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1.
PLoS One ; 17(6): e0263595, 2022.
Article in English | MEDLINE | ID: covidwho-1875082

ABSTRACT

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.


Subject(s)
COVID-19 , Stroke , COVID-19/complications , COVID-19/therapy , Hospitalization , Humans , Prognosis , Risk Factors
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321631

ABSTRACT

Background: Neurological COVID-19 disease has been reported widely, but often without using standard case definitions or detailed diagnostic work up. Several meta-analyses, based on such reports, describe the neurological diagnoses but give little information on outcomes and risk factors.Methods: We conducted an individual patient data meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute, and extracted aggregate data from published reports. We analysed features associated with poor outcome (moderate to severe sequelae or death, 3-6, on the modified Rankin scale) using multivariable models. Findings: We identified 381 studies (31 unpublished) describing 4443 patients with COVID-19 and neurological disease: 83 of these provided IPD for 1979 (45%) patients. Encephalopathy (978 [49%]) and cerebrovascular events (506 [26%]), were the most common diagnoses in the IPD database and aggregate data. Respiratory and systemic symptoms preceded neurological features in 93% of patients;one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41] overall), and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-Dimer. Overall, 30-day mortality was 30% (27-32). The hazard of death was reduced for patients in the WHO European region, but increased in low- and lower-middle-income countries. Interpretation: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission. Funding This study was funded by the UK Medical Research Council’s Global Effort on COVID-19 Programme (MR/V033441/1);UK National Institute for Health Research (NIHR)-funded Global Health Research Group on Acute Brain Infections (17/63/110);and the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907), at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant Nos. IS-HPU-1112-10117 and NIHR200907).Declaration of Interests: BS reports a grant from UKRI/DHSC Global Effort on COVID-19 Research (Medical Research Council) and non-financial support from UK National Institute for Health Research Global Health Research Group on Brain Infections. SL and TS are supported by a grant from the EU Zika Preparedness Latin American Network consortium (ZikaPLAN). ZikaPLAN has received funding from the EU's Horizon 2020 research and innovation programme under grant agreement number 734584. LCG reports non-financial support from Pfizer, non-financial support from Gilead. LB reports grants from GlaxoSmithKline, Research England and Wellcome Trust. AMBM reports grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq/Brazil, and São Paulo Research Foundation FAPESP/Brazil. AP reports personal fees from ZAMBON, UCB , BIOMARIN, and ABBvie pharma. TS was an adviser to the GlaxoSmithKline Ebola Vaccine programme, chaired a Siemens Diagnostics clinical advisory board, and advises the WHO Brain Health Unit Forum on Neurology and COVID-19;TS has also previously filed a patent for a test for bacterial meningitis based on a blood test (GB 1606537.7, April 14, 2016), and has grants from the UK Medical Research Council and National Institute for Health Research. All other authors declare no conflict of interest

3.
BMC Public Health ; 21(1): 1216, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1282252

ABSTRACT

BACKGROUND: As COVID-19 death rates have risen and health-care systems have experienced increased demand, national testing strategies have come under scrutiny. Utilising qualitative interview data from a larger COVID-19 study, this paper provides insights into influences on and the enactment of national COVID-19 testing strategies for health care workers (HCWs) in English NHS settings during wave one of the COVID-19 pandemic (March-August 2020). Through the findings we aim to inform learning about COVID-19 testing policies and practices; and to inform future pandemic diagnostic preparedness. METHODS: A remote qualitative, semi-structured longitudinal interview method was employed with a purposive snowball sample of senior scientific advisors to the UK Government on COVID-19, and HCWs employed in NHS primary and secondary health care settings in England. Twenty-four interviews from 13 participants were selected from the larger project dataset using a key term search, as not all of the transcripts contained references to testing. Framework analysis was informed by the non-adoption, abandonment, scale-up, spread, and sustainability of patient-facing health and care technologies implementation framework (NASSS) and by normalisation process theory (NPT). RESULTS: Our account highlights tensions between the communication and implementation of national testing developments; scientific advisor and HCW perceptions about infectiousness; and uncertainties about the responsibility for testing and its implications at the local level. CONCLUSIONS: Consideration must be given to the implications of mass NHS staff testing, including the accuracy of information communicated to HCWs; how HCWs interpret, manage, and act on testing guidance; and the influence these have on health care organisations and services.


Subject(s)
COVID-19 , State Medicine , COVID-19 Testing , England , Health Personnel , Humans , Pandemics , Policy , SARS-CoV-2
5.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1000

ABSTRACT

Background: The COVID-19 pandemic, caused by SARS-CoV-2, is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentatio

6.
Lancet Neurol ; 19(9): 767-783, 2020 09.
Article in English | MEDLINE | ID: covidwho-626383

ABSTRACT

BACKGROUND: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. RECENT DEVELOPMENTS: A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2-6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. WHERE NEXT?: Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/epidemiology , Nervous System Diseases/diagnostic imaging , Nervous System Diseases/epidemiology , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Animals , COVID-19 , Coronavirus Infections/diagnosis , Humans , Nervous System Diseases/virology , Pandemics , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology
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