Neurologic Complications With Vaccines: What We Know, What We Don't, and What We Should Do

Neurology.org - Dr. Avindra Nath (NIH) - First published April 25, 2023 Researchers at the National Institutes of Health have evaluated neurological side-effects to the Covid vaccines. While this topic may be seen as controversial, these researchers have attempted to publish several case reports and studies. The National Institutes of Health have not provided guidance or official communication on the research that has been done there. This latest study covers a comprehensive review of what is known about the Covid vaccines so far, potential solutions for future acknowledgement, research and therapies.  

A Short Summary:

“Despite such measures, vaccines are not without side effects including those that impact the nervous system. Numerous case reports and case series point to these possibilities… Action is needed that brings together manufactures, health care agencies, clinical and bench scientists and legislatures on a global platform to investigate vaccine related neurological adverse events and develop ways to prevent and treat them.”  

Potential neurological complications to watch for 

"The published literature has a large list of case reports and case series with a wide variety of neurological manifestations attributed to vaccines. While most side effects of vaccines are benign and transient, such as headache or fatigue, more serious side effects, including devastating neurological complications may occur." "The same data set reveals that serious neurologic complications after vaccine administration across all vaccine types are extremely rare. Nonetheless neurological manifestations that are potentially attributed to vaccines include immune mediated syndromes; major categories of which include Guillain Barre Syndrome, small fiber neuropathies, transverse myelitis and acute disseminated encephalomyelitis." Spectrum of neurological complications following COVID-19 vaccination, Neurol Sci 2022; 43(1):3-40.  

Challenges to document complications

"Milder complications may have predominantly subjective symptoms which can be challenging to document. For example, our group reported cases of peripheral neuropathies temporally associated with the SARS-CoV-2 vaccines.12 Many patients had subjective symptoms that were dismissed. Diagnosis required skin biopsies and/or autonomic testing, procedures that are only available in specialized centers. This poses challenges in diagnosing these conditions at a global level."

Neuropathic symptoms with SARS-CoV-2 vaccination

  "Often these manifestations occur weeks or days after the vaccination and since it can also occur following many other infections or even without an identifiable precipitating cause, it is challenging to determine the exact cause or to attribute it to the vaccination. Certain manifestations such as tachycardia and allergic reactions can occur within minutes of the injection and others such as fever, chills, myalgia, arthralgia, and injection site reaction can occur within a day or so. Due to the close temporal association, these complications are relatively easier to attribute to the vaccine and leaves little prospect of an alternative etiology." "It is possible to raise concern about cause and effect when a rare manifestation occurs soon after an exposure to an agent even if a small population is affected and if the background rate of such a manifestation is rare in the unvaccinated population...This back and forth of associations highlights the complexity of associating a rare neurological disease with vaccinations with the risk of false attributions to the vaccine resulting in damaging consequences." "Further, neurological manifestations are often hard to diagnose, they require special expertise and may require sophisticated investigations which are not readily available. The medical system is also overburdened, and patients report long wait-times before they can see a neurologist. Considering the exposure of hundreds of millions or possibly billions of people to these vaccines even a rare event could affect a substantial number of individuals. Thus, larger active surveillance programs that pay special attention to gathering information on neurological complications and where information can be gathered prospectively are necessary."  

There is a great need to conduct research for identifying the underlying factors and subcellular mechanisms that result in the neurological manifestations from vaccines. Research may also guide the development of safer vaccines.

 

Etiology and Therapy

"Most likely mechanisms causing vaccine-mediated neurological manifestations are related to aberrant immune responses. Hence, one would reason that immunotherapies would be a reasonable treatment option. In fact, several case reports and case series seem to support this approach."  

Responsibility of Monitoring Safety

"Role of various organizations and possible solutions Vaccine adverse event monitoring is not the portfolio of the National Institutes of Health (NIH) which is focused on disease oriented and fundamental research. The United States Food and Drug Administration (FDA) evaluates the risks of the vaccines prior to approval. This is a rigorous process and picks up the common side effects. For example, the phase III randomized clinical trials of the mRNA vaccines show 12.5 additional serious adverse events per 10,000 vaccinated compared to placebo." (paper)

No one has primary responsibility for investigating the mechanisms and treatments for side effects of vaccines.

   

PREP ACT and Manufacturer Immunity

"Thus, the bill provides immunity to drug companies from being sued for any unforeseeable side effect of vaccines. The PREP Act created a fund called the Countermeasures Injury Compensation Program (CICP). This provides compensation to the people who may have been injured from the vaccine. This was done to incentivize the companies to take on the risk for development of the vaccines. However, no funds were obligated to provide any provisions for studying the underlying mechanisms of these side effects, for developing ways to prevent them or for treating them…

As a result, there is a gap in knowledge about the post-marketing neurological side effects of the vaccines, and lack of an organized effort to provide a definitive diagnosis or develop treatments for these patients"

"A simple solution might be to convene all stakeholders preferably at a global level to investigate the side effects and provide funding to conduct research to study and treat them (Table 2). Cooperation of the vaccine manufacturers would be critical since only they have access to proprietary information about the vaccines. This will help develop a better understanding of the spectrum of post-marketing side effects, identify those that are causally related and help develop ways of mitigating them. Above all it will build public trust and will go a long way towards reassuring them about the safety of vaccines."  

Future research needed to study neurological complications of vaccines

1. Expansion of active surveillance programs
2. Develop tools for gathering precise information on neurological complications
3. Genetic susceptibility studies
4. Immune profiling of individuals with neurological manifestations
5. Determine association with comorbidities
6. Develop animal models
7. Conduct clinical trials for prevention and treatment of adverse events