A Ray of Hope and a Lot of Question Marks

covid-19 vaccine safety
Dr. Naor Bar-Zeev

News of the U.S. approving and beginning distribution of a COVID vaccine raised hopes that the fight against the deadly pandemic might be turning a corner. It also raised a great many questions about the vaccine’s safety and what effect it will likely have on the virus’ trajectory.

To address some of these issues, Hamodia spoke with Dr. Naor Bar-Zeev, Director of Epidemiology at Johns Hopkins International Vaccine Access Center, pediatric infectious diseases physician and associate professor at Johns Hopkins Global Disease Epidemiology and Control program, to give readers a better understanding of some of the relevant topics.

What is usually done in 10 years was done in one. What was done differently from the development of other vaccines, and is there anything about that which lends weight to concerns over safety and effectiveness?

The key thing that makes most vaccine trials take quite a bit of time is that they cannot progress until a significant number of outcomes have been observed. There are two main points that changed that here. Firstly, trials depend on recruitment, which depends on money. Here, governments, especially the U.S. government, poured billions of dollars into the project, and a large number of people was recruited quickly.

The other difference here was that it did not take long to get results because, unfortunately, COVID-19 is very common. If you are testing a vaccine against bacterial meningitis, it could take quite a while until people involved in trials are exposed to it. Here, the disease occurs all the time, so it did not take long to look at the different results between those vaccinated and those who received placebos.

The other main issue is that there is usually a lot of red tape, and developers have to get approval through an adversarial process with the FDA [Food and Drug Administration]. Regulators are very picky, and if they find something technical that they don’t like in the process of data collection or the like, they might send it back even if the objection has nothing to do with safety. Now, that approach usually makes sense, because the only losers are a company looking to make profits, but we have a need to do something about COVID-19 right away. So here the regulators set out in advance exactly what they wanted companies to do, they were part of the oversight from the start. In the U.S. the regulators actually raised the bar and made things more difficult in some ways for companies, but better for the public. Because they were part of that process throughout, things ran more smoothly and correctly the first time.

Normally, if different companies are developing similar products, the safety data is reviewed individually. In this instance, there was one common board monitoring all safety data, which moved things along and increased the probability of quickly finding any adverse events.

On top of all that, in general you had a lot of people working very hard on this over weekends, nights and holidays. A huge effort was made to move things as quickly as possible, given that each day means avoidable deaths.

Since testing has taken less than a year, it seems impossible to know much about the long-term effects that the vaccine will have. How much should this knowledge gap concern people?

It’s a very legitimate concern. None of the vaccines have full product approval yet, and the trials are still ongoing. In this instance, emergency use authorization was granted, which means that the data make a clear case that the benefits outweigh the risks. We don’t know everything, but we feel it is safe enough to tell people that they are better off with it than without it.

Even when vaccine development goes for 10 or 15 years, we don’t know everything; certainly not what will happen longer term than the span of the trial. In those cases, you still run phase 4 trials [after the early research stage] that follow the vaccine over a long period of time to look at what longer-term effects will be.

The U.S. has the strongest safety standards on vaccines in the world, and they will continue to look carefully at outcomes. Now that it is being given to health care workers, that will produce an even bigger pool of data to look at.

But saying concerns are legitimate does not mean people should not take it. You have to look at both sides of the coin, that is, the risks of taking the vaccine versus the risks of not taking it. At this point, the risk of death or severe outcomes from COVID-19 outweighs the risks of the vaccine.

It’s never going to be 100% safe. The goal is to make sure adverse outcomes are very rare. When a disease itself becomes rare enough, it sometimes makes sense to stop giving a vaccine or a certain vaccine because the balance goes the other way. That’s what happened with the live polio virus vaccine, which is no longer used in most places and has been replaced with a safer alternative. When that happens, it’s a sign the vaccine succeeded so well that the disease is no longer a major threat.

Is there any existing vaccine research or scientific data in general that help address concerns over gaps left by the relatively short span of COVID-19 vaccine trials?

These vaccines use RNA, which is a chemical all life uses, and it breaks down quickly. The RNA provides the blueprint to the cell, and the cell reads it and uses its own natural mechanisms to make a protein identical to the surface binding protein of COVID-19. It then presents it directly to cells of the immune system to teach the body how to fight COVID-19. This blueprint is like the genetic code, but being RNA, it never enters the nucleus of the human cell. It never mixes with our DNA — it fundamentally cannot — and it is very rapidly degraded. In fact, there is nothing biological in the vaccine. It is certainly not using the COVID-19 virus itself. The vaccine does not infect you with COVID-19. The concept is one that is fundamentally safe and carries few risks. But as ever, we must remain vigilant and on the lookout for unanticipated risks.

There might be an immediate adverse reaction like headaches or pain at the injection site. These symptoms might be worse after the second dose, and they might be more common and more severe in younger people who have more active immune systems. But they should go away in 24 to 48 hours and do not mean the vaccine is dangerous.

covid-19 vaccine safety
Charles Hill, on the housekeeping staff at Kaiser Permanente in San Rafael, Calif., is the first to receive the COVID-19 vaccine in Marin County, administered by registered nurse Itamar Bikszer, December 16. (Alan Dep/Marin Independent Journal via AP)

Even if we have not seen how these vaccines will play out in the long term, the indicators do not raise any cause for concern. Studies looked at how they impacted organ function, and they all came out okay. They looked at other reactions that might show the body signaling something or at potential immune issues, but these studies didn’t raise any concerns either.

This is the first time that an RNA vaccine will be on the market, but there have been trials with it before for influenza and rabies and also, importantly, as a potential anti-cancer vaccines for a number of human cancers. None of those showed any long-term negative impacts, though admittedly those studies were small.

The reason none of the other RNA vaccines ever made it to market was not because of safety concerns, but because it is technically very challenging to deliver RNA, since it breaks down very fast once it is in the syringe. But here, there was an opportunity to take all that had been learned about them and harness a lot of resources that weren’t available before to use against the pandemic.

Are there preexisting conditions that could potentially pose a more serious risk for taking the vaccine?

There have been cases of allergic reactions, which are being investigated. It is to be expected that someone somewhere will be allergic to a new product. It’s not a major cause for public concern because these events are among the most rare adverse events. It’s to be expected, and it’s unlikely to be a widespread phenomenon, though given the very wide scale of the vaccine program and given media reporting, we will quickly hear of even rare events occurring all over the world.

The ones who usually have problems getting vaccines are people with immune deficiency, but since this vaccine does not contain an infectious agent, there should be no reason to be concerned about that, which is great news because these are the people who are most vulnerable to COVID-19. It’s also tested well with people with various comorbidities, which gives a lot of hope that this vaccine will help those who are most at risk.

Several health experts in countries like Japan and South Korea, where high levels of public compliance with health guidelines has led to the virus remaining mostly under control, said they are not in a rush to have vaccines distributed and would like to first observe their effects. What is your opinion of their position? Is this approach impractical for the West, where governments have had a harder time enforcing restrictions?

It’s been very difficult to maintain control of the pandemic in the U.S. That being the case, it seems the best bet to rein in the virus here is with a vaccine. Every country has to consider what is the best policy for them. Countries like New Zealand and Australia, which have virtually no cases, do still have plans in place to obtain and roll out the vaccine. Containment has come at great social and economic cost. Not every country has the capacity needed to store and deliver RNA vaccines, since they need ultracold transport systems because of the fragility of the RNA. We are fortunate that the U.S. has this capacity, though it won’t be easy to arrange the logistics.

Are the risks of the vaccine worth taking for younger healthy people, who generally experience mild to moderate COVID-19 cases?

We’re not up to that stage yet, and by the time we get there, we will have a lot more data based on the millions [of vaccinations] they are hoping to give to higher-risk groups, including young health care workers, which will give us better answers to that question. I believe the benefits will still outweigh the risks, but we should know much more once we get to that step.

Should those who already had COVID-19 take the vaccine? Does it pose any additional risk to them?

It’s important to understand as background to this question, and to the issue in general, that getting the body to produce an immune response often takes more than one exposure. Basically, what happens is the first time it is exposed, the immune system begins to take notes, and then the second time, it says, “Okay, this is something serious. Get ready to deal with it.” That’s why these vaccines need two doses — one to prime the immune system and another three or four weeks later to boost it and hopefully make it long-lasting. Only one leading vaccine candidate, using a different technology, may end up working with a single dose.

Second episodes of COVID-19 are still very uncommon, but we don’t know how long immunity lasts and for how much longer it will remain a rare event. At present there are no data to suggest that people who have already had COVID-19 need fewer doses. In fact, fundamental to RNA vaccines is that they can be given multiple times if needed, which is not the case for some other vaccines. Again, because the vaccine is not the actual virus, there is no reason to think it would be harmful to people who have had COVID-19 in the past, and we have every reason to think it would be worthwhile for them to take it.

Many major Jewish communities have had 50%–70% rates of COVID infections already. In recent months transmission has continued, but at a relatively slow rate, especially given the level at which communal life has continued to operate. Is that the type of trajectory that the vaccine is likely to bring to the rest of society — a situation where COVID remains but spreads much less rapidly?

Firstly, even though there is less spread, you are still seeing individual mortality. In Lakewood, for example, even if there are only 200-300 cases each week, there have still been COVID-19 deaths there since Rosh Hashanah. The hope is that once vaccines get to high-risk populations, mortality rates will drop significantly.

At the moment, vaccine trials are designed to have an impact on disease, not infection rates. We really hope that vaccines will interrupt community transmission also. There is some evidence that they will, but that is not yet proven. It will take quite a few months, and possibly special studies, to see how much the vaccine affects transmission, but if by vaccinating vulnerable groups and reaching all who need this protection, we achieve a rapid decline in deaths and hospitalizations, then that will be a major achievement. Slowing transmission will be the next priority after that. In the meantime, because of uncertainty about impact on transmission, we should continue with masks and social distancing even if we have been vaccinated.

Besides the Pfizer and Moderna vaccines, there are dozens, if not hundreds, of others at some stage of research. Is it likely that other options will continue to emerge?

There are others going through trial stages, but once one gets approved it’s harder, including for ethical reasons, to continue with development. But it is still ongoing.

Also, the vaccines which have now achieved emergency use authorization achieved excellent efficacy results. The threshold for approval was set at 50% efficacy, and these are showing above 90%; you cannot expect much more than that. We hope this efficacy will also be durable and long-lasting, and that [the vaccines] will reduce transmission. If in the long run they do not significantly reduce transmission, though, there might be more of a push to look at other options.

From the layman’s perspective, is there any difference between the Moderna and Pfizer vaccines?

Not really. They use pretty much identical technology. The only difference is the way they stabilize the RNA.

Any closing thoughts on the matter?

I understand the reticence and fear that people have of the unknown, but knowing what we do, I would confidently give it to my aging parents and, once we get up to that stage, I would give it to my children. I have no hesitation taking it myself.

As it gets delivered to millions of people, stories will emerge of people who took the vaccine and were hospitalized the next day. It’s important to remember that right now it will mostly be going to people who are older and in fragile health, and we will need to have a mechanism in place to investigate these stories and clarify if there was any connection between the vaccine or if the proximity of events was a coincidence.

People also have to be aware that, especially in an age when information spreads rapidly on social media, many stories of adverse reactions are likely to emerge and receive public attention. If millions of people are getting vaccinated, you could hear about an adverse reaction one day in Scotland, and the next day in Guatemala, and the day after that in Australia … and start to feel like there is a real risk. It’s very important to keep these stories in perspective and to differentiate between something that poses a real level or risk and something that remains a very rare event.

Having said that, we also really have to make sure we detect real adverse events also, and not discount people’s concerns. We have to do our very best, and we are in this together.