influenza – Page 10 – Pediatric Infection Connection

A Noisy Week

Bud WiedermannFebruary 26, 2023February 26, 2023Leave a comment

Lots of pediatric infection-related meetings and reports this week, but actionable items for front-line care providers were sparse. It's not that the information wasn't interesting, but when all was said and done I couldn't come up with anything to change clinical practice. That type of noise is good, but I'll be more excited a few months from now when we might have actionable events from ongoing studies.

A 3-Day CDC Advisory Council on Immunization Practices (ACIP) Meeting

This ACIP meeting covered a lot of vaccine topics including vaccines for mpox, influenza, pneumococcus, meningococcus, polio, RSV (both pediatric/maternal and elderly adults), chikungunya, dengue, varicella, and our old friend covid. I wasn't able to view the sessions live but have reviewed many of the slides that were posted. The only vote at the meeting was to continue use of mpox vaccination pretty much as before; the rest of the meeting primarily consisted of updates. In the next few months we should be approaching some decisions particularly for RSV immunization of pregnant people to protect their newborns, long-acting monoclonal antibody treatment to prevent RSV in high-risk and/or all infants, 20-valent pneumococcal vaccines for children, and more.

With regard to RSV prevention, in the past I was struck by ACIP wording about anti-RSV monoclonal antibody therapy being labelled a "vaccine" when it really is a therapy. I now understand that the vaccine label would have made it easier to provide the intervention through the Vaccines for Children program; if it is a therapy, some infants will fall through the cracks in terms of access. AAP had a nice summary of these issues.

Pfizer presented data that they have submitted to FDA for maternal RSV immunization during pregnancy to prevent RSV in their newborns, but I won't show that data since it was only from the pharmaceutical company without separate analysis by ACIP or CDC. FDA/VRBPAC will discuss RSV vaccines for people 60 years of age and older (this also was discussed at the ACIP meeting) on February 28 and March 1, but it doesn't look like they will cover any pediatric issues at this meeting. However, if studies look good it is possible we will have new interventions to prevent RSV in young infants prior to next winter's RSV season.

Post-Acute Sequelae of COVID-19 (PASC)

I did attend a February 23 webinar on PASC in children and adolescents hoping to see some new data, but ultimately I was disappointed. That's not to say that progress hasn't been made, but the session was mainly a review of previous data and guidelines. I did learn that risk factors for PASC in children and adolescents include age greater than 12 years, unvaccinated status, and history of allergic disease. PASC symptoms were less common in vaccinated individuals than in the unvaccinated. Here's a peek at main symptom frequencies:

It was a good review session of general evaluation and treatment options, check out the complete slide deck.

PASC is really a tough issue, likely because it is still a mixture of at least 2 different processes. One includes all the end-organ damage from the infection itself, while the other comprises more vague manifestations such as brain fog, fatigue, and dysautonomia symptoms. I've been seeing children with these conditions long before the covid era, seemingly following a wide variety of otherwise run of the mill infections. I'm hoping the intense research focused on PASC will yield something useful for the larger body of individuals affected with what has been called myalgic encephalomyelitis/chronic fatigue syndrome. I dislike that term, it still sounds somewhat pejorative to my ears. Of note, the National Academies of Science, Engineering and Medicine is planning a series of workshops to better characterize a working definition for Long COVID.

We Still Have a Failure to Communicate

Just a quick mention of a study that reviewed US state and territory public health sites for readability and accessibility of their covid treatment information. Broadly speaking, most sites fell short of effective communication - wording too technical or at a high reading level, not helpful for individuals with communication barriers, etc. South Dakota was the best site, followed by Maine and Tennessee (would you have guessed these states coming out on top?). You might want to look at where your state scored. I'm hoping public health units see this article and work to improve their sites.

Enough Ivermectin Already?

Well, yet another study has shown no benefit of ivermectin as a covid therapy, this time using a higher dose. I was more enthralled with one of the accompanying editorials about the ethical principle of equipoise in performing clinical trials to deal with uncertainty in medicine. Simply put, it's a good idea to perform clinical trials to deal with uncertainty, but given that we always have uncertainty in medicine, when should we call it quits for these trials? Specifically, when does it become unethical to perform studies of ivermectin for covid in the hopes of finding some small niche where there might be benefit? That question has no easy answer. Ivermectin became a political pawn early in the pandemic; I fear the end result of that conflict is now wasted resources and unnecessary risks for trial subjects.

Better Data on Paxlovid Rebound

We were just talking about this last week, and now we have results of a prospective study that gives us perhaps even better data. Both viral and symptom rebound were slightly higher in the Paxlovid group compared to controls, but pretty much still in the same ballpark. For example, symptom rebound was about 14% in the treatment group and 9% in the controls. The prospective design of the study is more likely than retrospective studies to give "truer" numbers, and I think what we are seeing is that rebound is more common in untreated people than originally thought. From my viewpoint, the slight increase in rebound from Paxlovid is far outweighed by the benefit of treatment in preventing complications in high-risk individuals.

White Noise

Speaking of noise, this past week my wife and I watched Noah Bambach's adaptation of Don DeLillo's novel, White Noise. Buried somewhere in the few hundred books in our house is a copy of the novel, but neither of us could remember plot details. Fifteen minutes into the movie, we realized neither of us had ever read it!

It's an understatement to say that reviews of the movie were mixed; in fact, many were at the extremes of love or hate. This isn't surprising for a book that was said to be impossible to translate to the screen. Yes, the movie had its dragging and confusing moments, but I loved it so much that I decided to read the book. I'm almost done with it, and it's very interesting for me to see what elements Baumbach left out or changed substantially, versus other parts taken nearly verbatim from the book.

The book, written in 1985 and dealing with fears of mortality, a college professor and his family, and an "airborne toxic event," sadly translates very well to today's chaotic world. The movie was mostly true to the book's central themes, and the song and dance ending, a backdrop to the closing credits, made me smile. I'd recommend both the novel and the movie to folks who might enjoy a quirky, reflective view of modern life and be able to put up with some unevenness in presentation.

Death Valley Days

Bud WiedermannFebruary 5, 2023February 5, 2023Leave a comment

I've had a wonderful week, just returned from a west coast swing to visit a son and also do some hiking in Death Valley. In the meantime, the infectious disease world soldiers on.

Winter Virus Update

We continue to see good news from RESP-NET, though again with the concern particularly with covid that we don't have accurate case tracking, likely resulting in underreporting. XBB.1.5, as expected, appears to be sweeping westward across the country and is by far the dominant variant east of the Mississippi.

Covid Immunologic Insights

A couple of articles released recently bring up some interesting findings. First, researchers at WHO and multiple other academic institutions around the world performed a systematic review and meta-regression looking at protection from prior infection with or without vaccination against omicron infection. Not surprisingly, protection against infection itself waned very rapidly, but hybrid immunity (combination of prior infection plus vaccination) was relatively long-lasting for protection against severe disease and hospitalization: better than 90% at 12 months following last vaccination or infection. This is somewhat supportive of the proposal for annual covid vaccine boosters, although in practice it will be exceptionally impractical to determine individual prior infection status.

The other article was a detailed analysis of clonal T-cell responses to asymptomatic or mild covid infection, comparing adults and children. It is highly technical, mostly of interest to basic scientists, but I was intrigued by the finding that children did not develop effective adaptive immune responses compared to adults. This has important ramifications for future vaccine development.

More Measles Mess

We are already seeing measles outbreaks around the country, mostly isolated/contained, but given the pandemic-associated drop in childhood vaccination coverage we should prepare to see more. Now, researchers at U. Penn have reported relatively high rates of negative measles serologic testing in parturient patients at 2 Philadelphia hospitals. About 20% lacked protective antibodies to measles, an important finding not only for these patients but also for their newborns. For the babies, it's a bit of mixed news because maternal antibody will block response to measles vaccine in the first 6 months of life but also means that these infants could be unprotected very early in life. The main caveat for interpretation is that measles antibody is only a surrogate of protection from infection and thus we can't assume directly that the 20% rate corresponds to true lack of protection.

20 Mule Team Borax

I have vague memories of a television show, Death Valley Days, from my early childhood. Or, should I say what I do remember are the commercials for 20 Mule Team Borax, a laundry detergent still available today. Its main ingredient is sodium tetraborate, very toxic if taken internally or even used as a topical soak/bath. It's a sad state of affairs that I wasn't surprised that borax is yet another toxic compound advocated for use in the covid era, this time by anti-vaxxers as a bath component to reverse the effects of covid vaccination. Bad idea.

Of course, kicking up the trail dust in Death Valley, I couldn't help but think about health risks and not just from tumbling 5000 feet down the Dante's View trail. Death Valley is coccidioidomycosis territory, so if I develop a respiratory illness within the incubation period (1-3 weeks), I'll remind my physician to keep it in the differential diagnosis!

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!

Another Week in the ID World

Bud WiedermannJanuary 22, 2023January 22, 2023Leave a comment

A few interesting items last week. I also enjoyed the CDC COCA call on Saturday - not much new stuff, but a nice summary of issues surrounding covid variants and immune escape among other topics. The recording should be posted soon. It was mostly geared towards adult care.

Tripledemic Receding

I made a great (for me) discovery of RESP-NET - I'm not sure if it is new or if I just wasn't aware of its existence, but it tracks the 3 viruses of interest all on one page. Here is the most recent view:

This is an interactive graph, note on the left side and at the top there are multiple views. The age group 5-17 years is selected here and you can see that downward trends are present for combined respiratory virus-associated hospitalizations as well as for influenza and RSV. Covid doesn't have a consistent downward trend but the recent data (which may be affected by reporting delays) also is heading down. Let's hope so.

Vaccine Coverage

CDC just started reporting covid vaccine rates for children under 5 years of age. It's not pretty and is similar for all ages.

Again, this is an interactive graph, so you can look at rates by sex and age.

A Brief Word on Variants

Here is the latest. Also, I may not have mentioned this before, but if you look at the top right the NOWCAST designation for the past 3 weeks indicates this is a forecast, not based on data collected those specific weeks. The variant data always have a lag time to allow time for sequencing to be performed. For example, the latest actual data we have on this graph is for the week ending December 31, 2022.

Are you starting to get too confused about variant nomenclature? I am. As a quick review, the original omicron variant that appeared in 2021 was BA.1. In January 2022 it was mostly replaced by BA.2. Subsequently we've seen new omicron lineage variants labelled BA.3, BA.4, BA.5, and XE.

The variants taking over in the US now are labelled XBB and BQ.1 and are descended from the BA.5 sublineage. (XBB is a recombinant of BA.2.10.1 and BA.2.75 sublineages, not to confuse you more.) XBB has a high level of immune escape (i.e. immunity from vaccines and prior infection is lessened and current monoclonal antibody therapies are less effective) and also probably enhanced binding to the ACE2 receptor on our cells.

On the other hand, it appears that BF.7 is circulating now in China - this is a sublineage of BA.5 that hasn't taken off in the rest of the world so far.

Wastewater

Wastewater is a very important source of data on what variants are active and when we might see covid surges. Unfortunately I don't think the CDC data presentations for wastewater are very helpful, and the data sources are scattered sporadically throughout the country. This is because reporting has been on a voluntary basis; if you live in a blue state area, you have a better chance of early alerts from wastewater testing. Several national agencies are working on a better network for wastewater testing, but the legal and ethical issues are significant. For example, one could also choose to test collection sites for drugs of abuse and then target police actions to a specific region - those working on a better process want to restrict wastewater testing to just public health uses that do not stigmatize or otherwise target communities for other reasons. I attended a nice summary of the situation provided by the National Academies of Sciences, Engineering, and Medicine (NASEM) which is studying the issue and has produced a preliminary report.

Is My Spice Rack Going to Kill Me?

No, but the closest I come to hoarding behavior is my spice armamentarium. I did a quick count and noted 105 unique spices in my kitchen cupboard, and that doesn't count the maybe 40 or so extra large bags plus maybe 6 different kinds of salt I have on hand.

Last week the lay press picked up on a study that first appeared last September. It looked at contamination rates for people making turkey patties and lettuce salad. The participants were told they were evaluating new recipes, but in fact the turkey meat was laced with a harmless bacteriophage that was then tracked to see where it ended up after the food preparation. It turned out the spice jars were a prime source of contamination. The study didn't seem to address the amount of contamination, but at least it should serve as a good reminder that hand and dish washing during food preparation should be thorough.

I don't plan to wash all of my spice jars, as you might imagine I'm a stickler for food hygiene when I'm cooking!

Fear the Snail

Well, not really. But a recent issue of the Journal of Infectious Diseases reported new trematodes found to be carried by snails in California and elsewhere. These agents have the potential to infect humans, with transmission most likely in a manner seen with angiostrongyliasis in Hawaii. Bottom line, don't eat raw snails on a dare (yes, some people have done this and become infected), and make sure your produce is washed well - you never know when a snail has slimed its way across that piece of lettuce.

Looking Forward to This Week

CDC will release new guidelines for covid testing that will likely de-emphasize routine screening of asymptomatic individuals. The draft is being reviewed now, so expect something fairly soon, perhaps this week.

Also, FDA/VRBPAC will meet on January 26 to start planning covid vaccine strategy going forward. As of today (January 22) the agenda still has not been posted but "the discussion will include consideration of the composition and schedule of the primary series and booster vaccinations" for covid vaccines. I plan to listen in though I don't expect any final decision to be made at this meeting.

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.

Tag: influenza