I know, we're tired of hearing about Covid. But the virus is still with us, and case rates have begun to creep up again.
On Monday, the FDA approved the use of updated Covid vaccines manufactured by Pfizer and Moderna. On Tuesday, the CDC recommended that all Americans 6 months of age and older receive at least one dose. As of today, the vaccines are already being shipped to local pharmacies around the U.S.
In this newsletter, I want to address three questions:
1. How worried should you be now about Covid?
2. Are the new vaccines effective and safe?
3. Should you get one of the new vaccines?
There's data of relevance to each question, but none of it is a slam-dunk. The answer to each question depends on how you interpret the data.
I will answer these questions as best I can. I'll be concrete. But my purpose isn't to persuade you of anything. Rather, I just want to share the most relevant data, and talk about how we might think about it.
(Next week I'll be examining why mixed messaging, misinformation, and disinformation about the new vaccines have already begun to emerge.)
1. How worried should you be now about Covid?
That depends on what data you look at, and how you interpret it.
I see a need for caution but not fear, based on two kinds of evidence:
(a) Case rates.
Hospitalizations and deaths from Covid have increased slightly each week since early July. Although infection rates are no longer monitored, evidence from other sources, such as wastewater analysis, confirms that we've been experiencing another summer surge.
Some experts see no cause for alarm, because hospitalization and death rates are much lower now than were at the height of the pandemic.
For example, for the week ending August 26 of this year, there were over 17,400 new Covid hospitalizations, and more than 600 deaths. Around the same time in 2021, hospitalization rates were about five times higher, while death rates were over 20 times higher.
Given that case rates are relatively low – and increasing more slowly than they did in previous years – some experts are quite unperturbed. As a Johns Hopkins immunologist told the New York Times last week, “These increases are more alarming by statistics than in reality."
I consider that an unfortunate choice of words. Statistics are one way to describe reality; they're not necessarily opposed to it. For instance, by September 2, the rate of new hospitalizations per week had increased to 18,871. The numbers are probably slightly higher now. Thus, every day, nearly two Americans per minute are being hospitalized for Covid. Whether or not you find that alarming, it's hard to see any difference between the statistics and the "reality" of the situation.
People who are unvaccinated and/or vulnerable (due to age or health status) still constitute a disproportionate number of Covid hospitalizations and deaths, so if you don't fall into one of those categories, your chances of one of these outcomes are lower. Still, it's impossible to determine personal risk from general statistics. All you can say is that there's a hierarchy of risk: At the top, the lowest risk comes from being fully vaccinated and boosted (or having had Covid recently), and being cautious about social interaction.
In sum, we're experiencing a summer surge in Covid-driven hospitalizations and deaths, but at a much lower rate than in previous years. I see a need for caution but not alarm.
(b) Variant characteristics.
A quick look at Covid variants is relevant to the question of how worried we should be, and to my later discussion of how effective the new vaccines are.
Omicron is the only type of Covid currently infecting people. Omicron now has dozens of variants (lineages and sub-lineages), each representing a different genetic makeup.
Right now the main Covid variants include the XBB family (about 70% of cases and decreasing), EG.5 (about 15% and increasing), and FL.1.5.1 (about 6% and increasing).
Among the many XBB sub-lineages, case rates for XBB.1.5, which prompted development of the new vaccines, is around 12% and decreasing.
(The CDC calculated these percentages in August; they'll be different for September, but EG.5 is expected to become increasingly dominant.)
The BA.2.86 variant, known informally as Pirola, is still quite rare. BA.2.86 caused a lot of concern when it was first detected because it's so different, genetically speaking, from its predecessors. However, new data has revealed some encouraging news.
Although BA.2.86 is relatively good at escaping neutralizing antibodies, it's not so good at infecting our cells once in our bodies. It's unclear how this trade-off will affect actual rates and severities of infection, but experts are reassured by the data and less alarmed than before about this variant. In addition, prior infection with an XBB variant seems to prevent BA.2.86 infection, as do the new vaccines.
None of the variants currently circulating, including BA.2.86, appear to be appreciably more dangerous than their predecessors, although EG.5 may be slightly more transmissible.
In sum, although the coronavirus continues to mutate at a rapid rate, the new variants don't seem to affect people more severely than older ones did.
You might sense a contradiction here. If the new variants are no more dangerous than older ones, why are hospitalizations and death rates increasing? Leading epidemiologists such as Katelyn Jetelina have pointed to two causes: Waning protection (some people aren't boosting, or the effectiveness of their last shot is wearing off) and changes in behavior (more travel, and more time spent indoors to escape the heat).
In other words, although the new mutations aren't more dangerous, severe outcomes are increasing because people are less protected but spending more time around each other. Again, I think this calls for caution but not alarm.
2. Are the new vaccines effective and safe?
Yes, I think so, although the data are preliminary.
The FDA approved the new vaccines based on "the totality of the evidence". In other words, the FDA considered indirect evidence, such as what we know about currently circulating variants and vaccines, as well as direct evidence.
However, the direct evidence was not obtained from clinical trials comparing people who do vs. don't get vaccinated (which is how we obtained the most well-known direct evidence for the effectiveness and safety of the original vaccines.)
For the new vaccines, the FDA reviewed immunogenicity data. This means that people received one of the new vaccines and, later on, their variant-specific antibody levels were measured.
The details are important. Although I am persuaded that the vaccines are effective and safe, the data are not as strong as one would like.
These data come from an ongoing study, led by a Moderna researcher, in which 50 people received Moderna's new vaccine, and 51 people received Moderna's older bivalent vaccine. (For all participants, this was their fifth dose of a vaccine. None of the participants was to known to have had a Covid infection in at least 3 months.)
Although this new vaccine is monovalent, meaning that it was designed to neutralize just one variant (XBB.1.5), the researchers tested how well it handled other variants currently circulating in the U.S.
15 days after the injection, the researchers found that relevant antibody responses had increased more among the new vaccine group. Neutralizing effects of the antibody responses were found not only for XBB.1.5, but also for many other XBB variants, for the two variants that are becoming more prevalent (EG.5 and FL.1.5.1), and for BA.2.86, that still-rare variant of greatest concern. There were no serious adverse effects for the new vaccines; side effects were comparable to the older formulations.
This is good news. The study suggests that the new vaccines are safe as well as effective at preventing infection by any of the new variants. The data corroborate findings from animal research that both Pfizer and Moderna reported to the DNA. Still, the study is limited in at least three ways:
–The sample is small.
–The methods are somewhat indirect. (Antibody response in lab tests is not the same as real-world effectiveness).
–Long-term immune response has not been studied. (15 days is not much time).
Here's why I'm not overly concerned by these limitations:
Regarding sample size, yes, this a small sample, statistically speaking, but most peoples' immune systems work in approximately the same way. The new data show changes in antibody levels that would be expected on the basis of how the older vaccines work. In short, small samples are not as problematic in this context as in others. The main contribution of larger samples will probably turn out to be a better understanding of diversity in immune response, including exceptional cases where the new vaccine may be ineffective or unsafe.
Regarding the indirectness of immunogenicity measures, yes, it would be preferable to have real-world data, but prior studies do show that lab performance is consistent with real-world effectiveness. (I used the term "consistent" rather than "highly correlated", because we don't know exactly how much protection is conferred by any specific immunological response. The data simply show that the new vaccines stimulate antibody responses comparable to those spurred by earlier vaccines against earlier variants.)
Regarding long-term immune response, yes, it would be preferable to know what antibody levels are like for periods of time longer than 15 days. But "the totality of the evidence", which includes what we know about the performance of the old vaccines and the composition of the new ones, indicates that effectiveness will persist and then slowly decline over time. For this reason, the FDA's approval notice suggests that the new vaccines (or updated versions) will need to be taken annually.
In sum, the new vaccines appear to be effective and safe, based on preliminary, less-than-ideal evidence. We won't have data on their real-world performance for at least a few months.
3. Should you get one of the new vaccines?
In my opinion, yes, based on what I've written so far.
Studies on the original vaccines as well as the new ones indicate that as the virus mutates, vaccine effectiveness is fairly comparable across closely-related variants. Thus, the new vaccines should continue to be effective, at least for a while, as the virus continues to mutate.
(If you're medically unable to take one of the mRNA vaccines – Pfizer or Moderna – the CDC recommendation includes Novavax, which is still under FDA review, as well as others that may be developed in the near future. Once the FDA approves Novavax, it will become available for use.)
As for when you get vaccinated, and which vaccine you choose, I'll offer my opinions here, but again, my purpose isn't to persuade but rather to share the data that's most relevant to making the decision.
Timing is clearly important. Getting vaccinated within 2 to 3 months of your most recent vaccination or infection won't help (or hurt) your immune system's response to the virus. So, it makes sense to wait, but for how long?
There's a bit of a trade-off here. The longer you wait, the more your immune system will benefit once you do get vaccinated. Studies show that waiting 8 months to a year, if not longer, increases the effectiveness of Covid vaccines. However, the longer you wait, the more vulnerable you'll be, because existing protection will gradually dissipate and, meanwhile, you'll be exposed to more people.
I don't think the data support highly specific recommendations about timing. There's some squishiness introduced by individual variability, by the possibility of slight differences between the bivalent vaccines used in the aforementioned studies and the new vaccines, etc. Here's what I consider the safest conclusions:
(a) If you're unvaccinated, and/or never got boosted, then regardless of who you are, you should get one of the new vaccines right away, or 3 months after an infection.
(b) If you're elderly and/or highly vulnerable (e.g., immunocompromised), you should get a new vaccine right away, or 3 months after your last booster or infection.
(65 is usually cited as the cut-off age for being highly vulnerabl, but I think you need to be honest with yourself about your health. Individuals who are less than 65 may be vulnerable, while slightly older individuals may not be. People don't typically wake up on the morning of their 65th birthday in a substantially poorer health than the previous day.)
(c) If you're not elderly and you're in reasonably good health, then 6 to 8 months after your last booster or infection may be a good time to get one of the new vaccines. (I say "may be" because during this time period, you'll have a low but slightly increasing risk of infection, depending on your social behavior.)
(d) If you're between 6 months and 5 years of age, let me compliment you on your reading skills. Following the CDC, I suggest that you get one dose of either of the new vaccines, unless you're under 5 and unvaccinated, in which case additional doses are recommended.
As for which vaccine to choose, it's unclear whether Pfizer or Moderna will differ in safety and effectiveness at any age. I wouldn't wait to find out, because that could take a while (and prior data suggests that any differences would be small).
As for whether the vaccine you choose is the same or different as your previous one, studies on these two vaccines have not consistently demonstrated any advantages (or disadvantages) of switching from one to the other. The same holds for mixing Novavax with one of the two mRNA varieties (Pfizer or Moderna).
Finally, experts agree that getting two or all three fall vaccines (Covid, influenza, and RSV) at the same time will neither create health risks nor diminish the effectiveness of any one of those jabs. The immune system will respond separately to the components of each vaccine, just as it does on a daily basis to different kinds of invaders we're exposed to. It sounds a little hard on the arms, but not unsafe.
Conclusion
I recommend getting one of the two new Covid vaccines. Immediately if you've never been vaccinated or had Covid; otherwise, sometime between 3 and 6-8 months after your last booster or infection, depending on your age and health. I don't think you should be overly concerned about which of the new vaccines you get, or whether you get that vaccine at the same time as other fall vaccines. If, for medical reasons, you're unable to take one of the new mRNA vaccines, I recommend Novavax once it receives FDA approval.
In this newsletter I've suggested that the evidence for the effectiveness and safety of the new vaccines is persuasive though limited. Those limitations are part of the reason we've begun receiving mixed messages from some researchers and clinicians about who should be getting vaccinated. Of course, we're also hearing quite a bit from the anti-vax community. Next week I'll be discussing these mixed messages as well as the undiluted, deeply virulent opposition to the new vaccines.
Thanks for reading!
Ken, great summary of the mRNA vaccine data!
Generic and AI-manufactured.