects with COVID-19 were symptomatic (SYM) and eight were asymptomatic (ASYM) at the time of testing. FMD and reactive hyperemia were not different between COVID and control groups. However, FMD was lower in SYM (3.8 ± 0.6%) compared with ASYM (6.8 ± 0.9%; P = 0.007) and control (6.8 ± 0.6%; P = 0.003) with no difference between ASYM and control. Similarly, peak blood velocity following cuff release was lower in SYM (47 ± 8 cm/s) compared with ASYM (64 ± 19 cm/s; P = 0.025) and control (61 ± 14 cm/s; P = 0.036). CVMR and arterial stiffness were not different between any groups. In summary, peripheral macrovascular and microvascular function, but not cerebral vascular function or central arterial stiffness were blunted in young adults symptomatic beyond the acute phase of COVID-19. In contrast, those who were asymptomatic had similar vascular function compared with controls who never had COVID-19.NEW & NOTEWORTHY This study was the first to investigate the persistent effects of COVID-19 on vascular function in otherwise healthy young adults. We demonstrated that peripheral macrovascular and microvascular vasodilation was significantly blunted in young adults still symptomatic from COVID-19 beyond the acute phase (>4 wk from diagnosis), whereas those who become asymptomatic have similar vascular function compared with controls who never had COVID-19. In contrast, cerebral vascular function and central arterial stiffness were unaffected irrespective of COVID-19 symptomology.


Subject(s)
COVID-19/complications , Cerebrovascular Circulation , Regional Blood Flow , Vasodilation , Adult , Blood Flow Velocity , COVID-19/diagnosis , COVID-19/physiopathology , Female , Humans , Male , Vascular Stiffness
6.
J Clin Invest ; 131(8)2021 04 15.
Article in English | MEDLINE | ID: covidwho-1291498

ABSTRACT

BACKGROUNDThe coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although some patients totally recover from COVID-19 pneumonia, the disease's long-term effects on the brain still need to be explored.METHODSWe recruited 51 patients with 2 subtypes of COVID-19 (19 mild and 32 severe) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI 3 months after discharge. Changes in gray matter morphometry, cerebral blood flow (CBF), and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers was further analyzed.RESULTSCompared with healthy controls, the decrease in cortical thickness/CBF and the changes in WM microstructure were more severe in patients with severe disease than in those with mild disease, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF, and tract parameters were significantly correlated (P < 0.05) with the inflammatory markers C-reactive protein, procalcitonin, and interleukin 6.CONCLUSIONIndirect injury related to inflammatory storm may damage the brain, altering cerebral volume, CBF, and WM tracts. COVID-19-related hypoxemia and dysfunction of vascular endothelium may also contribute to neurological changes. The abnormalities in these brain areas need to be monitored during recovery, which could help clinicians understand the potential neurological sequelae of COVID-19.FUNDINGNatural Science Foundation of China.


Subject(s)
COVID-19/diagnostic imaging , Cerebrovascular Circulation/physiology , SARS-CoV-2 , Aged , Brain/blood supply , Brain/diagnostic imaging , Brain/pathology , C-Reactive Protein/metabolism , COVID-19/epidemiology , COVID-19/physiopathology , Case-Control Studies , China/epidemiology , Diffusion Tensor Imaging , Echo-Planar Imaging , Female , Follow-Up Studies , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Imaging, Three-Dimensional , Inflammation Mediators/blood , Interleukin-6/blood , Male , Middle Aged , Neuroimaging , Pandemics , Procalcitonin/blood , Severity of Illness Index , Time Factors , White Matter/diagnostic imaging , White Matter/pathology
7.
Stroke ; 52(7): 2422-2426, 2021 07.
Article in English | MEDLINE | ID: covidwho-1195875

ABSTRACT

BACKGROUND AND PURPOSE: Stroke may complicate coronavirus disease 2019 (COVID-19) infection based on clinical hypercoagulability. We investigated whether transcranial Doppler ultrasound has utility for identifying microemboli and clinically relevant cerebral blood flow velocities (CBFVs) in COVID-19. METHODS: We performed transcranial Doppler for a consecutive series of patients with confirmed or suspected COVID-19 infection admitted to 2 intensive care units at a large academic center including evaluation for microembolic signals. Variables specific to hypercoagulability and blood flow including transthoracic echocardiography were analyzed as a part of routine care. RESULTS: Twenty-six patients were included in this analysis, 16 with confirmed COVID-19 infection. Of those, 2 had acute ischemic stroke secondary to large vessel occlusion. Ten non-COVID stroke patients were included for comparison. Two COVID-negative patients had severe acute respiratory distress syndrome and stroke due to large vessel occlusion. In patients with COVID-19, relatively low CBFVs were observed diffusely at median hospital day 4 (interquartile range, 3-9) despite low hematocrit (29.5% [25.7%-31.6%]); CBFVs in comparable COVID-negative stroke patients were significantly higher compared with COVID-positive stroke patients. Microembolic signals were not detected in any patient. Median left ventricular ejection fraction was 60% (interquartile range, 60%-65%). CBFVs were correlated with arterial oxygen content, and C-reactive protein (Spearman ρ=0.28 [P=0.04]; 0.58 [P<0.001], respectively) but not with left ventricular ejection fraction (ρ=-0.18; P=0.42). CONCLUSIONS: In this cohort of critically ill patients with COVID-19 infection, we observed lower than expected CBFVs in setting of low arterial oxygen content and low hematocrit but not associated with suppression of cardiac output.


Subject(s)
Blood Flow Velocity , Brain/diagnostic imaging , COVID-19/diagnostic imaging , Cerebrovascular Circulation , Ischemic Stroke/diagnostic imaging , Adult , Aged , Blood Gas Analysis , Brain/blood supply , C-Reactive Protein/metabolism , COVID-19/physiopathology , Case-Control Studies , Critical Illness , Female , Humans , Ischemic Stroke/physiopathology , Male , Middle Aged , Oxygen/blood , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/physiopathology , SARS-CoV-2 , Stroke Volume/physiology , Ultrasonography, Doppler, Transcranial
8.
Auton Neurosci ; 233: 102810, 2021 07.
Article in English | MEDLINE | ID: covidwho-1188308

ABSTRACT

We have considered some of the available evidence to account for the impact of SARS-CoV on the regulatory control of the autonomic nervous and respiratory systems. Apart from stimulating general interest in the subject, our hope was to provide putative explanations for some of the patients' symptoms based on described physiological and pathophysiological mechanisms seen in other diseases. Herein, we have focused on the carotid bodies. In this hypothetical viewpoint, we have discussed the plasticity of the carotid body chemoreflex and made a comparison between acute and chronic exposures to high altitude with COVID-19. From these discussions, we have postulated that the sensitivity of the hypoxic ventilatory response may well determine the outcome of disease severity and those that live at high altitude may be more resistant. We have provided insight into silent hypoxia and attempted to explain an absence of ventilatory drive and anxiety yet maintenance of consciousness. In an attempt to discover more about the mysteries of COVID-19, we conclude with questions and some hypothetical studies that may answer them.


Subject(s)
Autonomic Nervous System/physiopathology , COVID-19/physiopathology , Carotid Body/physiopathology , Altitude , Carbon Dioxide/metabolism , Cerebrovascular Circulation , Humans , Hypoxia/physiopathology
9.
J Clin Invest ; 131(8)2021 04 15.
Article in English | MEDLINE | ID: covidwho-1186425

ABSTRACT

Several coronavirus disease 2019 (COVID-19) studies have focused on neuropathology. In this issue of the JCI, Qin, Wu, and Chen et al. focused specifically on people whose acute infection lacked obvious neurological involvement. Severely infected patients showed abnormal gray matter volumes, white matter diffusion, and cerebral blood flow compared with healthy controls and those with mild infection. The data remain associative rather than mechanistic, but correlations with systemic immune markers suggest effects of inflammation, hypercoagulation, or other aspects of disease severity. Mechanistic research is warranted. Given the lack of obvious neurological symptoms, neurocognitive assessments were not performed, but the findings suggest that such assessments may be warranted in severely affected patients, even without obvious symptoms. Further, studying CNS involvement of other disorders with overlapping pathophysiologies such as inflammation, coagulation, hypoxia, or direct viral infection may reveal the causes for COVID-19-related neuropathology.


Subject(s)
COVID-19 , Nervous System Diseases , Brain/diagnostic imaging , Cerebrovascular Circulation , Humans , SARS-CoV-2
10.
J Clin Invest ; 131(8)2021 04 15.
Article in English | MEDLINE | ID: covidwho-1186424

ABSTRACT

BACKGROUNDThe coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although some patients totally recover from COVID-19 pneumonia, the disease's long-term effects on the brain still need to be explored.METHODSWe recruited 51 patients with 2 subtypes of COVID-19 (19 mild and 32 severe) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI 3 months after discharge. Changes in gray matter morphometry, cerebral blood flow (CBF), and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers was further analyzed.RESULTSCompared with healthy controls, the decrease in cortical thickness/CBF and the changes in WM microstructure were more severe in patients with severe disease than in those with mild disease, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF, and tract parameters were significantly correlated (P < 0.05) with the inflammatory markers C-reactive protein, procalcitonin, and interleukin 6.CONCLUSIONIndirect injury related to inflammatory storm may damage the brain, altering cerebral volume, CBF, and WM tracts. COVID-19-related hypoxemia and dysfunction of vascular endothelium may also contribute to neurological changes. The abnormalities in these brain areas need to be monitored during recovery, which could help clinicians understand the potential neurological sequelae of COVID-19.FUNDINGNatural Science Foundation of China.


Subject(s)
COVID-19/diagnostic imaging , Cerebrovascular Circulation/physiology , SARS-CoV-2 , Aged , Brain/blood supply , Brain/diagnostic imaging , Brain/pathology , C-Reactive Protein/metabolism , COVID-19/epidemiology , COVID-19/physiopathology , Case-Control Studies , China/epidemiology , Diffusion Tensor Imaging , Echo-Planar Imaging , Female , Follow-Up Studies , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Imaging, Three-Dimensional , Inflammation Mediators/blood , Interleukin-6/blood , Male , Middle Aged , Neuroimaging , Pandemics , Procalcitonin/blood , Severity of Illness Index , Time Factors , White Matter/diagnostic imaging , White Matter/pathology
11.
Crit Care ; 25(1): 111, 2021 03 19.
Article in English | MEDLINE | ID: covidwho-1143245

ABSTRACT

BACKGROUND: In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics. METHODS: This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO2) removal (ECCO2R). Arterial blood gas values (oxygen saturation [SpO2], partial pressure of oxygen [PaO2] and of carbon dioxide [PaCO2]) and cerebral oxygenation (rSO2) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients. RESULTS: Forty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57-69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO2 and PaCO2 values, but cerebral oxygenation decreased significantly (52 [51-54]% vs. 49 [47-50]%, p < 0.001). After PP, a significant increase was observed in PaO2 (from 62 [56-71] to 82 [76-87] mmHg, p = 0.005) and rSO2 (from 53 [52-54]% to 60 [59-64]%, p = 0.005). The use of iNO increased PaO2 (from 65 [67-73] to 72 [67-73] mmHg, p = 0.015) and rSO2 (from 53 [51-56]% to 57 [55-59]%, p = 0.007). The use of ECCO2R decreased PaO2 (from 75 [75-79] to 64 [60-70] mmHg, p = 0.009), with reduction of rSO2 values (59 [56-65]% vs. 56 [53-62]%, p = 0.002). In the whole population, a significant relationship was found between SpO2 and rSO2 (R = 0.62, p < 0.001) and between PaO2 and rSO2 (R0 0.54, p < 0.001). CONCLUSIONS: Rescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs. Registration The study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).


Subject(s)
COVID-19/therapy , Cerebrovascular Circulation , Oxygen/blood , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Aged , COVID-19/complications , Female , Humans , Italy , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/virology , Treatment Outcome
13.
Curr Pain Headache Rep ; 25(3): 19, 2021 Feb 25.
Article in English | MEDLINE | ID: covidwho-1100995

ABSTRACT

PURPOSE OF REVIEW: This review provides an updated discussion on the clinical presentation, diagnosis and radiographic features, mechanisms, associations and epidemiology, treatment, and prognosis of posterior reversible encephalopathy syndrome (PRES). Headache is common in PRES, though headache associated with PRES was not identified as a separate entity in the 2018 International Classification of Headache Disorders. Here, we review the relevant literature and suggest criteria for consideration of its inclusion. RECENT FINDINGS: COVID-19 has been identified as a potential risk factor for PRES, with a prevalence of 1-4% in patients with SARS-CoV-2 infection undergoing neuroimaging, thus making a discussion of its identification and treatment particularly timely given the ongoing global pandemic at the time of this writing. PRES is a neuro-clinical syndrome with specific imaging findings. The clinical manifestations of PRES include headache, seizures, encephalopathy, visual disturbances, and focal neurologic deficits. Associations with PRES include renal failure, preeclampsia and eclampsia, autoimmune conditions, and immunosuppression. PRES is theorized to be a syndrome of disordered autoregulation and endothelial dysfunction resulting in preferential hyperperfusion of the posterior circulation. Treatment typically focuses on treating the underlying cause and removal of the offending agents.


Subject(s)
Endothelium/physiopathology , Headache/physiopathology , Posterior Leukoencephalopathy Syndrome/physiopathology , Seizures/physiopathology , Vision Disorders/physiopathology , Acute Chest Syndrome/epidemiology , Aminolevulinic Acid/analogs & derivatives , Anemia, Sickle Cell/epidemiology , Autoimmune Diseases/epidemiology , Blood-Brain Barrier/metabolism , Brain Edema/diagnostic imaging , Brain Edema/physiopathology , COVID-19/epidemiology , Cerebrovascular Circulation/physiology , Cytokines/metabolism , Eclampsia/epidemiology , Female , Homeostasis/physiology , Humans , Hypertension/physiopathology , Magnetic Resonance Imaging , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , Posterior Leukoencephalopathy Syndrome/epidemiology , Posterior Leukoencephalopathy Syndrome/therapy , Pre-Eclampsia/epidemiology , Pregnancy , Prognosis , Renal Insufficiency/epidemiology , SARS-CoV-2 , Vasospasm, Intracranial/physiopathology
14.
J Stroke Cerebrovasc Dis ; 30(5): 105642, 2021 May.
Article in English | MEDLINE | ID: covidwho-1091714

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has resulted in unprecedented strain on the health care system. An adaptive strategy for the handling of thrombectomy for patients with large vessel occlusion has evolved at our center to optimize patient care while also minimizing risk of virus transmission. The purpose of this study was to evaluate the effects of the new thrombectomy protocol by comparing thrombectomy times and patient outcomes during the pandemic and pre pandemic period. METHODS: A retrospective cohort study was conducted on patients who underwent emergent thrombectomy from April 4th, 2020 to August 25th, 2020 (pandemic period) and between December 2nd, 2019 to April 3rd, 2020 (pre-pandemic period). The new protocol centered on a standardized approach to airway management in patients considered 'high-risk' for infection. An array of patient-specific factors and outcomes were compared between the two groups. RESULTS: A total of 126 patients were included in the study. There was no significant difference in door-to-recanalization or other time parameters between the two groups (138 minutes during the pandemic vs. 129 minutes pre-pandemic; p=0.37). However, outcomes measured as discharge modified Rankin Scale (mRS) were worse for patients during the pandemic (mRS ≤ 2, 10/58; 17.2% during pandemic vs. 24/68; 35.3% pre-pandemic, p = 0.02). No neurointerventional providers have been found to contract COVID-19. CONCLUSION: Our approach to mechanical thrombectomy during the COVID-19 era was associated with similar recanalization rates but worse clinical outcomes compared to pre pandemic period. Further studies are necessary to identify factors contributing to worse outcomes during this ongoing pandemic.


Subject(s)
Arterial Occlusive Diseases/surgery , COVID-19 , Cerebrovascular Disorders/surgery , Endovascular Procedures/methods , Pandemics , Stroke/surgery , Aged , Aged, 80 and over , Airway Management , Cerebrovascular Circulation , Clinical Protocols , Female , Humans , Male , Middle Aged , Retrospective Studies , Thrombectomy , Time-to-Treatment , Treatment Outcome
16.
Stroke ; 52(1): 260-270, 2021 01.
Article in English | MEDLINE | ID: covidwho-916325

ABSTRACT

BACKGROUND AND PURPOSE: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with an increased rate of cerebrovascular events including ischemic stroke and intracerebral hemorrhage. The mechanisms underlying cerebral endothelial susceptibility and response to SARS-CoV-2 are unknown yet critical to understanding the association of SARS-CoV-2 infection with cerebrovascular events. METHODS: Endothelial cells were isolated from human brain and analyzed by RNA sequencing. Human umbilical vein and human brain microvascular cells were used in both monolayer culture and endothelialized within a 3-dimensional printed vascular model of the middle cerebral artery. Gene expression levels were measured by quantitative polymerase chain reaction and direct RNA hybridization. Recombinant SARS-CoV-2 S protein and S protein-containing liposomes were used to measure endothelial binding by immunocytochemistry. RESULTS: ACE2 (angiotensin-converting enzyme-2) mRNA levels were low in human brain and monolayer endothelial cell culture. Within the 3-dimensional printed vascular model, ACE2 gene expression and protein levels were progressively increased by vessel size and flow rates. SARS-CoV-2 S protein-containing liposomes were detected in human umbilical vein endothelial cells and human brain microvascular endothelial cells in 3-dimensional middle cerebral artery models but not in monolayer culture consistent with flow dependency of ACE2 expression. Binding of SARS-CoV-2 S protein triggered 83 unique genes in human brain endothelial cells including upregulation of complement component C3. CONCLUSIONS: Brain endothelial cells are susceptible to direct SARS-CoV-2 infection through flow-dependent expression of ACE2. Viral S protein binding triggers a unique gene expression profile in brain endothelia that may explain the association of SARS-CoV-2 infection with cerebrovascular events.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Endothelial Cells/virology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Transcriptome , Brain/metabolism , Brain/virology , COVID-19/metabolism , Cells, Cultured , Cerebrovascular Circulation/physiology , Endothelial Cells/metabolism , Humans , Models, Anatomic , Stress, Mechanical
18.
Turk J Med Sci ; 51(2): 435-439, 2021 04 30.
Article in English | MEDLINE | ID: covidwho-836298

ABSTRACT

Background/aim: Coronavirus 2019 disease (Covid-19) was first seen in December 2019 and afterwards it became pandemic. Several systemic involvements have been reported in Covid-19 patients. In this study, it was aimed to investigate the cerebrovascular hemodynamics in patients with Covid-19. Materials and methods: The sample of this study included 20 patients hospitalized in our clinic diagnosed with Covid-19 via PCR modality and 20 healthy volunteers of similar age and sex. Bilateral middle cerebral arteries were investigated with transcranial Doppler ultrasonography. Basal cerebral blood flow velocities and vasomotor reactivity rates were determined and statistically compared. Results: When patient and control groups were compared, the mean blood flow velocity was found to be higher in Covid-19 patients than in the healthy volunteers and it was statistically significant (P = 0.00). The mean vasomotor reactivity rates values were found to be lower in the Covid-19 group than the healthy group and was also statistically significant (P = 0.00). Conclusion: An increase in basal cerebral blood velocity and a decrease in vasomotor reactivity rates in patients with Covid-19 can be considered as an indicator of dysfunction of cerebral hemodynamics in the central nervous system and this can be evaluated as a result of endothelial dysfunction.


Subject(s)
Blood Flow Velocity/physiology , COVID-19/physiopathology , Cerebrovascular Circulation/physiology , Hemodynamics/physiology , Middle Cerebral Artery/physiopathology , Vasomotor System/physiopathology , Adult , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , Case-Control Studies , Female , Humans , Male , Middle Aged , Middle Cerebral Artery/diagnostic imaging , SARS-CoV-2 , Ultrasonography, Doppler, Transcranial , Vasomotor System/diagnostic imaging , Young Adult
19.
Neuroepidemiology ; 54(5): 370-374, 2020.
Article in English | MEDLINE | ID: covidwho-713643

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) causes the coronavirus disease 2019 (COVID-19). It quickly became pandemic, and so did a new concern about COVID-19 infections increasing the risk for cerebrovascular diseases. There is an association between COVID-19 illness in people and acute stroke. Several chemical, mechanical, and/or inflammatory central nervous system pathologies are proposed to explain how this viral infection might induce acute cerebrovascular disease. Timely available evaluation and/or intervention is imperative for patients with concerns about acute cerebrovascular issues.


Subject(s)
Betacoronavirus , Brain/virology , Cerebrovascular Circulation/physiology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Stroke/etiology , Stroke/virology , Betacoronavirus/metabolism , Brain/metabolism , Brain Ischemia/etiology , Brain Ischemia/metabolism , Brain Ischemia/virology , COVID-19 , Coronavirus Infections/metabolism , Humans , Pandemics , Pneumonia, Viral/metabolism , SARS-CoV-2 , Stroke/metabolism
20.
J Neurol Sci ; 417: 117078, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-695321

ABSTRACT

BACKGROUND AND AIM: COVID-19 pandemic has resulted in an unprecedented increased usage of Personal protective equipment (PPE) by healthcare-workers. PPE usage causes headache in majority of users. We evaluated changes in cerebral hemodynamics among healthcare-workers using PPE. METHODS: Frontline healthcare-workers donning PPE at our tertiary center were included. Demographics, co-morbidities and blood-pressure were recorded. Transcranial Doppler (TCD) monitoring of middle cerebral artery was performed with 2-MHz probe. Mean flow velocity (MFV) and pulsatility index (PI) were recorded at baseline, after donning N95 respirator-mask, and after donning powered air-purifying respirator (PAPR), when indicated. End-tidal carbon-dioxide (ET-CO2) pressure was recorded for participants donning PAPR in addition to the N95 respirator-mask. RESULTS: A total of 154 healthcare-workers (mean age 29 ± 12 years, 67% women) were included. Migraine was the commonest co-morbidity in 38 (25%) individuals while 123 (80%) developed de-novo headache due to N95 mask. Donning of N95 respirator-mask resulted in significant increase in MFV (4.4 ± 10.4 cm/s, p < 0.001) and decrease in PI (0.13 ± 0.12; p < 0.001) while ET-CO2 increased by 3.1 ± 1.2 mmHg (p < 0.001). TCD monitoring in 24 (16%) participants donning PAPR and N95 respirator mask together showed normalization of PI, accompanied by normalization of ET-CO2 values within 5-min. Combined use of N95 respirator-mask and PAPR was more comfortable as compared to N95 respirator-mask alone. CONCLUSION: Use of N95 respirator-mask results in significant alterations in cerebral hemodynamics. However, these effects are mitigated by the use of additional PAPR. We recommend the use of PAPR together with the N95 mask for healthcare-workers doing longer duties in the hospital wards.


Subject(s)
Betacoronavirus , Health Personnel , Masks/adverse effects , Occupational Diseases/prevention & control , Pandemics , Respiratory Protective Devices , Adult , Blood Flow Velocity , COVID-19 , Carbon Dioxide/analysis , Cerebrovascular Circulation , Coronavirus Infections/prevention & control , Cross-Sectional Studies , Female , Headache/etiology , Hemodynamics , Humans , Male , Middle Cerebral Artery/diagnostic imaging , Middle Cerebral Artery/physiopathology , Occupational Diseases/etiology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pulsatile Flow , SARS-CoV-2 , Ultrasonography, Doppler, Transcranial , Young Adult
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