Jan 30 2023

COVID and Hybrid Immunity

As many experts predicted, the COVID-19 pandemic is slowly sliding into an endemic infection. A pandemic is essentially when an epidemic goes worldwide. Endemic means that an infection is here to stay. It is no longer considered an “outbreak” but is constantly spreading around a population without having to be introduced. The flu, for example, is endemic, although it is also seasonal. Measles was endemic in the US, but then was eliminated through vaccination and was reduced to isolated outbreaks. However, it is transitioning to being endemic again because of vaccine hesitancy.

While we are all anxious for the COVID-19 pandemic to be over, I don’t remember any expert claiming that the virus would go away, or be eliminated to any significant degree. Rather, it would simply become like the flu, an endemic simmering infection that becomes part of the background. The only question has been – what is the best path to transition from pandemic to endemic? Some argued that perhaps the best path was to simply let the pandemic run its course, and create immunity through natural infection. This has always been an unscientific and dangerous suggestion, because that path leads through a maximum of disease and death.

The evidence clearly shows that the best path to minimizing COVID while ending its pandemic status was through a combination of vaccination and infection. We have no choice about the infection part because there is no plausible way to reduce it to zero (as China discovered). But we do want to reduce the spread of COVID, especially to vulnerable populations, while reducing the risk of serious illness, hospitalization and death through vaccination. Pandemics always eventually burn themselves out, even in the pre-vaccination era, but we don’t want that to happen from a plague-level decimation.

Evidence has been building that the best immunity from COVID is through hybrid immunity – a combination of vaccination and breakthrough infection. I managed to go two years without getting COVID, for example, but eventually succumbed once mask-wearing no longer became commonplace. However, by that time I had been fully vaccinated and boosted, so when I did get COVID it was indistinguishable from a fairly mild cold. If there weren’t a pandemic (and I didn’t test positive) I would have just thought I had a summer cold. Hybrid immunity works either way, whether you were infected then vaccinated, or vaccinated and then contracted COVID (the preferred order).¬†

Now, as we transition to COVID being endemic, how do we leverage hybrid immunity to minimize the impact of the disease? The FDA is contemplating simply advising an annual COVID booster, just like the flu. And as with the flu vaccine, the booster will be modified each year to track the latest variants. There isn’t yet an expert consensus on this move, as some warn that there are still many unknowns about COVID. From what I have seen, however, it is a reasonable idea. Even if it is not optimal in terms of immunity, we need to balance that against what the public will tolerate and comply with in terms of a public health program. The best treatment plan means nothing if people won’t comply. An annual COVID shot (to go with the flu shot) might be the best compromise for a sustainable vaccination effort.

But also – there is some recent evidence that might indicate an annual shot may be best in terms of maximizing hybrid immunity. The study looked at hybrid immunity, and specifically the delay between vaccination and infection. They found that up to the 400 day study period, longer gaps between the two resulted in greater overall immunity. The researchers speculate that memory B cells, the cells primarily responsible for remembering past infections and cranking out antibodies when a new exposure occurs, increase over time. They don’t quickly emerge, but rather build up over time. Given memory B-cells enough time to maximize their population then also maximized hybrid immunity resulting from an infection (and this works the other way around as well). So once someone does get infected, they should wait to get boosted. The optimal delay in terms of benefit is not clear, and likely has to be individualized depending on previous vaccination status, and overall health status. But this is a helpful guide.¬†This information may impact the debate about going to an annual booster, favoring that strategy.

So while antibody levels themselves tend to fall over time (since infection or vaccination), immune memory cells tend to increase over time. This is probably another reason why pandemics tend to burn out, and why unexposed populations tend to be so vulnerable to infections (think of the infections introduced from Europe to native Americans).

I think there are two take-aways from this recent study, and the recent reviews linked above. The first is that hybrid immunity is the best. This does not mean that someone should go out of their way to get exposed to COVID. That defeats the purpose, which is to reduce infection. You will probably get exposed at some point, and if you never do, then obviously you don’t have to worry about it. But we should seek out vaccination. Getting vaccinated and boosted is the best strategy. If you do get exposed then it will reduce the severity and risk of death from COVID, and will result in hybrid immunity. This is a good thing to have as the virus mutates, spawns new variants, and becomes endemic. This is like getting the flu vaccine every year – it gives you some cumulative immunity from the flu.

The vaccine is how we transition to an endemic infection while minimizing death and disease.



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