In the past week, I’ve heard many patients share their optimism upon hearing that phase 1 trials of a coronavirus vaccine are beginning. While I do believe that unprecedented cooperation from international scientific teams will lead to swift advances, I tend to agree with most health-care experts who predict that a safe, effective vaccine is at least a year away.
As a practicing pharmacist who owns and operates a vaccination clinic, several considerations immediately come to mind. These are based on the questions most commonly asked by patients. When I think about administering a vaccine for coronavirus, I want to be able to help patients decide about risks/benefits by examining common questions such as:
How likely am I to be exposed to the disease? How likely am I to spread it to others? Before getting a vaccine, you want to know the risk in your community. I wouldn’t usually recommend a typhoid vaccine for someone going to a resort in St Lucia – where risk is very low – but I would push hard for it if they were headed to a high-risk area like Pakistan.
In some cases, as with the flu shot, I have so many patients tell me, “I never get the flu”. At that point, I turn the discussion to the possibility of becoming a carrier who infects those in the vulnerable population. In the case of coronavirus, the prevalence and risk of spreading the virus will almost certainly be quite high even by the time a vaccine is developed in 12 to 18 months.
How effective is the vaccine at preventing the disease? Believe it or not, all vaccines are not 100% barriers against contracting the disease. Take the typhoid vaccine, for example, which is only about 50-70% effective. It works, but still requires behavioural measures to prevent getting sick. Or the older shingles vaccine Zostivax, which has since been replaced by the superior Shingrix. This initially led to questions about what to do about individuals who were already immunized: could they and should they be re-immunized? How long to wait between immunizations? Can the government carry the costs of reimmunizing everyone? We very might well run into a similar scenario as enhanced versions of the COVID vaccine become available, particularly if the vaccine mutates to produce strains covered by one vaccine but not another.
What are the side effects, both short and long-term, of getting the vaccine vs. getting the disease? Is anything known about rare but serious adverse reactions? This is the ultimate risk-benefit ratio, and one that will be hard for practitioners to ascertain at the outset if trials are fast-tracked. We have a pretty good idea right now that the virus has about a 1% fatality rate in the general population and about a 10% fatality rate in vulnerable populations, including those over 75 years of age. We still don’t know if getting the disease leads to long-term immunity or tissue damage.
Compare that to yellow fever, a disease that is usually asymptomatic but in a small number of cases where symptoms like jaundice do occur, the death rate is nearly 50%. Normally, for a vaccine to be approved the incidence of adverse effects must be extremely low, but when the risk of dying from the disease is high that may not be the case. Before giving the yellow fever vaccine I carefully explain to the patient that there are well-documented risks:
Occurrence per million doses
Mild (headache, sore muscles, fever): 100,000-300,000
Anaphylaxis: 13
YEL-AND (nonfatal
but serious neurological effects): 8
YEL-ADV (organ failure with about a 50% mortality rate): 3
And those numbers are for a person under 60 with no underlying health conditions. These numbers are then balanced with the risk of disease, which depend on several things including location of travel, season, duration of exposure, activities while travelling, and local rate of virus transmission at the time of travel. Discovering rare but serious adverse reactions requires vaccinating a lot of people. How will we know those numbers when the new vaccine comes to market? And if you don’t know the numbers, how can you make an informed decision?
How many doses are in the primary series? How long does immunity last after the primary series? When do I need a booster? I expect that this won’t be known right away, since blood tests will have to be conducted over time to determine the answers. At this point, I’m not sure that anyone knows the levels of antibodies required to be protective. In many cases, recommendations change as research develops. The yellow fever vaccine, which used to require a booster every 10 years, was recently declared protective for life with one dose. Researchers have discovered that for one brand of vaccine against Japanese encephalitis (Ixiaro), people had just as good protection if the booster was given just 7 days after the first dose instead of the usual 28 days (which made things much easier for last-minute travellers). Additionally, there is always a subset of individuals known as “non-responders.” These are people who show little or no immunity in a serology test despite getting vaccinated with the same product and series as everyone else. It is unlikely that I will have concrete answers about projected immunity and non-responders when the vaccine comes to market, but if data show enough initial response in most people that may not matter.
Does my age/gender/ethnicity/underlying health conditions affect how well the vaccine works or how likely I am to experience side effects? This is a tricky one. I recall research from several years ago that indicated that initial vaccine and drug trials generally include a healthy, younger population and, because of the risk of pregnancy, fewer women. That may have changed and perhaps it will be different for this vaccine since it is intended for everyone, but unless it is tested using a large, diverse population, we may not have these answers up-front. Data regarding pregnant patients, the elderly and vulnerable people, those on immunosuppressive drugs or undergoing chemotherapy tend to either be extrapolated or gathered carefully over a long period of time. How will the recommendations for those people be developed?
How much does the vaccine cost? The expectation is that this vaccine will be rolled out in mass numbers, free of charge. But what will that take? Will pharmacists be primary providers, like they are with the flu vaccine? If so, how can they handle the demand after suffering severe financial blows during the crisis? Pharmacists are not publicly funded health-care providers. There is no billing code for a pharmacist to bill OHIP for administering a vaccine like a doctor can. That’s why, if you have opted to have a vaccine injected/administered at your local pharmacy, there was probably a $15-$20 fee for the pharmacist’s time. The exception is the flu shot, for which a pharmacy (not a pharmacist) is given a billing code that pays $7.50 to the pharmacy for each dose administered. The reimbursement is so low considering the pharmacist’s time, materials and space required that some pharmacies have moved away from providing the service. The government will have to determine the most cost-effective way to mass-administer the vaccine in a safe way, so pharmacies are a good choice if pharmacists can be adequately reimbursed for the additional education and time required to do the job properly.
I’m not a microbiologist, so perhaps there are answers to my questions coming. I’m simply presenting the considerations any immunizer would discuss with a patient prior to giving a vaccine and pointing out that the information we need is not going to be found in one magical petri dish in the next few months. Science is the continual interpretation of new data to better understand how things work, and the factual publication of those interpretations so practitioners like me can help patients make evidence-based decisions. To me, giving a new vaccine I know little about is as scary as not giving an established one because the patient thinks it contains a mind-control device. As much as we want a vaccine (and fast), we want to be able to make an informed choice about what we are doing to stop the disease from spreading.