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New Findings on Neurologic Effects of COVID-19 in Kids, Adults, and MS Patients

Article In Brief

This AAN plenary session highlights the neurologic effects of COVID-19 in children, adults, and individuals with multiple sclerosis.

This year's Hot Topics Plenary at the 2021 virtual AAN Annual Meeting covered the subject on most people's minds this year—COVID-19. The focus? New findings on the neurologic effects of COVID-19 in children and adults—and in particular in people with multiple sclerosis (MS).

A team of British investigators in one study reported that half of those who developed the rare but serious condition linked to COVID-19, multisystem inflammatory syndrome in children (MIS-C), had significant neurologic signs or symptoms when they entered the hospital.

Another international team reported that in adults, those with pre-existing neurologic diseases were at greatly increased risk of being hospitalized and dying if they developed COVID-19, and new-onset neurologic complications were a common complication among all patients hospitalized due to the illness.

A third study from Italy found that people with MS taking anti-CD20 therapies (ocrelizumab or rituximab) were at twice the risk of severe or fatal outcomes compared to MS patients taking other therapies. In contrast, those receiving interferon had half the risk of such outcomes compared to other MS patients.

Altogether, the new studies demonstrate the continued torrid pace of COVID-19 research bubbling out of academic centers around the world.

“There is still so much we don't know about this virus,” said Paul George, MD, PhD, FAAN, vice chair of AAN's Science Committee and assistant professor of neurology and neurological sciences at Stanford School of Medicine. “The fact that so many develop neurologic signs and symptoms shows the effect this virus has on the nervous system and indicates the further research that needs to be performed to help neurologists better treat these symptoms.”

Natalia S. Rost, MD, FAAN, chair of AAN's Science Committee and chief of the stroke division in the department of neurology at Harvard Medical School, told Neurology Today: “The neurologic symptoms caused by the disease and the possible long-term neurologic effects reinforce the need to better understand COVID-19 and the need for development of effective therapies.”

Neurologic Symptoms in Children

The study of MIS-C involved 46 children who presented at Great Ormond Street Hospital between April 4, 2020, and September 1, 2020, fulfilling the criteria for the disorder.

Criteria included fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with more than two organ systems involved. In addition, subjects must be positive for current or recent SARS-CoV-2 infection or recent exposure to a suspected or confirmed case.

The median age of the children was 10.2 years. Thirty of the children (65.2 percent) were boys, and 37 (80.4 percent) were not White. Twenty-four of the children (52.2. percent) had new-onset neurological symptoms, including headaches (n=24), encephalopathy (n=14), dysarthria/dysphonia (n=6), hallucinations (n=6), ataxia (n=4), peripheral nerve involvement (n=3), and seizures (n=1).

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“The neurologic symptoms caused by the disease and the possible long-term neurologic effects reinforce the need to better understand COVID-19 and the need for development of effective therapies.”—DR. NATALIA S. ROST

One of the patients had 118 leukocytes in CSF. An excess of slow activity was found in 14 out of 15 children who had an EEG, and myopathic and neuropathic changes were seen in four of seven who underwent nerve conduction studies, and electromyography children with neurological involvement had higher peak inflammatory markers and were more likely to require mechanical ventilation and inotropic support in PICU (p<0.05).

In a prepared statement, first author Omar Abdel-Mannan, MD, FAAN, of University College London urged neurologists and pediatricians to be on guard for the condition.

“Children who develop this condition should definitely be evaluated for neurologic symptoms and longer-term cognitive outcomes,” Dr. Abdel-Mannan said. “More studies are needed involving more children and following children to see how this condition changes over time and if there are any longer-term neurocognitive effects.”

Dr. Rost said the study “supports the data that the more severe manifestations of COVID-19 infection have a greater prevalence of the nervous system involvement.”

Neurologic Symptoms in Adults

Established on March 21, 2020, the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID) was co-founded by Sherry H-Y. Chou, MD, associate professor of critical care medicine, neurology, and neurosurgery at the University of Pittsburgh School of Medicine.

During the AAN's Neuro-COVID plenary session, Dr. Chou presented a first look at data from 214 patients in the European Academy of Neurology COVID-19 registry (ENERGY), 475 patients predominantly from the United States who had been entered into a neurology cohort (“COVID-Neuro”), and another 3,055 patients in a more general population of COVID-19 patients (“All-COVID”). All required hospitalizations.

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“Perhaps patients on interferon are less likely to be hospitalized as providers are less concerned about their overall risk for COVID-19 disease severity, given they may be less disabled, have fewer comorbidities, and not be immunosuppressed.”—DR. DINA JACOBS

The key findings of the analysis were that patients hospitalized for COVID-19 had a high rate of pre-existing neurologic disease, as well as a high rate of developing new-onset neurologic disorders, both of which significantly increased their risk of death.

Overall, 45 percent of the ENERGY patients had pre-existing neurologic disease, as did 36 percent of the COVID-Neuro patients and 23 percent of the All-COVID patients.

Clinically- or laboratory-verified new-onset neurologic disorders observed during hospitalization included acute encephalopathy—in 24 percent of the ENERGY group, 54 percent of COVID-Neuro patients, and 50 percent of All-COVID. Coma occurred in 10 percent, 25 percent, and 17 percent of the same patient groups, respectively. Stroke occurred in 19 percent of both the ENERGY and COVID-Neuro patients, but in only 3.1 percent of the All-COVID patients.

A peculiar pattern emerged in the incidence of self-reported vs. clinically verified neurologic disorders when broken down by age. The incidence of self-reported headache, for instance, was 49 percent among those under age 40, 45 percent among those aged 40 to 60, 33 percent among patients aged 61 to 80, and 23 percent in those over age 80. Likewise, the incidence of anosmia or ageusia was 41 percent among those under age 40, 28 percent among those between 40 and 80, and 23 percent among those over 80.

By contrast, the incidence of clinically-verified acute encephalopathy was observed in 33 percent of patients under 40, 41 percent of those aged 40 to 60, 58 percent of those aged 61 to 80, and 74 percent of patients over 80.

That divergent pattern between clinically verified and self-reported neurologic symptoms was also seen in the risk of death. Adjusted for confounding variables, the odds ratio for risk of death among COVID-19 patients with clinically verified signs and symptoms of neurologic disorders was 5.99 (p<0.001) compared to those without such signs and symptoms.

By contrast, Dr. Chou reported, “Headache and anosmia or ageusia were actually inversely associated with death.” Those who reported headache had just one-third the risk of death of those who did not. But, she added, “We do not believe there is a biologically protective effect where headache prevents one from dying of COVID-19. Perhaps the fact that someone is well enough to report such symptoms may drive this association.”

In summary, Dr. Chou said, “We found that acute encephalopathy, coma, and strokes are the most prevalent acute neurological manifestations in patients hospitalized for COVID-19. We also know now that having a clinically verified neurologic sign and syndrome increases mortality risk by nearly six-fold.”

In an interview with Neurology Today, Dr. Chou said: “Often in the press, people talk about having high blood pressure or diabetes as important underlying conditions to be concerned about. The take-home message of our study is that having a pre-existing neurologic condition is another strong risk factor for being hospitalized due to COVID-19.”

MS Treatments, COVID-19 Disease Severity

An Italian team of investigators analyzed outcomes in 902 MS patients with either confirmed or suspected COVID-19 and how they fared based on their MS therapy.

The number of patients who required ICU treatment or died was eight of 95 (8 percent) among those treated with anti-CD20 therapies; 0 of 84 among those treated with Interferon, and 37 or 723 (5 percent) among those treated with other drugs.

In a multivariable analysis, independent risk factors for a severe COVID-19 outcome were age (OR=1.05, p<0.001), score on the Expanding Disability Status Scale (OR=1.13, p=0.02), male sex (OR=1.44, p=0.057), and disease-modifying treatment used. Treatment with anti-CD20 therapies (ocrelizumab or rituximab) increased the risk of severe outcome (OR=1.99, p=0.035), and treatment with interferon reduced risk (OR=0.48, p=0.05) as compared to treatment with other disease-modifying MS therapies.

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“Often in the press, people talk about having high blood pressure or diabetes as important underlying conditions to be concerned about. The take-home message of our study is that having a pre-existing neurologic condition is another strong risk factor for being hospitalized due to COVID-19.”—DR. SHERRY H-Y. CHOU

Maria Pia Sormani, PhD, first author of the paper and a postdoctoral fellow in the department of health sciences at the University of Genoa, noted that the analysis controlled for confounding variables.

She added, however, that it would be unlikely for neurologists to switch the MS treatments they prescribe based solely on her study's findings. “The risk/benefit profile is probably in favor of continuing the high-power therapies,” she said.

Dina Jacobs, MD, clinical director of the Penn MS and Related Disorders Program at the University of Pennsylvania Hospital, said of the study's findings, “Perhaps patients on interferon are less likely to be hospitalized as providers are less concerned about their overall risk for COVID-19 disease severity, given they may be less disabled, have fewer comorbidities, and not be immunosuppressed.”

Dr. Jacobs also noted an age correlation with those taking anti-CD20s. “Younger patients drove the increased numbers of severe COVID-19 as defined by pneumonia or hospitalization.” That finding, she said, was surprising.

Link Up for More Information

• Abdel-Mannan O, Penner J, Hassell J, et al.AAN Abstract: Neurologic and radiographic findings associated with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children https://index.mirasmart.com/AAN2021/.
    • Sormani MP, De Rossi N, Schiavetti I, et al.AANAbstract S28.002: Different disease modifying therapies can increase or decrease Covid-19 severity in multiple sclerosis https://index.mirasmart.com/AAN2021/PDFfiles/AAN2021-002021.html.
      • Paul N, Safronova A, Altamirano V, et al.AAN Abstract S31.001: Acute hospital outcomes COVID-19 associated neurologic dysfunction https://index.mirasmart.com/AAN2021/PDFfiles/AAN2021-002053.html.