UPMC and Pitt Researchers Lead International Efforts to Study Neurological Complications of COVID-19 Infection

The emergence in humans of the novel coronavirus, SARS-CoV-2, which causes COVID-19 infections exploded into a worldwide pandemic in a few short months. Since its detection, the virus has spread to virtually every community on the planet with alarming rapidity and devastating consequences to individuals, communities, and entire nations. As of this writing, there have been over 10 million documented cases worldwide, with more than 500,000 fatalities. Controlling the spread of the infection and searching for effective treatments and vaccines is of utmost importance to mitigate the long-term effects of the disease. Understanding how the disease affects the body also is paramount.

While infection through the respiratory system is the hallmark of disease transmission and manifestation, many other symptoms and effects are emerging as a result of COVID-19 infection: immune system dysregulation, gastrointestinal disruptions, and clotting irregularities in some patients' blood. 

Add to this growing list of potential effects from COVID-19 infection an array of neurological complications – some minor and short-lived and others potentially fatal or long-lasting. 

Clinicians around the world have documented a troubling list of neurological symptoms, including a loss of smell and taste, strokes, seizures, encephalopathy, parainfectious autoimmune conditions, cognitive impairment, and others. 

COVID-19 is a heterogeneous disease that can have profound effects on the brain and nervous system of those it infects. Less apparent are the mechanisms driving these manifestations, who are most at risk for neurological complications of COVID-19, and what, if any, the long-term neurological consequences are of COVID-19 infection for individuals that recover.

Sherry H.-Y. Chou, MD, M.SC, FNCS, FCCM, associate professor of critical care medicine, neurology, and neurosurgery at the University of Pittsburgh School of Medicine, is leading an international research effort to better understand the potential neurological manifestations and impacts of COVID-19 infection. This work is currently funded through a grant from the Clinical and Translational Science Institute at the University of Pittsburgh.

"The pathways and mechanisms by which COVID-19 triggers neurological symptoms are not fully understood. It is unclear if the virus is directly targeting cellular or molecular processes in the brain and nervous system, or if the neurological complications we are seeing in patients are secondary effects arising due to systemic inflammatory responses, immune system dysregulation, hypoxia, or other factors,” says Dr. Chou. “It also may be a combination of these factors.”

International Efforts to Study COVID-19

Numerous efforts around the world are working in parallel and in collaboration to pry apart how the novel coronavirus that causes COVID-19 functions, and how, once a person is infected with the disease, it can disturb organs and their functions within the body.

One such international collaborative effort, endorsed by the Neurocritical Care Society and led by Dr. Sherry Chou and Ericka Fink, MD, MS, a colleague at the University of Pittsburgh and UPMC, is a multi-pronged effort to study COVID-19 outcomes and neurological manifestations of the disease in both adult and pediatric populations.

The Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID) was developed and launched in March to “Understand the prevalence, phenotypes, pathophysiology and prognostic implications of COVID-19 neurological syndromes.” More than 200 institutions representing all continents have joined the GCS-NeuroCOVID effort to capture and share data on neurological features observed in their COVID-19 patients.

“We are uncertain how prevalent neurological dysfunctions like stroke, encephalopathy, and delirium are in COVID-19 patients. The current evidence suggests they are less common than respiratory complications. However, when neurological injuries occur, they may persist or incompletely resolve leading to long-term deficits or disabilities. With COVID-19, we have far more questions than answers in this early phase of its existence in humans, which is why a study like GCS-NeuroCOVID is so important to conduct,” says Dr. Chou. 

GCS-NeuroCOVID was designed in a tiered manner to facilitate robust data collection and expand over time because of the inherent difficulties in conducting studies of a highly transmissible disease while also in the middle of fighting a global pandemic of the very same pathogen. 

The three-tiered approach of the study begins with the development and collection of common data elements that are designed to be pragmatic and a low burden to clinicians during this initial phase in the COVID-19 pandemic. Tier one data includes such elements as basic patient characteristics and medical history, neurological symptoms, initial laboratory findings, treatments given during their acute stay, and others. This data will help understand the prevalence of neurological complications in COVID-19 patients, severity, and possible trends in those likely to experience specific complications like stroke, neuropathy, or encephalopathy.

Tier 2 and 3 data include a more in-depth collection of specific neurologic phenotypes, diagnostic and laboratory data, and extended outcomes assessments beyond acute hospitalization. These metrics will provide a greater understanding of both acute and long-term neurological complications in COVID-19 patients.

“The scope of the COVID-19 pandemic – both its global geographic nature and how extensively it can affect the body – necessitates a collaborative, international approach to understanding the natural history of this disease, its acute neurological symptoms, and the yet unknown long-term consequences that could arise months or even years after the initial infection and recovery period,” says Dr. Chou.

References and Further Reading

• https://www.neurocriticalcare.org/research/covid-19-research-opportunities
• Needham EJ, Chou S H.-Y., Coles AJ, Menon DK. Neurological Implications of COVID-19 Infections. Neurocrit Care. 2020 Apr 28: 1-5. Epub ahead of print.
• Frontera J, Mainali S, Fink EL, Robertson CL, Schober M, Ziai W, Menon D, Kochanek PM, Suarez JI, Helbok R, McNett M, Chou S H.-Y., and the GCS-NeuroCOVID Study. Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Study Design and Rationale. Neurocrit Care. 2020 May: 22: 1-10. Epub ahead of print.

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