​As the number of cases of coronavirus, or COVID-19, grows globally and across the US, neurologists should be vigilant for possible signs of the virus and stay current on what precautions their institutions and public health officials are recommending for patients, neuroinfectious disease experts told Neurology Today.

COVID-19 has shown itself to be a respiratory disease marked by cough, fever, and shortness of breath, and in a small number of cases it can lead to severe respiratory problems and death. While understanding of the coronavirus is still unfolding, there are hints that it might have a neurologic component in some instances as well.

Kenneth L. Tyler, MD, FAAN, Louis Baum Endowed Professor and chair of neurology at University of Colorado School of Medicine, noted that earlier this year a report from three COVID-19-designated hospitals in Wuhan, China, indicated that more than one-third of coronavirus patients had some type of neurologic symptom, including altered consciousness, evidence of skeletal muscle damage, and acute cerebrovascular disease. [The report, which was posted online on a preprint server (MedRxiv), has not been peer-reviewed.]

"These [symptoms] were far more common in severe disease," Dr. Tyler said. "We still don't know whether the neurologic complications are reflective of direct viral injury or due to the secondary or systemic effects of infection."

Dr. Tyler said it makes sense that COVID-19 would have neurologic manifestations because other coronaviruses that affect humans can invade the central nervous system.

For instance, as cases accumulated during the outbreak of Middle East respiratory syndrome (MERS), some neurologic complications were reported, he said.

"There were rare reported cases of what seemed to be direct neurologic injury caused by the [MERS] virus," Dr. Tyler said. Rare neurological complications were also seen with severe acute respiratory syndrome (SARS), with at least one case showing evidence consistent with direct viral infection of the central nervous system, Dr. Tyler said.

"We should be vigilant to see if we are going to see that occur (with COVID-19) as more cases and experience accumulate," he said.

Patients in High-Risk Categories

Neurologists also need to stay vigilant as the coronavirus epidemic unfolds because many of their patients fall into high-risk categories that include older persons (generally 60 or older) and those with underlying medical conditions such as heart disease, lung disease, and diabetes.

People with neurologic conditions such as multiple sclerosis (MS), Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and myasthenia gravis, could also be at high risk and should be advised to follow advisories from the Centers for Disease Control and Prevention (CDC).

The National Medical Advisory Committee of the National MS Society advises people with MS to continue their disease-modifying therapies (DMTs), for example, and discuss risks with their physicians prior to stopping a DMT.

The CDC and other public health officials have urged high-risk individuals to stay away from crowded situations and travelling; specifically they have advised older Americans and those with underlying medical conditions to stay off cruise ships.

Dr. Tyler said a huge challenge presented by a novel virus such as COVID-19 is trying to understand "who gets this and why." On the other hand, he said, "we don't fully understand what components of the immune system are important in protecting against this."

Avindra Nath, MD, FAAN, intramural clinical director of the National Institute of Neurological Disorders and Stroke (NINDS), noted that early reports indicate some COVID-19 patients experience symptoms of headache, stiff neck, and muscle ache, which, he said, may be suggestive of viral meningitis.

It is possible that the respiratory aspect of COVID-19 is so overwhelming in patients who end up dying that they don't live long enough "for the virus to cause damage to the brain," said Dr. Nath, who is director of the Section of Infections of the Nervous System at NINDS. He added that deaths attributed to respiratory failure may in fact include brainstem involvement that is not apparent.

"Once you have multiorgan failure, the brain is compromised," he said, "making it difficult to differentiate between effects of the virus itself versus the effects of hypoxia and metabolic abnormalities."

Dr. Nath said the extent to which COVID-19 can affect the central nervous system will likely become apparent as more findings emerge from epidemiologic data and autopsy studies.

Cases Mount

On March 11, the World Health Organization (WHO) labelled the spread of COVID-19 a pandemic as the virus spread to more than 114 countries. As of today, there were more than 114,243 reported cases of COVID-19 worldwide and the virus had killed more than 4,000 people. In the US, there were more than 700 cases and 26 deaths. [As this story posts, these numbers are likely to increase.]

There is no antiviral therapy for COVID-19. According to the WHO, the global mortality rate for the novel virus is 3.4 percent, though experts say these estimates should be treated with caution because not all patients have concluded their illness (that is, recovered or died) and the true number of infections and full disease spectrum are unknown.

How to Advise Patients

Neurologists are facing questions from patients and families about whether they should take any extra precautions against the coronavirus because of their disease.

Shibani S. Mukerji, MD, PhD, associate director of the neuro-infectious diseases unit at Massachusetts General Hospital, said patients with ALS and other conditions that affect breathing should adhere to the CDC's recommendations for high-risk groups. She said patients and families that rely on a caregiver should have a contingency plan in place in case that person gets exposed to coronavirus and has to stay away.

Dr. Mukerji said it's a good idea for doctors, on their part, to instruct patients with minor cold-like illness to reschedule their appointments and to offer "telehealth visits" with patients as a way to reduce the potential for community transmission.

Dr. Mukerji, an associate professor of neurology at Harvard Medical School, said it also makes sense for attending physicians in hospitals to limit the number of residents and medical students in their entourage when they make bedside visits.

"We love teaching," she said, but cutting back the number of non-essential people doing rounds helps limit possible transmission of coronavirus and cuts back on the use of protective gear.

Dr. Mukerji said physicians should also disinfect their phones, pagers, and tablets, be strategic with their hands, and follow the proper technique for removing personal protective gear. (There are some good how-to video on YouTube, she said.)

"These are just good practices," she said. "Knowing that everyone in your organization knows how to wash their hands is not a small thing."

Felicia Chow, MD, MAS, a neurologist and expert in neuroinfectious diseases and HIV neurology at University of California, San Francisco (UCSF) and Zuckerberg San Francisco General Hospital, said she and her colleagues at UCSF were instructed to convert all in-person visits to video visits. At Zuckerberg San Francisco General, non-urgent patients are being scheduled for four weeks or more out.

"For many of our patients, a video visit is totally feasible and we can accomplish what needs to be done for a follow-up," Dr. Chow said. "In fact, many of my patients are travelling from far away and they actually prefer a video visit."

Dr. Chow said that while for now neurological complications do not seem to be a big concern with coronavirus, neurologists should stay up to date with reports coming out because "we may hear more as things evolve."

David B. Clifford, MD, FAAN, the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology at Washington University School of Medicine in St. Louis, said that neurologists need to be vigilant for the possible impact of coronavirus on their patients.

He said it is hoped that patients, such as those with multiple sclerosis who are taking immune-modulating therapies, are not at heightened risk of getting COVID-19, but he said patients should follow the general recommendations for avoiding high-risk situations.

"In general, I advise my patients to live their lives as fully as they can," he said. "However, we need more data from close observation of our patients as this pandemic evolves."

Disclosures: Drs. Tyler, Nath, Mukerji, Chow, and Clifford had no competing interests.

Link Up for More Information:

CDC resources on COVID-19: https://www.cdc.gov/coronavirus/2019-ncov/index.html. Accessed March 9, 2020.

World Health Organization resources on COVID-19: https://www.who.int/health-topics/coronavirus. Accessed March 9, 2020.

Beijing hospital confirms nervous system infections by novel coronavirus. http://www.china.org.cn/china/Off_the_Wire/2020-03/05/content_75778340.htm. Accessed March 10, 2020.

Mao L, Wang M, Chen S, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: A retrospective case series study. medRxiv 2020; Epub 2020 Feb 25.





