New Boosters Are Almost Here

I'm going to get one when I can. You?

Here is a quick update on the new and improved booster shots that are set to roll out shortly after Labor Day. The fact that Pfizer and Moderna were asked to dial up BA.4/BA.5 variant shots only 2 months ago, and are actually ready to deliver this soon is nothing short of miraculous, we can’t forget that. From a technological standpoint, this is fulfilling the promise of mRNA platforms to be quite nimble for this present mess, and against future emerging infectious diseases. The 2 month turnaround is feasible because these mRNA shots have already been given to billions of people, so we know they are relatively safe… and much safer than getting Covid.

However, these new BA.4/BA.5 boosters incorporate a leap of faith based on our experience with flu shots. I think it’s less of a leap and more of a skip. Each year the circulating types of influenza change around the world, and mouse models are used to test the effectiveness of candidate flu shots (instead of starting from scratch every year with human trials, which would just not work). Now this shortcut is also necessary to keep up with SARS-CoV2 mutations. These BA.4/BA.5 boosters have only been tested in mice in terms of immunogenicity. And they worked pretty well.

To be clear, the new Omicron boosters are actually bivalent boosters - meaning that they have some of the original shot’s mRNA and some of the new BA.4/BA.5 spike protein-encoding mRNA.

Many thought leaders think this bivalency is unfortunate, as some studies show just giving a pure BA.5 type shot would have been better at targeting the Omicron family (BA.1, BA2.12.1, BA.4, BA.5 and the whole ugly lineage). But who knows where the next variants are going to come from, and maybe a boost against the original virus would better help should another lineage spawn that is not like the Omicron family. Others argue that we are still priming the immune system pump too repeatedly against the old original virus, and therefore training it too narrowly. Yet still other studies have shown that with each additional shot of the original vaccine, all the way through a 4th shot, there is a consistent broadening of antibody and T-cell immunity against different variants! Broadening is good, narrowing is bad. Aren’t you glad there are experts out there trying their best to balance this stuff? I surely am, and I’m happy to translate this through a primary care doc filter.

So here is a pretest. This does not commit you to one choice or another in real life, but I’m just curious before the flurry of new information and perhaps this post affect your decision - are you planning on getting the new, updated booster?

I think a really tricky part of counseling people about the new boosters is going to be the lack of clear guidance coming from the CDC in terms of what prior Covid infection brings to the discussion. We know that hybrid immunity gained from some combination of prior vaccination, boosters, and infection is a powerful shield against hospitalization and death. For the many people I’ve been seeing this summer who were vaccinated, received one booster, and then got BA.5 Covid - will a BA.4/BA.5 boost early this Fall really help that much? It will be interesting to see if there is much guidance about this situation, but I doubt it. Once again, this thing moves so fast that it is impossible to set up trials to answer this question in a timely fashion. Trust in experts and consensus building are the best bets right now.

As for all things Covid, the risk category of the patient matters, and the most important risk factor for developing severe disease is age, particularly for those 65 and up. Although 65 does sound kind of coincidental, dovetailing with social security retirement age, Medicare eligibility, and all… probably some good conspiracy theories to be developed there. But seriously, there is no red line at 65, but rather a consistent upward slope of risk as we get older. All boosters, this one included, also slope upwards in terms of importance.

I personally plan to get the new booster. I want my immune system to be exposed to as many spike protein variations through vaccination as possible.

You will recall how skepticism about boosters, and especially 4th shots, ruled this country and led to only 32% of Americans getting any sort of booster at all. This is kind of sad for the country that discovered and heroicly brought mRNA vaccines to the world. Countries similar to the U.S. had double our booster rates. Not staying up to date with vaccines and boosters has proven to be the wrong call, as that early study out of Israel showing 4th shots were legit, was legit.

Sorry, I had to share this. MC Hammer was a part of my childhood.

So what happened in the U.S. this spring?

Among people age 50 and older, unvaccinated people had 29X the risk of dying from Covid compared to vaccinated and twice boosted people.

Comparing 1 booster versus 2 boosters, we saw that those over 50 with only 1 booster still had a 4X risk of dying compared to those who got 2 boosters.

Now the absolute reduction in numbers of deaths seen in this graph from the CDC is less impressive than the relative reduction, as usual. Hopefully we can more easily see the difference between absolute and relative risk reduction magnitude on this graph (I scribbled red and yellow marks upon it to highlight, but it still takes a little pondering):

Vaccination, boosters, and new boosters also aim to reduce the severity of disease, flu-like syndromes that can drag on for weeks, the risk of long Covid (PASC), and the contagiousness of those infected. Each vaccination does wear off in terms of preventing infection, but protection against hospitalization and death have thankfully remained durable.

Shots are still totally worth it, even though the virus has mutated to the point of being able to evade our immune system firewalls. Trials are ongoing that may produce nasal vaccines that protect our bodies more at the point of entry in the respiratory mucosa of the nose, throat, and airways. Many thought leaders are very confident that this next generation of nasal vaccines will be superior in reducing the actual spread of Covid (like we saw with the original shots preventing 90% of infections before this monster evolved past intramuscular vaccines). I am hopeful, too, as evidence from animal models show the nasal vaccines are working great to prevent infection. But I am also realistic, as nasal flu vaccines (admittedly against a totally different virus) have not been a game changer. We will have to wait and see.

I’ll look forward to sharing additional thoughts about the new boosters as we get closer to roll out, with Pfizer for 12 yo’s and older right after Labor Day we think, and Moderna for 18 and up shortly after that. For those of us who like free stuff, this will probably be the last round of free shots. Government pandemic funding is drying up, and purchasing will shift to health insurers and patients in the future most likely.

I’ve also been following Paxlovid developments like rebound and efficacy surveillance in The New England Journal of Medicine this week, and I’ll try to get another post out shortly to update you on that, too!

So for now, on balance, I think the potential benefits of another booster outweigh the potential risks. These bivalent boosters provide our first protection against a new variant like BA.5 since this whole thing started, and are really another great achievement in the history of medicine.

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