Last updated 4/02/21
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 100 million people have been infected and over 2 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 Australia is consistent with other parts of the world at 3.2% (28 Jan 2021). This means that on average, 3 out of every 100 people who contract COVID-19 do not survive and many more require treatment in intensive care or have long-term consequences. Although infection rates in Australia and New Zealand remain very low, recent outbreaks (mostly related to Quarantine breaches) in Sydney, Melbourne and Brisbane have shown that further cases are inevitable. Nine vaccines have now been formally tested in phase III clinical trials in adults, have been approved in some parts of the world and have proven to be highly effective and very safe. Preliminary results from the phase III trial of a tenth vaccine have just been released. The current recommendation is that all adults (16 years and over) should be vaccinated against COVID-19.
Three vaccines are being proposed for distribution to Australians from mid-February 2021. These are the Pfizer/BioNTech vaccine (10 m doses), the AstraZeneca/Oxford vaccine (initially 3.8 m doses with a total of 53.8 m doses) and the Novavax vaccine (51 m doses). All require a course of 2 doses. The Australian Government has also secured permission to manufacture the AstraZeneca, Moderna and Novavax vaccines, as well as some other vaccines still in development, here in Australia at the COVAX facility. 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.
(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 and many other countries. The Pfizer/BioNTech vaccine has been approved for use in Australia by the therapeutic goods administration (TGA) and will be 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], 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. The AstraZeneca vaccine is currently being considered by the TGA and is expected to be rolled out in the coming months in Australia.
Inactivated virus (SARS-CoV-2) vaccines
(Sinovac – “CoronaVac” [China], Bharat Biotech – “Covaxin” [India] and Sinopharm – “BBIBP-CorV” [China])
These vaccines use an inactivated form of the SARS-CoV-2 virus that causes COVID-19. The virus has been modified so that it is unable to replicate. These are not considered to be “live vaccines” and should not pose a risk to people on immunosuppressive therapies. Because the native virus is used these vaccines can give rise to longer lasting immunity. This is a traditional method of vaccination. CoronaVac is the only vaccine of this type to have data published so far. The CoronaVac vaccine has shown efficacy of 50.4 - 91.0% in Turkey, Brazil, Indonesia and Chile. Side effects included local pain (15%), swelling (1%), redness (1%), fatigue (10%), fever (3%), muscle aches (2%) and headache (1%) in an early phase study. These vaccines have been approved in China, India and a few other countries. These vaccines are not expected to be available in Australia.
(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 are 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 Novavax vaccine is expected to be made available in Australia later in the first half of 2021.
Frequently asked questions regarding the vaccines
As a pwMS, should I have the COVID-19 vaccination?
It is currently recommended that everyone over the age of 16 years should be vaccinated against COVID-19. There is no specific data relating to the administration of any of the vaccines to a pwMS, but studies in the US, EU and Australia are being conducted currently. However, 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. As a person with MS, you should be vaccinated.
Could the vaccine trigger a relapse of my MS?
There is currently no evidence to suggest that this might be the case. 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?
This has not been specifically researched, although studies are currently being undertaken in the US, EU and Australia to look at this. 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.
Will the vaccine still work if I am on treatment that is modifying or suppressing my immune system?
Studies looking at this question for the COVID-19 vaccination are currently being undertaken, including a study right here in Australia. Hopefully, these studies will provide information on the effectiveness of the vaccine in people on various therapies, but the results are unlikely to be available for some time. We know from studies with other vaccines that immunosuppressive treatments can reduce the effectiveness of vaccination to a variable degree, but it remains very worthwhile being vaccinated if you are on immunosuppressive therapy.
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 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.
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 TGA, who approve medications and vaccines in Australia, has been completed for the Pfizer/BioNTech vaccine and is currently under way for the AstraZeneca vaccine. The TGA 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 Australia, 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 Australia.
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 with the AstraZeneca (Oxford) vaccine?
It is true that there were 2 cases of transverse myelitis (demyelination of the spinal cord) out of 5,807 people who received the AstraZeneca vaccine, one of whom it was discovered had MS which had previously been unrecognised. These cases occurred at 10 and 14 days after the administration of either the first or second dose of vaccine. There was one case of transverse myelitis out of 5,829 people in the control group (who received the MenACWY meningococcal vaccine) at 68 days. All these cases were determined to be unrelated to the administration of either vaccine by an expert review panel. The difference in numbers between the two groups was not statistically significant (p=0.997). It is always difficult with relatively rare events of this nature in such studies. By way of comparison the data for “non-COVID related deaths” in this same study showed the reverse pattern; there was 1 death in the COVID-19 vaccinated group and 3 in the control group. It is always sad to think of this, but in such a large study over a period of time, some people will die from random causes. At the moment, there is nothing to suggest that the AstraZeneca vaccine is associated with an increased risk of transverse myelitis. 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. The TGA will only approve the AstraZeneca vaccine for use in Australia if they determine that it is safe after reviewing all the relevant information.
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 is happening 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. The TGA requested more information from Pfizer regarding these cases and after carefully reviewing the detailed information have concluded that the vaccine is safe and have approved it for use in Australia.
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. Leading Australian experts have stated that it is quite likely that COVID-19 infections may become a recurring phenomenon around the world and that outbreaks may occur from time to time. Whilst being vaccinated does not eliminate the risk of contracting COVID-19 at an individual level, it does very significantly reduce the risk and effectively removes the risk of getting severe disease and dying as a result of the infection. From a personal protection point of view, it is very important to be vaccinated. It is also likely that future travel, including international travel will be dependent on being able to prove that you have been vaccinated against COVID-19.
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 (Vic.), Prof Tomas Kalincik (Vic.), Prof Allan Kermode (WA), Prof Trevor Kilpatrick (Vic.), Dr Rajat Lahoria (ACT), Prof Jeannette Lechner-Scott (NSW), Dr Mark Marriott (Vic.), 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.)