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COVID-19 Research Opportunities Through the Neurocritical Care Society

By Currents Editor posted 05-20-2020 07:34


By Shraddha Mainali, MD; Sherry Chou, MD, MSc; Molly McNett, PhD, RN, CNRN, FNCS, FAAN; Raimund Helbok, MD, PhD; Jennifer Frontera, MD; Ericka L. Fink, MD, MS; Michelle Schober, MD; and Courtney L. Robertson, MD

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or the COVID-19 pandemic, is advancing at a rapid pace. The widespread nature of this virus has led to significant constraints in healthcare resources, forcing many hospital systems to limit and monitor resource utilization.

The overwhelmed healthcare systems are compelled to improvise in various ways to accommodate for rising demands of this pandemic. Attempts to minimize disease transmission has required hospitals to change their practices and policies in multiple ways, including changes in workflows, geographic cohorting of infected patients and use of telemedicine to provide patient care.

Given the rapidly evolving circumstances in the event of a global pandemic with possible shortages of necessary medications, equipment and medical personnel, this pandemic could significantly impact the outcomes of all hospitalized patients, including neurocritical care patients. There is an urgent need to understand the implications of these changes to guide safe standardized practices under resource-limited environments.

Furthermore, there is an emerging body of literature to suggest various neurological dysfunctions associated with COVID-19 infection. Multiple reports have suggested a spectrum of mild to severe neurological illnesses in patients with COVID-19, including headache, encephalopathy, hyposmia/anosmia, dysgeusia/ageusia, encephalitis, seizures, coma, Guillain Barre syndrome, and acute cerebrovascular events like ischemic and hemorrhagic strokes and cerebral venous sinus thromboses.1-4  

As critical care specialists invested in the care of critically ill patients with neurological injury and the frontline workers fighting the COVID-19 pandemic, understanding the prevalence, mechanisms, phenotypes and prognostic implications of COVID-19 related neurological dysfunctions falls within the purview of neurocritical care specialists.

Given this existing knowledge gap in areas pertaining to our specialty, a group of neurocritical care experts have teamed together to develop research protocols to evaluate these gaps in a systematic manner.5 There are currently three active studies related to COVID-19 with endorsement from the Neurocritical Care Society (NCS).

1. Neurocritical Care COVID-19 Outcomes Study
This prospective, multicenter global observational study aims to evaluate the impact of COVID-19 on outcomes of adult neurocritical care patients. With change in hospital protocols, including staffing changes and possibility of change in management location (ie, outside NCCU), there is a likelihood of adverse effect on patient outcomes

This study will focus on five major neurological and neurosurgical conditions managed in the NCCU:
  1. Ischemic stroke
  2. ICH
  3. SAH
  4. TBI
  5. Status epilepticus
All patients with the relevant diagnoses, regardless of COVID-19 status, will be enrolled in the study. The main variables in the study include basic epidemiological data, initial and final code status, clinical decisions to offer therapy in resource limited conditions (eg, intubation, ventilation, tracheostomy) and outcome at discharge.  We will also obtain information regarding delayed mortality using the SS death index from sites with IRB approval to do so.

We plan to collect data for 3 months in the midst of the global pandemic with a goal of rapid analysis and publication, so helpful information can be disseminated in a timely manner to guide development of standardized protocols for management of neurocritical care patients.

To date, there are 74 global sites enrolled in this study. Enrollment is ongoing and interested members can sign up to participate in this study here.

2. Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCoV): Adult Study
The Global Consortium to Study Neurological Dysfunction in COVID-19 (GCS-NeuroCoV) has been established with the goal of understanding the neurological dysfunctions associated with COVID-19 and the related outcomes. Given the increasing prevalence of COVID-19 and the rapidity of emerging information on neurological manifestations of COVID-19, mostly in pre-prints and non-peer reviewed format, it has become increasingly difficult to ascertain the causality versus co-infection/co-incidence of COVID-19 in patients with neurological illnesses. Therefore, there is an urgent need for a methodological approach to understand the neurological manifestations of COVID-19 and its impact on our patients.

This study aims to accurately capture prospective data with the goal of evaluating the prevalence, severity and neurological characteristics of COVID-19. This pragmatic study is deliberately designed to be launched in a three-tiered approach with a feasible plan for basic data collection in the first tier, and inclusion of more granular details and higher complexity study designs in higher tiers. This approach will allow for adjustment and addition of pertinent new neurological findings in higher tiers as new neurologic manifestations surface over time. Such an adaptable layered design may serve as a model for future studies that need rapid execution in the midst of pandemics or natural disasters.

A team of steering committee members was rapidly assembled to develop the Common Data Elements (CDEs) for the Tier 1 study in adult population (≥18 years). Tier 1 consists of a basic, practical, low-cost, CDE collection, which can be launched rapidly across many sites. This study is designed to have expedited ethical board review with waiver of informed consent.
As of May 12, there are 77 sites, including 17 countries and 5 continents registered for the Tier 1 study, with the study initiated in early April at multiple global sites. 

This study is open for enrollment and interested investigators can register their sites for participation here.

The tier 2 study consists of the prospective collection of functional and cognitive outcomes with greater details of clinical, laboratory and radiographic data performed as part of standard of care. This study is expected to require informed consent, so it is likely to have a limited number of participating sites depending on availability of local resources.
Tier 3 study involves the high complexity design including collection of experimental bio specimens, including blood and CSF, advanced electrophysiological and imaging analysis and histopathological assessment, along with longitudinal outcomes assessment over years to decades. Given the complex experimental design of Tier 3, only advanced research sites with available bandwidth and expertise to conduct such a study are expected to participate.
A team of global experts have been assembled to form scientific working groups to finalize the data elements for Tier 2 and Tier 3 studies, which are currently under development.
3. Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCoV): Pediatric Study
Parallel to the adult study, a multicenter pediatric core has established a three-tiered pediatric arm to this global research consortium with the aim to capture prevalence of neurologic dysfunctions in pediatric population, to evaluate specific neurological dysfunctions associated with COVID-19 and to examine patient outcomes related to these dysfunctions. 
The Tier 1 pediatric study is active for enrollment through December 2021, and involves data collection from the medical record during the hospital stay. To date, 75 sites have registered for this study globally. Upon registration, study materials including an ethical review board template, Case Report Form and Frequently Asked Questions documents, will be provided. Interested investigators can register their sites here.

The goal for Tier 2 in the pediatric population is to analyze child and family functional health and health-related quality of life outcomes between 30 and 90 days post hospital discharge. This arm of pediatric study is expected to require informed consent. For Tier 3, which is under development, the pediatric arm will align with the adult study in its design and creation of a biobank for mechanistic and diagnostic analyses.

These three studies are endorsed by the NCS, and a brief study description with registration links can be found on the NCS website.

A detailed description of the study has been accepted for published in Neurocritical Care.6

Study Team Members

The core adult study team members include Sherry Chou, MD,c MSc; Molly McNett, PhD, RN,CNRN; Shraddha Mainali, MD; Jennifer Frontera, MD and Raimund Helbok, MD, PhD. The core pediatric study team consists of Ericka L. Fink, MD, MS; Courtney L. Robertson, MD; and Michelle Schober, MD, on behalf of the Pediatric Neurocritical Care Research Group. Additional steering committee members and scientific advisors include Jose Suarez, MD; David Menon, MD, PhD; and Wendy Ziai, MD.


Pediatric Consortium Coordinators: Pamela Rubin, RN and David Maloney, BS; Department of Critical Care Medicine, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, USA

Pediatric Consortium Pediatric Neurointensivists: Dennis Simon, MD, Department of Critical Care Medicine, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA; Elizabeth Wells, MD, MHS, Division of Neurology, Children's National Hospital, Washington, DC, USA; Juan Piantino, MD, Division of Neurology, Oregon Health & Science University; Andrew Geneslaw, MD, Department of Pediatrics, Morgan Stanley Children’s Hospital


Adult Consortium Team:  Michal Hammond, MD, Ali J Smith, Department of Critical Care Medicine, University of Pittsburgh.  Haley Roberts, BS, The Ohio State University.  Nicole Paul, BS and Lauren Kaplan, BS, University of Pittsburgh School of Medicine. Dr. Carlos Villamizar-Rosales, MD; Valeria Altamirano, MS; Aditya D. Sharma, University of Pittsburgh


Neurocritical Care Society, NCRC, NCRN

In addition, we would like to thank all our global partners and collaborators for their utmost support and enthusiasm in moving this important study forward.




  1. Asadi-Pooya AA and Simani L. Central nervous system manifestations of COVID-19: A systematic review. J Neurol Sci. 2020;413:116832.
  2. Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, Franciotta D, Baldanti F, Daturi R, Postorino P, Cavallini A and Micieli G. Guillain-Barre Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020.
  3. Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L, Liu C and Yang C. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020.
  4. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, Boulay C, Fafi-Kremer S, Ohana M, Anheim M and Meziani F. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020.
  5. Needham EJ, Chou SH, Coles AJ and Menon DK. Neurological Implications of COVID-19 Infections Neurocrit Care United States; 2020.
  6. Frontera J, Mainali S, Fink E, Robertson C, Schber M, Ziai DM, Kochanek PM, Suarez J, Helbok R, McNett M, Chou SH. Global ConsortiumStudy of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Study Design and Rationale.Neurocrit Care United States; 2020.

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