I'm still in my semi-hiatus in posting while trying to figure out a new look for the website and its content. I don't think I can ever stop browsing all my feeds from around the world, and this past week seems to be mostly annoying noise. Such as .....
HHS withdrew funding from several grants to the AAP, presumably for being too woke. Note that the AAP is party to a suit against the HHS for its changes to the vaccine schedule.
The Acting Director of the CDC signed off on the ACIP's recommendation to change hepatitis B vaccine use, no surprise. I was slightly intrigued that he did not sign off on the second vote involving use of serologic testing to determine need for subsequent doses for those newborns who received a first dose. Readers may recall from my December 7 post that this second vote was clear proof that ACIP members were not acting based on any science, even contrived science. Look to AAP and other qualified organizations for vaccine advice.
FDA has ongoing issues with industry noncompliance with food recalls, highlighted by the infant botulism outbreak connected to ByHeart brand infant formula. Apparently this is a longstanding general problem that predates the current administration.
CDC awarded an unsolicited research grant to study hepatitis B vaccine to a group at the University of Southern Denmark that has long been criticized for faulty research methods and promoting an anti-vaccine agenda. The grant was never opened to competitive submissions, not that it would have mattered since the awardee was predetermined. The December 2025 issue of the journal Vaccine (subscription required) has an article spelling out concerns with this research group.
Ending this section with some good news, WHO declared Brazil has eliminated mother-to-child transmission of HIV. This is an amazing accomplishment for a large country. Will the US ever get there?
Hotspots for influenza-like-illness (includes flu and other respiratory pathogens) are growing but scattered.
JAMA (subscription required) had a nice Perspective on influenza A H3N2 subclade K. I had mentioned previously that early data from England suggests that our current influenza vaccines will have some effectiveness against significant illness caused by this subclade, even though it has drifted somewhat from the H3N2 vaccine strain.
Measles
We have reached 1958 cases and counting for this calendar year. South Carolina has had 60 cases in the past 2 weeks alone, and other outbreaks are appearing.
Location of cases in the past 2 weeks, as of December 19.
NEJM published a nice review article of the disease. I appreciated the concise listing of complication rates seen in developed countries.
A Less Noisy Week Ahead?
At least I hope so. I'm looking forward to a few gatherings with friends and family. Have a quiet, happy, wonderful week.
It's not that I was expecting things to get better, but I didn't think we'd be seeing threats not only to the viability of the ACIP but now to the CDC itself. FDA and NIH also may be destined for near-irrelevance if current trends continue.
In the midst of this vaccine chaos, two more professional societies have stepped up. This past week the American College of Obstetricians and Gynecologists posted their recommendations for vaccination during pregnancy to include covid, influenza, and RSV. Unlike the AAP's recent recommendations (see last week's post), ACOG's referenced the Vaccine Integrity Project data and had an extensive bibliography. The recommendations are sound and should now be the preferred authority for vaccination during pregnancy. I hope the AAP will soon deliver a technical report for covid and RSV that incorporates VIP data.
Also, the American College of Cardiology published guidelines for adult immunization in the context of cardiovascular care. Vaccines covered are a bit broader, not only including covid, flu, and RSV but also pneumococcus and zoster. I also liked their table on FAQs from patients and suggested responses. Though the VIP data aren't mentioned (it did not focus on cardiovascular disease), the recommendations are sound and should be consulted when deciding on recommendations for adults with cardiovascular disease, including teenagers and young adults.
Who Can Receive a Covid Vaccine?
This is the biggest vaccine mess presently. At least the FDA updated its covid page last week. FDA revoked the emergency use authorization for the Pfizer vaccine for children under 5 years of age, not because of any new data but because they could. So, the Pfizer vaccine can only be used for pediatric patients starting at age 5 years, if they have a qualifying underlying condition. Those underlying conditions haven't changed recently and still appear in CDC's pediatric covid recommendations dated June 11, 2025. The Moderna vaccine is approved for use in children down to 6 months of age, but only with the presence of at least 1 high risk condition per FDA. Note that other entities have recognized that age 6-23 months is at higher risk for hospitalization, including ICU hospitalization. The Novavax vaccine is still approved starting at age 12 years, with the presence of at least 1 high-risk condition.
The FDA is requiring all 3 covid vaccine manufacturers to embark on new studies, throwing out previous immunogenicity studies which were used to approve minor strain changes in the vaccines, similar to flu vaccine changes each year. FDA is claiming (via executive fiat) that these now aren't good enough. The current FDA justification is: "First, the prior standard in CBER was acceptance of small immunogenicity studies using human sera, largely aimed at demonstrating numerical improvements in antibody formation against prevailing strains. These studies lacked formal statistical prespecification and power to test a clear scientific hypothesis. These studies were largely conducted, in CBER OCD’s opinion, to provide nominal justification for a strain change, even while there has been substantial uncertainty in whether such changes were necessary and/or beneficial. Moreover, these studies were not confined to the population of the current COVID-19 regulatory scheme, namely persons with 1+ risk factors for severe disease younger than age of 65 years and all those older than the age of 65 years." FDA will now require much larger randomized trials and also will require new trials to look at persistence of spike protein after vaccination (a rare occurrence at best, and likely less common than with infection itself) and a possible link to long covid. Mostly I see these new study requirements as a way to introduce even higher vaccine hesitance in the general population and to make it more expensive and difficult for vaccine manufacturers to continue covid vaccine production.
Healthcare providers have a lot to figure out in the coming weeks. First, how will ACIP's September meeting (now scheduled for September 18 and 19) alter covid vaccine recommendations? Second, how might practices and pharmacies be limited in administering covid vaccines, especially to children whose parents desire their healthy children to be vaccinated? Pharmacies in a few states are required by law to follow CDC guidelines only, and changing that requires changing state laws which could take time. Based on signals from the manufacturers, I expect the new mRNA vaccines, based on the LP.8.1 variant, to be available as early as next week.
Regardless of how this plays out in the next few weeks, practitioners need to be aware of the new FDA and ACIP recommendations as well as the more scientifically-based AAP recommendations. Also, the same issues as last year regarding dosing intervals for those needing a 2-dose regimen and the differences in dosage by age are still operative. A lot to swallow, but I expect more help from AAP and others as availability becomes clearer.
Clesrovimab for RSV Prevention
This week's MMWR summarized the outcomes of the June 2025 ACIP meeting that resulted in a recommendation to add clesrovimab as another option for RSV prevention in infants whose mothers did not receive RSV vaccine during pregnancy. It contains a lot of good information, here's an example of how to counsel mothers about choosing vaccination during pregnancy versus administering monoclonal antibody to their newborn infant:
Unfortunately, we're looking at an ominous turn that was signaled at the June ACIP meeting. Now one of the new ACIP members, an anti-vaccine proponent, is promoting ridiculous social media postings about safety of clesrovimab and also presuming it extends to nirsevimab. I think this may be a focus at September's ACIP meeting, with the ultimate goal of getting rid of monoclonal antibody prophylaxis for RSV in infants. I hope I'm wrong.
Bottom line, RSV prevention is indicated for all infants for their first RSV season, it is tremendously effective at preventing hospitalizations.
Chikungunya Vaccine Changes
Perhaps less of an issue as summer vacation season winds down, but I'm sort of getting whiplash with the back and forth of FDA consideration of the live chikungunya vaccine. There have been legitimate concerns about serious adverse events in older adults, including encephalitis in a vaccine recipient. On May 9 of this year, FDA issued a pause in administering this vaccine to those older than age 60. Then earlier this month, on August 6, that pause was lifted. Then on August 22 the license was completely suspended. I'm not sure what new information was available between August 6 and 22 other than a few more SAEs reported. I don't think it's necessarily wrong to take it off the market in the US, but the back and forth is a little unusual for the FDA of the old days. Fortunately another chikungunya vaccine is available and does not contain live virus, so US residents traveling to high risk areas have an alternative. I do see that the live viral vaccine is still available in Europe after a short pause. It will be interesting to see if they follow suit with the US.
Did We All Forget?
My August 17 post included an oseltamivir quiz - scenarios to determine willingness to prescribe antiviral treatment for influenza, based on national guidelines. I promised to include the answers in my August 24 post but I completely forgot. Apparently, since I didn't receive any messages about my omission, all of you forgot about it as well (or maybe just didn't care). Alas, you can't get off that easily. Here's a reminder of the outpatient scenario questions that were sent to variety of different pediatric providers.
1.a. A 6-year-old otherwise healthy male presents for a sick visit on his 2nd day of illness with cough, congestion, body aches, and intermittent fevers. In clinic he is afebrile, SpO2 98%, respiratory rate 24, and his lung exam is overall normal despite intermittent coughing fits. His rapid influenza test returns positive.
1.b. A 6-year-old otherwise healthy male presents for a sick visit on his 4th day of illness with cough, congestion, body aches, and intermittent fevers. In clinic he is afebrile, SpO2 98%, respiratory rate 24, and his lung exam is overall normal despite intermittent coughing fits. His rapid influenza test returns positive
2. An 8-year-old female with mild persistent asthma presents to the emergency department with 3 to 4 days of low-grade fevers and cough, now with 1 day of progressive shortness of breath and fast breathing at home. In triage she was found to be in moderate respiratory distress. She responds well to bronchodilators and steroids for her asthma exacerbation and is safe to discharge home. Prior to discharge her rapid influenza test returns positive.
3. A 10-month-old ex-full-term female is seen in urgent care for increased work of breathing. She is on day 5 of illness. She has mild respiratory distress that improves with suctioning, her SpO2 is 95% and respiratory rate is 36. She appears overall comfortable and well hydrated. Her rapid influenza test is positive.
4. A 1-year-old otherwise healthy female presents to urgent care for 2 days of vomiting and diarrhea. She has had slightly decreased oral intake and wet diapers. Her 5-year-old sibling has known influenza, and the infant’s rapid influenza test is also positive. In clinic, the infant is afebrile with stable vitals, well appearing, adequately hydrated, and has a benign respiratory and abdominal exam.
According to various guidelines, all of these scenarios except one are indications to initiate oseltamivir therapy. The exception? It's vignette 1.b. above - the duration of illness is longer than recommended to initiate treatment in a healthy 6-year-old. What really interested me were the responses of the study participants. Participants who had managed the most cases of flu, i.e. the most experienced in the group, recommended oseltamivir the least frequently, only a third of the time. The general tone of the responses suggested to the study authors that practitioners are therapeutic nihilists when it comes to influenza treatment. However, we have fairly good evidence that oseltamivir is beneficial in influenza in many instances, avoiding medically-attended illness and shortening duration of symptoms. I'm generally a therapeutic nihilist, but show me the evidence and I'll change my tune as I have with oseltamivir for flu.
If you remember nothing else, know that if you don't plan on treating influenza with an antiviral agent in a particular patient, there is no point in testing for influenza. At least save money. Keep this in mind during our upcoming flu season.
I'm Not a Nihilist
Although I admitted I lean towards therapeutic nihilism unless evidence suggests otherwise, I'm not generally a nihilist about life. I realized this is a Debbie Downer post this week, ergo the quote at the top of this post attributed, not quite accurately, to the nihilist philosopher Friedrich Nietsche. The exact quote is in his 4-part tome Thus Spake (or Spoke) Zarathustra: "[O]ne must still have chaos in one, to give birth to a dancing star."
I never took a philosophy class and have never read anything by Nietsche except for the portion above. However, I am well versed in a variety other cultural matters, and I believe the correct source for the quote in the title is Mel Brooks. I hope that link provides enough cheer to counteract this downer post.
Now that FDA has authorized the Pfizer COVID-19 vaccine for children 5-11 years of age, we await the CDC/ACIP recommendations for use. And, somewhat hidden in all of this, what about the leading causes of death in children other than COVID?
Which 5-11 yo Children Should Receive COVID-19 Vaccine?
CDC didn't ask me, but my short answer is to recommend for all of them. The only scenario where this might not be true is if a child's risk of being infected with SARS-CoV-2 is extremely low for the next several months. Like for other respiratory viruses, science has difficulty predicting timing and intensity of infection surges, but most think it is unlikely we have seen the last of COVID-19 disease in this country. Also, even if a child was infected in the past, we have no idea how long any immunity might last nor how to use antibody testing to determine a specific child is immune. Yes, if vaccine is in short supply (which sounds like will not be the case), priority should be given to children living in areas with high infection rates, having underlying risk factors for COVID-19 infections, or having contact with others at high risk for complications.
FDA scientists presented 6 epidemiologic scenarios at last week's meeting, all leading to the conclusion that benefits outweigh risks for vaccination of children in this age group. Also, remember that these open public hearings involve a lot of thinking out loud by the members, not conducive to sound bites. These are experts with various backgrounds trying to think through the data in real time. Some of the press accounts failed to recognize this and reported concerns that in some cases overshadowed the vote of 17 in favor with 1 abstention and none against authorizing the vaccine for this age group.
COVID-19 is a Major Cause of Death in U.S. Children; What About the Other Causes?
The FDA/VRBPAC discussions mentioned the leading causes of death in children 5-11 years of age in the US. COVID-19 tied (with suicide) for 8th place in the past year, according to data in the CDC WONDER database. Let's not lose track of the others on the list. In order, they are accidents, cancer, congenital malformations, assault, heart disease, chronic lower respiratory disease, influenza and pneumonia, cerebrovascular disease, and septicemia. During the pandemic, regular medical care has understandably been overshadowed by COVID-19 concerns. Please encourage your families to continue to seek regular preventive care as well as illness care, rather than "putting it off" until SARS-CoV-2 calms down. We continue to see some children presenting relatively late in the course of their illnesses, sometimes resulting in an emergency situation that might have been avoided with earlier medical care.
I'll touch on 2 versions of flooding today, first with regard to the perhaps outdated FDA rules for acting on data in the midst of a pandemic and secondly with respect to the flood of calls and visits we all might experience if a COVID-19 vaccine is authorized for children later this month.
Has the FDA Become Antediluvian?
The term, said to have been used first in the 17th century, literally means "before the flood" (as in Noah, not Curt). I wasn't able to watch the FDA VRBPAC proceedings regarding Moderna boosters on October 14 but did catch almost all of the live presentations for the Janssen (J&J) boosters on October 15. I've perused all the meeting materials for both days. Suffice to say that this included a virtual "flood" of new data, but we should have formal ACIP/CDC recommendations for both sometime this week. Let me mention just 1 key study that leads to my charge of antediluvianism and is already misrepresented in the lay press.
The so-called "Mix and Match" study is an unpublished NIH-funded trial designed to determine whether it is safe to boost with a COVID-19 vaccine product different from that used in the primary series and to characterize the resulting immune response. Note that it was not designed to determine what is the best product to boost a particular primary series, but some pundits have attempted to skew the data to that purpose in spite of comments to the contrary by Dr. Kirsten Lyke who presented the data. While it is true that participants who originally received a dose of J&J vaccine had higher antibody levels when boosted with Moderna or Pfizer vaccines compared to a J&J boost, the study simply wasn't designed to know how that translates clinically. Limitations include the very small numbers of participants (50 in each of the 3 booster groups, or 150 total participants) as well as the short follow up period to date, only 29 days after the boosters. This is particularly important because it is already suspected that an adenoviral-vector vaccine similar to the J&J vaccine has very different antibody kinetics compared to the mRNA products leading to a much slower decline in antibody. With this difference, it could be that levels following a booster dose could continue to rise after 29 days and thus not yet detected in the NIH study. The NIH study is planned to measure these kinetics in the coming months. Also know that the trial enrolled down to age 18 years of age only.
I thought the FDA could have been a bit more flexible in allowing some conclusions regarding mix and match options starting even now, ergo my antediluvian reference. The study's safety data did not reveal any real concerns, and given those results I think it is biologically implausible that serious adverse events such as myocarditis are likely. Allowing mixing would make booster dosing much easier from a public health implementation standpoint. We'll see if some official FDA statement or ACIP recommendation permits mixing. Most importantly, in terms of public health no matter what we do with boosters the emphasis should be on vaccinating the unvaccinated.
Future Flood of Frantic Fonecalls
October 26 is circled and blocked off on my calendar. That's the day FDA/VRBPAC meets to discuss the Pfizer vaccine data for 5-11 year-old children. None of the meeting materials are posted yet, but it is likely that the antibody data in this immunobridging study look good if we believe Pfizer's press releases. What I'm not sure about is how much safety data FDA will require before authorizing use. This was a relatively small study, less than 10 thousand subjects even with an expanded safety cohort enrolled a few months after the start of the original study and thus shorter follow up period. If the vaccine is authorized for this age group, note that you can't use any old Pfizer vaccine stock you might have in your office. The doses are different and will be all new vials; it will take a bit of time to distribute.
Yesterday, October 30, was a day off for me. To celebrate, I attended the 7-hour online meeting of the Advisory Committee on Immunization Practices (ACIP) of the CDC. The topic was COVID-19 vaccines. This was the last regular meeting of the ACIP until February, although they will convene on an emergency basis before that time if/when a COVID-19 vaccine trial has enough data to merit discussion. Everyone fully expects that to happen within the next few to several weeks.
The day included presentations from 14 speakers representing FDA, CDC, and vaccine manufacturers and covered regulatory, ethical, scientific, and other topics. I found the modeling discussion most enlightening; it was an attempt to display various outcomes for infection rates and deaths based on how effective a potential vaccine might be, what groups are prioritized for vaccine administration in the early stages of vaccine deployment, and what the US epidemic curve is doing at the time immunization is begun. It was definitely not intended to be a predictive model but rather a general methodology to use whenever a vaccine is ready to be released for use. At that time, more specific data regarding vaccine efficacy and current epidemiology can be plugged into the model to help guide early deployment. More about the modeling later. Here are my take-home points for pediatric healthcare providers distilled from those 7 hours.
Worldwide we now have over 200 COVID-19 vaccines in various stages of study. Honing down to the US, we have 5 vaccines in either Phase I or Phase II testing in humans and 4 in Phase III. Let's focus on the Phase III products since 1 or more of those likely will have results to report in the next few weeks to months. Two of them, AZD1222 (AstraZeneca/Oxford, the UK vaccine you've probably heard a lot about) and Ad26CoV2S1 (Janssen) were paused for safety monitoring but now have resumed recruiting volunteers, though the AstraZeneca product is still on hold in the US. mRNA-BMT162 (Pfizer/BioNTech) is recruiting still but is far along, having enrolled around 42,000 subjects of which about 35,000 have received the second dose of the 2-dose series. Finally, mRNA-1273 from Moderna has completed enrollment of around 30,000 people of whom ~25,000 have received the second and final dose of that series. Most likely we will hear trial results on the Moderna product within a few weeks.
An FDA representative (full disclosure, happens to be a longtime colleague and friend of mine) provided an overview of how FDA rules will be applied in this situation. Again, you've probably seen a lot about this, with some back and forth on the application of product release under Emergency Use Authorization (EUA) which can only be applied in national emergency situations like we have now. Understand that in general EUA is a "lower bar" to clear than is full licensure, but the FDA has very clearly laid out their requirements in this situation. It's really a balance of ensuring safety but not delaying consideration for EUA for such a prolonged period of time that we find ourselves in a worse hole with cases and deaths.
Let's get to the modelling discussion. The group at CDC stratified the population into 5 age groups, 0-4 years of age, 5-17, 18-49, 50-64, and 65+. Note that this oldest category consists of 55 million people nationally (including yours truly!). They also stratified by low-risk or high-risk, the latter consisting of at least 1 of the following medical conditions: COPD, heart disease, diabetes, kidney disease, or obesity. Nationally 40% of adults, 100 million people total, fall into the high risk category. Another interesting tidbit is that ~40% of adults 18-64 years of age, or 80 million people, are classified as essential workers; 1/4 of those are healthcare workers. The modelers made various assumptions about vaccine efficacy in different age groups, etc, and the main focus of their presentation was in Phase 1 distribution of 200 million courses of vaccine. This phase has been divided into Phase 1A consisting of healthcare personnel (20 million courses) and Phase 1B for adults 65+, high-risk adults, and essential workers (180 million courses total). The modeling discussion was most interesting in trying to prioritize Phase 1B individuals - which of those 3 groups should go first, second, third. Various modeling assumptions and outcomes (i.e. what strategy prevents the most infections versus what prevents the most deaths) produced slightly different suggestions for vaccine prioritization.
What was most important, however, was that the timing of vaccine in relation to the epidemic surges going on was by far the biggest determinant of how effective a vaccine will be at any of these outcomes. This isn't surprising particularly, it's why we don't target annual flu vaccination to start in the middle of our annual epidemics. However, the modelling numbers were impressive and point to the main take-home message for all of us: it has never been more important than right now to use those SARS-CoV2 mitigation strategies. Failure to do so diminishes the benefit from a COVID-19 vaccine and makes it even more likely that we'll see more preventable deaths and more harm to our economy.
A few other interesting details from the session. Federal officials are working hard to reach out to everyone in our society to provide vaccine information, including providing information sheets in >20 languages. Also, vaccine recipients will be asked to use a smartphone app to provide real-time feedback for safety monitoring and illness after vaccination. CDC officials provided a brief review of the evidence to date regarding possibility of reinfection with SARS-CoV2. So far this is at most an uncommon event in the first 3 months following infection, but possibly could become more common if immunity wanes later after natural infection. Multiple individuals weighed in regarding vaccination during pregnancy. New data from CDC, so far unpublished, indicate that pregnant women are at higher risk for worse outcomes with COVID-19 (earlier published data were a bit more equivocal). We likely won't have a lot of data on vaccine safety in this population very soon, and it seems that pregnancy will be listed as a precaution but not a contraindication for vaccination.
Which brings us to our final group, children. We need to be very careful with the safety of any vaccine being administered to a healthy child, particularly for an infection that has a much lower complication rate than in adults. So far, we have no pediatric data at all about these vaccines. Certainly children will eventually be enrolled in vaccine trials, once we have sufficient longer term safety and efficacy information from the adult studies. We'll have to be a little patient here.
There is so much more I'd love to tell you about this session, but I've probably already used up some of that patience you need to save waiting for the pediatric vaccine trials. Soon more details from this meeting will be available at the ACIP website. Just know this: I am very reassured with the transparency surrounding vaccine development and distribution, and I am confident I'll see enough of the results from these trials that I'll be able to judge independently whether or not to recommend a vaccine for a specific group. Although you won't be providing COVID-19 vaccine for your pediatric patients anytime soon, you undoubtedly will hear a lot of vaccine questions from your patients and families. A primary care provider is probably the most important individual to help families with vaccine decisions, now more than ever. Whenever a vaccine becomes available for use in the US, of course I'll let you know what I think but know that ACIP/CDC will have toolkits available for you to consult and assess as well.
In the meantime, please ensure all your patients receive their seasonal flu vaccine and are practicing safe COVID-19 mitigation strategies.
