Usually, I come to you with data. That will continue. But this newsletter is called Inside Medicine, and when this journey started, I promised to take you behind the scenes on my life as a physician working both in an emergency room and as a public health researcher.
Lately I’ve been doing two things: seeing patients in the ER and trying to figure out what is going on with coronavirus Delta variant—and therefore, whether boosters are actually necessary right now.
On the ground here in Massachusetts, the scene is fairly straightforward. We are seeing breakthrough cases among partially and fully vaccinated people. Most of them are either mildly symptomatic, or they feel terrible but are not truly at risk of developing severe disease. I’ve admitted exactly one Covid-19 breakthrough case to the hospital, and it was possibly unrelated. In other words, the vaccines are doing what we told you they would do: They’re keeping you safe.
I’ve admitted exactly one Covid-19 breakthrough case to the hospital, and it was possibly unrelated. In other words, the vaccines are doing what we told you they would do: They’re keeping you safe.
Meanwhile, most of the people who are sick enough to require hospitalization are the unvaccinated. In fact, the sickest patients I have treated recently are not middle aged and older vaccinated patients with breakthrough infections, but younger unvaccinated adults. To me, that means the current rise in hospitalizations would best be combatted by getting more people a first or second dose of a Covid-19 vaccine, as opposed to boosting people who are likely to do well, if infected. In fact, a recent Boston Globe story on Delta outbreaks in Massachusetts nursing homes all but buried a key fact: While most of the new infections had occurred among vaccinated individuals (which, as we’ve discussed before, is a predictable statistical phenomenon in areas with extremely high vaccination rates, such as Massachusetts nursing homes), most of the cases were asymptomatic or mild. While exact rates of hospitalization were not given, I’ve been looking through the Massachusetts public data and over the last several days, only one nursing home in the entire state reported a Covid-19 death. Last winter, Covid-19 deaths among nursing home residents in multiple facilities were a daily occurrence. In other words, infections are up, but the vaccine is providing excellent protection, even now that Delta has taken over in Massachusetts, like virtually everywhere else in the United States.
This matches the anecdotal stories in my “regular life.” Breakthrough infections are clearly happening and are often quite cumbersome. (I really don’t feel like losing my sense of taste, even temporarily!) But mostly, they have not been dangerous. Also good news is that new data has emerged suggesting that Long Covid is less likely after breakthrough infections.
So where does that leave us on booster shots? I’ve spent the better part of a week pouring through a variety of papers on this topic. I've never read more and yet been more confused about any Covid-19 topic. What I still can’t sort out are the answers to the following questions. They’re the ones we all need to be asking, and need to have answered, before we line up for another dose.
I’ve spent the better part of a week pouring through a variety of papers on this topic. I've never read more and yet been more confused about any Covid-19 topic.
1. Are breakthrough infections rising because of waning immunity as the population gets further and further in time from their original vaccinations? Or is what we are seeing just the effect of Delta itself, which seems to slip out of the clasp of our vaccine-induced antibodies with greater ease than previous versions of the coronavirus?
2. Are the documented modest decreases in vaccine effectiveness wrapped up in the vaccines’ now lowered abilities to stave off infections altogether? Or is what we are seeing the result of a decrease in the vaccines’ abilities to help our bodies respond to a breakthrough infection sufficiently such that we do not develop severe illness? While falling antibody levels have been bandied about, the reality is that we don’t know whether those lower levels render a person more susceptible to infection, but still able to fend off illness severe enough to require hospitalization.
3. Is a 3rd dose of an mRNA coronavirus vaccine (Pfizer or Moderna) associated with any adverse effects that would outweigh the benefits in any subpopulation? The calculation for older people may end up being relatively straightforward, because they have the highest risk of severe illness and the lowest risk of serious adverse effects from the vaccines. Also, we at least have a sense of the safety, since hundreds of thousands of seniors in Israel have received a 3rd dose and, so far, we have not heard of a major uptick in side effects. Meanwhile, there’s data to suggest that boosted-breakthrough infections (that is, breakthrough infections in people who have received three doses) are less common, though how long that protection lasts matters. If the added protection is short-lived, the argument for boosters would be significantly weaker. But for other groups the calculations might be far trickier. For example, after one dose, young males had a small but detectable rate of developing myocarditis, an inflammatory condition of the heart. A large majority of those cases were mild, and given what we know about Covid-19, even in the young in whom the risks are relatively lower, well worth it. But after two doses, the rates of myocarditis were far higher, with around seven times as many cases reported than after the 1st dose. Myocarditis cases reported after the 2nd dose were also more likely to cause serious cases, though again a small minority of cases were anything other than mild. What rates would a 3rd dose bring young males? The answers are impossible to know. It could be that the rate and severity of myocarditis would be similar to those associated with the 1st dose. After all, the 3rd dose would be coming many months after the most recent dose, rather than just a few weeks later, as was the case with 2nd doses. Alternatively, given waning antibody levels, a 3rd dose now could simply replicate what happened after 2nd doses. But the worst case is that the rate and severity of myocarditis after a 3rd dose could again skyrocket as it did after the 1st dose. If the rate went up by seven times once again, that would be a major problem.
And no matter which of these possibilities comes to pass, we still need to know what benefit the boosters will provide in exchange. Are boosted-breakthrough cases possible? Yes, we already know that, though they are believed to be less common (thus the steady drumbeat towards boosting). Are boosted-breakthrough cases less likely to require hospitalization than fully vaccinated breakthrough cases? Based on the Israel data, that seems likely among seniors at least, at least temporarily. But the key to making an informed choice is knowing how many Covid-19 hospitalizations would be prevented and over what period of time? Would the number be less or more than the hospitalizations associated with adverse reactions stemming from the booster itself? Also, are boosted-breakthrough cases less contagious than fully vaccinated breakthrough ones? This matters because some populations will need to consider the risk they pose to others. For example, healthcare workers would need to consider their patients, some of whom may be unvaccinated or inadequately protected (including immunocompromised people with insufficient protection, despite vaccination).
Lastly, I’ve been having conversations with some of the smartest doctors and experts in the United States about these questions. Nobody I have spoken to has the answers. That bothers me, because some of them are in government and have genuine influence. There’s a sense of pressure. A feeling of being rushed. That’s dangerous. We need our policies to follow the science, not the other way around.
There’s a sense of pressure. A feeling of being rushed. That’s dangerous. We need our policies to follow the science, not the other way around.
This week two highly respected officials at the US Food and Drug Administration announced they would soon resign. Many experts are convinced (as I am) that the resignations were in protest against what has become a tainted process. If that’s the case, and word gets out that the science has been short-cut, something that has not happened in the coronavirus vaccine development story until now, the push towards boosting everyone will lower not raise vaccine confidence.
Where do you stand on boosters? Do you feel that you have enough information to make a good choice? Leave your comments below and join the conversation.
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References and further reading:
Long Covid appears less likely after breakthrough cases: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00460-6/fulltext
A preprint from Israel on boosted seniors. A very complicated paper that I hope to write more about soon: https://www.gov.il/BlobFolder/reports/vaccine-efficacy-safety-follow-up-committee/he/files_publications_corona_booster-27082021.pdf
Two highly respected FDA officials announced they will leave the FDA soon, moves seen as motivated by discontent with the administration's booster push: https://www.nytimes.com/2021/08/31/us/politics/fda-vaccine-regulators-booster-shots.html
*A caveat. In this column, I do not address whether giving 3rd doses in the United States before others around the world have even had access to a 1st dose is ethical. Here, I’m focused on the science, the direct benefits and possible harms of a 3rd dose. One way of framing this question would be, “If everyone on Earth was already fully vaccinated, would offering everyone a booster be beneficial?”