MS: Busting the Myths
October 4, 2021 | Covid-19, Uncategorised
The current number one health priority around the world is rapid and efficient roll out of an effective vaccine to contain the COVID-19 pandemic. More than 200 million people have been infected and over 4.5 million have died worldwide. Numerous factors known to increase the risk of complications and death from COVID-19 have been clearly defined (age over 60, obesity, diabetes, heart disease, lung disease, high blood pressure, pregnancy and Black, Hispanic and Aboriginal ethnicity). A number of priority groups have been identified based on this evidence for the roll out of vaccination programs, but this will also be influenced by service delivery factors (e.g. healthcare workers).
Evidence shows that a person with multiple sclerosis (PwMS) is no more likely to develop COVID-19 or its complications, including if on treatment (with the possible exception of those on ocrelizumab who may be at very slightly increased risk). Those with secondary progressive MS and higher levels of disability may be at increased risk of complications from COVID-19.
The mortality from COVID-19 in New Zealand is 0.6% compared with other parts of the world at 3.2% (29 Sept 2021). This means worldwide that on average, 3 out of every 100 unvaccinated people who contract COVID-19 do not survive and many more require treatment in intensive care or have long-term consequences. Since the introduction of COVID-19 vaccinations the death rate from COVID-19 in Australia has fallen to 1.4%. The infection rates in Australia and New Zealand remain very low, recent outbreaks (mostly related to Quarantine breaches) have shown that further cases are inevitable. Currently only the Pfizer vaccine is available and used in New Zealand. However, Medsafe have also recently approved for use the AstraZeneca and Janssen vaccines but it is unknown if and when these will be made available. These have all been shown to be highly effective and very safe even against the newer variants of SARS-CoV-2. The current recommendation is that all adults and children 12 years and over should be vaccinated against COVID-19.
Below we will consider the issues relevant to these vaccines and closely related products that might be available in other parts of the world for those living overseas.
mRNA vaccines (Pfizer/BioNTech – “Comirnaty” and Moderna – “Moderna mRNA”)
These vaccines use mRNA and our cells own protein manufacturing mechanism to produce the “spike” protein of the SARS-CoV-2 virus that causes COVID-19. This in turn triggers an immunological reaction against the spike protein thereby conferring immunity. This is a new mechanism for vaccination. These vaccines have proven to be 95% effective in large phase III, placebo-controlled, clinical trials. Serious adverse events were seen no more frequently in those receiving the vaccine versus those who received placebo (sham injections). The only side effects that were seen in slightly higher numbers in those receiving the vaccine were local injection site reactions, chills/fever, headache and fatigue/tiredness. These were mostly mild or moderate in severity. These vaccines do not contain eggs, preservatives or latex. From the way that these vaccines work it is not anticipated that there would be any additional risk of adverse outcomes and side effects in a PwMS, including those on treatment. It is considered that for a PwMS the risks of contracting COVID-19 far outweigh any potential risk from the vaccine. These vaccines have been authorised for use in US, EU, UK, Canada, Australia and many other countries. The Pfizer/BioNTech vaccine has been approved for use in New Zealand by the Medsafe and was the first COVID-19 vaccine to be rolled out in February 2021. The Moderna vaccine may become available in Australia later.
DNA/viral vector vaccines (AstraZeneca – “Covishield” [Oxford], Janssen Pharmaceutica “Johnson & Johnson (JNJ) Vaccine”, Gamalaya Institute – “Gam-COVID-Vac or Sputnik V” [Russia] and CanSino Biologics – “Convidicea” [China])
These vaccines use a copy of the DNA for the spike protein that has been inserted into an adenovirus (common cold virus) vector that has been modified in such a way that it is unable to replicate itself but can still deliver DNA to our cells. The DNA is used by our cells to make the spike protein and produce an immune response and immunity to the virus that causes COVID-19. This is a commonly used mechanism for many existing vaccines. The AstraZeneca vaccine was 60- 90% effective in a large phase III, placebo-controlled, clinical trial. The commonest side effects included headache, tiredness and muscle aches. Less is known about the efficacy of the Sputnik V vaccine but reports of this being 50-90% have been published. From the way that these vaccines work it is not perceived that they would be associated with any additional risks or issues for a PwMS, including those on treatment. These vaccines have been authorised for use in UK, Russia, India and several other countries. Medsafe has granted provisional approval of the AstraZeneca vaccine for individuals age 18 years of age and older. However, provisional approval does not mean that we have committed to using the AstraZeneca vaccine in New Zealand.
Protein vaccines (Vector – EpiVacCorona [Russia] and Novavax – “NVX-CoV2373”)
These vaccines use the spike protein or a part of the protein together with an “adjuvant” that stimulates the body’s immune system. This is also a relatively new approach to vaccination. Data for the Novavax vaccine have just been released indicating an efficacy of 89.3%. No safety data is available yet. It is not anticipated that these types of vaccines would pose any additional risks to a PwMS, including those on treatment. One example of this type of vaccine (Vector) has been authorised for use in Russia. The New Zealand Government has agreed with Novavax to purchase 10.72 million doses of the vaccine, enough for 5.36 million people. Medsafe have not yet approved use of the Novavax vaccine and New Zealand is unlikely to receive it until later in 2021.
Frequently asked questions
As a PwMS, should I have the COVID-19 vaccination?
It is currently recommended that everyone 12 years and over should be vaccinated against COVID-19. There is no theoretical reason why any of the currently available vaccines should pose any particular risk to a PwMS. The risks of COVID-19 are very real, are higher in a PwMS who has higher levels of disability, and far outweigh any conceivable risks from the vaccines. There is now clear evidence that all of the vaccines are safe in PwMS. As a person with MS, you should be vaccinated.
Could the vaccine trigger a relapse of my MS?
Several studies have now shown that there is no increased risk of relapse following vaccination for COVID-19. All of the COVID-19 vaccines can produce side effects that include fever and fatigue. Fever can on rare occasions cause a re-emergence of previous MS symptoms (a so-called “pseudo-relapse”), but it is widely thought that this only lasts as long as the fever is present (usually less than 24 hours with these vaccines) and does not imply any new inflammation or damage to the nervous system. Similarly, fatigue due to vaccination can be similar to and might compound MS-related fatigue, but this should only be temporary.
What if I am on treatment that is modifying or suppressing my immune system?
None of the currently available vaccines are “live-attenuated virus” vaccines and do not pose any risk of causing the disease which they are aiming to prevent. They are therefore considered to be safe in people who are immunosuppressed. There is now considerable experience from around the world indicating that COVID-19 vaccination is safe in PwMS, including those on therapy.
Will the vaccine still work if I am on treatment that is modifying or suppressing my immune system?
Research over the past year indicates that antibody responses (the immunological response that provides protection after vaccination) to the COVID-19 vaccines is reduced in PwMS taking fingolimod (Gilenya) and ocrelizumab (Ocrevus). What is not clear at this stage is whether or not this is associated with any increased risk of getting COVID-19 or its complications. Of note, cellular immune responses to COVID-19 vaccines in PwMS taking ocrelizumab have been shown to be normal and it is these responses that are more important when fighting viral infections. Finally, there has been no trend from around the world that people on immunosuppressive treatments are any more likely to do poorly with COVID-19 infection post-vaccination, although this effect might be hard to detect due to relatively small numbers. Antibody responses to COVID-19 vaccines in PwMS on other therapies do not appear to be significantly affected.
How should I time my vaccination in relation to my treatment?
The practicalities are that you should receive your vaccine whenever it is offered to you. The timing of this will be decided by local government health officials based upon your age, risk profile and other factors (e.g. work in healthcare/travel industry). For those on intermittent immunosuppressive therapies (e.g. ocrelizumab, alemtuzumab, cladribine) it would be sensible to ensure that your vaccinations are completed several weeks prior to your treatment and avoid being vaccinated for several months afterwards. This is in order to maximise the effectiveness of the vaccine and avoid any overlap of side-effects which might cause confusion, rather than because of any safety concerns. For natalizumab (Tysabri) avoiding vaccination during the week of your infusion would be wise simply to avoid confusion over any side effects. For all other treatments timing of your vaccination should be determined by availability of the vaccine. If you are considering delaying your vaccination or your MS treatment, please discuss this with your neurologist first.
Note: Alemtuzumab and Cladribine are not funded treatments in NZ.
Should I stop, delay or hold off on starting my MS therapy until after I have been vaccinated?
It is not recommended that you suspend your MS therapy around the time of your vaccination unless on the advice of your neurologist. The risks to your long-term health of developing a re-occurrence of your MS on stopping therapy are far greater than any potential risks from vaccination. For those on intermittent therapies or who are just about to start a new therapy there may be some scope to better coordinate the timing of your therapy with any planned vaccination, but this should only be done in consultation with your neurologist to ensure that the risks of any delay with your therapy will be minimal or can be reduced in some way.
The clinical trials and approval processes have been accelerated; how can I be sure that the vaccines are safe?
The clinical trials and approval processes used in each country or region to assess the safety of medications and vaccines have been identical to normal processes, they have simply been undertaken more rapidly than usual because of the urgency of the situation. The process of approval by the Medsafe, who approve medications and vaccines in NZ, has been completed for the Pfizer/BioNTech, AstraZeneca and Janssen vaccines. Medsafe are following their usual procedure and will only approve a vaccine for COVID-19 once they are satisfied that it is safe. Whilst some of the technology being used in the vaccines is new, this technology has been in development over many years and the process of testing the vaccines in pre-clinical studies and then clinical trials has been just the same as in the past. The clinical trials for these vaccines have involved 10’s of thousands of participants. In addition, by the time these vaccines are being administered in NZ, many millions of people will have been vaccinated worldwide and if there were any rare safety concerns these would likely have come to light before they are used in NZ.
As a PwMS which vaccine would be best for me?
Whilst there are some small differences in the efficacy and side effect profiles for each of the vaccines, all of the COVID-19 vaccines that are currently available are very effective and very safe. All the vaccines have shown that they effectively remove the risk of dying from COVID-19. You should therefore have the vaccine that is offered to you. This is likely to be determined by prioritisation and local availability.
What about the cases of transverse myelitis and Bell’s palsy following COVID-19 vaccination?
There have been case reports of transverse myelitis (demyelination of the spinal cord) occurring COVID-19 vaccination and there are several studies indicating an increased risk of Bell’s palsy (drooping of one side of the face) following COVID-19 vaccination. However, these risks are thought to be small and transverse myelitis and Bell’s palsy has also been noted to occur in cases of COVID-19. In the past there have been concerns about MS relapses being triggered by vaccination. This, in part, stems from what was probably a real association between certain early vaccines (e.g. an early Rabies vaccine which is no-longer used) and a rare form of demyelination known as acute disseminated encephalomyelitis (ADEM). However, all recent large-scale studies of vaccination programs and the risk of demyelination (MS) have shown no association.
What about the risk of blood clots?
There have been a small number of well documented cases of thrombotic thrombocytopenia following administration of the AstraZeneca vaccine (and the Janssen/Johnson & Johnson vaccine). This is a rare form of immune mediated venous thrombosis which can be serious if it involves veins around the brain or vessels in the lungs. The risk of this complication is estimated to be 1 in 500,000. The condition is more common in women and those under 50 years of age.
What about the deaths reported in Norway that may be related to the Pfizer vaccine?
Most countries in the world have mechanisms in place to monitor the safety of medicines and vaccines after they have been approved for use in the community. This is often the only way that rare side effects can be detected. Regulatory bodies will often be asked to investigate unusual occurrences such as a cluster of deaths or other unusual medical outcomes that could potentially be related to a particular product. This is precisely what happened in Norway. Often these investigations will show that the suspected association is in fact just a random cluster of an unusual outcome. However, if it is demonstrated that there is a link or that a particular group of people is at risk of a particular adverse outcome, then appropriate recommendations and amendments to vaccination procedures will be made. Medsafe fully reviewed the information on the Pfizer vaccine after carefully reviewing the detailed information have concluded that the vaccine is safe and have approved it for use in New Zealand.
What if I have had a previous allergic reaction to a vaccination?
You should advise the person administering the COVID-19 vaccine if you have ever had an allergic reaction to either an earlier dose of the COVID-19 vaccine or any other vaccination. Some vaccines do contain other components to which some people can react. Some of the COVID-19 vaccines have specifically avoided having any of the common precipitants for these types of reaction. The person administering the vaccine will be able to advise on whether or not it will be safe to proceed with the particular vaccine being offered.
Could I just wait until everyone else has been vaccinated and rely on “herd immunity” to protect me?
The sooner that as many people as possible get vaccinated against COVID-19 the safer we will all be. Relying on everyone else to be vaccinated to prevent you individually being exposed is unlikely to be an effective strategy. In fact, it is becoming clear that heard-immunity is unlikely to be effective for COVID-19 until vaccination rates reach 95% or more. In contrast, the personal protection conferred by COVID-19 vaccination is considerable with the risk of hospitalization being reduced by 93% and the risk of death being almost zero. It also seems likely that easing of personal restrictions and ability to travel may be subject to vaccination status.
Will I need a booster vaccination?
It is unclear at this stage if booster doses of COVID-19 vaccines will be required. Currently there are no definite plans for this in New Zealand. However, some experts have stated that it is quite likely that COVID-19 infections may become a recurring phenomenon around the world and that outbreaks will continue to occur from time to time. In this scenario it is likely that booster doses will be recommended for all. It may also be advisable for PwMS on certain medications (fingolimod and ocrelizumab, possible also following completion of alemtuzumab and AHSCT) will be recommended to have a booster dose.
Signatories
Prof Michael Barnett NSW
Dr Heidi Beadnall NSW
Dr Mike Boggild QLD
Dr Karyn Boundy SA
Prof Simon Broadley QLD
Prof Helmut Butzkueven VIC
Dr Katherine Buzzard VIC
Prof Bill Carrol WA
Dr Laura Clarke QLD
Dr Nicholas Crump VIC
Dr Jane Frith NSW
Dr Natasha Gerbis NSW
Dr Mahtab Ghadiri NSW
Dr Lauren Giles TAS
Dr Kerryn Green QLD
Dr Lesley-Ann Hall SA
Dr Todd Hardy NSW
Prof Simon Hawke NSW
Prof Suzanne Hodgkinson NSW
Prof Tomas Kalincik VIC
Prof Allan Kermode WA
Prof Trevor Kilpatrick VIC
Dr Rajat Lahoria ACT
Prof Jeannette Lechner-Scott NSW
Prof Pamela McCombe QLD
Dr Mastura Monif VIC
Dr Jennifer Pereira NZ
Prof John Pollard NSW
Dr Sudarshini Ramanathan NSW
Dr Stephen Reddel NSW
Dr Izanne Roos VIC
Dr Cameron Shaw VIC
Dr Marion Simpson VIC
Dr Olga Skibina VIC
A/Prof Mark Slee SA
Dr Judith Spies NSW
Prof Bruce Taylor TAS
A/Prof Anneke van der Walt VIC
Prof Steve Vucic NSW
A/Prof Ernie Willoughby NZ