omicron variant – Pediatric Infection Connection

Seeing You in September

Bud WiedermannSeptember 1, 2024September 2, 2024Leave a comment

This month always bring me back to The Happenings version of "See You in September;" I remember it fondly from my junior high school era. The Harvest Month often is a transition period from summer to fall/winter infections.

The Respiratory Infection Front

Right on schedule, the ACIP published its official flu vaccine recommendations. Nothing new in there, but it's a good one-stop shopping place for seasonal flu information. Things remain calm on the overall respiratory illness view, and covid may have reached its peak.

However, I'm still waiting for covid wastewater trends to start heading down in most areas of the country (same link as above). We may not be out of the woods yet.

Also note that the covid vaccine from Novavax was authorized by FDA this week. I'll be interested to see how effectiveness compares to that of the mRNA vaccines; Novavax targets a slightly earlier variant (JN.1) than the Pfizer and Moderna products which used KP.2. KP.2 is decreasing in prevalence in the US but still is more closely related to the current variants KP.3.1.1, KP.2.3, KP.3, and LB.1.

We have more longterm follow-up information about myocarditis and covid, looking at both vaccine- and natural infection-associated complications compared to other ("conventional") etiologies. It looked specifically at individuals 12-49 years of age hospitalized with myocarditis. Without going into great detail, it was clear that vaccine-associated complications were less common than with myocarditis associated with conventional or SARS-CoV-2 infection; however, confidence intervals were wide for several of the outcomes due to low numbers of events.

I was excited to see a new update from the HIVE (Household Influenza Vaccine Evaluation) program that has been monitoring households in Michigan since 2010 and was expanded to cover other respiratory infections in later years. The new update covers the years 2015-2022. (The watermark in the figures below signifies this is an accepted manuscript that hasn't yet appeared in the print journal.) Even though it's limited to southeast Michigan, it is valuable data because it is an ongoing active surveillance program in these volunteer households and gives us a glimpse of how the pandemic affected other virus epidemiology.

Far Away Challenges

Mpox continues to rage in the DRC and other areas of Africa, with exported cases appearing in far-flung countries. In addition to vaccine, these countries need better front line diagnostic tests. WHO has requested test manufacturers to apply for emergency approval.

On the polio front in Gaza, we've all heard the good news that there will be a pause in fighting to allow for vaccine administration, but it remains to be seen if this will really happen. Regardless, this will be an extremely difficult undertaking, targeting over 600,000 unprotected children in the region.

Bugs Transmitting Bugs

Healthcare providers and the general public are understandably reeling from all the information about various outbreaks of vector-borne infections. It's important to keep in mind 2 main points: 1) Nothing is happening this year that hasn't happened before in the US. This is the season for vector-borne viral infections. 2) Global warming has increased both the range of these vectors, introducing these infections to areas that haven't seen them in past years, and also increased the season length that these infections circulate. We could see increases in all these infections in coming years.

Here's a breakdown of some of the viruses being hyped in the news.

West Nile Virus

Approximately 70-80% of infections are asymptomatic. The most feared complication, neuroinvasive disease, occurs in <1% of all infections but has a 10% mortality and higher rates of permanent neurologic sequelae such as paralysis. So far in 2024, we have had 289 cases from 33 states in the US, with 195 being neuroinvasive (reflecting the fact that only the worst cases get tested for WNV, not any change in asymptomatic rates). Here are some maps for prior years in the US:

As of now, nothing out of the ordinary for West Nile disease in the US. But, it's pretty common if you recognize that we're only identifying maybe 1% of infections.

Dengue

Here the risk is very high in Puerto Rico, but otherwise mostly restricted to travelers from the current epidemic/endemic areas. Some border states, especially Florida, are more likely to see autochthonous (locally acquired) cases. The asymptomatic infection rate is about 75%; 5% of the symptomatic infections progress to severe dengue with capillary leak syndrome and/or hemorrhagic complications. IMPORTANT CLINICAL PEARL: severe dengue usually appears when things otherwise look good - start of afebrile phase after 2-7 days of the febrile phase. This is the time to be very vigilant if dengue is suspected. The slide below (#42 in the pdf) is taken from a wonderful IDSA/CDC Clinician Call webinar this past week, available at https://www.idsociety.org/globalassets/idsa/multimedia/clinician-call-slides--qa/8-28-2024-clinician-call.pdf and https://www.idsociety.org/multimedia/clinician-calls/cdcidsa-clinician-call-update-on-dengue--other-vector-borne-diseases/.

Here are some numbers from the main CDC website above.

For 2024, the only locally acquired cases in the US have been in Puerto Rico (2676 cases), US Virgin Islands (85), and Florida (21), though those numbers are certain to rise since the season isn't over and reporting in general is delayed. If you add in the travel-associated cases, we've seen a little over 4000 in the US.

Oropouche Virus

This is a relatively mild illness for the most part. The asymptomatic infection rate is around 40%, but 4% of those with symptoms will develop neuroinvasive disease. Now there is concern for vertical transmission in pregnant people, still not completely clear. Management guidelines for infants with possible intrauterine infection are updated and available.

Although I was aware of Oropouche virus previously, this is the first year I've ever heard of the term "sloth fever" which only applies if you acquire the infection in the jungle. This is a slide from that same IDSA/CDC webinar, slide 69 in the pdf.

Oropouche may be over with in South America now, and the main risk area remaining is Cuba. CDC reported 21 US cases in travelers returning from Cuba.

Eastern Equine Encephalitis

Saving the worst for last. It's very uncommon, but you definitely don't want EEE. The encephalitis picture occurs in <5% of those infected with EEE virus, but of those with encephalitis the mortality rate is 30%, and 50% of survivors have permanent sequelae.

We've had 4 cases in 2024 so far. Here's data from prior years:

This is a horrible disease. Certainly precautions such as mosquito spraying and personal protection from bites should be implemented in areas where the virus has been identified.

Earworms

Not wanting to end on a depressing note from the rare but severe EEE disease, I thought of earworms. I'm not referring to the real earworm infecting corn ears, nor RFK Jr.'s brain worm, but rather the more contemporary use of the term. Last week I went down the rabbit hole for the Maurice Williams song "Stay," and this entire past week I've been unable to get it out of my head. Maybe I'll replace it with "See You in September."

I Ain’t Worried*

Bud WiedermannJuly 7, 2024July 7, 2024Leave a comment

H5N1 Human Victim #4

Now we can add a fourth case this year of avian flu in a human residing in the US, again a mild case with conjunctivitis in an individual in close contact with infected dairy cows. No surprise there, but I'm waiting to see what happens with all the summer state fairs that provide more opportunities for human exposure to infected poultry and mammals.

Summer Covid Watching

The bottom line in the US is that covid infections are likely still pretty low, and we don't really know if we'll see a significant surge in the next few months. Any prediction is harder these days because our monitoring systems are probably the worst they've been in the past 4 years. On a national public health level, post-pandemic reporting and tracking have been relaxed and made voluntary, which for many healthcare institutions and jurisdictions can mean no reporting at all. On an individual level, people are less likely to seek testing or treatment, probably due to a combination of numbness from years of being on the edge plus relatively lower disease severity.

I'm focusing on a few data sites.

First is the CDC's Respiratory Virus Weekly Snapshot. The percentage of positive tests sheds some light in disease activity, still cloaked in individual behaviors in seeking testing in the first place and lack of reporting from most home testing. The recent covid percentage is trending up, though not at the level of fall 2022.

Covid wastewater trending is helpful and perhaps the least altered by changes in practice over time. Unfortunately, vast areas of the country have no reporting. Activity levels are rising particularly in the western US, but still well below prior surges. I noted that wastewater updating took a holiday last week, so we're missing the most recent numbers.

Second, I'm keeping a watch on relative predominance of different variants, with an eye to how effective our next vaccines will be. The top 4 variants currently are KP.3, KP.2, LB.1, and KP.1.1. Any late summer or fall surge likely would include one or more of these. I'm waiting for more data on how well serum from recipients of the new vaccines will neutralize these variants in vitro.

Should I Change My Annual NJ Beach Trip?

A flurry of beach closings due to poor water quality last week. I couldn't find any national consortium on this, so you'll need to look at specific states to find out what's going on at your beach rental house this summer. In my browsing I particularly liked the Massachusetts interactive water quality dashboard; Massachusetts seems to be one of the harder-hit states.

Meanwhile, a bit farther south:

Only 1 site in NJ is closed currently, I'm OK!

*

The song I Ain't Worried was written for the beach football scene in the movie Top Gun: Maverick. It was conceived early in the pandemic (when we were worried!) and was an upbeat breather contrasting with the intensity in the rest of the movie. Not a bad antidote for your summer worries, whatever they may be.

Meh

Bud WiedermannJune 30, 2024June 30, 2024Leave a comment

I had expected last week's ACIP meeting to include more presentations and discussions about which covid strain to include in our fall vaccine. I viewed only a small portion of the meeting live (darn those pesky patient care issues!), so I probably missed any brief mention of strains; the slides themselves didn't address strain selection, other than to go with the FDA's statement for use of JN.1 lineage with preference for KP.2 if possible. I still found some interesting details about covid and nirsevimab and will share those with you. Perhaps meh is a bit of a harsh judgement, but I love the word.

In the meantime, thankfully still not much going on in the pediatric infectious diseases world this summer.

Love That New Technology

The CRISPR technology has been in the news for a long time. In case you had forgotten, like I did, it stands for Clustered Regularly Interspaced Short Palindromic Repeats and is now reported to have high sensitivity and specificity for detecting antiviral drug resistance and influenza subtype rapidly enough to be used as a point-of-need assay. The study itself requires journal subscription (thank you, GWU faculty status) to read in full. Investigators studied influenza isolates from the 2020-21 season looking primarily at AH1N1 and AH3N2 strains. The report is highly technical, beyond my ability to critique the laboratory methods, but the take-home message is important: if such a method is scalable (e.g. cheap enough) to employ across the world, including in resource-poor communities, it would be a boon to early warnings of resistant and/or new flu strains. I'm keeping my fingers crossed.

I must applaud scientists in this realm for their acronym constructions: in addition to CRISPR and others, they also used DETECTR (DNA endonuclease-targeted CRISPR trans reporter) and SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) assays. Elementary, my dear Watson. (And, that phrase never appeared in any of Arthur Conan Doyle's writings!)

Dengue HAN

Perfect timing after my mention of dengue last week, the CDC issued a Health Alert Network warning about dengue in the US. According to the Pan American Health Organization, early signs are that cases in the Americas this year will exceed last year's numbers, a year that was already much higher than previous years. Here's an example from the report of what's going on in the Caribbean subregion:

Puerto Rico is under a healthcare emergency because of dengue, and we will certainly have cases of autochthonous (acquired in the US without travel to an endemic area) transmission in the mainland US again this year, primarily in Florida and other southern states. The HAN is worth reading.

This would be a good time to review clinical presentations of dengue and be prepared to investigate/obtain consultation for suspected cases.

Pustules and Vesicles in Afebrile Infants <60 Days of Age

Pediatrics had a nice retrospective review of 183 infants from 6 academic hospital-based pediatric dermatology practices. It's open access and has a nice suggested management algorithm.

Note the first branch in the algorithm details key features to decide whether HSV evaluation and treatment is recommended.

ACIP Meeting Highlights

The regular meeting was spread over 3 days last week. Slides are posted, and I picked out a few that contained interesting new information.

First, even with all the problems of supply chain and late administration, nirsevimab appears to have been incredibly effective in preventing RSV hospitalizations and healthcare visits.

Yes, that's about 98% effectiveness in preventing hospitalization, with very narrow confidence intervals. When this slide was shown it elicited a round of applause from the committee members. This is truly remarkable. Similar results were seen using a different RSV surveillance method. Both the above and below slides are from the Payne presentation on June 28.

It appears we'll have better availability of nirsevimab for the next RSV season, so please prepare for that. I find myself fantasizing of some future day when new pediatric trainees won't see hordes of infants hospitalized with RSV bronchiolitis, with worried parents at the bedside.

Second, although I mentioned I didn't see any new data/discussion about strain selection, the covid vaccine discussion had useful updates about epidemiology and risk factors, mainly from the Haver presentation on June 27.

About half of children hospitalized for covid had no underlying risk factors; we already knew that, but here's a more detailed breakdown. Note that these numbers are for the past year, at time when virtually all US children had some prior antibody from infection and/or vaccine.

Here is the vaccination status, including the low numbers who received the 2023-24 version, of the hospitalized children:

One BIG disappointment for me with the presentations: there was no mention of a control group - i.e. what are the rates of underlying medical conditions and 2023-24 vaccine status in the pediatric population as a whole? Adjusting for rates in the general population would provide a better estimate of the relative contributions of risk factors and vaccination to more serious outcomes and give us a better handle on the magnitude of benefit of vaccination, for example. Still, nothing has changed; for the individual child, covid vaccination is better than not being vaccinated, even factoring in the low rates of serious outcomes and adverse vaccine events in children.

The 2023-24 vaccine was highly effective against emergency department and urgent care visits in all age groups, though waning of protection over time was seen. Lack of enough events of hospitalized children precluded reliable estimates of VE against pediatric hospitalizations. (Link-Gelles presentation June 27.)

Bird Flu

Exciting (to me) news that CDC is collaborating with the Michigan health officials to carry out a seroprevalence study for H5N1 infection in Michigan dairy workers. This should produce much better information about asymptomatic and mild infection in humans and possibly lead to more clues about transmission.

Covid Uptick?

Still a question, but positive test percentages are increasing, albeit at a low level and predominantly driven by western states.

Wastewater variant detection is lacking across the country, see all the block dots (no sequencing data) below, but you can magnify your area of the country and find a few sites with enough data to determine predominant covid strain.

For example, in my neck of the woods most of the sites have no sequencing data. Of the 2 that did, one showed a predominance of KP.2 and the other LB.1. Nationally, KP.3 is starting to exceed KP.2. Again, we're still at low numbers.

A Tip of the Hat to "The Simpsons."

I knew that "meh" might have been adopted from a Yiddish term meaning so-so or unimpressive, but it looks like a 1994 episode of the TV series The Simpsons, featuring ultraconservative Sideshow Bob, popularized the term. Lisa Simpson was investigating voter fraud as the reason Sideshow Bob was elected as Springfield's mayor, and the "meh" word was uttered by a Hall of Records bureaucrat when Lisa expressed disbelief that he would give her the entire mayoral voting records that should have been kept secret. (Thie episode is available only with subscription, but I verified the quote at about 15:30 time in the recording.)

Voter fraud 30 years ago?

Backtracking

Bud WiedermannJune 16, 2024June 16, 2024Leave a comment

My long-suffering (try putting up with me for 40+ years) wife, a retired general pediatrician, thought my posting about the FDA VRBPAC meeting was a bit too detailed for front-line healthcare providers. Reading it again, she's right, but of course I'll push back a little bit given that FDA has backtracked on the committee's recommendation. First, a few other updates.

Wild-type Polio Update

Thankfully we haven't had any recent polio appearances in the US, but it's a bit discouraging to see what's going on worldwide. The Global Polio Eradication Initiative reported 1 case of wild-type polio in each of 2 countries, Afghanistan and Pakistan. Here's the complete list for the week which includes vaccine-derived cases and environmental sampling as well:

Afghanistan: one WPV1 case
Pakistan: one WPV1 case and 20 positive environmental samples
Côte d’Ivoire: three cVDPV2-positive environmental samples
DR Congo: one cVDPV1 case
Ghana: one cVDPV2-positive environmental sample
Liberia: four cVDPV2-positive environmental samples
Niger: one cVDPV2-positive environmental sample
Sierra Leone: six cVDPV2-positive environmental samples
South Sudan: one cVDPV2 case
Yemen: three cVDPV2 cases

Remember that paralytic polio cases represent only the tip of the iceberg for polio infections; the vast majority of infections are asymptomatic, with a few percent manifesting as nonspecific febrile illnesses. Paralytic polio cases comprise less than 1% of infections. So, the appearance of 1 case can imply that at least 100 more infections were present in an area.

Can Infants Spread C diff in Households?

Asymptomatic Clostridioides difficile carriage is common in infants, and the organism seldom causes illness under 2 years of age. That's why you don't want to test for C diff in younger children. An interesting new study suggests, but by no means proves, that these asymptomatic carriers might be the source of household spread which could include spread to more vulnerable individuals.

Thirty families were recruited at their child's 4-month checkup to participate in this longitudinal study where participants mailed soiled infant diapers every 2 weeks to the study site, until the infants reached 8-9 months of age. Rectal swabs from mothers, and sometimes from fathers, were mailed at the same time but in separately sealed containers. (Sorry, but I couldn't help but wonder if the mail carriers had to put up with some unusual package odors!) The specimens were tested for C diff and positive samples were strain-typed and tested for toxin production.

Probably the researchers would have needed to perform more frequent sampling to prove the directionality of transmission, i.e. infant to adult or vice-versa, but they did note that the adults, compared to the infants, seldom were the initial positive carriers in these families. Sharing of C diff strains in the families was common and more often implicated infant to adult directionality. C diff prevalence in infants was 50.0-71.4%, including nontoxigenic strains, while maternal positivity was 20.0-40.0% and fathers were 20.0-37.5% positive. None of the infants or parents developed symptoms.

Something to keep in mind, but please don't start testing infants for C diff.

Misinformation Tracking

A recent article tried to look at patterns of misinformation and flagged content on Facebook. Unfortunately subscription is required for full article access, but the abstract is an accurate summary. Based on numbers of pageviews, the authors felt that unflagged content on Facebook was more likely to be influential.

The authors used a complicated (to me) combination of crowd-sourcing and machine learning to derive estimates of vaccine hesitancy and matching to pageviews. They concluded "...We estimate that the impact of unflagged content that nonetheless encouraged vaccine skepticism was 46-fold greater than that of misinformation flagged by fact-checkers." This unflagged content predominantly consisted of real facts, e.g. rare deaths following vaccination, that then were misinterpreted by viewers as the vaccine causing the death rather than within the expected death rate based on the general population, regardless of vaccination status. A classic misinterpretation due to lack of a control group!

Along the same lines, I noted with sadness that the Stanford Internet Observatory that tracks misinformation is shutting down, in large part due to lawsuits and online attacks received by staffers. Enough said.

The Flu Front

Not to be overly concerned, but a brief CDC report demonstrated spread of neuraminidase mutations in influenza A H1N1 strains in the US, showing reduced susceptibility to oseltamivir. We'll hope these don't become more common.

On the positive side, a NEJM article demonstrated that heat readily inactivates the current influenza A H5N1 strains showing up in cows' milk. I didn't see any earth-shattering news on H5N1 in the past week, but I happened upon the AAP Red Book's outbreak pages for the topic and really liked their bullet summary for current status in different populations:

People: 3 cases (in 2024)
Person-to-person spread: None
Current public health risk: Low
Dairy Cows: Ongoing multi-state outbreak
Wild Birds: Widespread
Poultry Flocks: Sporadic outbreaks
Mammals: Sporadic infections

Apparently these outbreak pages are free to the general public, so check it out. (IMHO every pediatric healthcare provider should have a Red Book subscription, included in AAP membership.)

Covid Vaccine Backtracking

Initially following the FDA VRBPAC meeting on June 5, FDA recommended that the JN.1 covid strain be utilized in the next iteration of covid vaccines. On June 13 they amended this, stating that "if feasible" the KP.2 subvariant should be used instead. What's going on?

After a day-long discussion, the VRBPAC members were asked to vote on whether or not to choose a monovalent JN.1-lineage strain to use in the next vaccine. The vote was unanimous in favor of this. As seen in the section of the lineage chart below, the JN.1 lineage includes that purple JN.1 strain at the left, as well as all the subvariants derived from it.

The VRBPAC vote didn't specify which of all those strains to pick. The discussion following the vote did address that, with the important concerns being whether newer subvariants like KP.2 and KP.3 might be dominant this fall and could evolve further to be more antigenically distinct than JN.1. In that scenario, a JN.1-based vaccine might be less effective. On the other hand, KP.2 might prove to be a worse choice if its derivatives became more antigenically distinct from other subvariants that might predominate in the fall. This is too tough to predict now. (I was also interested that CDC stated they aren't emphasizing research on using generative artificial intelligence as a predictive tool.)

I was monitoring the VRBPAC meeting in real time, and it was clear that Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, leaned more towards using the KP.2 subvariant, and I guess eventually this view prevailed. I'm not quite clear why the initial guidance didn't say that since I don't see any startling new information this past week. Here's the latest variant picture from the same link as above.

As always, the last 2 fortnight periods are only estimates; in the past, these estimates have been fairly accurate predictors. The 6/8/24 bar isn't that different from 5/25/24 in that KP.2, KP.3 and LB.1 seem to be trending towards dominance while JN.1 itself fades. It's important to remember that in general across the US covid activity is pretty low, with a few spots of minor uptick but nothing approaching a big surge so far.

Shifting towards the KP.2 variant as the vaccine component won't affect the Moderna and Pfizer planning, they were already working on both JN.1- and KP.2-based vaccines. However, Novavax won't be able to supply a KP.2 vaccine for another 6 months. They would however be able to have a JN.1 vaccine by fall. That "if feasible" phrase in the FDA announcement seems to leave the door open to allow Novavax to continue with JN.1 vaccine production; the company submitted an FDA application for authorization of this vaccine on June 14, the day after the new FDA announcement. I'll be interested to see how the discussion goes at the CDC ACIP meeting in a couple weeks.

The Eight Queens Puzzle

I was looking up the term backtracking to see where it came from (apparently it showed up in 1870), but instead found another use of the term in computer science, specifically computer algorithms. That led me to the eight queens puzzle.

Apparently there are 92 separate solutions to this puzzle, first published in 1848. Subsequently the puzzle was expanded to all natural numbers, the n queens puzzle, for which solutions exist for all of them except the numbers 2 and 3. The chessboard then has n rows and columns. This is a dangerous rabbit hole into which I hope I never fall.

Happy Father's Day to all you dads, granddads, step-dads, and every other iteration!

Belated Eloquence of the Inarticulate

Bud WiedermannJune 9, 2024June 9, 2024Leave a comment

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.

Tag: omicron variant