COVID-19 Neurological Disease: a Global Meta-Analysis and Prospective Case Control Study in Brazil, India and Malawi.

Lead Research Organisation: University of Liverpool
Department Name: Institute of Infection and Global Health

Abstract

Most patients with COVID-19 have cough and breathing problems. However, we are now seeing patients with neurological (brain) disease too. We want to understand why to help us improve treatment.
1. Doctors are publishing reports of single or small groups of patients, or registries. These describe patients in different ways using different definitions. This means it is hard to see the full range of brain disease. Through our global network, we will pull together data from all patients (published or not) to produce a single large report.
2. We want to understand why some patients with COVID-19 get neurological disease. We will therefore conduct a study in Brazil, India and Malawi. We will compare patients with and without neurological disease, to identify risk factors for neurological disease. We are especially interested in those factors which could be treated, such as lack of oxygen in the blood.
3. We will also look at outcomes for neurological patients, again looking at factors associated with a bad outcome.
4. We have a strong Patient, Public and Community Engagement and Involvement Programme, and good links to the World Health Organisation (WHO) and national policymakers. These will help to ensure our information rapidly informs clinical guidelines to improve patient management and save lives.
5. We will also train doctors and scientists in such research to improve their knowledge and skills, and build capacity.

Technical Summary

Building on our NIHR Global Health Research Group on Acute Brain Infections ("Brain Infections Global" or, "BIGlobal"), which we have recently repurposed to start understanding COVID-19 neurology, we will:
1. Conduct an individual patient data meta-analysis of patients with COVID-19associated neurological disease, identified through the BIGlobal COVID-Neuro Network to define the full spectrum of manifestations.
2. Establish a prospective case control study of hospitalised COVID-19 patients in Brazil, India and Malawi, comparing those with neurological disease to those patients without neurological disease, focusing on risk factors which may be modifiable.
3. Examine outcomes of hospitalised patients with COVID-19 associated neurological disease, looking for prognostic factors associated with a poor outcome.
4. Building on our strong Patient, Public and Community Engagement and Involvement Programme, and close relationship with WHO and national policymakers, use the information from 1, 2, and 3, above to develop national and international clinical care guidelines to improve patient outcomes and reduce disability.
5. Strengthen capacity for emerging brain infections research in partner countries.

The case control study will test the primary hypothesis that among hospitalised patients with COVID-19, acute neurological disease is associated with hypoxia. The meta-analysis, case control study, and work with policymakers will run in parallel, to ensure rapid delivery of the changes needed to impact on practice. The study builds on 25 years of research on brain and emerging infections from the Liverpool group, much of which has been translated into new policy and practice.

Publications

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Drake TM (2020) Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study. in American journal of respiratory and critical care medicine

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Ellul M (2020) Defining causality in COVID-19 and neurological disorders. in Journal of neurology, neurosurgery, and psychiatry

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Ellul MA (2020) Neurological associations of COVID-19. in The Lancet. Neurology

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Netravathi M (2022) COVID-19 vaccine associated demyelination & its association with MOG antibody. in Multiple sclerosis and related disorders

 
Description EAN-ESCMID Guidelines on Autoimmune Encephalitis
Geographic Reach Multiple continents/international 
Policy Influence Type Contribution to new or Improved professional practice
 
Description EAN-ESCMID Guidelines on Infectious Encephalitis
Geographic Reach Multiple continents/international 
Policy Influence Type Contribution to new or Improved professional practice
 
Description Medicines and Healthcare products Regulatory Agency (MHRA) Covid-19 Vaccine Risk Benefit Expert Working Group
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
URL https://www.gov.uk/government/organisations/commission-on-human-medicines/about/membership
 
Description The House of Lords Science and Technology Committee hearing
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
URL https://committees.parliament.uk/event/1910/formal-meeting-oral-evidence-session/
 
Description Brain Infections Global 
Organisation Oswaldo Cruz Foundation (Fiocruz)
Department Fiocruz Pernambuco
Country Brazil 
Sector Hospitals 
PI Contribution Collaboration on NIHR Global health Research Group
Collaborator Contribution Collaboration on NIHR Global health Research Group
Impact see publications
Start Year 2019
 
Description Centre for Disease Control, Atlanta, Georgia, USA 
Organisation Centers for Disease Control and Prevention (CDC)
Department Vector-borne diseases
Country United States 
Sector Public 
PI Contribution (Marc Fischer, Susan Hills, Japanese encephalitis control, since 2008)
Collaborator Contribution collaboration
Impact SEE PUBLICATIONS
Start Year 2008
 
Description Fundação Oswaldo Cruz, (FIOCRUZ) collaboration on Zika 
Organisation Oswaldo Cruz Foundation (Fiocruz)
Country Brazil 
Sector Public 
PI Contribution Collaboration on Zika
Collaborator Contribution Collaboration on Zika
Impact New publications, and grants, see other sections
Start Year 2016
 
Description The Global Health Network (TGHN) 
Organisation The Global Health Network
Country Global 
Sector Charity/Non Profit 
PI Contribution I am chairing a webinar series on Neurological Associations of COVID-19. My team is responsible for the scientific content of the series. My team has also convenied the virtual Liverpool Neurological Infectious Diseases Course.
Collaborator Contribution TGHN is hosting the webinar and courses.
Impact Webinar series: https://braininfectionsglobal.tghn.org/webinars/, attended by several hundred attendees globally. NeuroID course: https://braininfectionsglobal.tghn.org/brain-infections-global-training/liverpool-neurological-infectious-diseases-course/, attended by 560 attendees from 59 countries across all continents.
Start Year 2020
 
Description 17th International Symposium on NeuroVirology | 2021 Conference on HIV in the Nervous System - Plenary Talk, 2nd June 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact TS gave the plenary talk 'Neurological COVID - Causes, Complications, and Conundrums' at the 17th International Symposium on NeuroVirology | 2021 Conference on HIV in the Nervous System.
Year(s) Of Engagement Activity 2021
URL http://isnv.org/virtual21/Agenda_ISNV_Virtual21.pdf
 
Description BBC One - Question Time 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Topical debate in which guests from the worlds of politics and the media answer questions posed by members of the public.
Year(s) Of Engagement Activity 2020
URL https://www.bbc.co.uk/iplayer/episode/m000ggsk/question-time-2020-19032020
 
Description BNA2021 Festival of Neuroscience - COVID-19 and neuroscience talk, 14th April 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact TS gave a talk entitled 'Brain Infections Global COVID-Neuro Network' at Session two - Characterising COVID-19 with cohort studies: providing future evidence of the British Neuroscience Association conference.
Year(s) Of Engagement Activity 2021
URL https://meetings.bna.org.uk/bna2021/programme_information/special-sessions/covid19/
 
Description BR?INCAST Podcast with Sotiris Posporelis and Dr Tom Pollack 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact BR?INCAST is a weekly 30-minute conversation with inspiring people from all around the world sharing their love about the most fascinating thing that happened to your headyour brain! From the microscopic magic of a molecular scientist to the all-encompassing worldview of a philosopher, from up-and-coming PhD students to well-established professors, BR?INCAST is open to everyone that's curious! Nah, it's not seriousthe brain is too interesting to be serious! Just cast your brain aside (see what I did there?) and enjoy.
Year(s) Of Engagement Activity 2021
URL https://maudsleylearning.com/webinars-podcasts/braincast-webinar/world-encephalitis-day-experts-take...
 
Description Brain Infections Webinars 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The webinars are held monthly in conjunction with The Global Health Network and are open sessions for policy makers, academics and clinicians.

Initially the focus was on Covid-19 but in recent months has moved to a variety of Brain Infections.

The learning objective of these webinars is to gain insights into practice in different settings through knowledge exchange with fellow participants.
Year(s) Of Engagement Activity 2020,2021,2022
URL https://braininfectionsglobal.tghn.org/covid-neuro/webinars/
 
Description Chaired and presented in the Neuroinfection Session at The Brain Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Tom Solomon presented 'Emerging Causes of Brain Infection' and chaired the Neuroinfection session at the 2021 Brain Conference.
Year(s) Of Engagement Activity 2021
URL https://thebrainconference.co.uk/previous-conferences/
 
Description Covid for Kids - Barnes Children's Literature Festival, 27th June 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact This year's Barnes Children's Literature Festival presents particular challenges because of the pandemic. Luckily, Professor Tom Solomon an emerging infections expert at the centre of the UK response is on his way to Barnes with his new event, Covid for Kids at 1pm on Sunday 27th June, where you'll have the chance to ask him your questions! First up though, he answers a couple of ours!
Year(s) Of Engagement Activity 2021
URL https://www.barneskidslitfest.org/news/covid-for-kids-with-professor-tom-solomon/
 
Description Covid for Kids interview with Shelagh Fogarty 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Professor Tom Solomon discussing his new Covid for kids show
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=D5uqzqmWN_c&t=57s
 
Description Ebola threat to UK and Africa: Pollock and Solomon - BBC News Interview, 12th July 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact BBC interview with Professor Tom Solomon and Andrew Neil discussing the crisis and the transmission.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=3ETB4QIIM90&t=27s
 
Description Granada Reports interview with Professor Tom Solomon discussing the impact in foreign aid reductio, 3rd July 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Granada Reports interview with Professor Tom Solomon, discussing the impact of funding cuts in scientific research.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=ReNB93y0si4
 
Description How to handle the pandemic | Edinburgh Science Festival 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact In late 2019 reports of an unknown virus began to emerge from the Chinese province of Hubei. 18 months later, the world is still in the grip of the worst pandemic in living memory, with over 3 million lives lost. Governments around the world have deployed a range of strategies to steer their nations through the crisis - but who got it right? This event brings together international experts who have advocated different approaches to attempt to find out how to handle a pandemic Hosted by Director of the UK's Emerging Infections Research Unit Tom Solomon, join Chair of the WHO's Global Outbreak Alert and Response Network Dale Fisher, behavioural scientist and Scottish government advisor Linda Bauld and epidemiologist Tim Spector for a keynote discussion.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=hyAgqn3tV1g
 
Description ITV Granada Debate, 10th June 2021 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Debate about local lockdowns, the spread of the variant, vaccinations and opening up on the 21st June.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=5FliX2m6bOg&t=44s
 
Description Keynote speech at World Encephalitis Day Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Tom Solomon gave the keynote speech at the World Encephalitis Day Conference. He is President of the Encephalitis Society.
Year(s) Of Engagement Activity 2021
URL https://wedconf.org/
 
Description Liverpool FC, Atletico Madrid, and the coronavirus outbreak - BBC Breakfast Interview, 17th March 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Professor Tom Solomon contributes to this BBC Breakfast piece on the controversy around the football match played between Liverpool FC and Atletico Madrid at Anfield, which meant Spanish football fans would travel from Madrid, which at the time was experiencing an outbreak of the coronavirus.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=0JozskflxlI
 
Description NIMH Neurologic and Psychiatric Effects of SARS-CoV-2 Meeting Presentation, 14th July 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact TS presented a talk titled 'CNS Manifestations of COVID-19 ' in Session I: Clinical Neurologic and Psychiatric Manifestations of Acute COVID-19.
Year(s) Of Engagement Activity 2021
URL https://www.nimh.nih.gov/news/media/2021/neurologic-and-psychiatric-effects-of-sars-cov-2-meeting-da...
 
Description Prof Tom Solomon discusses the Commons Science and Technology Committee report BBC Breakfast News, 12th October 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Professor Tom Solomon, Professor of Neurology and Director of the UK Emerging Infections Research Unit at the University of Liverpool talks to Charlie Stayt and Sally Nugent with Anita Astle, Director of Wren Hall nursing homes discusses the lessons learned and the initial UK Government response to Covid-19, compared to that of countries who had experienced SARS, MARS and other health crises in a new Public Health report on BBC Breakfast News on Tuesday 12 October 2021.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=9BzzEqzAZbw
 
Description Prof Tom Solomon discusses the new UK Government new Covid19 restrictions on BBC Breakfast News, 9th December 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Tom Solomon CBE, Professor of Neurology and Director of the UK Emerging Infections Research Unit at the University of Liverpool with Stephen Reicher, Professor of Social Psychology at the University of St. Andrews and member of the SAGE subcommittee talk to Charlie Stayt and Naga Munchetty about the UK Governments' new 'Plan B' Covid19 restrictions and how this intervention will mean lower community transmission of the new Omicron variant and fewer hospital admissions over the Festive season and beyond.
Professors Solomon and Reicher also discuss the continued role of vaccination, self-isolation and ventilation in public settings in the run up to Christmas.
Professor Solomon also re-emphasises the critical importance of vaccinating the rest of the world in the fight against new and emerging Covid19 variants.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=OqLFhAk2R0o
 
Description Professor Tom Solomon featured on Roald Dahl Special - TRT Interview, 28th July 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Professor Tom Solomon talk about Roald Dahl and book 'Marvellous Medicine' and more.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=jSA1ofjRPnw&t=15s
 
Description Radio 4 Interview Broadcasting House, 16th May 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact BBC Radio 4 Interview with Prof Tom Solomon and Paddy O'Connell 16th May 2021
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=XA5YCmAphz8&t=50s
 
Description Radio 5 live Covid for Kids interview, 25th June 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Tom Solomon promoting his Barnes Children's Literature Festival show, Covid for Kids - a family-friendly interactive show
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=SPsGpG6fGkY&t=1s
 
Description Roald Dahl Interview - Times Radio, 17th March 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Professor Tom Solomon appears on Times Radio to discuss To Olivia, Sky's recent drama about the tragic loss of Roald Dahl and Patricia Neal's daughter, Olivia. Hosted by Daniel Finkelstein and also featuring To Olivia's producer, Donall McCusker.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=imvv1UDSknk
 
Description Scouse Science Podcast - Host 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The Scouse Science Podcast
In front of a live online audience, award-winning science communicator, doctor and researcher Professor Tom Solomon hosts a regular discussion of cutting-edge science in Liverpool and its wider impact on society. In each program, Tom talks with a leading researcher on the scientific progress being made and chats about the broader implications with a famous face.
Year(s) Of Engagement Activity 2020,2021,2022
URL https://www.liverpool.ac.uk/health-and-life-sciences/engage-with-us/scouse-science/
 
Description The anniversary of the first coronavirus lockdown in the NorthWest - ITV News Interview, 24th March 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Professor Tom Solomon talks to Tim Scott, ITV News, on the anniversary of the first UK coronavirus lockdown, in a piece that looks back at the pandemic over the past year, and ahead to when the pandemic may end.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=Z6dmUJS-6_I&t=10s
 
Description The new Omicron variant - Prof Tom Solomon on BBC Breakfast News, 6th December 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Tom Solomon CBE, Professor of Neurology and Director of the UK Emerging Infections Research Unit at the University of Liverpool talks to Dan Walker and Sally Nugent about the current unknowns of the new Omicron variant and the challenge of tweaking the current Covid19 vaccines. Tom also discusses the critical importance of vaccination not only to protect the UK but to protect the rest of the world, especially lower income countries.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=2YygKbibxIQ
 
Description The new tablet to treat COVID-19 - Prof Tom Solomon CBE on BBC Breakfast News, 5th November 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Tom Solomon CBE, Professor of Neurology and Director of the UK Emerging Infections Research Unit at the University of Liverpool talks to Charlie Stayt and Naga Munchetty about the newly-approved Covid-19 drug treatment; Molnupiravir, how it was developed, it's effects and efficacy and who should be taking it. Tom also explains how the new Public Health Government ventilation recommendations launched today can be adopted over the festive period.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=a0ZA2ccrx_o
 
Description Tom Solomon CBE talks with Naga Munchetty & Charlie Stayt, BBC Breakfast, about his honour. 12th June 2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Tom Solomon CBE is Naga and Charlie's first guest on the famous red sofa since the start of the pandemic, talking about receiving his award in the Queen's Birthday Honours List 2021. 12th June 2021
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=ncAj6MKFjdQ&t=355s