By Dr. Gareth Parry

There have now been 4 cases of GBS following the Pfizer COVID vaccine reported in the medical literature in about 5.5 billion doses given. There has also been one case in NZ that we are reporting. Four of the cases, including ours, followed the 1st vaccine dose and one followed the 2nd. So, 5 cases from 5.5 billion doses is still a vanishingly small number and is absolutely not regarded as a causative association. Nonetheless it will be important to continue to monitor the situation with all of the vaccines.

By Dr. Gareth Parry

UPDATE  3:

What has happened in this rapidly evolving story of COVID-19 and its association with GBS/CIDP since my previous report from December 2020?  The biggest development, of course, is the introduction of four different vaccines.  Insufficient time has elapsed for there have been any change in the number of new cases of infection resulting from vaccination but there has been an encouraging decline in new cases nonetheless.  Perhaps the widely reviled public health measures of universal mask wearing and social distancing have made a difference.  To date, there have been nearly 120 million cases confirmed world-wide, but the true number of infected individuals is certainly much higher, partly because of the lack of resources in under-developed countries to carry out community surveillance testing and partly because asymptomatic cases usually do not seek testing.  After all, by some estimates, only about 40% of infected people show symptoms of infection.  About 2% (2.5 million people) have died.  In NZ there have been there have been nearly 2500 cases with 26 deaths (~1%).  Both the number of cases and the number of deaths speaks to the excellence of our response to this pandemic and the medical care available to infected individuals.

Let me now review the situation with regard to COVID-19 and the vaccinations in relationship to GBS and CIDP.

COVID-19 and GBS/CIDP:  Sporadic reports of GBS following CIVID-19 infection continue to appear but the numbers remain extremely small.  There has been no independent corroboration of the earlier report that there was a 2.6 times greater frequency of GBS during the time of COVID-19 pandemic.  In fact, a report in December 2020 specifically refuted this earlier claim, showing no increase in GBS numbers in the UK during the pandemic.  Rather, GBS numbers declined perhaps because social isolation resulted in fewer cases of other infections that might trigger GBS.  As of October 2020, there had been only 37 cases of GBS reported in the medical literature.  While there have undoubtedly been many cases that have not been reported this still represents a tiny risk given the staggering number of infections noted above.  Contrary to some previous suggestions, the pattern of GBS following COVID-19 infection and its severity does not differ significantly from GBS associated with other infections.  In fact, in one report, only 16% of patients required intensive care unit (ICU) management and none died whereas more usually 30%-40% of GBS patients require ICU management and about 5% die.  Thus, with the usual caveats about the rapidly evolving state of our knowledge, it appears that COVID-19 infection may rarely trigger GBS, but the risk is extremely small and the GBS does not differ in any significant way from GBS triggered by other infections.  There have been no reports COVID-19 triggering a second attack of GBS or causing a relapse in patients with CIDP.

COVID-19 vaccinations and GBS:  On rare occasions GBS is triggered by vaccination, most notably to the single influenza vaccine used in the US in 1976.  There is, understandably, considerable anxiety amongst GBS and CIDP patients regarding the risk of COVID-19 vaccinations causing GBS recurrence or CIDP relapse.  There have been four vaccines approved after clinical testing in tens of thousands of volunteers showing dramatic effectiveness with minimal risk.  The studies showed that the vaccines reduced the risk of developing infection by 70%-90% and severe illness was essentially eliminated, even with the vaccines that were less effective in preventing infection. The good news is that since approval by regulatory bodies, there have been about 20 million doses of the various vaccines given and there have been no cases of GBS that could be attributed to exposure to any of the vaccines.  Nor have there been any confirmed cases of other autoimmune diseases attributable to the vaccines.  The important facts to understand concerning COVID-19 and vaccination are these:

1. Unless we stay in our own little bubble, neither travelling abroad nor welcoming visitors from abroad, the risk of getting COVID-19 infection, although unable to be quantified, are certainly significant.
2. If you get COVID-19 infection you may get very sick and there is a 1%-2% chance that you will die. There is also the condition of “long COVID” which can have a long-term impact on quality of life.
3. The chances of getting GBS, having a recurrence of prior GBS, or having a relapse of CIDP following COVID-19 infection are vanishingly small.
4. Each of the currently available vaccines is effective in preventing disease and eliminating severe disease.
5. It is unlikely that drugs commonly used to treat CIDP such as steroids, IVIg or azathioprine will impair the effectiveness of the vaccines but treatment with rituximab, a drug occasionally used in CIDP, is likely to reduce vaccine effectiveness.
6. None of the vaccines has been associated with GBS, recurrence of prior GBS or relapse of CIDP.

GET THE VACCINE WHEN IT IS OFFERED TO YOU AND HELP US ACHIEVE HERD IMMUNITY.  WHILE YOU’RE AT IT, GET THE ‘FLU VACCINE ALTHOUGH IT WOULD BE PRUDENT TO HAVE THEM A FEW WEEKS APART TO MINIMIZE SIDE EFFECTS.  THERE IS NO EVIDENCE THAT GETTING TWO VACCINES INCREASES THE RISK OF ANYTHING.

The current news cycle and the Internet are awash with information about the COVID-19 pandemic and its implications for our health, much of it contradictory.  One of the problems is that pronouncements and recommendations are based on inadequate knowledge because this is a new phenomenon that science is still trying to get its collective mind around.  I am neither a virologist nor an epidemiologist, but I do know about GBS, CIDP and related diseases their treatment and a little about the immune system.  I will try in this brief communication to provide some sensible guidance to patients who have had GBS in the past and for those who currently have CIDP or another of the related chronic immune-mediated neuropathies.  I will put it in the form of questions that have been or should have been posed along with my answers based on what knowledge we currently have; However, remember that this is a rapidly evolving field and recommendations may change as we learn more.  You can also get information from the GBS/CIDP Foundation International here.

UPDATE 2:

This “rapidly evolving field”, to quote my previous communication, has indeed rapidly evolved.  In this week’s New England Journal of Medicine, the top-rated clinical medical journal in the world, there is a report of five patients who developed GBS associated with COVID-19 infection.  This report is much more persuasive than the prior one I wrote about.  I have reviewed the clinical reports and there is no doubt that they did have GBS and the interval between the infection and the onset of GBS was 5-10 days, typical of the interval for other infections.  Also, the number of cases seen from a relatively small population in Northern Italy suggest that the association was not coincidental.  These five GBS cases occurred among about 1200 COVID-19 patients admitted to the same hospitals but, of course, there were many other cases admitted to other hospitals and occurring in the community but not admitted to a hospital.  Nonetheless, this report does suggest that COVID-19 may be a GBS trigger for some susceptible individuals.  Whether this is just a nonspecific viral trigger or will represent an increased susceptibility with COVID-19, resembles that seen with the EB virus (that causes glandular fever) and Zika virus remains to be seen.  I have requested that my neurological colleagues around NZ test all GBS patients for COVID-19 and to communicate the result to Dr Taylor or to me.  It will be interesting to see if there is a spike in GBS cases during this epidemic.

For those wishing to read about the cases the link to the article is:

https://www.nejm.org/doi/full/10.1056/NEJMc2009191?query=RP

UPDATE 1:

A few weeks ago I wrote that COVID-19 did not appear to trigger GBS.  Has anything changed?  Probably not but I need to stress again that “…..my answers (were) based on what knowledge we currently have” and “that this is a rapidly evolving field and recommendations may change as we learn more”.  There is a change in the information regarding GBS and COVID-19 but is that change meaningful?  Let’s look at the facts.

A week ago, a single case of COVID-19-associated GBS was reported.  The case was seen in January, early in the course of this pandemic, and the GBS occurred prior to the diagnosis of COVID-19 infection.  Eight days after being admitted to the hospital with GBS the patient developed cough and fever and was diagnosed with COVID-19 infection.  There are a few reasons to suspect that the association is no more than coincidental:

1. In this reported case, the GBS occurred prior to symptomatic infection whereas GBS usually follows symptomatic infection by 10-20 days. Of course, we know that individuals may contract the virus up to 2 weeks before they manifest symptoms which is why we are asked to isolate for 2 weeks.  Thus, it is remotely possible that the asymptomatic viral infection triggered an immune response that led to GBS much more rapidly than usual.
2. One of the factors that predicts severe GBS is a short interval between the inciting event (infection in most cases) and development of weakness. In this reported case the GBS pre-dated symptomatic infection so the interval between viral exposure and weakness must have been extremely short and yet the GBS was very mild with rapid and complete recovery.
3. Perhaps most importantly, this is the first case of GBS associated with the virus despite there being more than 1.7 million confirmed cases (as of April 12, 2020) since December 2019 and probably many more that have not been diagnosed. The incidence of GBS is roughly 2 cases for every 100,000 of the population every year so if COVID-19 was a trigger for GBS we would have expected to see about 30 cases, not just this one.

“It is incident to physicians, I am afraid, beyond all other men, to mistake subsequence for consequence.”

Dr Samuel Johnson (1709-1784)

Samuel Johnson made this observation about 300 years ago but it is just as true today and while he made the comment about physicians it is equally true for the entire human race, including those who should know better such as the physicians who wrote the Lancet article.  Just because “B” follows “A” it does not mean that “B” was caused by “A”.  The authors of the article were quick to acknowledge that this association may just be a coincidence but the headlines generated screamed “First case of GBS associated with COVID-19” which is the message that gets out to the GBS community. We cannot yet say with complete certainty that there is no chance that COVID-19 could trigger GBS but this single case does not change the validity of what I had wrote three weeks ago.  As more data emerges we may learn that there is a link but, in the meantime, don’t panic.

Those who wish to read an executive summary of the reported GBS case can access it at: https://www.medscape.com/viewarticle/928424?nlid=134948_3405&src=WNL_mdplsnews_200410_mscpedit_neur&uac=317419EZ&spon=26&impID=2342098&faf=1

The article also provides a link to the original report that was published in Lancet Neurology.