Thread by @PeterKolchinsky

Turns out that COVID vaccination would ideally have been a 3-dose course (day 0, Day 21-28, & one more shot at 6 months), akin to what we do when vaccinating kids & even adults against many pathogens. But ideals are going to be compromised… here’s why…cdc.gov/vaccines/paren…

Data from all major vaccine trials now show that immunity wanes gradually after first two shots… AND the virus mutates to build its resistance (ie delta variant). 2/

Vaccines still protect at 6m, but while their efficacy was 95% against original strain shortly after the peak of immunity after the 2nd dose, it drops down to being 40-80% protective against delta infection by 6m (still something!). 3/

What’s key though is that after 6m, vaccine still great at blunting disease severity, making you 7-12x less likely to be hospitalized IF infected than if you weren’t vaccinated & got infected (ie 85-92% protection against hospitalization-grade covid). medrxiv.org/content/10.110…

But waning immunity against any infection means the virus can still spread (mildly or even unnoticed) through many vaccinated people as we get out 6m past vaccination, until it finds vulnerable people for whom even a 15% residual risk of hospitalization is high. 5/

And of course there are the willfully unvaccinated. As much as everyone else may wish that they would get vaccinated (and I do support mandates), everyone deserves what herd immunity the rest of us can offer. So that’s where the 3rd dose comes in. 6/

Data from Moderna, Pfizer/BioNtech, & Novavax show 3rd dose can rocket neutralizing antibody levels up even higher (~4x) than they were after 2nd dose. That offers strong protection against all variants could plausibly last a year. cnn.com/2021/07/28/hea…

Ideally, everyone would get 3rd dose of a vaccine around 6m or as soon thereafter as possible. But we don’t have enough doses for that while we try to get even the first 2 doses out to the rest of the world so they can benefit from the protection we’ve enjoyed. Does CDC agree? 8/

Not quite. Like CDC initially played down masks to prevent shortage for healthcare workers (then reverse itself), CDC is avoiding saying 3rd dose is needed. But as w/ masks, once supply issues solved, CDC will likely acknowledge logic of 3rd dose for primary vaccination schedule.

By then, odds are few of us who got our initial shots early 2021 will be within 6 months of our first dose. So ideals are necessarily being compromised. We’ll simply have to make do with getting that 3rd shot whenever it becomes available. We’ll do better in future pandemics. 10/

Some may take a nationalistic approach and say “America paid for the doses so Americans should get all they want”. Ok, but that’s just one perspective. Maybe that’s not the kind of country we should be. & helping end global pandemic helps America, too. 11/

Still, I could see American administration trying to do both, have America be a good globally citizen but also skew a bit towards protecting Americans better. We are already seeing recommendations to give a 3rd dose to immunocompromised people. 12/

As supply expands, recommendations could be expanded to giving 3rd dose to everyone over 70, 60, 50, etc, as we saw w/ initial vaccine rollout. Healthcare workers & teachers should again be prioritized to offer stronger herd immunity to those they protect. 13/

Many of us still do what we can to shield our unvaccinated kids. Their risks are indeed low from COVID, but reports of complications from even mild infections are unsettling. So until we know more, we shield ours. Fortunately, studies for kids ages 6m & up are underway. 14/

While data from pediatric studies are officially projected to come next year, my guess is we’ll see them much sooner. I don’t doubt they’ll be effective in kids; that’s not really in question. FDA understandably wants to see safety to make sure we know benefit-risk trade-off. 15/

Once kids are vaccinated, parents might worry less about their own waning immunity not offering herd protection to their kids. So that 3rd shot wouldn’t feel as urgent. But right now, I hate thinking that my waning immunity could let me pass the virus to my unvaccinated kids.

It’s that herd immunity issue that makes masks rational even for the vaccinated. No sense bringing the virus home to your unvaccinated kids. Once they are vaccinated, we don’t have to hope for herd immunity as much. 17/

But even mild COVID isn’t fun, & masks protect against other infections. So even if just thinking about yourself, esp the further out you get from vaccination, consider merits of masks in at least some public setting, especially crowded indoor ones. 18/

Of course, if you have any member of your family who resists vaccination and who you really love (I’ve got one), then keeping yourself from getting infected is all you can do to protect them. So you’ll want a 3rd dose and/or to wear a mask (also helps muffle your grumbling). 18/

Technically, those who already had an infection can consider that to be like first shot, so they likely would be fine w/ one shot and then a 2nd one 6 months later. JNJ vaccine counts as 2 shots; getting extra shot of other vaccine good idea when you can. 19/

You might think if we need shot at 6 months, maybe need shot every 6m. It’s possible, esp w/ new@variants (yikes Vega! kidding, not a Greek letter), but again, data show that antibody levels after 3rd shot are even higher than after 2nd. So protection likely better, longer. 19/

And once kids of vaccine-accepting parents can be vaccinated, these parents won’t fear a rising risk of mild infection as long as can count on everyone being protected against serious infection. So annual shots will likely be good enough for long run (mix w/ flu vaccine). 20/

Tolerability… mRNA vaccines are as uncomfortable when you get 6m booster as after 2nd shot. They really rev up immune system. It may put some off. But older people, who need 6m booster most, actually tolerate mRNA much better than younger people, so if it’s available, take it.

Fortunately protein-based vaccines are coming (I know, like waiting for Godot…), good for two reasons: 1) they are better tolerated than mRNA and 2) they will dramatically increase global supply, easing guilt over getting 3rd dose when others haven’t gotten first two. 23/

Bottom line: when 3rd dose is available to you, whether at 6 months or anytime after, it makes sense to take it. It will help you & protect others around you. If I had to guess, boosters will be available to all who want them in US by YE21. 24/

Since I wrote thread, US announced that it will roll out 8 month booster shots. That’s great. Realistically can’t deploy quickly enough to get everyone a dose by 6m. So 8m is realistic goal. Means those who got 1st dose Feb-April will get booster by Oct-Dec. Aug/Sept less fun.