Jennifer Frontera, MD

“Overall, trying to keep patients out of the hospital with preventative medicine or early therapeutics is important because I think most people would agree that neurological injury following COVID is one of the worst-case scenarios. It has a profound impact on return to work, functional status, and even quality of life in terms of being able to participate in baseline activities, be it work, leisure, household chores, whatever. The impact can be long lasting.”

Following the publication of a study evaluating neurological complications in 251 hospitalized patients with COVID-19, future research is needed to investigate the elevated levels of neurodegenerative biomarkers in this patient population. Investigators found that levels were elevated to, or higher than, in those with Alzheimer disease, suggesting that there is a significant amount of brain injury for some patients during acute COVID-19 infection. 

We sat down with Jennifer Frontera, MD, lead author on the study, to learn more about study design, as well as directions for additional research. According to Frontera, looking at these biomarkers over time will be important, as existing studies suggest that while they may be high in the acute setting, they may decline with time. 

Frontera further discussed takeaways from the study, stressing the need to recognize encephalopathy, which was the most frequent neurological type of injury that investigators witness in the patient population, and treating underlying etiologies. Injuries occurring during the acute phase of COVID-19 may have lasting effects, she said, also noting that preventive measures such as vaccinations and masking, as well as newer antiviral medications and monoclonal antibodies such as sotrovimab.

REFERENCE
Frontera JA, Boutajangout A, Masurkar AV, et al. Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer’s dementia. 

. Published online January 13, 2022. doi:10.1002/alz.12556.

Videos

The professor of neurology at NYU Langone Grossman School of Medicine discussed future research for neurological complications in patients hospitalized with COVID-19 infection. [WATCH TIME: 4 minutes]

Future Research for Blood Biomarkers in Patients Hospitalized With COVID-19: Jennifer Frontera, MD 

“We looked at those markers, that were primarily collected at the time of admission for COVID hospitalization, and then we correlated them with evidence of neurological injury—clinically, most commonly, encephalopathy, which was the most frequent neurological type of injury that we witnessed in these hospitalized COVID patients.”

 evaluated neurological complications in 251 hospitalized patients with COVID-19, with data suggesting neurodegenerative biomarkers in these patients were elevated to, or higher than, levels observed in patients with Alzheimer disease. Investigators also found higher levels of 7 markers of brain damage in patients with COVID-19 with neurological symptoms than those without them, and even higher levels in patients who died in the hospital compared with those who were discharged. 

Findings suggest that there is a significant amount of brain injury for some patients during acute COVID-19 infection, according to lead author Jennifer Frontera, MD, professor of neurology, NYU Langone Grossman School of Medicine. Frontera spoke with 

 on the study design, which involved investigators looking at banked blood specimens—collected from hospitalized patients between March 10, 2020, and May 20, 2020—and checking for brain injury markers using single-molecule array technology. 

Frontera further delved into findings pertaining to patients with more severe COVID-19 infection, meaning they were more hypoxic or had multisystem organ failure. These patients, she said, were more likely to have elevations in neurodegenerative biomarkers, as well as symptomatology reflective of neurological injury. 

REFERENCES
1. Blood markers of brain damage are higher over short term in patients who have COVID-19 than in people who have Alzheimer’s disease. News release. NYU Langone Health. January 13, 2022. Accessed January 13, 2022. https://nyulangone.org/news/blood-markers-brain-damage-are-higher-over-short-term-patients-who-have-covid-19-people-who-have-alzheimers-disease
2. Frontera JA, Boutajangout A, Masurkar AV, et al. Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer’s dementia. 

A recent study found that blood markers of brain damage were higher in patients with COVID-19 than in those with Alzheimer disease. [WATCH TIME: 4 minutes]

Higher Levels of Neurodegenerative Biomarkers in Hospitalized Patients With COVID-19: Jennifer Frontera, MD

"I’ve never seen such sick patients. I’ve never seen so many people dying or deteriorating simultaneously. I probably still haven’t even fully processed the effects of that.”

While the data collected on COVID-19 has primarily been about its pathology and how it may impact those with preexisting conditions, an aspect that has not been subject of much focus has been its effect on the mental state of frontline clinicians. During the heights of the pandemic, hospital staff are commonly overworked, hospital buildings remain overflooded, and clinicians face an increased amount of death with no vaccine or treatments readily available to help.

A recently published dataset from Leah Croll, MD, resident in the neurology department at NYU Langone in New York City, looked at how the pandemic has affected those on the frontline at NYU Langone on specific psychosocial feelings such as 

. The results showed that 79% and 83% of frontline workers and faculty staff, respectively, expressed that they were dealing with fear and anxiety, along with 38% of the total population who suggested they may be struggling with depression.

Croll’s colleague, Jennifer Frontera, MD, professor of neurology, NYU Langone Grossman School of Medicine, and neurointensivist, claims the amount of death she saw was stunning, even as someone accustomed to seeing patients in their weakest stages of disease. In an interview with 

, Frontera discussed her experience even further and touched on aspects such as burnout and long-term mental state for patients who are released from the hospital.

The professor of neurology at the NYU Langone Grossman School of Medicine detailed the ways the COVID-19 pandemic impacted mental health of frontline clinicians.

Jennifer Frontera, MD: Mental Health Toll of Pandemic on Frontline Workers

"The normal number of people that die and the number of people that died during the COVID-19 surge were certainly different. When you can see that someone died of ARDS related to COVID, it’s easier to ascribe it to that factor.”

As the death toll in the United States has exceeded 200,000, many within the country have speculated the specifics of the count, and whether or not a patient’s death was directly caused by COVID-19 or an underlying symptom. Throughout the year, the data on the associations between the virus and neurologic symptoms have been well documented, with patients who contracted the virus showing slightly increased rates of stroke, encephalopathy, and hypoxic/ischemic injury, among others.

Despite the growing amount of research, questions remain about how COVID-19 affects specific pathologies within the brain. Determining cause of death can sometimes be easy if a patient has acute respiratory distress syndrome (ARDS), but other factors are not as clear cut, according to Jennifer Frontera, MD. Frontera, a professor of neurology at the NYU Langone Grossman School of Medicine, has served on the frontlines during the pandemic, and recently 

 that outlined new neurologic disorders documented in patients with COVID-19.

There are a number of challenges clinicians face when determining whether a patient has died from the virus, a symptom associated, or something that may have been underlying prior to diagnosis. Frontera sat down with 

 to discuss these challenges, and why excess mortality serves as an important statistic when understanding the virus’s surge in particular cities.

The professor of neurology at the NYU Langone Grossman School of Medicine outlined the confusion on whether deaths are related to COVID-19, a symptom associated, or previously unidentified underlying condition.

Jennifer Frontera, MD: Challenges in Determining Death Directly Related to COVID-19

"Can the virus get in the brain? It appears it can, but is it just entering tissue that’s already damaged? I don’t know.”

Throughout the COVID-19 pandemic, researchers have tried to understand whether the virus has a direct effect on the pathology of neurologic disorders. One of the earliest papers published in the 

, prominent agitation and confusion, and corticospinal tract signs. Increased rates of stroke, Guillain-Barré syndrome, and hypoxic/ischemic injury have also been documented among patients with COVID-19.

Recently released data from Jennifer Frontera, MD, and colleagues found that 13.5% of patients with COVID-19 hospitalized during the study timeframe developed a new neurologic disorder. They also found that patients with neurologic disorders were more often male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment scores.

The incidence of stroke, found in 1.9% of study population, has been a topic of discussion after 

 indicated a low risk of stroke. Frontera, a professor of neurology at the NYU Langone Grossman School of Medicine, believes that her research stands in good positioning along with what has published. She sat down with 

to discuss some of the inconsistencies in what has previously been reported and how those compare to her data.

The professor of neurology at the NYU Langone Grossman School of Medicine gave her thoughts on how her recently published data on neurologic disorders in COVID-19 compare to previously reported data. 

Jennifer Frontera, MD: Comparing COVID-19 Neurologic Data

"Toxic metabolic encephalopathy was the most common neurological disorder that we saw in the context of COVID. We know that that's common in general and hospitalized patients, but the severity of it was somewhat surprising to us, I would say.”

Throughout the COVID-19 pandemic, researchers have been trying to uncover more data detailing how the virus may impact neurologic pathology. In contrast to prior retrospective studies that focused on the conglomerate prevalence of non-specific neurologic symptoms along with neurologic diagnoses, Jennifer Frontera, MD, and her colleagues applied rigorous, standardized criteria to identify the prevalence of specific neurologic diagnoses in a prospective fashion.

Frontera, a professor of neurology at the NYU Langone Grossman School of Medicine, and colleagues found that 

 hospitalized during the study timeframe developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. Among them included toxic/metabolic encephalopathy, seizure, stroke, and hypoxic/ischemic injury.

 concerning some of the preliminary data on COVID-19 that had been published. We reconvened for another discussion, this time to get her perspective and thoughts on her study data, and whether the identified levels of new neurologic disorders surprised her.

The professor of neurology at the NYU Langone Grossman School of Medicine gave her reaction to the data she and colleagues published on neurologic disorders in patients with COVID-19. 

Jennifer Frontera, MD: Neurologic Implications of COVID-19 Infection

“We do certainly need to understand more about what’s going on with kids who have COVID-19—there are probably certain pediatric populations that are more susceptible or prone to having poorer outcomes than the general population.”

In early April, 1 of the first multi-case studies of neurologic manifestations of COVID-19 demonstrated complex central nervous system (CNS) involvement, thus raising further questions about its pathological mechanism. 

The retrospective case series, published in 

 found that neurologic symptoms including central and peripheral nervous system and skeletal muscular manifestations were commonly reported in patients with COVID-19.

Jennifer Frontera, MD, professor of neurology, NYU Langone, told 

 that although the data is promising, there are limitations and much of it is on still broad spectrum at the moment. The data itself does not differentiate between different strains of the virus nor does it detail the overlap from common neurologic symptoms to those caused by the virus.

Frontera discussed her thoughts on the data she has looked at, as well as her recommendations for how the data could be narrowed down to find more conclusive results.

The professor of neurology at NYU Langone shares her thoughts on the clinical data that has been released so far on patients with COVID-19.

Jennifer Frontera, MD: Reaction to COVID-19 Data

“We really do want to encourage folks that the organization in many of these hospitals is much better than it was at the beginning of this pandemic.”

As the curve of the COVID-19 pandemic takes a declining turn, the need for following protocol and maintaining social distancing becomes even more crucial, especially to prevent a second wave. While hospitals are still feeling the effects of overcrowding, doctors are still requesting that those who need medical attention seek it rather than forego a trip to the physician.

Jennifer Frontera, professor of neurology, NYU Langone, tells 

 that although we must maintain the course, patients should not be avoiding the hospital if they have a serious condition because of the fear of contracting the virus. She feels that in timely cases, such as strokes, patients must still seek emergency room care and should not feel the need to stay at home.

, Frontera details the importance of seeking emergency room care despite levels of COVID-19 being higher in a hospital setting. She also gives an overview of the standard protocol patients with neurologic symptoms should continue to follow.

The professor of neurology at NYU Langone gives her input on those who are nervous to take hospital trips, as well as the protocol for patients with neurological disorders as COVID-19 slows down.

Jennifer Frontera, MD: Utilizing Hospitals Amid COVID-19 

“The things that predispose folks to pulmonary manifestations are probably going to drive risk more so than other factors.”

The effects of COVID-19 on patients who are compromised has been well documented since the start of the pandemic. Social distancing and preventive measures have been put in place to not only slow the spread, but keep those who are of older age, have weaker immune systems, and/or have potentially life-threatening conditions away from the general population.

Jennifer Frontera, MD, professor of neurology, NYU Langone, claims that there is not enough data to support the thought that those with underlying neurologic conditions may be more at risk to the virus, but she does see the overlap. For instance, those who suffer from dementia and Alzheimer disease may be generally of older age, a factor that increases the risk of COVID-19 mortality.

, Frontera describes the ongoing research dedicated towards learning more about the risk factors associated with neurologic disorders and COVID-19. Additionally, she emphasizes why the need for long-term data is crucial to learning more about its effects.

The professor of neurology at NYU Langone discussed the risk of COVID-19 in patients with neurological disorders.

Jennifer Frontera, MD: Risk of COVID-19 in Patients With Neurologic Disorders

“We get to this point where we don’t know how much is casual versus causal because strokes happen in a high frequency within the population anyway.”

As the COVID-19 pandemic continues to sweep the country, neurologists are continually learning more about the neurological symptoms associated with the disease. At the moment, gathering imaging data has been challenging due to the lack of resources, overcrowding in hospitals, and difficulties transporting patients.

Jennifer Frontera, MD, professor of neurology, NYU Langone, is among many doctors in New York City who have been dedicating their time to care for patients with COVID-19 who also have preexisting neurologic conditions. She told 

that while a multitude of symptoms and conditions have been observed in this patient population, there is not enough evidence to make vast assumptions at this point.

In this interview, Frontera provides in-depth detail on her personal encounters with COVID-19 in a hospital setting and the documented neurologic symptoms she has seen in these patients. She also provides insight on the overlap surrounding neurologic symptoms that may or may not have been triggered by COVID-19.

The professor of neurology at NYU Langone detailed the neurologic symptoms that have been observed in patients with COVID-19.