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Bhagteshwar Singh

Bio: Bhagteshwar Singh is an academic researcher from University of Liverpool. The author has contributed to research in topics: Medicine & Vaccination. The author has an hindex of 8, co-authored 18 publications receiving 1112 citations. Previous affiliations of Bhagteshwar Singh include Christian Medical College & Hospital & Royal Liverpool University Hospital.

Papers
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Journal ArticleDOI
TL;DR: 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 and the proportion of infections leading to neurological disease will probably remain small.
Abstract: Summary 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-Barre 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-Barre 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.

884 citations

Journal ArticleDOI
TL;DR: The COVID-19 pandemic, caused by SARS-CoV-2, is of a scale not seen since the 1918 influenza pandemic and so much of the population infected, the overall number of neurological patients, and their associated health, social and economic costs, may be large.
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 presentation is with respiratory disease, neurological manifestations are being recognised increasingly. Based on knowledge of other coronaviruses, especially those that caused the SARS and MERS epidemics, we might expect to see rare cases of central nervous system (CNS) and peripheral nervous system (PNS) disease caused by SARS-CoV-2. Recent developments: A growing number of case reports and series describe a wide array of neurological manifestations, but many lack detail, reflecting the challenge of studying such patients. Encephalopathy is relatively common, being reported for 93 patients in total, including 16 (7.5%) of 214 hospitalised COVID-19 patients in Wuhan, China, and 40 (69%) of 58 in intensive care with COVID-19 in France. Encephalitis has been described in 8 patients to date, and Guillain-Barre syndrome in 19 patients. SARS-CoV-2 is detected in the cerebrospinal fluid of some patients. Anosmia and ageusia are common and may 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 1.6-6% of hospitalised COVID-19 cases. So far, 88 patients have been described, mostly with ischaemic stroke, who frequently have vascular events in the context of a pro-inflammatory hypercoagulable state with elevated CRP, 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, such as hypoxic encephalopathy and critical care neuropathy, from those caused directly or indirectly by the virus; these include infectious, para- and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barre syndrome. Recognising SARS-CoV-2 neurological disease in patients whose respiratory infection is mild or asymptomatic may prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will remain small. However, these patients may be left with severe neurological sequelae. With so much of the population infected, the overall number of neurological patients, and their associated health, social and economic costs, may be large. Healthcare planners and policymakers must prepare for this eventuality. The many ongoing studies investigating the neurological association will increase our knowledge base.

458 citations

Journal ArticleDOI
TL;DR: This is a protocol for a Cochrane Review (Intervention) to evaluate the effects of chloroquine and hydroxychloroquine as an antiviral treatment on death and time to clearance of the virus from clinical samples and recovery in people with COVID-19.
Abstract: Background The coronavirus disease 2019 (COVID‐19) pandemic has resulted in substantial mortality. Some specialists proposed chloroquine (CQ) and hydroxychloroquine (HCQ) for treating or preventing the disease. The efficacy and safety of these drugs have been assessed in randomized controlled trials. Objectives To evaluate the effects of chloroquine (CQ) or hydroxychloroquine (HCQ) for 1) treating people with COVID‐19 on death and time to clearance of the virus; 2) preventing infection in people at risk of SARS‐CoV‐2 exposure; 3) preventing infection in people exposed to SARS‐CoV‐2. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Current Controlled Trials (www.controlled‐trials.com), and the COVID‐19‐specific resources www.covid‐nma.com and covid‐19.cochrane.org, for studies of any publication status and in any language. We performed all searches up to 15 September 2020. We contacted researchers to identify unpublished and ongoing studies. Selection criteria We included randomized controlled trials (RCTs) testing chloroquine or hydroxychloroquine in people with COVID‐19, people at risk of COVID‐19 exposure, and people exposed to COVID‐19. Adverse events (any, serious, and QT‐interval prolongation on electrocardiogram) were also extracted. Data collection and analysis Two review authors independently assessed eligibility of search results, extracted data from the included studies, and assessed risk of bias using the Cochrane ‘Risk of bias’ tool. We contacted study authors for clarification and additional data for some studies. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs). We performed meta‐analysis using a random‐effects model for outcomes where pooling of effect estimates was appropriate.

156 citations

Journal ArticleDOI
TL;DR: Investigation of the association of vitamin D receptor (VDR) polymorphisms and serum 25(OH)D with susceptibility to, and response to treatment of, multidrug-resistant tuberculosis (MDR-TB) in comparison with drug-susceptible pulmonary TB (DS-PTB) and healthy controls finds VDR gene polymorphism and hypovitaminosis D may predispose to MDR- TB.
Abstract: Setting All India Institute of Medical Sciences and Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, New Delhi, India. Objective To investigate the association of vitamin D receptor (VDR) polymorphisms and serum 25(OH)D with susceptibility to, and response to treatment of, multidrug-resistant tuberculosis (MDR-TB) in comparison with drug-susceptible pulmonary TB (DS-PTB) and healthy controls. Design Cross-sectional study. Methods A total of 897 participants from northern India were consecutively enrolled into three groups (MDR-TB 354, DS-PTB 338, controls 205). Genotypic and allelic frequencies of FokI, BsmI and TaqI VDR polymorphisms, and serum 25(OH)D, calcium and intact parathyroid hormone were measured in all participants. In those with active TB, disease severity, time to sputum smear and culture conversion were correlated with VDR genotype and biochemical parameters. Results FokI Ff genotype and TaqI t allele correlated positively with MDR-TB; Ff genotype and f allele of FokI frequency were higher in both TB groups. BsmI Bb genotype correlated inversely with MDR-TB. Serum 25(OH)D concentrations were significantly lowest in MDR-TB, correlating inversely with time to sputum smear conversion. Conclusions VDR gene polymorphisms and hypovitaminosis D may predispose to MDR-TB. Lower serum 25(OH)D may increase time to MDR-TB sputum smear negativity.

69 citations


Cited by
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Journal ArticleDOI
TL;DR: Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.

7,493 citations

Journal ArticleDOI
TL;DR: A comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae is provided in this paper, where the authors discuss relevant considerations for the multidisciplinary care of COPD survivors and propose a framework for the identification of those at high risk for COPD and their coordinated management through dedicated COPD clinics.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

2,307 citations

Journal ArticleDOI
TL;DR: In this article, the authors provided robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis, using data obtained from the TriNetX electronic health records network (with over 81 million patients).

1,162 citations

Journal ArticleDOI
Aravinthan Varatharaj1, Aravinthan Varatharaj2, Naomi Thomas3, Mark Ellul4, Mark Ellul5, Mark Ellul6, Nicholas W. S. Davies, Thomas A Pollak7, Elizabeth L Tenorio8, Mustafa Sultan3, Ava Easton5, Gerome Breen7, Michael S. Zandi9, Jonathan P. Coles10, Hadi Manji9, Rustam Al-Shahi Salman11, David K. Menon10, Timothy R Nicholson7, Laura A Benjamin5, Laura A Benjamin9, Alan Carson11, Craig J. Smith12, Martin R Turner13, Tom Solomon6, Tom Solomon4, Tom Solomon5, Rachel Kneen6, Rachel Kneen5, Sarah Pett14, Ian Galea2, Ian Galea1, Rhys H. Thomas15, Rhys H. Thomas3, Benedict D Michael6, Benedict D Michael5, Benedict D Michael4, Claire Allen, Neil Archibald, James Arkell, Peter Arthur-Farraj, Mark R. Baker, Harriet A. Ball, Verity Bradley-Barker, Zoe Brown, Stefania Bruno, Lois Carey, Christopher Carswell, Annie Chakrabarti, James Choulerton, Mazen Daher, Ruth Davies, Rafael Di Marco Barros, Sofia Dima, Rachel Dunley, Dipankar Dutta, Richard James Booth Ellis, Alex Everitt, Joseph Fady, Patricia Fearon, Leonora Fisniku, Ivie Gbinigie, Alan Gemski, Emma Gillies, Effrossyni Gkrania-Klotsas, Julie Grigg, Hisham Hamdalla, Jack Hubbett, Neil Hunter, Anne-Catherine Huys, Ihmoda Ihmoda, Sissi Ispoglou, Ashwani Jha, Ramzi Joussi, Dheeraj Kalladka, Hind Khalifeh, Sander Kooij, Guru Kumar, Sandar Kyaw, Lucia Li, Edward Littleton, Malcolm R. Macleod, Mary Joan MacLeod, Barbara Madigan, Vikram Mahadasa, Manonmani Manoharan, Richard Marigold, Isaac Marks, Paul M. Matthews, Michael Mccormick, Caroline Mcinnes, Antonio Metastasio, Philip Milburn-McNulty, Clinton Mitchell, Duncan Mitchell, Clare Morgans, Huw R. Morris, Jasper M. Morrow, Ahmed Mubarak Mohamed, Paula Mulvenna, Louis Murphy, Robert Namushi, Edward J Newman, Wendy Phillips, Ashwin Pinto, David A Price, Harald Proschel, Terry Quinn, Deborah Ramsey, Christine Roffe, Amy L Ross Russell, Neshika Samarasekera, Stephen Sawcer, Walee Sayed, Lakshmanan Sekaran, Jordi Serra-Mestres, Victoria K. Snowdon, Gayle Strike, James Sun, Christina Tang, Mark Vrana, Ryckie G. Wade, Chris Wharton, Lou Wiblin, Iryna Boubriak, Katie Herman, Gordon T. Plant 
TL;DR: This is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19 and provides valuable and timely data that are urgently needed by clinicians, researchers, and funders.

990 citations

Journal ArticleDOI
01 Oct 2020-Brain
TL;DR: A case series of 43 patients with neurological complications of SARS-CoV-2 infection includes encephalopathies, encephalitis, acute disseminated encephalomyelitis with haemorrhagic change, transverse myelitis, ischaemic stroke, and Guillain-Barré syndrome.
Abstract: Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barre syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

839 citations