Dr. Bill Moss, Professor and Executive Director of the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public Health
As researchers continue to learn more about the novel coronavirus, a critical goal has been understanding how the immune system recovers from COVID-19, and how long any potential immunity might last. Recent anecdotes circulating in news and social media about individuals becoming infected with COVID-19 twice pose new questions for epidemiologists and immunologists as the scientific community works to develop a vaccine for the virus and as some speculate about what it would take to achieve herd immunity. To understand what we know thus far about immunity and COVID-19 – and where researchers are headed – we caught up with Dr. Bill Moss, Professor and Executive Director of the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public Health.
What does it mean for someone to be immune from an infectious disease?
Immunity from an infectious disease means the body’s immune system has previously responded to the pathogen – which is often a bacteria or a virus – that causes the infection. This happens either from infection with the pathogen itself or from a vaccine. Then, when someone is re-exposed to the pathogen, they don’t get sick. However, it’s more of a spectrum than an absolute, as there are different levels of immunity. A strong immune response may prevent infection, but most immune responses prevent disease.
Once someone recovers from a novel coronavirus infection, are they then immune from the virus?
Yes, on some level—and that’s the key question: how strong is the immunity and how long does it last? Right now, we don’t know. We do have some evidence that recovered patients will be immune; we just don’t know for how long. The next step is to identify individuals who’ve had a confirmed COVID-19 infection, have recovered, and then test negative for the virus. If these individuals then get re-exposed, we’ll be able to see if they also become re-infected.
Obviously, that’s not easy to do and it takes time. For one thing, the exposure part is hard to measure. One potential solution is to study healthcare workers because they’re already at high risk of re-exposure due to their work. However, it’s hard to test and see if they’ve not been infected, and it’s even harder to show they were exposed but not infected.
One trick we can use to assess whether a person was exposed to the virus is to see if they have an increase in their antibody levels. If there’s a jump in antibodies, you can then assume that the immune system has seen the virus. If they’re also symptom free, then that’s a good sign that they’ve fought off a second infection, but it’s tricky to demonstrate it.
Another consideration is that people who have a mild or asymptomatic infection could also have a lower immunity level. There’s already some evidence for this idea. We also know that in animal and monkey models, a certain level and type of antibody response correlates with immunity and protection – so a more severe infection might lead to a higher immunity level. We haven’t proven it yet, but we have a good idea based on our knowledge of how other viral infections work.
For other coronaviruses, we do know immunity doesn’t last very long, maybe on the order of months to years.
Do people who have recovered from a COVID-19 infection still need to maintain public health measures like staying home, keeping six feet apart, washing their hands, and wearing masks?
Yes, absolutely. The biggest reason is because, to answer this question definitively, we need to know the duration of a person’s protective immunity from COVID-19. Essentially, after someone has recovered, can they get re-infected and, if so, are they potentially contagious to other people? Right now, the presumptive answer is probably not, but until we can say for sure we all need to follow the public health guidelines.
The other part of this question we need to answer is: are people who have recovered fully protected, or are they susceptible to reinfection? Until we really know for sure, it’s probably safest for those individuals to maintain measures like physical distancing and wearing masks.
There have been anecdotal cases of people who continued to test positive even after they recover. How unusual is this for an infectious disease? Are there other possible explanations?
There’s some interesting work being done that shows how people who’ve recovered can still test positive on a PCR (polymerase chain reaction) test, that is with a molecular test that detects the virus RNA, even several months later. The belief is that they’re not still contagious, but they still have remnants of the virus in their system. It’s an interesting phenomenon – and one we’ve seen in other viruses, like measles virus, but it’s something we need to understand more fully.
There are some viral infections that are well known and that do cause what we call a “persistent infection,” like HIV, hepatitis C, and chickenpox, for example. So, we do know that certain viruses can persist, but coronaviruses are a subset that does not behave that way, as far as we know. They’re much more likely to cause a classic acute viral infection: you become infected, recover, and are then immune. We have learned that a virus – or part of it – can still be detected up to months later, but that’s not the same as a persistent infection.
What’s interesting about this is that other viruses have shown similar attributes. Like I mentioned, measles is an interesting corollary. It’s the classic acute viral infection: you get it, recover or die – and if you recover the virus clears quickly within days, granting the survivor lifelong immunity. But as a study I was a part of showed, children in Zambia who had measles could still have the virus turn up on a PCR test a month to three months later, much to our surprise. We have a lot of unanswered questions to still nail down around this – are the tests responding to stray pieces of RNA? Or is there a low level of viral replication going on? We’re still learning about it.
For SARS-CoV-2, right now it’s especially hard to tease out exactly whether people are experiencing a new viral infection or a persistent remnant. For a reinfection, we would have to see someone become symptomatic again and become sick, and we would have to genotype the virus to see if it’s the same virus or a different virus. I would say that most people testing positive within three months of a prior infection – that’s probably a remnant of viral RNA and not a reinfection, but it’s important to distinguish between the two.
How does a vaccine bring about immunity?
A vaccine mimics the body’s immune response to a natural infection, but without the dangers of the actual disease. For COVID-19, there are multiple types of vaccines in development right now, and though they all work quite differently, the goal is the same: to show the immune system an aspect of COVID-19 – which is most commonly the spike protein on the surface of the virus that it uses to gain entry into human cells. The body’s immune system then learns to bind to that spike protein and prevent it from entering the body’s cells. It differs from a “natural” infection because it avoids the peril of a serious infection from something like COVID-19. A fully tested and approved vaccine might cause some tenderness, muscle aches, or mild fever, but nothing as severe as a natural infection from a virus like COVID-19.
What is herd immunity and how could it be achieved for COVID-19?
Herd immunity is a level of population immunity where transmission begins to slow instead of accelerating, and that’s what we really need to truly slow the spread of this novel coronavirus. It’s a reasonable goal if we have a safe, effective vaccine and if it is widely accepted by the public. Take measles, again, as an example – it’s much more contagious and requires a really high level of vaccine use by the public, which is what makes it so hard to control and eliminate. Let’s say for COVID-19 we need 50% to 70% of the population to be immune in order to reach herd immunity – and that’s just a guess – then that’s a lot more achievable than needing to have 95% of people immune to keep the population safe from measles. Still, there are a lot of “ifs” in that idea, like the existence of a safe vaccine and a willingness for the public to take the vaccine, and there are already some signs of resistance to people taking the vaccine.
Another thing about herd immunity – and it’s one thing that makes COVID-19 particularly interesting – is that you have to sustain that herd immunity threshold over time because new susceptible people come from births. So, for a disease like measles, the infection of young children is what keeps the virus going. What’s promising then about COVID-19 is that, thus far, it has caused fewer active infections among young children, and it may even be less transmissible by them. If that’s the case, it’ll make it easier to hit that herd immunity threshold and bring the transmission rate down. It could mean that new births, in the next few years, might not contribute as much to transmission, which would allow for better herd immunity.
Unfortunately, all of these issues are pretty complex. But I think we’ll learn a lot about immunity to this particular virus from the phase 3 vaccine trials that are just starting up, as of late July. It’ll give us a lot of insight about immunity and its duration, and we’ll also start to learn more from the studies that are following up on confirmed infections. By the end of the year, we’ll simply know a lot more about how the immune system responds to the virus, and the more we learn about the virus the closer we’ll be to finding safe, effective vaccines.