Subscribe to eTOC

Neurovirologists—On How to Advise Neurology Patients on COVID-19 Vaccines

Vaccines for COVID-19 are on the way, promising to surely, if only slowly, reduce the rates of infection and death from the world's worst pandemic in a century. But questions remain, pending more publication of the results in peer-reviewed journals, about how long immunity will last and the best ways to distribute and administer the vaccine.

Neurology Today spoke with three experts in neurovirology about what neurologists should know about the vaccines and how they may advise their patients about getting vaccinated.

“The widespread availability and administration of the vaccines is going to be a game-changer," said Kenneth L. Tyler, MD, FAAN, the Louise Baum endowed chair of neurology at University of Colorado School of School of Medicine. “The tunnel we are in is still long, but there is a light at the end."

Vaccines Are Safe and Effective

Among the many vaccines being developed worldwide, three have announced early results that are highly promising. The first and most important message from all three experts is that these three vaccines—from Pfizer and BioNTech, Moderna, and AstraZeneca—appear to be safe for neurology patients across the spectrum.

“These are not vaccines made from a live or attenuated virus, and there is no evidence that I've seen that they will be contraindicated in any patient with a neurologic disorder," said Joseph R. Berger, MD, FAAN, professor of neurology at the Hospital of the University of Pennsylvania.

“We have immunized our patients for years, and we haven't seen issues arising from that," including the seasonal flu, said Richard Nowak, MD, assistant professor of neurology at Yale School of Medicine.

And the efficacy of at least two of the three is nothing short of spectacular, Dr. Tyler said. “I was stunned by the results as I understand them of the Moderna and Pfizer vaccines: greater than 90 percent efficacy, a significant reduction in case numbers, good immunogenic responses across racial and age groups, minimal acute reactions, and minimal safety concerns. And all this was put together in less than a year—I think that is remarkable."

How They Work

The Pfizer/BioNTech and Moderna vaccines both deliver messenger RNA for the SARS-CoV-2 spike protein, “probably the most important protein on the virus," explained Dr. Berger, because it allows the virus to bind to human angiotensin-2 receptor, expressed by lung, vascular tissue, brain, and other tissues. The mRNA is enclosed within “lipid nanoparticles," which encapsulate and protect it. Once injected, the mRNA is taken up by muscle cells, which express the spike protein and display it on the cell surface. Immune system recognition of this foreign protein leads to a rapid and robust immune response.

“The speed with which these vaccines have been developed, and their efficacy and safety, suggest this approach may be the way to go for vaccine development in the future," Dr. Berger said.

The AstraZeneca vaccine takes a different approach, delivering the gene for the spike protein on board a non-replicating chimpanzee adenovirus; uptake and expression of the gene again leads to display of the protein and an immune response.

Many other companies are developing their own vaccines, using these and other strategies, and it appears likely that by early 2021, vaccines will be available, if in limited supply, throughout the US.

Meanwhile, the US Food and Drug Administration has approved the emergency use authorization request from Moderna and Pfizer/BioNTech for their mRNA vaccine—BNT162b2— for people aged 16 and older. To date, the UK and Canada have granted limited approval to this vaccine, and hospitals in the UK have begun to immunize people this week.

On December 10, the New England Journal of Medicine published findings today for the BNT162b2 vaccine. More than 43,000 individuals ages 16 and above were randomized to receive two 30-μg doses of vaccine or placebo, 21 days apart.

Among the data released:

  • Eight individuals in the vaccine group, and 162 in the placebo group, developed COVID-19 at least seven days after the second dose, for an effectiveness of 95 percent.
  • The vaccine's effectiveness was largely independent of age, sex, race, ethnicity, obesity, and presence of pre-existing conditions.
  • Mild-to-moderate injection site pain occurred in more than three-quarters of younger patients and more than two-thirds of older patients receiving the vaccine. Fatigue, headache, and muscle pain were also common.
  • While the study was not designed to test the efficacy of a single dose, it was observed to be 51 percent efficacious in the time between the two doses.

“This rigorous demonstration of safety and efficacy less than 11 months [after development of the vaccine was begun] provides a practical demonstration that RNA-based vaccines, which require only viral genetic sequence information to initiate development, are a major new tool to combat pandemics and other infectious disease outbreaks," the authors concluded.

Who Will Get the  Vaccine First?

Priorities for vaccination are still being discussed, and there does not appear to be a single nationwide determination of who should be vaccinated first. Instead, it appears states will be charged with making their own decisions; some states may devolve that responsibility even further down the chain. First responders and hospital personnel involved in critical care are likely to be high on every list.

Some neurology patients may receive priority by virtue of their condition, such as those with weakened respiratory systems due to neuromuscular disease. Because of the high risk of mortality, frail patients—from advanced Parkinson's disease, multiple sclerosis, or amyotrophic lateral sclerosis, for instance, might also receive priority. Patients with dementia may be candidates for early treatment, Dr. Tyler noted, if they are unable to consistently practice social distancing or wear a mask.

Patients with multiple sclerosis or myasthenia gravis who receive immunosuppressive therapy are not at higher risk of contracting COVID-19, according to a recent study co-authored by Dr. Nowak. The study collected data from over 33,000 patients with an autoimmune neuromuscular disease and over 42,000 patients with multiple sclerosis. Those receiving immunosuppressive therapy did not become infected with COVID-19 at any higher rate than those not receiving it, but if immunosuppressed neuromuscular patients did become infected, they required hospitalization more than twice as often as the non-immunosuppressed patients.

Vaccine Timing for Immunosuppressed Patients

Vaccination of patients receiving immunosuppressive therapy may require consideration of timing and potential modification of treatment, said Dr. Nowak. “The major question is what baseline therapy the patient is on, because this can affect the efficacy of the immunization. For example, if the patient is receiving B cell depletion therapy, such as with rituximab, the effectiveness of the vaccine may be diminished."

That was the conclusion of the recently published VELOCE study, which showed that the B cell depletor ocrelizumab led to a blunted antibody response to a variety of antigens.

To avoid this problem, Dr. Nowak recommends timing vaccine administration towards the end of the treatment cycle, just before the next dose is due, typically six months after the last one. “That allows the patient to mount an adequate immune response to the vaccine. Then two weeks later, we can start again with immunosuppression. This is not new—we do this with the flu shot every year," he said.

“Some of our oncology colleagues may immunize even three months after the last treatment," he continued, “because there are B cells emerging. We can't detect them in the circulation, but they may be in the bone marrow. That said, I usually wait the full six months, plus or minus a couple weeks. I am much more comfortable about the effectiveness of the vaccine at that point."

Dr. Nowak has begun to talk with his patients about adjustments to treatment timing to allow vaccination, but without definite access to the vaccine, it is still too early to make firm plans for delaying a treatment.

Prospects for the Future

What does the future hold? “By my nature, I am an extreme optimist," Dr. Berger said. “By the end of the summer, I expect almost all of the United States population is going to have been vaccinated, and this will all be very much in our rearview mirror. I think a year from now, if not sooner, we are going to go back to shaking hands, back to seeing each other without masks. We are going to go back to being the social creatures that we are, and it is going to happen very rapidly in my opinion."

Dr. Nowak is not so sure. “A year from now, things are certainly going to be better, but I think we are still going to be in the process of vaccinating people, and people will still be getting COVID-19. The impact will start to lessen, but it will probably be at least a couple years before it is a non-issue."

“I think the odds for personal protection from the vaccine are excellent," Dr. Tyler said, meaning that someone who has been vaccinated is likely to be able to have confidence that they are immune. “But we are going to have to work hard to get dissemination, administration and widespread uptake of vaccination to a broad enough population to generate herd immunity. That's what we will need to break the back of the epidemic, and that's more challenging. But I am optimistic."

Disclosures: Drs. Tyler, Berger, and Nowak have no disclosures relevant to this story.​

Link Up for More Information:

Bar-Or A, Calkwood JC, Chognot C, et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Neurology 2020;95(14):e1999-e2008.

Kovvuru S, Nalleballe K, Onteddu SR, et al. Immunosuppression in chronic autoimmune neurological disorders during the COVID-19 pandemic. J Neurol Sci 2020:117230.

Polack FP, Thomas SJ, Kitchen N, et al, for the C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; Epub 2020 Dec 10.