May 04 2020

COVID-19 Immunity and Vaccines

We appear to be at the beginning of the end of the first wave of COVID-19 (at least in the US – other countries are at different places). We are at the point where states are starting to relax the physical distancing requirements, and there is discussion about how to transition to the next phase. That next phase might include disease tracking, targeted isolation, and “immunity passports.” But planning this next phase is complicated by the fact that we still do not fully understand this virus. We don’t know if there will be a second wave (or more), if it is seasonal, and if you can catch it twice. How we handle this next phase will likely determine if there is a second wave.

But what comes after that? When can we transition to the final phase – return to normal, even if it is a new normal? These next transitions will depend largely on the natural immunity that results from infection, and how long it will take to create a vaccine and how effective that vaccine is. Here is what we know and don’t know so far.

The big question for the next phase is – how much immunity results from natural infection? This is a more complicated question than it may first seem. But the short answer is, we don’t know.

The adaptive part of the immune system will remember infections, B-cells that create specific antibodies targeting the infecting organism will develop throughout an infection, and some of those B-cells are memory B-cells – they will hang around for a long time, ready to produce specific antibodies the next time the same organism is encountered. But there are important variables to how effective this adaptive immune strategy is. the virus or infecting organism itself is the main variable. What parts of itself does it expose to the immune system? Perhaps the critical functional proteins are hidden deep within folds that antibodies cannot get to. Another variable is how quickly does it mutate? If the parts that antibodies can target change quickly, then immunity does not last. Some organisms also evolve specific strategies to evade or compromise the immune system.

Another variable is the severity of the infection itself. The more severe and long lasting the infection, the greater the stimulation to the immune system and the greater the adaptive response.

So with COVID-19 here are the specific questions. First, how much immunity results from an infection and how long does that immunity last? There is no question that a person with a functioning immune system will form adaptive immunity, the question is how much and how long. Again, we don’t know, but we have clues from other coronaviruses. The ones that cause the common cold produce immunity that lasts perhaps only months. It is possible to get reinfected in the same year with the same coronavirus. The more severe infections, SARS and MERS, create immunity that lasts only 2-3 years. So as the family, the coronavirus seems to be resistant to long term immunity.

It is also very likely that the milder infections, especially the asymptomatic carriers, have less immunity as a result. At one point there was speculation that California may be having a milder COVID-19 experience because in the Fall there were lots of asymptomatic cases going around. This theory has largely been dismissed, COVID-19 was simply not around in the Fall. In one recent study from China, 30% of subjects with a mild infection failed to even develop high levels of neutralizing antibodies.  The WHO also points out that right now we have no evidence the antibodies that do form protect from reinfection.

Immunity is also not an all-or-none phenomenon. You can have partial immunity, which means you still get infected but the disease is less severe. It is also possible to pass on the virus even if you have enough immunity to prevent an illness in yourself.

At present we are not sure if individuals can be reinfected with SARS-Cov2. Early reports of people who appeared to have COVID-19, recovered, then tested positive have been questioned. It’s possible they never had COVID-19, or their initial test was a false positive, or their subsequent test was a false positive. Once infected, viral particles (junk) may be circulating, not causing an infection but triggering a positive test.

What does all this mean? Experts believe that the COVID-19 pandemic is as bad as it is partly because it is a novel infection, which means the entire world is naive and without specific resistance. The virus has very fertile ground in which to spread. Once the virus makes its way around the world, that will no longer be the case. A percentage of the population will have some immunity from prior exposure, and so later waves of infection should not be as severe. That is the hope, anyway. But we really don’t know how significant immunity will be. If it is partial and short-lived, each wave may find a relatively unprotected population in which to spread.

If we assume the most likely “average” estimates of COVID-19 immunity, it seems most likely there will be partial immunity only, lasting 2-3 years like the other severe coronaviruses. But of course there is a lot of variability possible around this average result. This may slow subsequent waves, but not stop them. All this could mean that we will not be able to transition to the final stage of new normal until we have a vaccine.

Vaccines work by exposing the immune system to either dead or weak viruses, or parts of an infecting organism, in order to trigger immunity without having to go through an infection. However, vaccines can be tricky to make. Scientists need to find out which kind of neutralizing antibodies are the most effective, stable over time (resistant to mutations), and easy to create. But vaccine-created antibodies suffer all the vulnerabilities as natural immunity. The one big advantage is that you can give people the equivalent exposure of a severe infection, so you may be able to create with a vaccine better immunity than a mild infection would.

The other potential advantage (and “potential” is a big caveat here) is that vaccines can produce more thorough immunity in a population. If nearly everyone gets the vaccine, that is more complete coverage than is likely even in a pandemic. Not everyone is going to get COVID-19. So it seems likely that we really need to control this pandemic until a working vaccine is available that will finally enable us to transition to the final stage of back to near normal.

That new normal will likely include COVID-19 as a new endemic human illness. We’ll see. Given that immunity to coronaviruses are generally short lived, it seem more likely that the vaccine will have to be given regularly than the other end of the spectrum in which a single vaccine produces life-long immunity. If I had to guess I would predict that once we do develop a vaccine it will be given every year like the flu vaccine (and perhaps even rolled into the flu vaccine, if that is technically possible).

I want to emphasize that this summary is mostly about what we don’t know. These are the questions we need to answer in order to understand this disease well enough to really know what it’s going to take to control it. But I am also giving the high-probability guesses, but they are just that – guesses.


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