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1.
Ther Adv Neurol Disord ; 15: 17562864221099472, 2022.
Article in English | MEDLINE | ID: covidwho-1868990

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation dose in COVID-19. Objective: We aim to systematically assess the currently available data regarding the effects of different dosing regimens of low molecular weight heparin and/or fondaparinux (LMWH/F) on mortality risk as well as the risk of arterial/venous thrombotic events and hemorrhagic complications in confirmed COVID-19 cases. Design: We conducted a living systematic review and meta-analysis on the effects of different LMWH/F doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients. Data Sources and Methods: MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database, and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH/F among confirmed COVID-19 cases. Results: Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between LMWH/F and mortality during the following comparisons: (1) no LMWH/F versus any LMWH/F; (2) prophylactic versus higher than prophylactic LMWH/F; (3) prophylactic versus therapeutic LMWH/F; (4) intermediate versus therapeutic LMWH/F; and (5) lower than therapeutic versus therapeutic LMWH/F. Mortality was higher in patients receiving prophylactic versus intermediate LMWH/F (OR = 2.01; 95% CI: 1.19-3.39). However, this effect was mostly driven by observational data. No associations were detected between the intensity of LMWH/F and the risk of thrombotic and hemorrhagic events, except the lower risk for hemorrhage in patients on prophylactic compared to higher LMWH/F doses. Conclusion: The risk for all-cause mortality was higher in patients receiving prophylactic LMWH/F compared to those on an intermediate dose of LMWH/F, based on observational data. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies. Registration: The study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (Registration number: CRD42021229771).

3.
J Neurol ; 269(7): 3413-3419, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1782801

ABSTRACT

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis (CVST) has been reported as a rare adverse event in association with thrombosis-thrombocytopenia syndrome (TTS) following COVID-19 vaccination. METHODS:  We performed a systematic review and meta-analysis of investigator-initiated registries including confirmed CVST cases, with the aim to calculate (1) the odds ratio of TTS-CVST versus non-TTS-CVST after vector-based vaccines and (2) after non-vector-based vaccines, (3) the in-hospital mortality ratio of TTS-CVST compared to non-TTS-CVST; and (4) the dependency or death at discharge among TTS-CVST compared to non-TTS-CVST cases. RESULTS: Two eligible studies were included in the meta-analysis, comprising a total of 211 patients with CVST associated with COVID-19 vaccination. Vector-based COVID-19 vaccination was associated with a higher likelihood of TTS-associated CVST than with non-TTS-CVST (OR: 52.34, 95% CI 9.58-285.98). TTS-CVST was also associated with higher likelihood of in-hospital mortality (OR: 13.29; 95% CI 3.96-44.60) and death or dependency at discharge compared to non-TTS-CVST (OR: 6.70; 95% CI 3.15-14.26). TTS-CVST was recorded with a shorter interval between vaccination and symptom onset [Mean Difference (MD):-6.54 days; 95% CI - 12.64 to - 0.45], affecting younger patients (MD:-9.00 years; 95% CI - 14.02 to - 3.99) without risk factors for thromboses (OR:2.34; 95% CI 1.26-4.33), and was complicated more frequently with intracerebral hemorrhage (OR:3.60; 95% CI 1.31-9.87) and concomitant thromboses in other sites (OR:11.85; 95% CI 3.51-39.98) compared to non-TTS-CVST cases. CONCLUSIONS: TTS-CVST following COVID-19 vaccination has distinct risk factor profile, clinical phenotype and prognosis compared to non-TTS-CVST. Further epidemiological data are required to evaluate the impact of different treatment strategies on outcome of TTS-CVST cases following COVID-19 vaccination.


Subject(s)
COVID-19 , Sinus Thrombosis, Intracranial , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Risk Factors , Sinus Thrombosis, Intracranial/diagnosis , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/etiology , Vaccination/adverse effects
4.
Ther Adv Chronic Dis ; 13: 20406223221076890, 2022.
Article in English | MEDLINE | ID: covidwho-1779561

ABSTRACT

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for 'long-COVID' diagnosis. Nevertheless, 'long-COVID' is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of 'long-COVID' encompass fatigue; 'brain fog'; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of 'long-COVID', neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological 'long-COVID' sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological 'long-COVID' sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for 'long-COVID' are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological 'long-COVID' symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological 'long-COVID' sequelae.

5.
Neurology ; 97(21): e2136-e2147, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1596718

ABSTRACT

BACKGROUND AND OBJECTIVES: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; I 2 = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; I 2 = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors. DISCUSSION: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION INFORMATION: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Sinus Thrombosis, Intracranial , Thrombocytopenia , Thrombosis , COVID-19/epidemiology , Female , Humans , Middle Aged , SARS-CoV-2 , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/etiology
6.
Neurology ; 97(21): e2136-e2147, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1456030

ABSTRACT

BACKGROUND AND OBJECTIVES: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; I 2 = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; I 2 = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors. DISCUSSION: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION INFORMATION: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Sinus Thrombosis, Intracranial , Thrombocytopenia , Thrombosis , COVID-19/epidemiology , Female , Humans , Middle Aged , SARS-CoV-2 , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/etiology
8.
Ther Adv Neurol Disord ; 14: 17562864211029540, 2021.
Article in English | MEDLINE | ID: covidwho-1311238

ABSTRACT

BACKGROUND: An alarming cerebro/cardiovascular collateral damage, reflected by a decline in admissions for acute stroke (AS) and acute coronary syndrome (ACS), was observed during the initial phase of the COVID-19 pandemic, thereby leading to a re-design of public campaigns. However, there are limited data regarding the AS and ACS hospitalization rates during the second wave of the pandemic, which was followed by re-imposition of lockdowns. METHODS: We calculated the rate of AS and ACS hospitalizations from three representative tertiary care hospitals in Greece during a 2-month period (November-December 2020) of the second wave of the COVID-19 pandemic compared with the corresponding control period in 2019 from three representative tertiary care hospitals in Greece. This was a follow-up study with identical design to our previous report evaluating AS and ACS hospitalizations during the first wave of the pandemic (March-April 2020). RESULTS: Compared with 2019, there was a 34% relative reduction of AS hospitalizations [incidence rate ratio (IRR): 0.66, 95% confidence interval (CI): 0.48-0.92, p = 0.013] and 33% relative reduction of ACS hospitalizations (IRR: 0.67, 95% CI: 0.54-0.83, p < 0.001) during the second wave of the COVID-19 pandemic. The relative reduction was smaller and did not reach the level of statistical significance for the respective syndromes (haemorrhagic stroke: IRR 0.87, 95% CI: 0.41-1.82, p = 0.71; ST-elevation myocardial infarction: IRR 0.81, 95% CI: 0.57-1.14, p = 0.22). CONCLUSION: AS and ACS hospitalizations were persistently reduced during the second wave of the COVID-19 pandemic compared with 2019 in Greece. This decline was similar to the observations during the first wave despite the large differences in the epidemiological COVID-19 burden. Lockdowns, a common characteristic in both waves, appear to have a detrimental indirect impact on cerebro/cardiovascular diseases in the general population.

10.
Eur J Neurol ; 28(10): 3517-3529, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1177407

ABSTRACT

BACKGROUND AND PURPOSE: Mounting evidence supports an association between Guillain-Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, GBSs in the setting of coronavirus disease 2019 (COVID-19) remains poorly characterized, whilst GBSs prevalence amongst COVID-19 patients has not been previously systematically evaluated using a meta-analytical approach. METHODS: A systematic review and meta-analysis of observational cohort and case series studies reporting on the occurrence, clinical characteristics and outcomes of patients with COVID-19-associated GBSs was performed. A random-effects model was used to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), compared to non-COVID-19, contemporary or historical GBSs patients. RESULTS: Eighteen eligible studies (11 cohorts, seven case series) were identified including a total of 136,746 COVID-19 patients. Amongst COVID-19 patients, including hospitalized and non-hospitalized cases, the pooled GBSs prevalence was 0.15‰ (95% CI 0%-0.49‰; I2  = 96%). Compared with non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds for demyelinating GBSs subtypes (OR 3.27, 95% CI 1.32%-8.09%; I2  = 0%). In SARS-CoV-2-infected patients, olfactory or concomitant cranial nerve involvement was noted in 41.4% (95% CI 3.5%-60.4%; I2  = 46%) and 42.8% (95% CI 32.8%-53%; I2  = 0%) of the patients, respectively. Clinical outcomes including in-hospital mortality were comparable between COVID-19 GBSs patients and non-infected contemporary or historical GBSs controls. CONCLUSION: GBSs prevalence was estimated at 15 cases per 100,000 SARS-CoV-2 infections. COVID-19 appears to be associated with an increased likelihood of GBSs and with demyelinating GBSs variants in particular.


Subject(s)
COVID-19 , Guillain-Barre Syndrome , Guillain-Barre Syndrome/epidemiology , Hospital Mortality , Humans , Prevalence , SARS-CoV-2
11.
Ther Adv Neurol Disord ; 13: 1756286420978004, 2020.
Article in English | MEDLINE | ID: covidwho-972457

ABSTRACT

Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as 'red flags' to alarm clinicians in recognizing COVID-19-related stroke.

12.
Ann Neurol ; 89(2): 380-388, 2021 02.
Article in English | MEDLINE | ID: covidwho-938391

ABSTRACT

OBJECTIVE: Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and highlight the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations. METHODS: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: We identified 18 cohort studies including 67,845 patients. Among patients with SARS-CoV-2, 1.3% (95% CI = 0.9-1.6%, I2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I2 = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43-8.92, I2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I2 = 0%). Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I2 = 0%). SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65-3.10, I2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I2 = 0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Odds of in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I2 = 45%). INTERPRETATION: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380-388.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Hospital Mortality , SARS-CoV-2 , Stroke/epidemiology , Case-Control Studies , Comorbidity , Humans , Thrombectomy/statistics & numerical data , Thrombolytic Therapy/statistics & numerical data
13.
Ther Adv Neurol Disord ; 13: 1756286420932036, 2020.
Article in English | MEDLINE | ID: covidwho-610846

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide, with a vast majority of confirmed cases presenting with respiratory symptoms. Potential neurological manifestations and their pathophysiological mechanisms have not been thoroughly established. In this narrative review, we sought to present the neurological manifestations associated with coronavirus disease 2019 (COVID-19). Case reports, case series, editorials, reviews, case-control and cohort studies were evaluated, and relevant information was abstracted. Various reports of neurological manifestations of previous coronavirus epidemics provide a roadmap regarding potential neurological complications of COVID-19, due to many shared characteristics between these viruses and SARS-CoV-2. Studies from the current pandemic are accumulating and report COVID-19 patients presenting with dizziness, headache, myalgias, hypogeusia and hyposmia, but also with more serious manifestations including polyneuropathy, myositis, cerebrovascular diseases, encephalitis and encephalopathy. However, discrimination between causal relationship and incidental comorbidity is often difficult. Severe COVID-19 shares common risk factors with cerebrovascular diseases, and it is currently unclear whether the infection per se represents an independent stroke risk factor. Regardless of any direct or indirect neurological manifestations, the COVID-19 pandemic has a huge impact on the management of neurological patients, whether infected or not. In particular, the majority of stroke services worldwide have been negatively influenced in terms of care delivery and fear to access healthcare services. The effect on healthcare quality in the field of other neurological diseases is additionally evaluated.

14.
Am J Physiol Endocrinol Metab ; 319(1): E105-E109, 2020 07 01.
Article in English | MEDLINE | ID: covidwho-382078

ABSTRACT

Recent reports have shown a strong association between obesity and the severity of COVID-19 infection, even in the absence of other comorbidities. After infecting the host cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a hyperinflammatory reaction through the excessive release of cytokines, a condition known as "cytokine storm," while inducing lymphopenia and a disrupted immune response. Obesity is associated with chronic low-grade inflammation and immune dysregulation, but the exact mechanisms through which it exacerbates COVID-19 infection are not fully clarified. The production of increased amounts of cytokines such as TNFα, IL-1, IL-6, and monocyte chemoattractant protein (MCP-1) lead to oxidative stress and defective function of innate and adaptive immunity, whereas the activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome seems to play a crucial role in the pathogenesis of the infection. Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients. The successful use of anti-inflammatory agents such as IL-1 and IL-6 blockers in similar hyperinflammatory settings, like that of rheumatoid arthritis, has triggered the discussion of whether such agents could be administrated in selected patients with COVID-19 disease.


Subject(s)
Coronavirus Infections/physiopathology , Obesity/virology , Pneumonia, Viral/physiopathology , Adaptive Immunity , Betacoronavirus , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Cytokine Release Syndrome/virology , Endothelium/physiopathology , Heart/physiopathology , Heart/virology , Humans , Immunity, Innate , Inflammation , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Oxidative Stress , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , Risk Factors , SARS-CoV-2 , Thrombosis/physiopathology , Vascular Stiffness
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