Thread by @Bob_Wachter

My thinking about booster #2 has shifted a bit in the past few days. Here's a 🧵

First of all, on Tuesday I decided to mix-and-match: I got Moderna after 3 Pfizers. The side effects were similar as with my Pfizers – just mild arm ache. Some folks have worse, of course. (1/25)

When the evidence became clear last summer that booster #1 was needed, the general thinking was that it would deliver long-lasting protection. Why? Shots 1 & 2 had been given very close together (for good reasons), which didn’t give the immune system much time to mature. (2/25)

Ergo, a boost 6-8 months later would lead to long-lasting coverage…or so we thought. Perhaps we’d need a yearly booster (maybe combo w/ flu shot) but not more often than that.
So we were surprised that protection waned 4-6 mths after booster 1, leaving us now to ponder...(3/25)

…whether 2nd boost is needed. Until this week, a reasonable bet was that booster #2 would protect for 4-6 more months, matching #1.
But out comes a new Israeli study @NEJM showing booster #2 offers great (~3-fold) protection against SEVERE infection (ie hospitalization)...(4/25)

…for at least 2 months & maybe longer (the @NEJM study followed patients for only 6-8 weeks). But the good (2-fold) protection against SYMPTOMATIC infection appeared to by gone at 2 mths. nejm.org/doi/full/10.10…
This finding is a bit of a shocker & merits some rethinking.(5/25)

Let’s throw a couple of other factors into this confusing brew. First, I’m increasingly concerned about long-term effects of a Covid infection. Recently, we’ve seen convincing evidence that, on top of Long Covid symptoms, Covid infection is associated w/ ⬆long-term risk… (6/25)

…of several bad things:
- Cardiovascular events such as heart attacks and strokes nature.com/articles/s4159…
- Decreased brain volume (possibly associated w/ cognitive decline) nature.com/articles/s4158…
- Diabetes sciencedirect.com/science/articl…
- Blood clots bmj.com/content/377/bm… (7/25)

There's substantial uncertainty around all these findings – particularly the degree to which vax may ⬇the risk (ie, is a breakthrough infection less likely to raise risk than infection in unvaxxed person), whether the risks are the same with an Omicron infection (vs. … (8/25)

…a prior variant), and if antiviral Rx makes a difference. But for now, as someone who has not had Covid (that I know of), I still believe that preventing a symptomatic infection is a worthy goal – even though I know my chances of dying of Covid (after 3 OR 4 shots) are… (9/25)

…quite low. The question: what am I willing to do to prevent symptomatic Covid? Am I willing to take a booster every 2-3 months? For me, probably yes, at least for a while – maybe until we have better boosters or a sure supply of Paxlovid or other effective antivirals,… (10/25)

… along w/ evidence they⬇Long Covid risks. To those who say that a shot every few mths to prevent a bad disease is impossible, I’d ask them to talk to someone w/ Type 1 diabetes, who takes shots daily. There’s the “immune exhaustion” argument (too many shots will cause…(11/25)

… the immune system to wear out), which is theoretical but may prove quite real. More study needed.

So based on what we now know, let’s think about both decisions I made this week when I got booster #2: 1) now vs. later, and 2) mix-and-match vs. stick with the same vax. (12/25)

Now or later: I’ve argued against trying to “time the market” – holding off on a shot now to try to time the period of max efficacy with a possible surge later in the year. But the short-lived efficacy of the 2nd booster shifts my thinking on this one, at least a little. (13/25)

For those @ low risk of a serious infection (eg, healthy 50-year-old), the argument to wait is stronger. As @DLeonhardt pointed out yesterday nytimes.com/2022/04/06/bri…, we’re still unsure why we’re NOT seeing a big BA.2-associated surge. But (notwithstanding a mild uptick…(14/25)

… in the Northeast & plenty of high-profile cases), Covid case rates remain low.
So, if I was on the “now or wait” fence last week, the new Israeli data would push me to “wait.” (For me, a 64-year-old w/ mild asthma, I’d still go w/ "now," but it would be a closer call.)(15/25)

Second, the question of mix-and-match. I chose to mix because of theoretical evidence that it provides broader immunologic coverage than using the same mRNA, & some real evidence that Moderna is a bit more effective than Pfizer. The Israeli data comes from people who got…(16/25)

… 4 Pfizers. I can’t prove a switch to Moderna would have led to longer efficacy, but it’s a possibility. So I’m glad I chose mix-and-match. (@ZekeEmanuel says he'd switch to J&J.)
Here too, if I were on the fence, the new data might push me to mix-and-match. And yes,… (17/25)

… – though now we’re in a data-free zone – I’d probably mix-and-match in the other direction too (get Pfizer after 3 Modernas), thinking the evidence supporting broader immunity from M-&-M trumps the minimally ⬆efficacy of Moderna. But now we’re truly hand-waving.(18/25)

The FDA advisory committee meeting yesterday spent a lot of time on re-jiggered boosters, particularly ones specifically targeted against Omicron. statnews.com/2022/04/06/tra… Bottom line: no evidence yet that they’ll be better or more long-lasting, & it’ll take at least…(19/25)

…6 months to sort it out. So if your reason to wait is that you’re holding out for a better booster, it won't come anytime soon & thus isn't a good reason to delay now. We should learn the answer in the Fall, and so it might influence a Booster #3 decision at that time. (20/25)

How about folks who had an Omicron breakthrough infection? I’d stick with my rec that someone who had Omicron after 3 shots should wait before getting a 2nd booster. I don’t think the Israeli data changes that equation, other than to make it more likely… (21/25)

… that the Omicron infection-related immunity may also wane a bit faster than we thought. So if I had a breakthru in Jan-Feb & was at reasonably high risk (>age 65, let’s say), I might be thinking about a booster in May-June; perhaps sooner if there are signs of a surge. (22/25)

How about masking? For those of us who don’t want to get Covid, consider your protection to be quite high for ~2 months after a 2nd booster or a booster plus breakthrough. By the time you’re in month 3-4, you should deem your level of protection to have dropped… (23/25)

…significantly, & masking decisions should be made accordingly – meaning that in areas w/ low case-rates (<10/100K/day), it’s fairly safe to go maskless indoors, but in areas of⬆transmission you should consider yourself pretty vulnerable 3 months after booster #2. Drat. (24/25)

Sorry – just when it seems like we can ditch the 3-dimensional chess set, things have gotten even more complex. But such is life in the Covid World.
I hope this is helpful as you make your own decisions in the face of significant uncertainty & rapidly evolving evidence. (25/end)