COVID-19 vaccine booster – Page 3 – Pediatric Infection Connection

Hope Springs Eternal

Bud WiedermannJanuary 29, 2023January 29, 2023Leave a comment

An interesting week with the FDA VRBPAC meeting and release of a few new studies, but still no word from CDC on relaxing covid testing for asymptomatic individuals. Bottom line though, some more reasons to remain optimistic. Let's dive in.

RESP-NET

Trends continue downward overall as well as individually for covid, flu, and RSV in RESP-NET. This bodes well, although in the pandemic era anything seems possible. Of course still worthwhile to get flu and covid vaccines if eligible.

You might be interested to have a peek at the WHO influenza information, what is pictured below is current as of January 8. It is more or less a typical global flu picture.

As you can see, southern hemisphere activity is low for the most part, with a predominance influenza B and A H1N1pdm09 strains rather than the AH3N2 that predominated earlier. This change in strains is typical at the end of a flu season, both the B and H1N1 strains are well covered by this year's vaccine.

Covid Vaccine Horizon

As planned, the FDA VRBPAC did meet last Thursday. I was able to watch most of the day's proceedings. (It was a long day, you can watch a recording of the whole thing if you want!) Presentations by Pfizer, Moderna, Novavax, FDA, CDC, and others were followed by multiple questions and discussions, all very good. Rather than lull you to sleep with too many details, let me try to summarize key points which were all about simplification. First, the VRBPAC members voted unanimously to recommend harmonization of the covid vaccines going forward. By that I mean that each manufacturer will be providing the same vaccine for both primary series and boosters. So, we won't need to worry about whether a monovalent or bivalent vaccine is needed for a particular individual. If the FDA follows these recommendations and CDC/ACIP agrees, only the bivalent vaccines will be used for primary and booster series - we won't be able to access the monovalent mRNA vaccines. I certainly concur with this - we have had so much lost in translation in implementing covid vaccination in the US, it is too confusing for providers and vaccinees - and data are very reassuring that the bivalent mRNA vaccines have an excellent safety profile and at least equivalent efficacy, if not a little better. More on that later.

Not to be forgotten, we have a third vaccine from Novavax also authorized in the US. It is an adjuvanted vaccine that does not involve mRNA technology, and studies have shown excellent safety and efficacy in adults. Pediatric studies have lagged considerably and the company did not present any substantive new data for young children.

What remains confusing still is how individuals with prior infection but no prior vaccination will be treated. Probably one dose of vaccine would suffice, but how do we verify prior infection for an individual? Also, how do we determine exceptions to what could be a recommendation for annual covid vaccination for most people? Those exceptions include elderly, immunocompromised, and perhaps young children. Will some of them be recommended to receive 2 vaccines per year? Although this is a move towards simplicity, none of this is easy, and the devil will be in the details. I hope the CDC and other agencies are up to the communication task.

Expect more updates on timing and composition of vaccines to be available in late summer/early fall. Churning out an mRNA vaccine targeting newer variants takes about 100 days, maybe a little longer for the Novavax vaccine. It looks like the VRBPAC will be meeting again around May. We should all be very thankful for the efforts of VRBPAC staff and committee members.

Advice for Immunocompromised

Speaking of communication (pun intended), CDC has a nice graphic and somewhat clearer guidance for immunocompromised folks.

This definitely helps, but we all know that not all immunocompromise is equal, so the vaccine nuances (especially whether to administer subsequent doses once or twice a year) will be tough to explain for those with milder underlying conditions.

New Studies of Bivalent Covid Vaccines

Last week saw publication of three updates of results of bivalent covid boosters; all were discussed at the FDA meeting. First, a group at the University of North Carolina reported state data suggesting bivalent vaccine efficacy was pretty good against some of the newer omicron variants. The bivalent boosted individuals (study included ages 12 years and up) had better protection against severe infection than did those who received the monovalent booster. However, numbers were small resulting in wide confidence intervals, and as always protection lessened with longer time after boosting.

CDC reported early estimates of bivalent booster protection against BA.5 and XBB/XBB.1.5 sublineage variants in adults. The study had the same caveat about small numbers and wide confidence intervals, but again a suggestion that the bivalent booster might be performing better than the monovalent booster for these newer omicron variants.

Finally, a study just looking at the Pfizer vaccine showed somewhat better serum neutralization activity against the newer variants in adults who received the bivalent booster compared to those who received just the monovalent booster. This is an important study but less helpful since it is looking at a surrogate marker (neutralization levels) rather than true vaccine efficacy.

More Good News About mRNA Vaccines in Children

A large meta-analysis published last week provides more information about the excellent safety and efficacy of covid mRNA vaccines in children in the 5-11-year-old age group. Benefits far outweigh any risks from these vaccines.

Vaccine Conversations: AAP to the Rescue

The American Academy of Pediatrics published a 49-page report on methods for productive discussions of vaccines with families. If you don't have time to wade through that, AAP will have a 1-hour webinar this Thursday, February 2. I don't think you need to be an AAP member to attend.

Hope

The line "hope springs eternal" is buried somewhere in Alexander Pope's poem An Essay on Man. I also learned that it was the title of a 2018 indie film. I'm not planning to look into either Pope's poem or the movie. However, I can recommend the book I'm reading now, Sea of Tranquility by Emily St. John Mandel, especially if you've read any of her earlier books. It's contains a story of a fictional pandemic, but since I haven't finished it I don't know whether the ending is hopeful or not!

Adventures in My Rabbit Hole

Bud WiedermannJanuary 15, 2023January 15, 2023Leave a comment

By my rough estimate, I've been in my private rabbit hole of infectious diseases and microbiology for over 50 years. Certainly covid has prolonged my stay. This past week I saw a number of new publications that are worth mentioning, I'll try to be succinct!

Tripledemic Tracking

After pausing for data entry to somewhat catch up after the holiday lull, let's look at the landscape.

Influenza

According to FLUVIEW, the country as a whole is seeing continued decline in flu cases. Remember I'm showing you just the hospitalizations confirmed to be flu, as a most accurate tally. Note that the dashed line is to call attention to the lag in reporting the past few weeks. Let's hope we don't see a rebound.

COVID-19

Percent positivity continues to rise, but a little tougher to determine accurate infection rates given all the nuances we've discussed recently.

The XBB.1.5 variant continues to hold the lion's share of the variant proportion in the US. I was interested to see that, at least so far, this variant is not a big deal in the U K. I expect that to change.

RSV

RSV-NET shows a continued decline in RSV infections, with the caveat that we might still be experiencing delayed reporting from the holidays. I don't expect RSV to trouble us any more this winter.

More on Long Covid

A new analysis from Israel suggests that most symptoms of long covid tend to resolve at 1 year follow-up for those individuals who had mild covid illness originally. This is an analysis from a large database which can have its own misleading reporting issues, but in the past this same database has had a good track record for being correct.

Bivalent Covid Vaccine Boosters No Better Than Monovalent?

Two small studies (here and here) in last week's NEJM suggest this is the case, from comparisons of antibody responses. I first commented on these studies last October when they were only in preprint form. Note these studies did not include children, so we could see some different results when those analyses are performed. The accompanying editorial by Paul Offit is a good read. It is essentially an "I told you so" discussion. Some may recall that he was the only member of the FDA VRBPAC panel last summer who voted against moving forward with the bivalent boosters. His main argument was that we didn't know if they were any better than monovalent boosters against the emerging variants, and these small studies appear to confirm his suspicions.

Please be aware this doesn't mean that bivalent boosters are worse, just that they may be no better than boosting with the monovalent vaccine, at least for now. Stay tuned for what should be a very stimulating discussion of future vaccine plans at the next FDA VRBPAC meeting on January 26.

A Clue to Myocarditis Mechanism Following Covid Vaccine?

Researchers in Boston reported results from 61 adolescents and young adults (16 who developed myocarditis and 45 who did not) who had received either the Pfizer or Moderna mRNA vaccines. They found an association of circulating spike protein in blood samples with the myocarditis group. They also looked at immune and cytokine patterns in the subjects. The discussion portion of the article brings up many possible explanations for how intact spike protein might be involved in the pathogenesis of myocarditis, but this is all very preliminary. Now we need more studies to confirm this association and further explore the immunologic phenomena accompanying it.

Note that nothing in this study changes the bottom line for vaccine advice: benefits of covid vaccination outweigh risks when we are considering myocarditis or any other endpoint for COVID-19.

Everything Old is New Again

No one seems to know definitely who first coined this phrase, but I mention it here to remind all healthcare providers to be on the lookout for those "old" vaccine-preventable diseases such as measles, mumps, rubella, and even diphtheria. This week the CDC gave us figures for vaccination rates in kindergarteners during the 2021-22 school year: not encouraging, but also not surprising. Another publication provided some some explanation for why we see problems with mumps outbreaks even in fully vaccinated adolescents and young adults. (Spoiler alert, it is waning immunity.) If any healthcare provider is a little fuzzy on diagnosis and management of these diseases, please review!

Speaking of old, I found that Alice's Adventures in Wonderland was published in 1865, and Down the Rabbit-Hole is the title of the first chapter. Maybe I'll reread it one of these years.

Covid Milestones?

Bud WiedermannDecember 11, 2022December 11, 2022Leave a comment

Last week the New England Journal of Medicine published a perspective announcing a milestone in the pandemic. Also, we reached another milestone of sorts with the authorization of bivalent covid vaccines down to 6 months of age. I think the milestone designation is a bit overhyped, but the topics are worth exploring.

Vaccine Correlate of Protection (CoP)

The NEJM blurb's title was a bit misleading, saying this milestone had been attained. It depends on how you define CoP, but at this point we don't have an antibody or other cutoff that anyone can point to as a true CoP. The authors acknowledge this in the text. It's worth thinking about what we have so far and what barriers we face in finding a true CoP for covid.

Healthcare providers pretty much know that multiple measures of immune response can be analyzed, but it's quite a challenge to figure out which of those measurements correlate with protection. It is clear that both serum anti-spike IgG antibody and anti-SARS-CoV-2 neutralizing antibody titers correlate pretty well with protection from infection and illness; the higher the titer, the less likely the outcome will occur. However, there is still no specific number to predict with reasonable confidence that an individual is protected from a specific outcome. The reasons (and barriers) are multiple: 1) covid is a respiratory mucosal infection that can be invasive into the bloodstream - mucosal antibody might be a better target for a CoP, but that is a much more difficult set of circumstances; 2) antibody levels decline after vaccination, so an individual's titer at one point in time is going to fall fairly quickly; 3) assays have been performed in different labs with slightly different techniques - the lab methods need to be standardized going forward; and 4) the current CoPs were obtained primarily from data on previously uninfected subjects who received anti-spike vaccines before omicron and even delta variants had appeared - sort of a moving target or wack-a-mole problem we've faced with covid all along.

All this aside, even the current CoPs are extremely helpful to evaluate and approve newer version of covid-19 vaccines.

Bivalent Vaccines Authorized for Younger Children

FDA has authorized, and ACIP recommended, that both Pfizer and Moderna bivalent vaccines now be used for booster/third dosing in children starting at 6 months of age. Details are available at the linked websites. The endpoint for the current authorization is age 5 years for Pfizer and age 6 years for Moderna, just because of different age cutoffs used for the original vaccine trials by the 2 companies. The wording is a little confusing due to the nature of prior authorizations of the monovalent vaccines.

Moderna's monovalent vaccine was originally authorized as a 2-dose series based on immunogenicity, safety, and efficacy data in children ages 6 months through 5 years. Thus, the Moderna bivalent vaccine is designated as a booster dose to be given at least 2 months after the 2-dose primary series is completed.

Conversely, the Pfizer dose is not a booster, but is considered part of a 3-dose primary series. Pfizer's original studies of the monovalent vaccine in this age group did not meet immunogenicity targets in the 2- through 4-year-old age group and thus was eventually authorized as a 3-dose series for the 6-month through 4-years age group.

Don't let this confuse healthcare providers or families. Essentially both Pfizer and Moderna dosing should be considered as a 3-dose package. Whether the third dose is called part of the primary series or a booster shouldn't matter in practical terms. I'm hoping CDC and ACIP will clarify this in their online materials for families.

I don't see any compelling reason to favor one product over the other in this age group, I would just recommend choosing whichever is more convenient to obtain. A bigger problem is the extremely low vaccination rate in this population. (You will need to click the "Age" tab in the first graph section to see the data.)

Who Cares About Milestones Anyway?

In a relatively short time I will achieve what some people call a milestone, becoming a septuagenarian. I don't plan on feeling any differently. For this whole milestone thing, I can only say, Bah! Humbug!

A Few Good Reads This Week

Bud WiedermannNovember 13, 2022November 13, 2022Leave a comment

I love to read. However, I've got a long ways to go to match comedian Mel Brooks's literary appetite. In a recent NY Times interview (sorry, subscription only), his past reading list is prolific. I suppose he could be exaggerating to pull our collective legs, but I doubt it.

Compared to the previous week, it wasn't difficult to find new articles to talk about this week. I'll just pick a few.

A mAb-Less Winter

I stole this phrase from Dr. William Werbel, an adult infectious diseases physician and researcher at Johns Hopkins, speaking at a CDC/IDSA Clinician Call webinar on November 12. It's a great sound bite of how variants are changing our prophylactic and therapeutic landscape for COVID-19 particularly with regard to use of monoclonal antibody products.

It's getting tough to keep track of all the variants going around, but keep in mind we are seeing exclusively omicron subvariants. We haven't had a major change in variant type since omicron appeared almost a year ago. Here's the latest picture from the CDC:

What you can see most recently is the decrease in proportion of BA.5 accompanied mainly by increases in BQ.1, BQ.1.1, and a little of BF.7. It's still a bit early to understand all of the clinical implications of these newer sublineages, but the main concern is that they appear to have specific mutations that limit the effectiveness of current monoclonal antibody preparations we have come to rely upon.

Bebtelovimab is the only monoclonal antibody effective for treatment currently, but laboratory studies strongly suggest that it loses significant potency with mutations in the 444 region; BQ.1 and BQ.1.1 have the K444T mutation. Similarly, Evusheld (combination of tixagevimab and cilgavimab) is an important agent for prophylaxis of SARS-CoV-2 infection, long-acting and widely recommended (though underutilized) for individuals with immune compromise. Evusheld loses potency against viruses with mutations in either the 444 or 346 regions. BQ.1 has the K444T mutation only, BF.7 has the R346T mutation only, and BQ.1.1 has both mutations, Together, these 3 subvariants comprise over half of the circulating viruses in the US and are rising. Thus the concern that this winter will leave us stranded without effective monoclonal antibody products for treatment and prevention. Of course research is ongoing to develop new monoclonal antibody preparations, and we still have antiviral agents like ritonavir-boosted nirmatrelvir (Paxlovid), remdesivir (Veklury), and molnupiravir (Lagevrio) that appear to retain activity against new subvariants.

For the most part, monoclonal antibodies exert their effects by providing neutralizing antibody against the viruses. However, vaccines go a bit further to stimulate not only neutralizing antibody production in the recipient but also to activate other parts of the immune system to lower risks of infection and severe disease. I'll play the broken record again: everyone eligible should be vaccinated and boosted against COVID-19.

Covid and Kids

Two recent reports of covid and young children are helpful. One, from the CDC, was widely publicized. The other, from the UK, was not, at least not in the US that I could appreciate. Whenever I see data drawn from administrative databases I worry about drawing too many conclusions, because clinical details often are lacking or inaccurate. However, we do have some more refined clinical details in both of these studies.

The CDC report focuses on infants under 6 months of age during the time period June 2021 through August 2022 (first half mostly delta variant, second half omicron). What struck me most were the risk factors for hospitalization which did not change during the study period. Overall almost a quarter of all hospitalized infants had at least one risk factor for severe disease, with prematurity being most common. The proportion of infants with risk factors generally increased with age. This is clearly an alarm to promote immunization of pregnant people to protect not only themselves but their infants as well.

The UK study looked at deaths in children and young adults less than 20 years of age; having a national health system makes this data collection much more accurate than we can provide in the US. Over 13 million individuals comprise this UK age group, and the investigators identified almost 3 million covid infections during the study period of March 2020 through December 2021 (almost all pre-omicron). They found 185 deaths within 100 days of a positive SARS-CoV-2 test and then dug deeper with clinical questionnaires. Ultimately they concluded that 81 of the deaths were caused by covid with the remainder attributed to other causes. With this small number it's tough to break this down further, but about half of the non-covid death subjects had no comorbidities compared to about a quarter of the covid deaths. Within the covid death group, severe neurodisability was particularly striking to me at about one-third of that group. Note that during the study time period, covid vaccines were not available to the under 12-year-old population.

School Masking Works

This might be a case of closing the barn door after the horses have escaped, but we now have further evidence that masking works. The study from multiple institutions in Boston looked at covid incidence before and after school masking mandates were lifted and, although this was an observational study rather than a prospective randomized trial, it did confirm that masking can help prevent infection and illness. This should be useful should we encounter a severe upswing in covid cases in the future; masking could mitigate students missing school. Another important feature of this article is that schools with poor ventilation and higher rates of students with language barriers, disabilities, and low-income families are at highest risk of infection. The discussion portion of the article should be required reading for school administrators and policy experts.

My Homework Just Increased

But back to Mel Brooks, one of my all-time favorite entertainers and personalities. In the Times interview, he mentioned over 20 books/authors, plus 9 pieces of music and 4 entertainers, in a wide-ranging commentary on life influences. I think my reading list just doubled. I was totally taken aback when, asked about the best book he ever received as a gift, he mentioned Gogol's "Dead Souls" as a "life-changing gift" that he reads annually. I'll be searching for a copy in my area used bookstores.

Too Much Ado About Nothing?

Bud WiedermannNovember 6, 2022November 6, 2022Leave a comment

This will be a short post this week, not really that much new information going on in the world of pediatric infectious diseases. That's not to say pediatric healthcare providers aren't super busy, but the new information being published/promulgated isn't earth shattering. This again reminded me how important it is to avoid listening too closely to those who may tend towards sensationalizing health news without focusing on what's important. How do healthcare providers and the lay public sort through all the information?

A case in point is the recent wave of respiratory viral infections taxing pediatric healthcare settings. I've seen too many news reports touching on RSV but failing to give parents and families enough information on warning signs for more severe disease. I suspect this contributes to a lot of unnecessary visits to urgent care and emergency rooms for children with mild respiratory disease. Fortunately there are a few online resources that demonstrate the specific breathing signs that could warrant escalating to medical intervention.

We also need to be cognizant of the type of information being presented. For example, a Pfizer press release about antibody formation following the new bivalent covid vaccine. First, these are data announced by a for-profit company and not subject to any peer review. It is essentially an advertisement. Also, remember that these are just numbers, what we really want to know is how it protects against severe disease, and we don't have that data yet. Also, we'd like to know how it protects against new covid variants, not older ones. I'm not saying to ignore the information, it is important in understanding the immune response of bivalent vaccines. Just consider the source and the practical relevance of the data.

My last example, and then I'll try to silence my curmudgeonly comments for the week, is a recent report suggesting that individuals with more side effects following covid vaccination may be more likely to have higher antibody responses. Overall the studies on this particular subject have shown mixed results, and furthermore virtually everyone develops good immune responses regardless of whether they experience side effects or not. Again, monitoring this type of information is very important, it could lead to better understanding of how to improve vaccines, but it's not anything that would help anyone decide their own level of protection.

Shakespeare's play to which I referred in my title contains warning of sorts about the dangers of mis/disinformation. How did he know we'd be dealing with covid 400 years later?

Tag: COVID-19 vaccine booster