The COVID-19 Clinical Neuroscience Study (COVID-CNS)

COVID-19 patients frequently suffer brain problems during the infection and can be left with symptoms of brain injury. Similar problems have been seen in previous pandemics, including Spanish influenza over 100 years ago, but how and why this occurs is poorly understood.

We have already been notified of 800 UK patients with these complications due to COVID-19. We have a unique opportunity to understand how these problems occur and develop strategies to prevent and treat them. The questions we will ask include in whom does COVID-19 cause injury? Does it do this by invading the brain? Or by triggering excessive immune responses or interfering with the blood supply to nervous tissue?

We will answer these questions through in depth clinical, laboratory, and imaging studies of these 800 patients in comparison to 500 control patients (hospitalised during the pandemic with COVID-19 [400] or without COVID-19 [100]).

Without this understanding, we cannot determine whether anti-viral medication, or treatments that modulate the immune system or that improve blood supply will help, and if so in which patients.

We will apply this understanding through our World Health Organisation-commissioned Task Force (co-Chair Michael) to develop clinical care guidelines, identify patients for targeted clinical trials, and ultimately improve patient outcomes.

We will consent all participants to the NIHR BioResource, establishing COVID-CNS as a trial ready cohort and ensuring data and sample access for other researchers.

N.B. COVID-CNS is jointly led by co-PIs Benedict Michael and Gerome Breen

Acute neurological complications of COVID-19 affect 20-30% of hospitalised patients, including encephalopathy/delirium, encephalitis, stroke, and Parkinsonism. These are often otherwise unexplained (i.e. excluding risk factors/hypoxia/iatrogenic causes) and often occur in younger patients. Survivors frequently report cognitive impairment, fatigue, and depression. The limited regenerative capacity of the brain means these complications may cause lifelong disability.
There is an urgent, unmet need to understand the biological causes of acute neurological complications of COVID-19 and their sequelae.

In collaboration with CoroNerve and ISARIC-4C's, we have already identified 800 patients who have been hospitalised with these complications. We will:
(1) invite these patients to join the COVID-CNS NIHR BioResource, using existing HRA approvals and protocols;
(2) conduct a case control study to determine the phenotypes and genotypes of these patients relative to 500 previously hospitalised controls including those from ISARIC-4C's and PHOSP-COVID (400 with COVID-19; 100 non-COVID);
(3) collect data from clinical case notes and electronic records, then assess neurological/cognitive/psychiatric sequelae at 3-6 months post-discharge;
(4) analyse brain injury, virologic, and immunological mechanisms in serum and cerebrospinal fluid, and analyse acute MRI's and, at follow up, functional MRI to study the pathophysiology of these complications.

By understanding these mechanisms, we will be able to stratify patients into clinical care pathways and into trials using existing and novel therapies. We will apply this knowledge through our WHO-commissioned Task Force (co-Chair Michael) to have immediate impact on patient care and through our PPI programme. The NIHR BioResource will provide sustainability and, through linkage to the community cohort (n=35,000), will allow us to determine if similar, but milder, symptoms are being experienced more widely.