With more and more neurologists now having been vaccinated, several scenarios have arisen for which there is no clear guidance and for which policies have varied across institutions. We asked experts in neurovirology and neuroimmunology to consider those situations based on real-life questions from our readers.
Joseph R. Berger, MD, FAAN, professor of neurology at the Hospital of the University of Pennsylvania; Richard Nowak, MD, assistant professor of neurology at Yale School of Medicine; and Kenneth L. Tyler, MD, FAAN, the Louise Baum endowed chair of neurology at University of Colorado School of School of Medicine, offered their expertise and advice on how to handle those situations based on available information at this time. Excerpted below are their answers.
How long after you have been diagnosed with COVID-19 should you wait to be vaccinated?
“At a minimum, infected individuals should wait until they are asymptomatic and have completed their quarantine/isolation period for approximately 14 days," Dr. Tyler advised. “However, since there is evidence that natural infection provides at least transient protection against reinfection, it would be reasonable to wait 90 days, as protection likely extends at least that far after natural infection, and get vaccinated as appropriate for their assigned group."
“If you've had COVID and survived it, the thought is that you have a natural immunity to SARS-CoV-2," Dr. Berger said. “The durability of the immune response is uncertain," however, he continued, citing a few reports of people acquiring a repeat infection, but acknowledging that those have been typically mild.
Dr. Berger also pointed out that the downside of getting vaccinated on the heels of the infection is that the neutralizing antibody to the spike protein triggered by natural infection—in the case of Pfizer and Moderna vaccines—may blunt the magnitude of the response to the vaccine. “While unlikely to be dangerous, the immune response would be less robust," he speculated.
“While there are not specific rules per se, it would be important to wait until COVID-19 is fully resolved and the patient is asymptomatic," Dr. Nowak suggested. He would recommend waiting a minimum of one month but added that this may also depend on whether specific treatments were received by the patient that may result in needing to wait longer (up to three months).
What if you get vaccinated, only to discover that you are symptomatic hours or days later, and test positive? Will you risk a hyperimmune response and can you receive the second dose of the vaccine?
“This scenario is not so uncommon," Dr. Tyler said. “In the Pfizer vaccine trial, for example, 39 of the 50 individuals who got COVID in the vaccination group did so after their first dose and before their second dose. The data suggested that one dose provides 'partial protection' estimated at approximately 52 percent vaccine efficacy (95 percent CI was approximately 30-68 percent)."
Dr. Tyler acknowledged that recommendations were vague on how to handle this situation. He added that he would keep as close to the schedule as possible—if you are asymptomatic and out of quarantine or isolation, you should receive a second dose as originally close to scheduled. But, he added, “It is likely that the infection provides a layer of protection, so it would not be wrong to defer the second dose for say, 90 days, either."
Dr. Nowak concurred that the second of the two-shot vaccines should not be administered during the COVID illness, and all three experts agreed about an absence of data regarding a hyperimmune response.
Dr. Berger explained that the absence of reports thus far in many thousands of subjects who were vaccinated in the trials alone, makes this unlikely. “But I am open to changing my mind," he added, if additional reports indicate otherwise.
If you have one or more autoimmune conditions, are your risks of side effects greater?
“Remember that the Pfizer and Moderna vaccine are not live virus vaccines, so there is no contraindication to receiving them if you are immunocompromised or have an autoimmune condition," Dr. Tyler said. He also suggested that it may be worthwhile for those populations to undergo a COVID antibody test (of the type which detects antibodies to the S protein) about three weeks or so after vaccination to be certain that an antibody response developed. He speculated that some patients with autoimmune conditions could conceivably fail to make a robust response either due to immunomodulatory treatments or their underlying disease.
“Our rheumatology division at the University of Pennsylvania is recommending the vaccine to all their patients and we certainly are to our patients with multiple sclerosis, neuromyelitis optica, and other autoimmune neurologic disorders," said Dr. Berger, who agreed that there is no increased risk for those with autoimmune conditions.
“There is a concern that some of the drugs we use for these conditions, for example, anti-CD20 monoclonal antibodies for MS, will blunt the humoral immune response, and there is evidence of this as demonstrated by the VELOCE study with other vaccines. As a consequence of the latter study, we have been recommending that people avoid the vaccine proximate to their infusions, however, we simply need more data."
Dr. Nowak acknowledged that while individuals with autoimmune disorders may be at increased risk for infection due to immunosuppressive therapy, the literature provides perspective on the risk of exacerbations of disease and prior vaccinations.
“Multiple studies have demonstrated either no risk or a small to negligible increased risk of exacerbation or recurrence of myasthenia gravis and chronic inflammatory demyelinating polyneuropathy after influenza vaccination, for instance." Additionally, Dr. Nowak noted that in a recent, prospective, double-blind, randomized-controlled study, patients with MG did not experience clinical exacerbations following the influenza vaccine. “We do not have such data with COVID-19 vaccines as yet," he pointed out.
What if you are vaccinated, but cannot get the second vaccine within the recommended window? Can you still get it later?
“Yes, you should get it later as the effect of a single dose is incomplete and it is believed that a 'booster' helps insure more long-lasting immunity," said Dr. Tyler. He advised that the second dose should be administered as close to the originally scheduled date as is practical, as we do not know the effects of altering the tested schedule on efficacy or durability.
Dr. Berger agreed and mentioned efforts such as those in the UK (and discussions now in the US) to broaden the availability of the vaccine by providing only one dose with the second delayed until the population has been vaccinated.
“I concur with Tony Fauci on this one—that a robust immune response has only been demonstrated with the timing followed in studies of the second dose; on the other hand, were one to have it administered outside this time window, I would imagine that it would still elicit a boosted immune response."
Can we test for antibodies after the two doses, and if so, how long do we expect those to last?
“It is important to remember that the Pfizer and Moderna vaccines result in antibodies developing only against the S protein of the virus, whereas natural infection generates antibodies against a wide range of viral proteins," Dr. Tyler emphasized.
“Depending on the specific test, the emergency use authorization-approved antibody tests in US are designed to detect antibodies against either the S protein, which would be positive after vaccination or natural infection or the Nucleocapsid phosphoprotein N, which would not be positive after vaccination but would be after natural infection," he explained. “We generally presume antibody levels reach a peak at one to three weeks after infection or immunization, but we do not yet know how long they will last (after either natural infection or vaccination)."
“We do believe this will be at least three months after natural infection and likely longer (six or more months)," he added, “but we don't yet know if this will be the same or longer after vaccination, and it remains unclear for the moment, therefore, if repeated immunization—for example, on an annual basis, akin to [getting the] seasonal influenza—will be needed or whether this could be less frequent (akin to tetanus) or even (although unlikely) lifelong.
Can we still transmit the virus to others post-vaccination?
“We don't have any data yet on whether vaccination with the Pfizer or Moderna vaccines will decrease transmission," Dr. Tyler admitted. “Experience with polio vaccines suggested that the live oral vaccine was much better at stopping transmission as it generated high levels of mucosal immunity (IgA), whereas the killed polio vaccine (Salk) protected against paralytic disease but did not work as well in stopping transmission; it generated mostly IgG Abs which do reach mucosal surfaces but in smaller amounts, etc."
So, until these data are available for these vaccines—and it may differ depending on type of vaccine—Dr. Tyler advises that we should assume the major role of the vaccine is to prevent the vaccine recipient from getting symptomatically infected, but we do not know if it will stop recipients from getting infected and being asymptomatic yet still able to shed virus and infect others.
All three experts recommended that until this is known even vaccinated individuals should continue to use protective measures: wear masks, physically distance, and engage in hand washing.
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).
Zinman L, Thoma J, Kwong JC, et al. Safety of influenza vaccination in patients with myasthenia gravis: A population-based study. Muscle Nerve 2009;40(6):947-951.
Tackenberg B, Schneider M, Blaes F, et al. Acetylcholine receptor titers and clinical course after influenza vaccination in patients with myasthenia gravis: A doble-blind randomized controlled trial (ProPATIent Trial). EBioMedicine 2018; 28:143-150.
Kuitwaard K, Bos-Eyssen ME, Blomkwist-Markens PH, van Doorn PA. Recurrences, vaccinations and long-term symptoms in GBS and CIDP. J Peripher Nerv Syst 2009;14(4):310-315.