Neurological Complications of COVID-19 Are Focus of New NIH Grant Supplement to Cleveland Clinic Researchers

Many months after its emergence as a global pandemic, COVID-19 is still serving up more questions than answers. Yet like their counterparts around the globe, Cleveland Clinic researchers are continuing to pursue answers, and they’re doing so on multiple fronts. They’ve established a registry of patients tested for COVID-19 (currently at 32,786 enrollees, including 13,171 COVID-19-positive patients), created a biobank of specimens from infected individuals and published over 350 papers on COVID-19 to date, according to Lara Jehi, MD, MHCDS, Chief Research Information Officer for Cleveland Clinic and Director of the Outcomes Research Program in the Epilepsy Center.

Recently, Dr. Jehi expanded efforts on another front by applying for a COVID-19 supplement to a $3.4 million, five-year grant from the National Institutes of Health (NIH) that she and colleagues had received to create a nomogram (risk calculator) to predict seizure outcomes after resective epilepsy surgery. The supplemental grant of $308,000 was awarded for a one-year study to expand the focus to neurological complications of COVID-19 infection.

Leveraging existing infrastructure to study COVID-19

“Neurological complications that occur as a result of SARS-CoV-2 infection were not front and center until a few months into the pandemic,” Dr. Jehi observes. “Since we have experience in predictive modeling and genomic changes, I believed we could pair that expertise with the COVID-19 registry and biobank resources we have developed over the past six months to advance understanding of these neurological complications.”

She viewed the earlier epilepsy outcomes grant from NIH as a good fit for this effort because funding was also awarded to the Mayo Clinic and the University of Campinas in Brazil, giving the research team the ability to study neurological complications of COVID-19 in two of the largest hospital systems in the United States plus one in Latin America.

Focus of the grant supplement

Specifically, the focus of the urgent revision of the grant is to:

• Characterize the incidence of new-onset seizures, stroke and delirium in all patients diagnosed as COVID-19-positive across the Cleveland Clinic health system
• Create prediction models that allow for individual risk estimation for neurological complications during disease progression
• Identify molecular determinants of the underlying mechanisms for these neurological manifestations

The study will have two arms. One will be retrospective, to identify neurological complications observed from the registry data, and one will be prospective, with phone or digital follow-up of patients for six months after infection diagnosis.

COVID-19 nomogram publications

Previous research indicates that older age, smoking, diabetes, hypertension, cardiovascular disease, kidney disease, chronic lung disease and cancer correlate with progression to severe disease in patients hospitalized with COVID-19. “We hypothesize that these factors are similarly associated with a higher risk of neurological complications,” explains Dr. Jehi. “However, because these risk factors are not specific, occur in various combinations and have limited value as isolated indicators of specific neurological complications, there is a need for tools to guide decisions in clinical care and use of resources.”

Dr. Jehi and her Cleveland Clinic colleagues are uniquely qualified to create these tools, given that the nomogram concept originated with Michael Kattan, PhD, Chair of the Department of Quantitative Health Sciences in Cleveland Clinic Lerner Research Institute. Drs. Jehi and Kattan were principal authors of a paper published in Chest in June 2020 that described the first COVID-19 nomogram for use by healthcare providers to predict an individual patient’s likelihood of testing positive for COVID-19, along with outcomes such as disease severity and need for hospitalization. This risk prediction model, which has been deployed as a freely available online risk calculator to prioritize patients for testing, was developed using data from almost 12,000 patients enrolled in the Cleveland Clinic COVID-19 registry. Another paper by the group, published in PLOS One in August 2020, reported on a second nomogram that was developed and validated to help physicians predict which COVID-positive patients at greatest risk for hospitalization.

“Our goal is to create a suite of tools that clinicians can use to deliver personalized care and allocate resources for patients with COVID-19,” Dr. Jehi says.