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Tag: COVID-19 vaccine booster

Published on Leave a comment on Apologies Are In Order

My occasional blog editor, also my full-time wife, wasn't happy with the MAHA portion of last week's post. As she correctly pointed out, I assumed everyone knew what the MAHA report was all about. Last Monday I edited that part of the post to provide more context. However, after the revelations from this past week, I realize I owe apologies not just to blog readers but also to middle school students everywhere!

First let's look at a few non-MAHA topics.

Measles

Remember measles? I had said I'd just mention measles less frequently unless something noteworthy happened. Although measles remains in the news, the US situation is relatively calm. In the latest CDC update, numbers continue to rise but more slowly than earlier in the year. The Texas outbreak has mostly burned out, probably most susceptibles have been infected by now.

Now we'll wait to for the next hot spot, almost certain to crop up somewhere due to increased summer travel. Please remember to offer vaccine options to parents traveling with children who have received less than 2 MMR vaccine doses.

UK Covid Lessons Learned

Rather than play the blame game, the UK has followed through with plans to apply knowledge gained during the pandemic to help in future planning. In this instance, it's a "meta evaluation" of strategies enacted during the pandemic. The Department of Business, Energy, and Industrial Strategy (BEIS) was charged in October 2021 to track and evaluate short-term response, recovery planning for businesses and public services, and innovations following onset of the pandemic. They listed 6 key lessons learned, summarized starting on page 9 if you're curious.

Clearly the economic and public health structure in the UK is very different from the US, but I mention this report as an example of how a nation can plan productively without political overtones and avoiding emotional finger-pointing.

New Pathogens in Mastoiditis

French investigators report a retrospective study showing a shift in pathogens in acute mastoiditis in pediatric patients. The biggest changes involved an increase in group A streptococcus (S. pyogenes) and decrease in pneumococcus (S. pneumoniae).

This is useful information, though of course may not hold true in other locales.

What Does CDC Recommend for Covid Vaccinations?

The short answer? I don't know. After the HHS Secretary circumvented all transparency and science to declare that healthy children and pregnant people didn't need covid vaccines, new vaccine schedules appeared on the CDC web site. However, that same site included links to other pages that appear to contradict this guidance. Based on statements from HHS, the rationale for the change is that there is no evidence to recommend continuation of covid vaccines for these groups.

Just last week I noted that we didn't have enough information in children, due to both low numbers of reported cases and low vaccination rates, to make an accurate assessment of covid vaccine effectiveness in the past winter season. Presumably HHS has used this lack of evidence from this past winter to scuttle covid vaccine recommendations even though evidence of benefit exists from previous years. Most clinicians know that the absence of evidence is very different from evidence of absence of benefit.

We should all be watching for the next scheduled ACIP meeting June 25-27. The agenda hasn't yet been published, but this meeting is really the time for careful discussion and recommendations on vaccinations for covid and other infectious diseases. This is a critical time for ACIP members to cut through the politicization of vaccine policy and provide us with careful considerations.

Meanwhile, WHO tells us that 3 regions are experiencing surges in SARS-CoV-2 infections: Eastern Mediterranean, South-East Asian, and Western Pacific. All 3 regions are showing increases in the variant NB.1.8.1, a cousin of LP.8.1 and belonging to the JN.1 lineage. Similar to the situation in 2020, we may see a US surge starting in western states brought by travelers from the other side of the Pacific.

Early Childhood "Long COVID"

Investigators from a long list of institutions published an analysis that should improve our understanding of so-called long COVID in younger children. I've been concerned that long covid includes a variety of signs and symptoms that likely reflect different pathogenetic mechanisms, making it more difficult to plan and assess management strategies. For example, some manifestations seem more directly related to end-organ damage caused during the initial infection, whereas others, such as the vaguer symptoms of fatigue, behavioral changes, or mind fog may result from a post-infectious process similar to that seen with many other infections.

This cohort study followed 472 infants and toddlers and 539 preschool-aged children; both groups included infected and uninfected children. The investigators developed an index score based on signs and symptoms that they used to classify a child as having long covid. Here's the long list just to give you an idea of the complexity of the study:

The study findings do not translate immediately to changes in clinical practice, but I believe it's a very important step forward.

Formula for Future Flop

In the past few weeks we've seen a lot of services and research funding cancellations that pretty much guarantee we'll be in big trouble with current and future infectious diseases. Gone are grants for vaccine research for HIV and influenza H5N1 and other prepandemic mRNA products. In response to new FDA rulings, Moderna's license application for its combined covid/flu vaccine was withdrawn until results from ongoing studies are available. Uncertainty surrounds how covid vaccines incorporating a newer LP.8.1 variant will be assessed by FDA. Defunding of various projects at universities could devastate new advances in all areas of science including medicine.

HIV prevention and treatment funding has lessened both globally and in the US, with uncertain impact now. I'll mention parenthetically, since many news feeds picked it up, that I felt a prediction model for deaths resulting from loss of PEPFAR and USAID funding in Africa was short on details to mention more fully. The site did explain their prediction tool which really was just a set of simple assumptions and arithmetic set up in January and apparently on autopilot since that time. It doesn't have any update related to restoration of some of the programs' funding (still a bit vague to me) and, more importantly, has not attempted to verify any of its predictions with real world data in the past 4 months. So, not ready for prime time at the moment.

Middle School MAHA

In last week's blog I should have mentioned that I was only speaking about the infectious disease portion of the MAHA assessment; I am of course much more familiar with that literature than I am with studies of nutrition and other chronic health issues in children. Now we know that the report clearly was generated with artificial intelligence and contained numerous erroneous citations.

Last week I approximated the level of expertise of the assessment as perhaps appropriate for a middle school paper, but now I must retract that statement. The MAHA assessment's use of AI would be insulting to any middle schooler, assuming they were trained to proofread their assignment before turning it in.

It's been at least 10 years since the current HHS Secretary came on my radar with his ridiculous interpretations of science. I'd like to ignore him and just chalk up his inaccuracies to, as one of my good friends said, "his brain worm talking." Sadly he's too dangerous now and must be called out for his ongoing confabulations.

Published on Leave a comment on EBM is a Four-Letter Word

Don't worry, I can still count. The title of this post comes from one of my teaching aphorisms to remind medical providers that evidence-based medicine isn't some magical entity that can be invoked as a gold standard. In fact, personal opinion is a form of evidence, the lowest form of evidence because it is most subject to error due to known or unknown (explicit or implicit) personal bias. When I see a publication with "evidence-based" in the title I'm immediately wary of the content.

This past week was very busy for me, mostly because of the FDA VRBPAC meeting and its ramifications, all dealing with COVID-19. But first, I wanted to cover one topic unrelated to covid.

Our Shaky Relationship With Animals

Last week CDC published a great Surveillance Summary about enteric disease outbreaks associated with animals. This excludes foodborne outbreaks related to animal products; it deals with direct animal contact so won't help you with your Memorial Day weekend picnics.

The report covers the years 2009 - 2021, so mostly pre-pandemic. The numbers of illnesses and outbreaks didn't show a striking decline in 2020 and 2021.

You won't be surprised that Salmonella was the most common identified pathogen.

I found it very interesting that exposure in private homes was so prominently represented.

The animal type list afforded me a quick lesson in nomenclature - now I know the differences among various reptile categories.

Covid and Vaccines

I spent about 7 hours on Thursday watching, listening, and taking copious notes during the FDA VRBPAC meeting to recommend a strain for the new iteration of covid vaccines. Presentations from FDA, CDC, WHO, and the 3 US covid vaccine manufacturers took up the bulk of the meeting, followed by extensive discussions. The meeting was excellent for the most part, as always I learned a lot. However, a publication from 2 days earlier clearly cast a pall over the deliberations.

The publication, by FDA CBER director Dr. Vinay Prasad and FDA Commissioner Dr. Marty Makary was entitled "An Evidence-Based Approach to Covid-19 Vaccination," ergo the title of this post. It spelled out new FDA criteria for vaccine approval.

It wasn't clear whether just a change in vaccine composition would mandate new trials; influenza vaccine changes strain composition every year without necessitating new trials. Also uncertain was whether the existing vaccine would be available to those outside of the 65+ age group and the younger individuals with at least one risk factor. No mention of any allowance for the common occurrence about family visiting grandma with many risk factors, presumable you can either not visit or let grandma take her chances.

In his opening remarks to the VRBPAC, Dr. Prasad seemed to backtrack a little from the pronouncement, implying that this wasn't a final document and could be modified by further input. As a result, this is now clear as mud.

The appearance of the article just days before the VRBPAC meeting only highlighted how it changed the landscape for FDA regulation of covid vaccines. Here's the usual process for strain selection as shown in one FDA slide from the meeting:

This process occurs continuously at FDA, not just for the VRBPAC meetings. The Prasad/Makarty publication circumvents this process. It was clear from all of the meeting discussion that committee members were concerned that a change in vaccine composition now might trigger requirements for new clinical trials, delaying availability of an updated vaccine or, worst case scenario, being so expensive and difficult that vaccine manufacturers would abandon updating the vaccine.

Here's how one of my many information sources, Dr. Katelyn Jetelina of Your Local Epidemiologist, pictured the process change:

Covid vaccines are the most studied and monitored in the history of vaccinology, all starting with randomized, double-blind, placebo controlled randomized trials. Here's an example from the Pfizer presentation.

I did say at the top that I learned a lot from the meeting, so let's focus on those points. Note that some of the images have web links, but they aren't active in this post.

The #1 take home point from the entire day's meeting, which I didn't hear emphasized in various news reports, is that we are in a really good place for figuring out covid vaccine strain composition for the immediate future! That's because not much has changed, antigenically speaking, with circulating strains in the past year. Everything in the US so far this year is a close cousin of the JN.1 lineage.

In fact, the number of spike protein mutations (the target of all covid vaccines) has been relatively small since early 2024.

What this means antigenically is that, with only minor differences, sera from recipients of last fall's vaccine (mostly a KP.2 strain that is in the JN.1 lineage) neutralizes the newer variants quite well.

Not surprisingly, there are limitations to this information. First, we still don't know what level of neutralizing antibody confers protection against more severe covid illness, so we don't really have a target in mind. Second, the assays themselves aren't standardized across platforms, so we can't compare one lab's results directly with another's. Third, we have virtually no data regarding cell-mediated immune responses - these tests require a lot of blood and are time consuming. Fourth, this is all test tube and animal data, what we really want to know is how it works in the real world. Unfortunately we can't know that until after the vaccines are used widely.

Which brings us to the fifth limitation, which is mostly a good thing. We don't have as many data points to analyze as were available at the height of the pandemic. The good part of this is that we have really do have fewer people with serious infections. The bad side is that at the same time monitoring resources have scaled back considerably, including at the CDC as verified by some at the meeting. Also, individuals appear to be less likely to seek testing when they are ill. The smaller the sample size, the less robust the predictive power for the future.

In particular this is problematic in the pediatric population, a combination of fewer complications (a good thing) coupled with low vaccination rates. Thus, CDC could not provide any estimates of covid vaccine effectiveness in the pediatric population for the past year. Here's the conclusion statement about VE as is currently known:

A bit about seasonality and other covid epidemiology. It was clear during the meeting that terminology used in the past for influenza is infiltrating the world of SARS-CoV-2, particularly with the terms antigenic "drift" and "shift." The former is a minor change in antigenic properties in circulating strains, as we experience most years with flu and currently with covid; the latter is a more extreme change such as with the original Wuhan strain followed by delta and then by omicron.

Covid still doesn't have a predictable seasonality compared to influenza. We've seen recent trends towards surges in late summer/early fall and in winter, but covid never goes away.

Even with the lower levels recently, covid is still a tremendous problem.

Most hospitalizations (and deaths) are in the oldest age groups.

To the FDA's credit, they moved quickly to make a final statement about covid vaccine composition: "...the COVID-19 vaccines for use in the United States beginning in fall 2025 should be monovalent JN.1-lineage-based COVID-19 vaccines (2025-2026 Formula), preferentially using the LP.8.1 strain." In my opinion this accurately represents the consensus of discussion at the meeting. It remains to be seen what the 3 US vaccine manufacturers will do with this information given the vague requirements for new studies if a new variant is used. The mRNA vaccines from Prizer and Moderna can be produced quickly, likely available late summer. Novavax, which does not use the mRNA platform, takes a bit longer, plus FDA has placed new study requirements for them for the current vaccine that might require more studies. The Novavax representatives at the meeting did express confidence they could have vaccine ready by fall.

No crystal ball:

The big picture is that whether we use the existing KP.2-based vaccines going forward or switch to the LP.8.1 variant isn't a big deal - we don't have enough data to suggest one is going to be substantially more effective than the other.

I won't ramble on further about the VRBPAC meeting, though I realize I've used less than 10% of my meeting notes. As always, feel free to ask for more details if you're interested.

The MAHA Report was a HAHA

Or maybe BOOHOO is more appropriate. At 73 pages and over 500 footnotes, one would think there would be some substance to the report, an assessment intended to address chronic disease in children. It's a laudatory goal, but the conclusions seemed to have been made prior to writing the document. Snippets of medical publications were cited but clearly lacked context and many times seemed deliberately misleading to support the conclusions. The apparent authors were the members of the President's Make America Health Again Commission, consisting of cabinet members and other political appointees. Only two of the 14 members had medical backgrounds: the FDA Commissioner and the NIH Director. It most certainly was not a high quality scientific report, perhaps at a middle school student's level of understanding of data analysis. It is a political diatribe, not a balanced assessment of the literature.

The Commission also is charged with submitting a strategy based on this assessment, due in a little less than 3 months. I was saddened to read the assessment and won't comment further.

Memorial Day

It's a lovely holiday day in Maryland, take the opportunity to celebrate with family and friends. I recall that the poem most linked to this holiday, In Flanders Fields, was written by a physician.

https://commons.wikimedia.org/wiki/File:NZRSA_remembrance_poppy.jpg

Published on Leave a comment on Federal Fiat Flurry

Last week's pronouncements and next week's events could tell us a great deal about the new landscape for FDA, NIH, CDC, and other federal healthcare agencies. Bated breath time.

Action on April 15-16 ACIP Votes Appears

You might recall that the ACIP finally met, a regular meeting postponed from February, and voted on some items. Usually the CDC director weighs in within a day or 2 to approve (or not) the recommendations. Unfortunately we don't have a CDC director, so the decision making was kicked higher up the food chain. Now, a month later, we have some movement on the meeting action items.

The major changes are about chikungunya vaccine, probably not a huge concern for most US frontliine pediatric providers but still important. On May 13, the HHS Secretary approved everything that was voted on, you can see the brief statement by scrolling down and opening the April 15-16 tab. I don't think the delay was a big deal, but note that we also have a lot of new concerns about chikungunya. CDC Travelers' Health raised to level 2 (practice enhanced precautions) the level of concern for chikungunya for travelers to certain areas in the Indian Ocean where outbreaks are occurring: Mauritius, Mayotte, Reunion, Somalia, and Sri Lanka. WHO put out some more details about Mayotte and Reunion.

(Also note FDA and CDC jointly put out a message on May 9 for people 60 years and older to avoid the live chikungunya vaccine - they can use the virus-like particle vaccine just recommended above. The issues with the live vaccine also were discussed at the April ACIP meeting, though from the discussion I had thought they were going to put the cutoff at age 65 rather than 60.)

Cloudy COVID Vaccine Future?

Remember last week I said I was trying to figure out when WHO was meeting to discuss the next iteration of covid vaccine composition? Turns out they met on May 15 and recommended that "... monovalent JN.1 or KP.2 vaccines remain appropriate vaccine antigens; monovalent LP.8.1 is a suitable alternative vaccine antigen." Basically what is circulating now isn't that different antigenically with what current vaccines contain, though the LP.8.1 variant might be slightly different and maybe a better choice for the fall.

Here's where things get murky, especially for those in the US. We are supposed to hear word from the FDA director about new regulations for vaccine approvals; I, and many others far more expert than I, are worried that we're going to see unnecessary hurdles for vaccine approvals that might be severely limiting financially to vaccine manufacturers and serve to slow all vaccine advances. Will the current mRNA vaccines need to undergo further testing? If LP.8.1 is used, will that require an onerous trial impossible to carry out in a few month time period?

We have some reason to be worried because of what has happened to the Novavax covid vaccine, which you will recall is a more traditional vaccine not utilizing mRNA technology. It was expected to be approved (elevating from emergency use authorization) by FDA this spring, but now FDA is requiring more information, some of which will require new trials, and we're not even talking about trials for children less than 12 years of age that seem to be on permanent hold. You can read the FDA approval letter that spells out all the studies. The vaccine presumably is still available, but approval delay may mean the vaccine wouldn't be covered by insurance except in very limited circumstances.

Remember MERS?

Enough of my hand-wringing about US healthcare policy trends. Middle Eastern Respiratory Syndrome, another virulent coronavirus infection first identified in 2012, now is again causing problems in Saudi Arabia. Nine new cases were reported between March 1 and April 21, the majority being healthcare workers exposed to a hospitalized person. Two of the nine, neither a healthcare worker, died; the remainder have recovered. It's a good reminder to all healthcare providers to pay attention to travel history and be careful. Hoping this won't develop into a major problem in Saudi Arabia - you can see what this has looked like over the past 13 years:

New World Screwworm

You'd need to go back to my post of March 2, 2025, to refresh your memory about this disgusting and painful disease. It's been creeping northwards and is a big threat to animals mostly. Now the USDA has stopped importation of live animals from south of the border to protect US animals (and people), because of screwworm detection in cattle within 700 miles of our border with Mexico.

Hepatitis A in California

This wouldn't seem like big news - hepatitis A is a big problem in high risk groups such as drug users and homeless people. It's disconcerting, however, that a new blip of hepatitis A in Los Angeles County is occurring in people without risk factors - about half of the cases.

I hope public health workers can figure this out quickly and eliminate any new source of hepatitis A in this community.

Measles

I feel a duty to keep reporting on this, though I think we are in for the long haul and (I hope) not any big new outbreaks to rival Texas. Here goes:

Per CDC, we are up to 1024 confirmed cases as of May 15. I think we are over the biggest hump for now.

I"m going to go out on a limb and start just posting monthly about measles, unless something noteworthy comes up in the meantime.

My Newest Feathered Friend

Speaking of limbs, or in this case deck railing, say hello to a new friend I met, the great crested flycatcher, aka Myiarchus crinitus.

The main reason my post is appearing Sunday night instead of early afternoon is that I was visiting family in South Carolina where I happened upon this creature. He (or she, I'm not sure) doesn't appear in the US (outside of the southernmost tip of Florida) except during breeding season. It mostly hangs out in Central and South America. Don't worry, birds don't harbor New World screwworm.

Published on Leave a comment on One More Time This Summer

Summer is supposed to be the slowest season in my line of work, but it doesn't seem like it. I've had trouble keeping up with everything, including some old news that I just found out about today. Maurice Williams died on August 5. If that name doesn't ring a bell, stay tuned. Here's what's up for this last post of the summer.

Mpox

It looks like we can add Gabon to the list of countries with exported mpox, this in a 30-year-old man who had stayed in Uganda for 2 weeks. The notice doesn't state whether or not this is clade I, but given that it appears to have been acquired in Uganda there is a good chance that it is. The latest WHO news was posted on August 22, the same day we heard from the CDC about the US response.

By no means is this the next pandemic, but we are seeing global spread of the clade I strain via travelers. Most important is ensuring affected African countries receive adequate vaccine supplies soon. In the US, persons in high risk groups also should be vaccinated.

Measles Check-In

Oregon is the latest state in the measles outbreak spotlight. Nationally the cases are percolating along at a steady rate.

West Nile Virus

In my post last July 28, I was halfway kidding about waiting for symptoms of West Nile virus after all my mosquito bites. West Nile is in "full swing" in Europe currently. Now I see in today's Washington Post that Tony Fauci is back home after a 6-day hospitalization for West Nile infection. Although he is 83 years of age, that's a long hospitalization and I hope he didn't have serious neurologic or other complications. I wish him a speedy recovery.

A little trivia piece I discovered years ago, did you know West Nile virus was tried as a cancer treatment in the early 1950's? Research on using flaviviruses as oncolytic agents continues. Unfortunately the lead investigator of that 50's study is mostly remembered for a serious ethical breach, injecting tumor cells into prisoners to study tumor immunology.

Timing is Everything

I have a complicated plan for how I'm going to time when I get my flu and covid vaccines in the coming weeks, based on travel plans and guessing about peak flu season. At my age, waning immunity following vaccination could be clinically significant.

This brings me to an interesting study in the BMJ trying to define optimal timing for influenza vaccination in young children. It utilized data from an administrative database in the US for timing of vaccination of over 800,000 children ages 2-5 years during several flu seasons. Bottom line, it looked like October was optimal. I wouldn't necessarily alter plans based on this study; every flu season has slightly different timing. It's probably a better plan to just vaccinate when you can, whether it be at regular checkups or flu vaccine events on evenings and weekends.

Holding My Breath on Polio

I'm still hoping polio doesn't break loose in Gaza, but I'd be more hopeful if vaccine could be distributed there. WHO has full plans in place to distribute the relatively new novel oral polio vaccine type 2 (nOPV2) to about 640,000 children under 10 years of age in 2 campaigns separated by a month. Wastewater monitoring suggests this is the strain that caused the case recently detected in a child in Gaza; we're still waiting for confirmation from a regional lab in Lebanon. Now we just need an effective ceasefire to allow this and other humanitarian aid to be implemented.

Covid

The big news was the not surprising FDA approval and emergency use authorization of the KP.2-based mRNA vaccines from Pfizer and Moderna. Novavax approval is still pending due to a longer manufacturing process. As I've said many times, if one looks at the level of individuals, it's pretty clear that vaccination benefits outweigh risks for every age group. New interim recommendations are available from the CDC.

Here's a quick look at a few disease activity indicators over the past year:

Wastewater hasn't changed much nationally.

Regionally, only the Northeast seems to be rising, though still lower than most other regions.

We'll see what happens with covid (and measles) now that schools are starting back again.

In the midst of all this, we have a new study on long covid in children. It was a multicenter prospective cohort study of about 900 younger children and 4500 adolescents, most with covid infection but some not infected who served as controls. The report is loaded with data and complexities; I'm sure everyone in the field is looking it over closely.

It's tough to summarize the findings succinctly, but perhaps you can enlarge the figure below to see details. The darker color shades are the more prominent symptoms in each cluster. Clustering of types of symptoms varied between adolescents (12-17 years) and school-age children (6-11 years). I'm very happy to see this type of analysis; it is possible that different clusters have different pathogenetic mechanisms suggesting different treatment approaches. Clusters in the younger children were in the neurocognitive, pain, and GI domains, whereas loss of smell or taste, pain, and fatigue/malaise were highlighted for the adolescents.

This study won't change clinical practice immediately, but it is a major step forward in providing a framework to base treatment studies.

"No Good Songs Ever Came Out of the 1950s"

That probably inaccurate quote, heard when I switched my car's Sirius/XM to the 50's station, came from a musically-inclined and knowledgeable friend of mine. I'm pretty sure he uttered it just to get a rise out of me, which it did. IMHO, the 50's produced a lot of good songs and shouldn't be remembered just for some wacky West Nile virus studies.

The title of this week's post is a nod to Maurice Williams who wrote the song "Stay" in my birth year, 1953, but then put it on the shelf until he recorded it with the Zodiacs in 1959. It came out in 1960 and was a big hit at just 90 seconds in length. You may be more familiar with it from the 1977 cover with slightly altered lyrics by Jackson Browne, Rosemary Butler, and David Lindley (and the 9-minute mini-medley with "The Load Out") or from the 1987 movie "Dirty Dancing" that used the Williams original. Regardless of which of the couple dozen versions I listen to, this is one of those songs that always brings a smile to my face.

Published on Leave a comment on Belated Eloquence of the Inarticulate

The title above is one of several great turns of phrase in the book I just finished reading, Edith Wharton's Age of Innocence. It refers to an episode where the protagonist was at a loss for words during a poignant encounter and presumably only later thought of something better to have said. I've been there.

Next Round for Covid Vaccine

The FDA's Vaccine and Related Biological Products Advisory Committee finally had their meeting last week; it had been postponed to give a little more time to see which way the new SARS-CoV-2 variants were headed. I was able to listen in on most of the meeting and have reviewed all the documents. The vote was unanimous to choose a monovalent JN.1-based vaccine for the next iteration, no surprise and in agreement with the recent WHO decision I discussed recently. (For those interested, there is quite a bit of international collaboration on these types of decisions. See the ICMRA posting about covid vaccines.) Still, there were some interesting updates on covid in general. I'll try to distill this down into the main takeaways.

The Latest on Epidemiology (from Thornburg FDA presentation)

Current circulation of SARS-CoV-2 is relatively low. Although our reporting is not as reliable these days, looking just at percentage of positive covid tests in orange you can see we are in a lull now, though perhaps with a hint of an uptick. This is pretty similar to last summer when we saw a bit of a surge in summer into fall and winter. SARS-CoV-2 still has not come around to a winter seasonality seen with other coronaviruses of with influenza, making predictions for surges and vaccine composition very tough.

JN.1 lineages replaced XBB.1.5 lineages during winter 2023-2024. I like the depiction below because it's looking at normalized numbers of positive tests rather than a percentage of positive tests due to different variants. This gives a better appreciation of numbers of cases and shows that we are still talking about relatively low numbers compared to 2022.

Here's a closeup of the most recent part of the above slide showing that KP.2-like, KP.3, and other JN.1 derivatives are starting to take over, though still all at very low numbers.

The recent subvariants have very few differences from other JN.1-derived strains and antigenically are very similar. This has important meaning for vaccine choice - should it be the original JN.1 variant or one of these newer KP.2 or KP.3 type subvariants, currently at extremely low numbers? Look at the last 2 rows in the table below, showing that these newer subvariants have very few mutation differences from the earlier JN.1-like variants.

In a totally new and as yet unpublished CDC analysis, severity of JN.1 infections does not appear to be worse than earlier lineages. The trend was towards milder illness, though not statistically significantly different. Note these numbers are just for adults.

Vaccine Effectiveness in Children (from Link-Gelles FDA presentation)

This it tough to estimate because children generally have milder disease, plus so few children are vaccinated. Adult data is pretty favorable for VE; SGT failure is a faster method of testing and correlates will with JN.1 lineage strains. 2023-2024 VE drops a little with these strains compared to effectiveness against XBB lineage strains.

On the pediatric side, it's important to remember that the vast majority of US children have been infected with SARS-CoV-2 at some time in their lives - this has been apparent since late 2022.

So, it's important to determine any VE now in light of prior infection and vaccination. We can't rely on older estimates. Here's the best and latest estimates for VE in children who received vaccine in the past year. Confidence intervals are relatively wide, reflecting the small numbers able to be studied, but do show benefit in prevention of ED or urgent care use. VE wanes with time after vaccination as it does with all age groups, but there is clear benefit for covid vaccination of children.

David Wentworth, representing WHO, delivered a wonderful explanation of the complexities in choosing among current subvariants for vaccine inclusion. He had this great quote: "... antigenic evolution just speeds up waning immunity." The variant evolution we're seeing now is parallel, i.e. lots of different subvariants evolving on their own, in parallel, rather than one subvariant evolving into another, and then into another, etc. Parallel evolution is what XBB lineages did previously, and we're seeing it now in the JN.1 groups. The slide below demonstrates this process with a timeline on the X axis.

The dilemma in choosing composition of the next vaccine is that no one knows which way the very new subvariants will evolve in terms of antigenic similarity to earlier JN.1 strains. Currently, KP.2, KP.3, and JN.1.23 are within what is thought to be close proximity to JN.1 in terms of antigenic similarity and therefore a vaccine based on any of those likely will have cross-reactivity with one another, enough to provide protection. However, as illustrated by the arrows, it just isn't known how the offspring of the newer subvariants will evolve - will it be farther away from JN.1 and each other, or will it remain relatively stable?

No one can predict what next fall's or winter's subvariants will look like. Once they appear, new lab testing would need to be done, ideally using human serum containing antibody to the newer strains, which Wentworth stated would take about a month to produce. So, it's not something that can be turned around quickly.

Also, it bears mentioning that virtually all of the immunity studies involve neutralizing antibody. Antibody does correlate well with VE, but T-cell immunity also is important. We don't see as much data about this arm of the immune system because the studies are more difficult.

All 3 US vaccine manufacturers, Moderna, Pfizer, and Novavax, presented their new data at the meeting. They are developing and testing new vaccines "at risk," meaning the companies are making vaccines without funding currently, risking their own research and development dollars, hoping whatever they are working on will be recommended for the next covid vaccine rounds and allow them to recoup their investment. Moderna and Pfizer have both developed JN.1- and KP.2-based mRNA vaccines. Novavax, the adjuvanted protein-based vaccine, only developed a JN.1-based vaccine. The protein vaccine takes much longer to construct than do mRNA vaccines, about 6 months to get good data in all. So, if a KP.2 or other vaccine were recommended, Novavax would need to start over and wouldn't be ready until about December.

I don't usually like to use pharma slides to illustrate points, but this one from Pfizer isn't biased in favor of their product and I think nicely shows the current situation, including how closely related the newer subvariants are to JN.1.

In the discussion after the vote to have a monovalent JN.1-based vaccine, which could mean one based on KP.2, the majority of the group felt that using the JN.1 variant rather than KP.2 or another subvariant was the best route, both to allow Novavax to be ready this fall but also not to take a chance that fall and winter predominant subvariants might be more antigenically removed from KP.2 antigenically. All in all I felt this was the right choice, though I probably wouldn't have let Novavax's problems affect the decision; very few US residents have received Novavax in the past, though it is nice to have an alternative to mRNA vaccines available.

On June 7 the FDA formally recommended sticking with the JN.1 strain for this next vaccine round. Next step with be the CDC's Advisory Council on Immunization Practices meeting the end of this month, where the official seal of approval will be issued. I'm sure Moderna, Pfizer, and Novavax already are ramping up production.

NASEM Long Covid Report Available

Long covid remains a quagmire, lots of different symptoms, many of which are vague, and still no definite light shed on diagnosis and treatment of what is likely a heterogenous group of conditions requiring different approaches. The National Academies of Science, Engineering, and Medicine published their full report, available free online. I haven't gotten through all of it, it's pretty long, but it is of interest to those practitioners who see these patients. Most of the evidence is from adults, but it appears that pediatric patients tend to have a better prognosis, especially if improvements are occurring in the first year after onset. Note that a positive covid test is not required for diagnosis testing may not have been done at the time of the triggering infection and antigen or PCR tests will have reverted to negative by the time a long covid diagnosis is considered.

Doxycycline for Post-Exposure Prophylaxis of STIs

The official guidelines appeared this past week, although the gist of the recommendations had been floated previously. Particularly high risk groups are gay, bisexual, and other men who have sex with men and transgender women. The summary is very helpful for practitioners who may want to print out and post Box 1 and Box 2 in their workspaces. Note that the recommendations apply just to those high risk groups.

Summer Bugs!

Bugs in the sense of both insects and microbes. We now have more details about a new rickettsial agent, termed species C6269, that caused a Rocky Mountain Spotted Fever-like illness in 2 individuals in northern California last summer. Both had severe disease, were hospitalized and treated with doxycycline, and survived. As always, keep RMSF and other tick-borne diseases in mind during our warm months.

Speaking of bugs, our dog came down with a skin abscess, expertly debrided by her veterinarian. She is now enjoying chewable amoxicillin/clavulanate but is less thrilled with her "cone of shame." The vet had another bug concern, however. She didn't want the dog to spend much time outside - apparently it is also maggot season, and they love open dog wounds. The vet doesn't know I'm an ID doctor, and I was trying to come up with some clever comment on maggots but failed at that moment - belated eloquence of the inarticulate!

Courtesy of Wikipedia. Hope you aren't eating as you read this.

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