96 Comments
Oct 28, 2022Liked by Katelyn Jetelina

So disappointed in NPR . What a misleading, destructive headline.

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I will say, the actual interview was good. But the headline does damage. I was disappointed too, they are usually very good with this stuff

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Oct 28, 2022Liked by Katelyn Jetelina

Dr. Jetelina, Thanks again for the helpful update. If you can, I would appreciate your thoughts on whether we will continue to need additional boosters for COVID going forward and whether there may be any long term effects on the immune system with so many boosters. I have now received a total of 5 vaccinations at this point.

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I honestly don’t know. And no one knows. I will say, I think fewer and fewer people will keep getting them regardless. This time around the booster kicked my butt..again. I know it’s probably better than infection, but we *really* need better vaccines.

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I suspect we'll continue to see recommendations to boost, likely on an annual basis. I am less certain there's marked benefit from a multivalent vaccine (at least at this time). And, I concur that fewer will partake of the booster. I'm writing something now about how we've declared endemicity regardless of what the disease is doing to us.

Response to the vaccine varies widely among individuals. My clinical response to infection, as well as to the various vaccine exposures has uniformly been mild. That said, I had an upper respiratory infection 2 weeks after my bivalent (Moderna) booster that consistently tested negative (rAg and PCR) but was likely because the viral load was successfully driven down. Signs and symptoms were identical to my previous documented infections.

On the subject of "better" vaccines, creating a vaccine with sterilizing immunity is a non-trivial task; developing vaccines capable of preventing serious illness and/or death is somewhat easier to develop but harder to explain to the public (I'm not trying to condescend, you know this better than most). Developing a "better" vaccine to a coronavirus is a difficult task by itself because of the mutation potential. The drug companies focused on the obvious easy target, the spike protein and specifically the receptor binding domain rather than the capsid. I suspect the fabled pan-coronavirus vaccine will look at other targets.

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I suspect the optimal strategy would be to give the state of the art shots to the immunologically naive.

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Since there remains some serious questions about long (and even short) term efficacy of infection-acquired immunity (not to be confused with hybrid immunity -- infection-acquired AND vaccine-acquired) when looking at the Omicron subvariants, I do not think limiting the vaccine to immunologically naive is a great idea. That said, most of this country has selectively heard the news that the pandemic is over and we can resume our pre-COVID activities. We've decided as a nation that 300-500 deaths per day from a treatable and somewhat preventable disease is acceptable (as long as it's not MY family), and that masks are more trouble than they're worth.

Me? I'll continue to get boosted as recommended, based on the literature I'm following, and will provide the best information to my organization to allow its leadership to make appropriate recommendations. At this time, that recommendation includes following CDC Community Transmission levels (not Community Levels), and to pay attention to trends in hospitalization as a lagging indicator of cases, since we are effectively no longer testing (you are aware of the medical adage that, if you don't want to find a fever, you shouldn't check a temperature, of course). I continue to follow wastewater assays and look at the genotyped prevalence statistics.

Something we have to consider is the secondary pandemic of post-acute COVID syndrome. World Health Organization's estimate is that 6% of those infected are suffering from PACS or Long COVID. Some of these people are now unable to work or carry on with normal activities of daily living. The manifestations of Long COVID are several, and we're just starting to get a handle on how to even test for it, but I'm leaning toward a combination of auto-immune activation associated with long-persistence viral reservoirs in the body contributing to persistent vascular endothelial inflammatory processes. Finding assays to determine the process, and extent will be as important as finding the next great vaccine (although arguably, a nasal vaccine, targeting mucosal immunity, would be a game changer for preventing infection and further reducing severe disease), followed closely by determining ways to reverse the deleterious effects of the vaccine on the inflammatory process.

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Sorry, I didn't mean to suggest limiting it to naive. But maybe if there are two people, one of whom is naive and the other not, the naive person should get the multivalent and the one who's already has a degree of immunity should get whatever is available.

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We're not limited at this point on availability. I'm not sure there's a reason to restrict those with some additional immunity to the WA-1 monovalent historical vaccines. I'm not convinced imprinting is sufficiently strong as to make a case to restrict vaccines on that basis.

Hybrid immunity is, apparently, both durable and more effective. That said, with the exception of some new data I saw today on a Delta subvariant that's starting to emerge, most of the variant soup issues are derived from Omicron, and most of those BA.4/5. Yes, there are exceptions (BA.1.1, BA.2.10) but they're relatively minor.

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Eric Topol posted about a nucleotide based vaccine in early study, avoids immune escape and induced mucosal immunity. Hopefully less reactogenic and more lasting, variant proof vaccines get funded for research and become clinically available

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And now I've gotta go find Eric's post on that. Which isn't easy: He posts about a lot of things!

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As I read the article, I’m not seeing the nucleotide portion referenced—here’s the editorial https://www.science.org/doi/10.1126/sciimmunol.add9947

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Thanks for the references. The study itself suffers from low power at this point but is very promising. I've agreed with Topol that we need a mucosal-activating vaccine (in fact, I was arguing for one before I saw his references). There are issues, as the editorial notes, especially for the limitation in age groups and for immunocompromised patients. I remain appalled that Congress can't get their collective acts together to fund a second round of Warp Speed to support development, production and distribution of a nasal-administered vaccine.

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Here’s the vaccine against nucleotide capsid

https://www.science.org/doi/10.1126/scitranslmed.abq1945

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I agree

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https://www.science.org/doi/10.1126/science.abo2523

Link to the Science article on the vaccine

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founding

Thanks for the response. I assumed this but appreciate your thoughts. I've got asthma and the vaccine has not bothered me and I have not gotten COVID so I will count my blessings and keep reading your posts. Thanks again.

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Yeah, the way I see it, at least a booster only costs me one day at a time, on my own terms. I had swine flu in 2009 and it damn near killed me. That's enough pandemic respiratory diseases for one lifetime. I've had 7 covid shots so far because I work in person and can't afford to miss a day.

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Oct 28, 2022Liked by Katelyn Jetelina

Thank you! Great info. Will share with those I know who are currently refusing to get the Fall booster!

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Because the new bivalent boosters have been updated for Omicron, there seems to be a misconception among some of the newly boosted that they are now *completely* protected against the current variants. For some, this is their entire motivation for getting the updated booster.

They now have a false sense of security, and take on more risky behavior - indoor dining, flying without masks. Within weeks of their booster, they catch Covid.

For all the people I know who have gotten Covid in the last few weeks (a handful), they are all recently boosted with the bivalent. There’s a communication disconnect that needs to be addressed.

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Seems we're getting to the "personal decision" point. If I'm nearly as likely to transmit an infection whether or not vaccinated then to the extent I want/need to protect those around me I'll use physical measures like well-fitted mask, airflow, etc. I'll protect me by being up to date with vaccines. Recently missed a conference because they required proof of vaccination but masking optional. I understand the value of being physically together at scientific conferences so respect people's choices - but it wasn't very reassuring that THEY thought the policy was reassuring.

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I’ve spoken to more than a handful as part of my job. All are two weeks to a month out from bivalent and pretty disillusioned by infection. Most are mild infections, which I stress as a benefit, and these are phone interviews so I don’t have any real insight into behavior beyond what they tell me, but lack of short term protection won’t be great PR for those on the fence. We are doing brisk business still with bivalents (I’m a vaccinator as well), but these calls do seem to be fairly common. I’ve worked through the entire pandemic, in both the hospital and with the public, got all vaccines I’m eligible for, but still mask inside everywhere and only do takeout. No COVID, and have always tested regularly. I don’t think you have to be a hermit but I do think masking with at least a kn95 is probably key.

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Thank you for sharing this. I am similar in behavior, except that I do go to restaurants for outdoor dining when there is adequate spacing, good air flow (open on 3 sides), and , depending on case rates, I literally pay attention to the wind currents. We wear masks to check in at the restaurant and walk through. Quality masks are key!

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I have got covid twice with a well fitted N95 mask on so I don't feel safe anywhere but home :(

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That’s really scary to hear…sorry that happened to you!

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Similar happening in my corner of the world!

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Oct 28, 2022·edited Oct 28, 2022

To use a crude analogy, if a pill/device prevented pregnancy only 5% of the time, should it be called "contraception"? Or does calling it "contraception" cause the undesired outcome of unplanned pregnancies to increase?

It seems likely that the bivalent booster does help prevent some level of infection, but is that number 5% or 95%? There's some threshold where if the effectiveness is too low, the undesired outcome increases instead of decreases due to the gap in expectations vs reality. People who believe they are protected are more likely to take on risky behavior.

Unlike our pregnancy analogy, with a contagious disease, if more people become infected with covid, the transmission rate goes up, leading to second, third, and nth waves of more infection.

This is a messaging nightmare, because if people were told "get boosted, but unless you live like a hermit, you'll probably get covid anyway" (i.e., the truth), fewer people would get boosted, especially the young and healthy.

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Your key point here is that we're still failing at messaging. Communication has proven difficult for me during the pandemic, and I'm sure other scientists immersed in the work being done with COVID are in the same predicament. Things are moving so fast that my usual, pretty effective manner of communicating with patients and families has given way (sadly) to rapid-fire recitation of facts as we know them... today, but they're subject to change tomorrow. This isn't nearly so much the case in the last 4-6 months as it had been early in the pandemic when research publications contradicting what we thought we'd learned by a well-designed study were changed literally overnight, yet, still, it's hard to keep up with a day job and all the literature that's emerging. And then, you have to determine if the new literature is worth reading or is "noise" in the Signal to Noise equation.

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?4th goal would be reduction in long Covid and structural damage to the pulmonary, neurological, and other body systems.

For what is worth, I have not seen any of my patients who received the bivalent booster come down with Covid yet. Anecdotal and sure to change within the next two weeks

I’m in Philly, and the Phillies are energizing this city, and with bars and indoor get togethers we are sure to be a canary in the coal mine for xbb and the rest đŸ˜¬

But did you see that Castellanos catch? Realmuto hitting a 10th inning game winning home run (with what loooked like a mild concussion to me from a baseball ricocheting off his face earlier)?!

I’m hoping many on this team got their boosters, probably not, but they are surely boosting our morale

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Sorry. I lived in Houston for too long to be a Phillies fan right now!

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Go Phillies!

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It will be interesting to see if there's a significant difference between Moderna and Pfizer.

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Really?? Because the track record clearly indicates a significant advantage to Moderna. Among my friend network (I realize this is anecdotal from your perspective) all the breakthrough cases I know of appear to be Pfizer.

I feel like we could have a more frank discussion comparing the two if it weren't for the fact that they're publicly traded companies. If a prominent public health official came out and explicitly recommended Moderna there'd be an SEC investigation within days.

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Pre-omicron there were perceived benefits to Moderna. Post-omicron, not nearly so obvious. Moderna may run afoul of SEC but their science has been pretty good.

Breakthrough cases "happen" with Paxlovid, and post-mRNA vaccinations. And J&J, Novavax, etc. I'm pretty comfortable recommending whichever vaccine you can get. Period.

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From the Cell paper: "100% of mRNA or NVX-CoV2373 vaccinees make Spike memory CD4+ T cells." That's reassuring but I'm curious about what it reveals about the various 'omics in which the 'immunome' is woven. I've had 3 Moderna then 2 Pfizer. Essentially zero side effects. Hopefully I'm as protected as people who had moderate or worse 'side' effects of mRNA vaccines. The curious part is what does this reveal about the nature and practical consequences of the immune response?

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deletedNov 3, 2022·edited Nov 3, 2022
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Thank you for this post. :)

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I hope that you can shed some light on the problems of the immunosuppressed, particularly on those of us with solid organ transplants. I have a kidney transplant, and am thus immunosuppressed. It's VERY difficult to get any firm guidance from the transplant center, the ID doc, the nephrologist, or my PCP. Somewhere between 2.5 and 3% of the US population is immunosuppressed and we feel very forgotten, The CDC removing the requirement for masking in health care facilities has many of us feeling like our lives are simple not valued.

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CDC removing masking requirement in health care facilities makes me mad enough to bite! The immunosuppressed are a small part

Of the population, but a considerably larger part of the health care facility population. Why the hell is it ok for the unmasked staff, who are guaranteed to be treat Covid positive people every day, to put the immunosuppressive at risk? While they examine and treat them? So now the immunosuppressed are in waiting rooms and exam rooms with Covid positive people who are not masked. And if they become inpatients, there is no safeguarding them from being put with a Covid positive roommate, since admitted patients are no longer routinely tested for Covid.

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As far as I can tell, our local hospital system still requires masking in all indoor facilities and attempts to separate patients with signs of contagion, like fever, from the rest of the population. I believe these are necessary precautions, but their implementation leaves much to be desired. It's causing patients whose underlying problems need ongoing treatment, but who also catch bugs easily, to fall through the cracks.

Patients who show symptoms of contagion on the day of an in-person appointment are expected to reschedule or switch to telehealth. The telehealth does not work particularly well, not all doctors in the system do it, the patient portal is unclear on which appointments are telehealth and which aren't, and calling scheduling will not necessarily reach a scheduler in time to switch to telehealth if you can and should. Providers, for understandable reasons, are also more likely now to cancel patients' appointment without warning (for example, if they're symptomatic), and without an offer of rescheduling. This can delay accomplishing visits with providers for months, and may cause patients to give up on seeking care altogether.

I believe in the goal of doing more to separate potentially-contagious patients from other vulnerable patients – and of course, compared to separating patients, just wearing a damn mask should be relatively easy. But I can understand how difficulties implementing the separation might cause a system, especially a depleted one (and which one isn't these days?), to give up trying.

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But it is not that difficult to identify the contagious patients: a rapid test

does that pretty accurately: If you have enough damn Covid up your nose to make the test turn

positive you’ve got enough to be contagious; if you don’t you don’t. Fever is a sign of illness, not of Covid. You can be contagious with Covid without having a fever.

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Oct 29, 2022·edited Oct 29, 2022

I said our local hospital system attempts to separate patients by "signs of contagion", not COVID positivity. Our hospital's screening tool, at least the one used on patients, is apparently set up to try to keep anyone with any infectious airborne disease out of the "clean" suites, and is therefore symptom- and temperature-based, not COVID-test based. A negative COVID (or even COVID+flu) test isn't sufficient to clear screening if symptoms are present.

COVID isn't the only contagion that poses a danger to vulnerable patients. Flu, RSV, and other bugs also do. "Just a cold" – even when that's not euphemism for COVID or flu – can do a transplant patient in. Right now, a "chest cold" is going around the local schools that's not officially anything (it registers negative on COVID+flu tests), but which can be devastating to those with underlying conditions.

I support the ideal of hospital systems getting serious about airborne contagion, period, even if it's not COVID. Implementation isn't working here yet, though, because of the sheer number of people who have some symptoms on any given day, even if for perhaps non-contagious reasons (there is no sure way to tell).

People with active asthma and hay fever, for example, basically have to lie about their symptoms to get through screening, and hope they're making the right choice by fulfilling the spirit of screening, not the letter. They can only hope they're making the right choice: there is no sure way for even honest patients to be sure of the difference between just allergy/asthma crud and infectious crud, especially since not all infections cause fever.

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I had an allergy test last spring, for exactly this reason - positive skin tests for (1) grass pollen and (2) mold. No surprises there! So now I check things like the pollen count and the humidity levels before taking a rapid test.

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If we didn't have small kids spreading school germs, I'd be more confident that my seasonal allergies were just allergies. As it is, sigh...

https://www.theatlantic.com/health/archive/2022/10/rise-of-rsv-flu-covid-infections-kids/671947/

https://www.medpagetoday.com/opinion/second-opinions/101526

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What causes immunity to 'wear off' over time? Why doesn't it last years/decades (for the same pathogen) like it does for measles, mumps, polio? Or is it more that when the antibodies aren't needed for some time, their production wanes, but blast back up with re-exposure? (Also, what's the timecourse of T-cell capability after initial virus or vaccine exposure? In otherwise healthy people does it drop off with age?)

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My sense is that antibody immunity does probably wear off for all or most diseases, including the ones you mention. We we were just so successful at suppressing them at the population level that we (mercifully) never found put how long that immunity lasts. I fear we may soon find out.

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Really nice summary-thanks! Re: Retooling the B-cell 'factory,' is this reassuring about the concern of 'original antigenic sin,' where the factory wouldn't re-tool - where B-cells better attuned to the new variant wouldn't start being produced? I wish some of these media would invite you on to comment Katelyn - the standard commentators aren't taking that extra "let's dig a little deeper" step.

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AOS is an interesting concept but not completely "proven" (as much as anything in a biological system can be proven without outliers). We've seen B cells respond to new but similar antigens in other antigenic exposures before, so this isn't new, However, with all the hoopla about AOS and the articles from authoritative opinion sources, it needed to be addressed.

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Thanks for this! Very helpful. I am curious how these studies deal with the mix of immune conditions of the subjects - ie, some people have still never have covid, some had Wuhan, some had Delta, some had Omicron, and so on - plus some were boosted regularly and some were not, etc. I would think all that would make it harder to make sense of the results.

Relatedly, I have been confused by what I've read about how soon one should get the booster after infection. The CDC says 3 months, but I saw a small study that found that those who'd had covid less than 6 months before getting the booster had a "muted" B-cell response compared to those who had never been infected, suggesting that waiting longer would be better. The study was small and only followed subjects for 60 days. In my area, a lot of people are getting sick right now, so the idea boosting is appealing. But if one's current immunity is still very good 5 months out (especially after a bad bout), the boost might be counterproductive - the last thing one wants! [study link: https://www.medrxiv.org/content/10.1101/2022.08.30.22279344v1.full ]

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Is boosting with Novavax an option?

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Yes it is! And, a viable option. Their booster, though, isn’t bivalent. Their bivalent one should be coming out in a few months.

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I hope they make the bivalent Novavax booster available to us early adapters who already got the mRNA bivalent.

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I thought it was only authorized as a first booster dose (for those who have never been boosted), is that right?

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founding

As of now, that is correct.

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Me too.

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Thank you!

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Really appreciate the breakdown that you provide. I run a small meditation center and we have a Covid Task Force, who constantly use your information to help us make decisions about our Covid policies. Just upgraded my subscription. Thanks so much for all you are doing!

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Is it possible that if someone was infected, they shouldn't really wait for the optimal 2-3 months after infection to get the max benefit from the fall booster if that lands in the middle of holiday season or after because you can get other flu viruses in the meantime and thus further have to postpone getting the fall booster until you recover from the seasonal flu?

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FYI. - this is a recommendation, it's not a hard rule. Talk to your doctor.

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Thank you for the explanation about B cells' "factory update" that happens over time rather than instantly.

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What does this mean for imprinting? Are these studies worrisome in that regard? I read in the Washington Post "For scientists, these data are evidence of immunological imprinting, or antigenic sin — when a person’s first exposure to the virus biases their later responses." https://www.washingtonpost.com/health/2022/10/27/coronavirus-boosters-omicron/

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In general terms, I look at the mainstream media articles to see if they've identified a research article I've not reviewed, and if so, I harvest and read it. It's better, if you've the expertise, to not let even a relatively careful outlet like WaPo interpret the research for you.

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I suspect all this has more to do with the original vaccines still being pretty darn good due to affinity maturation. The bivalent shots aren't much better because the ones we had were already quite good.

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Great summary, as usual. I've been a little busy of late and haven't done my epi due diligence safe for my organization. I've also been watching flu a bit more actively.

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Thank you for getting this information out so quickly and so clearly! It’s extraordinarily unfortunate that there is not more visible scientific/medical leadership (FDA? CDC? Moderna/Pfizer?) clearly communicating before headlines run away with a partial message and little context for the public.

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