long covid – Pediatric Infection Connection

Broadening My Entomologic Horizons

Bud WiedermannOctober 5, 2025October 5, 2025Leave a comment

Almost too many new reports available this past week, I'll try to provide brief take-home points for each.

However, what didn't happen this week was any word from HHS/CDC about action on the votes at the most recent ACIP meeting. Until this is finalized, none of us know what to expect for MMR + V, hepatitis B, and covid vaccinations, making planning more difficult for all providers. Maybe that's not an accident. On a related topic, I still haven't seen any formal announcement about topics to be covered at the next ACIP meeting later this month.

The rabbit hole I fell down this week was tied to a tiny bug.

More on "Long Covid" in Children

This past week saw the publication of a much-awaited update from a large, federally-funded consortium of institutions looking at long covid symptoms in the pediatric population via a retrospective cohort. I've said in prior posts that "long covid" probably is a heterogenous collection of entities, at a minimum representing direct sequelae of infection of specific organ systems (pneumonia, myocarditis) plus the more vague symptoms ("brain fog," dysautonomia/postural orthostatic tachycardia syndrome (POTS)) that are seen following a large number of common infections and likely have a different underlying mechanism and treatment than those resulting from direct organ infection and damage.

The study itself is immense, and to fully understand the findings one should read not only the 12-page article itself but also the accompanying 54-page supplemental information (access through link in the main article). Short of investigators engaged in similar studies, I'm maybe one of the few people to attempt to get through everything, and it was tough.

For front line pediatric healthcare providers, the main take home message is to encourage your patients with long covid, or in the case of this article, Post-Acute Sequelae of SARS-CoV-2 infection (PASC), that much work is ongoing to find better diagnostic and therapeutic options for these individuals. Secondly, specifically for the current study, is that PASC is still happening during the omicron era, even in children who have been infected with SARS-CoV-2 previously. Repeated covid infections may increase the risk of PASC in children. In the authors' words, "reinfections might contribute to cumulative morbidity."

The current study included about 400,000 children and adolescents who had a first covid infection on or after January 1, 2022, and about 58,000 who had a second infection on or after this same date. Here's a snapshot of some of the data showing fairly large additional PASC risks from second infections.

And a comparison of outcomes from second versus first infection, substantial (with wide confidence intervals) for some but not all of the categories.

The investigators also performed a deep dive and found that this increased risk was maintained in vaccinated and unvaccinated individuals as well as with both severe and non-severe acute covid illnesses, but the study could not determine whether vaccination or illness severity made a big difference in PASC characteristics.

I think virtually all major pediatric centers have long covid evaluation clinics now; it's worth referring your patients to such a center to at least get some preliminary help in management even though we don't yet have definitive answers.

HPV Herd Protection Data

I'll be brief. This study of a little over 2300 adolescent and young adult women showed that herd immunity exists for the HPV serotypes in the 2- and 4-valent HPV vaccines, looking at unvaccinated versus individuals who received at least 1 HPV vaccine dose. So, the unvaccinated are benefitting from others in their cohort who have been vaccinated.

Here's hoping that HHS doesn't start to sow vaccine misinformation leading to lower HPV vaccine acceptance.

Cochrane RSV Vaccine Review - What Can We Take Away From This?

The Cochrane Collaboration is the gold standard of meta-analyses; if a meta-analysis is published there, one can be assured that proper statistical methods were applied. However, it's important to note that this doesn't mean that real-world clinicians can take the findings and apply them in their clinical practices. Mostly this is because the Cochrane analyses consider only high quality randomized controlled trials employing a cadre of research team members who ensure study enrollees comply with the study rules including follow up and testing. In other words, a far cry from what happens in real world practice.

This review of efficacy and safety of RSV vaccines fits the typical Cochrane review mold. Note first that it is a determination of efficacy, not effectiveness; the latter term implies real-world usage. Just looking at the efficacy of the maternal F protein-based vaccine versus placebo, vaccine efficacy in preventing infant hospitalization from RSV infection was 54% with 95% confidence interval of 27 - 51%, with high-certainty of evidence.

I like to direct front-line healthcare providers to the "plain language summaries" of Cochrane reviews that I think can be very helpful in discussions with patients and parents. Here are the key points from that summary for the RSV vaccine review:

"Key messages

Respiratory syncytial virus (RSV) prefusion vaccines reduced RSV illness in older adults. When pregnant women received RSV F protein‐based vaccines, their babies had fewer serious RSV illnesses. This was true for both approved and unapproved vaccines.
The effectiveness of RSV vaccines in women of childbearing age and the impact of live RSV vaccines on infants and children remain uncertain. These trials used unapproved vaccines.
Further research is needed looking at RSV vaccines in women of childbearing age and the effects of live vaccines on infants and children."

As implied above, the article has a lot more information about other RSV vaccines and populations, but understand that the real-world studies are what we really need to hang our hats on. Those are ongoing with already great results.

New CDC Tularemia Guidelines

Nothing too surprising here, just be aware the CDC has provided us with a comprehensive update for management of both naturally-acquired and bioterrorism-related tularemia with new recommendations for drugs of choice. It's an excellent summary that includes pediatric-specific recommendations and is one-stop shopping for anyone evaluating someone for tularemia. First line agents for treatment of children >1 month old are ciprofloxacin, levofloxacin, gentamicin, or doxycycline, and ciprofloxacin or gentamicin for children < 28 days of age. Other details including use in pregnancy and dosage information are provided.

Modeling Outcomes From Withholding Covid Vaccines During Pregnancy

Regular readers of this blog know that I'm very wary of "crystal ball" studies that try to model the future. However, given the ridiculous attacks from ACIP on covid vaccines for pregnant people, this one is worth mentioning. I won't bore you with the methodology, but here are the predicted case numbers for different vaccination rates:

NOTE for Figure 2.B, the title is in error. It should be Averted maternal COVID-19-related hospitalizations, not infant.

Something to tuck away for future reference.

Age Cutoff for 2-Dose Requirement for Flu Vaccine in Young Children

I've saved the best (IMHO) of this week's reports for last, a systematic review and meta-analysis of age-related benefits of a 2-dose influenza vaccine schedule for the first flu vaccine year in young children. Most pediatric healthcare providers are aware that current recommendations are that a 2-dose flu vaccine regimen for the first year a child under 9 years of age receives flu vaccine, followed by a single dose in subsequent flu seasons. (Older children being vaccinated for the first time just need 1 vaccine dose.) The authors included 51 studies with a total of over 400,000 children and came up with some perhaps surprising results.

This is a pretty complicated task, in part because vaccine effectiveness (or efficacy) for influenza always varies somewhat from year-to-year and by strain type, with VE generally better for influenza A than for influenza B. Also, low numbers didn't allow for good assessments of the live attenuated (nasal) flu vaccine. I tried to pick out what I thought was the most important message, which happened to be from a figure in the supplemental content.

Look at the lower right part of the figure for VE difference. What that is showing us is that children under 3 years of age benefitted from a 2-dose rather than a 1-dose vaccine regimen for that first flu vaccine year, to the tune of 28 percentage points difference. However, above 3 years of age that benefit disappeared.

Does that mean we should immediately stop the 2-dose regimen recommendation for the 3 - 8 year olds receiving their first season of flu vaccination? Heck no. The numbers of participants in the different groups in the studies are way too small with resultant wide confidence intervals, and the season-to-season variability is too great, to be able to make any firm recommendations. However, this report does point the way to a future study to look at redefining age cutoffs for the 2-dose regimen. I hope those are underway.

Minute Pirate Bugs

A few days ago I found myself in a bug-bite situation. I can't verify it independently without a high-powered magnifying glass, but I endured some mildly painful bites from some very tiny flying insects. My companions informed me I was being attacked by minute pirate bugs; many different species exist, these probably were of the genus Orius.

I think of insects mostly in terms of the diseases they can transmit to me, so I was immediately consumed with finding out what I needed to fear from these minuscule Hemipterae were injecting into me. The answer? Nothing.

These guys are tiny, 2-3 mm, so I could see little specks flying around but that's about it. Of course that small size is where the "minute" name arises. The "pirate" description indicates their fairly aggressive plundering of their prey, mainly other insects and their eggs. They are actually good for plants, controlling some insects such as thrips, aphids, mites, and moths that damage agricultural crops. Unfortunately, when they run out of insect prey in the fall, they turn to people like me. I guess it's a small price to pay for the good that they do.

Apologies Are In Order

Bud WiedermannJune 1, 2025June 1, 2025Leave a comment

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

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

Measles

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

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

UK Covid Lessons Learned

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

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

New Pathogens in Mastoiditis

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

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

What Does CDC Recommend for Covid Vaccinations?

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

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

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

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

Early Childhood "Long COVID"

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

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

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

Formula for Future Flop

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

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

Middle School MAHA

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

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

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

Word of the Week: Conundrum

Bud WiedermannDecember 15, 2024December 15, 2024Leave a comment

I was very underwhelmed by Oxford University's recently announced Word of the Year. Listening to last week's FDA VRBPAC discussion of RSV vaccines, another word kept cropping up time after time. More on that later.

Covid Updates

I had mixed feelings when I learned that the Netherlands had started a Long COVID Kids Choir, apparently also active in the UK and the US. On the one hand, it's great that these children have on outlet to express themselves, but on the other hand it reminds me how little we know about this condition.

On a more uniformly upbeat note, new data are available for effectiveness of the Pfizer XBB vaccine in children 5 - 17 years of age. This was a retrospective study from Kaiser Permanente Southern California looking at acute respiratory infection visits from October, 2023, through April, 2024. Because of the study design (standard test-negative case-control study) we only have odds ratios to describe results; number needed to vaccinate can be estimated from odds ratios with fudge factors, but I'm reluctant to go there. Here's the summary:

Basically, the vaccine was very effective in preventing hospital admission and ED/urgent care visits in this age group.

Temporal Thermometers Not the Greatest

Temperature measurement using temporal thermometers is pretty much a tradeoff - convenience versus accuracy. A new study from 5 EDs in a single system (apparently Mass General but hard to tell from the article) looked at around 1400 children who had both temporal and oral or rectal temperatures measured at the same time (within 30 minutes). The findings are summarized here; note mean discordance of about 1.5 F. Researchers found that age < 12 years was was associated with discordance.

The authors found that self-reported race was not a risk factor, important because skin color could plausibly affect temporal measurements. As an interesting aside, Black children were more likely to have temporal temps only, even correcting for severity of presenting complaint.

Avian Flu

I'm keeping a wary eye on new progress, mostly because I'm worried that not enough resources are being devoted to monitoring the situation. One new report provides helpful information. Two dairy farms voluntarily allowed investigators to look at prevalence and spread of influenza A H5N1 in their settings. Here's the "graphical abstract::

The authors mention the rarity of these types of studies possibly due to farm owners' worries about harm to their businesses from publicity about avian flu spread in their dairies.

CDC provided genetic sequencing information about the virus infecting the child in California who apparently has no known avian flu exposure risks. Analysis suggested that the strain was very similar to those previously seen in dairy and poultry farms as well as in humans, but they were unable to perform complete sequencing that could have allowed further tracking of the source of this child's infection. I guess due to privacy concerns, we have very little clinical information about this case. I'm even wondering how the child's strain came to be tested for H5N1 in the first place since not every influenza A detection undergoes further testing.

Regardless of uncertainties, these most recent reports do not suggest we need to heighten concern for human to human transmission of A H5N1.

DRC Mystery Disease

Shortly after my post last Sunday, WHO released a new update with a few more details but still no big findings. I can't even find their case definition anywhere. The initial statements that respiratory symptoms predominated would seem to make malaria, where positive tests have been seen in preliminary testing, a less likely explanation. Malnutrition seems to be a significant risk factor.

WRIS

Winter Respiratory Infection Season continues to mount with moderate level activity in the US driven primarily by RSV.

Epidemic trending (modeling data for predictions, from the same link as above) shows continued growth for covid ...

.... and especially for influenza.

It's still not too late for flu vaccine. Expect a surge soon if not already started in your area.

RSV Vaccine Conundrum

I was glued to my screen for much of last Thursday's FDA VRBPAC meeting, with the majority of the session devoted to discussion of pediatric RSV vaccine progress, or lack thereof. As I've mentioned in previous posts, RSV vaccine development for children was set back by a tragic trial in the 1960s where vaccine-associated enhanced respiratory disease (VAERD) resulted in 2 deaths of children who received vaccine and then subsequently were infected with wild-type RSV the following season. Through many scientific advances over the years, researchers determined that the cause of this enhanced disease was immunologic in nature, related to the vaccine causing recipients to develop a strong cellular immune response involving a specific class of T cells (Th2). This finding even influenced development of the mRNA covid vaccines which deliberately avoided this and ensured a Th1-predominant response and very safe vaccines.

Unfortunately, recent experiences in trials for Moderna RSV vaccines suggested that VAERD might be occurring in children under 2 years of age. Moderna was developing 2 mRNA RSV vaccines, 1 for RSV alone and another that also incorporated a human metapneumovirus vaccine. They were enrolling children in a phase 1 study this summer when the concerning signal arose. I am including slides from the FDA presentation. Here's the study overview and timeline of events this summer, from slide numbers 11 and 12.

I included the above to demonstrate that the safety constraints incorporated into the study worked exactly as intended. Enrollment was paused pending evaluation of the events, which is still ongoing. The imbalance between vaccine and placebo recipients is highlighted below:

Note the small number of children in the study, appropriate and typical for phase 1 trials. However, that makes analysis more difficult. I'll cut to the conundrum chase. Preliminary immunologic studies from patients in the Moderna trials suggest that the vaccine, as planned, produced Th1-predominant responses, and that the mechanism of the possible VAERD events is not due to Th2-primed cells. Furthermore, other immunologic data don't provide another plausible information for why this happened.

Of course, with so few trial subjects, it's possible that this imbalance of severe disease could be due to chance alone. Regardless, Moderna officials announced that they would be abandoning the mRNA RSV vaccine development but will continue to follow all the children already enrolled in their studies and perform further immunologic and other testing.

So, where does that leave us with RSV prevention? This took up much of the VRBPAC's discussion time. It's important to understand that the Moderna RSV vaccines were part of a larger group of pediatric RSV vaccines in various stages of development, 26 in all. Fifteen of these are live attenuated vaccines, and it should be noted that live-attenuated vaccines have never been shown to result in VAERD, with extensive validation for why that hasn't occurred. (I might add that your dog's kennel cough vaccine might contain one of these. Although Bordetella bronchiseptica is the most recognized cause of kennel cough, canine adenovirus - 2 and parainfluenza virus 5 are other common causes of kennel cough and also have been included in some intranasal dog vaccines for decades. Presumably most of us have been exposed to our dogs' live attenuated vaccine PIV5 strain many times, yet no human VAERD involving parainfluenza virus has ever been described.)

It is likely that future pediatric RSV trials will need to be judged on an even more individual basis, perhaps with separate constructs governing the various platform differences (live attenuated, viral-vectored, mRNA if anyone moves forward with this, and subunit protein) as well as mode of delivery - mucosal (intranasal) versus systemic by injection. In the meantime, we know that maternal immunization is highly effective, as is the infant monoclonal antibody nirsevimab. In that light, we also need development of newer monoclonal antibody products in case nirsevimab resistance appears, as well as better maternal vaccines that won't be so limited in timing of administration during pregnancy. Work is ongoing in all of these venues.

Conundrum

Of course I had to look into the origins of the word, but it turns out there is a lot of disagreement about this. I was most delighted to see the word explained as a "burlesque imitation of scholastic Latin." I was unaware that it was the title of a Jethro Tull instrumental song (I'm not much of a Tull fan) and an episode of Star Trek: The Next Generation (I am a fan, but don't remember the episode).

Have a great week, and don't forgot to offer flu and covid vaccines to your patients and families.

Tirade Time

Bud WiedermannSeptember 8, 2024September 8, 2024Leave a comment

It's unusually cool today in the Washington, DC, area, prompting my landscape designer wife to don her poison ivy hunting apparel and venture into the nether regions of our back yard to keep it safe for us.

We've had a lighter week in infectious diseases events. I'll take advantage of that to share a rare criticism of one of my favorite ID feeds. But first .....

Leptospirosis

This is a tough diagnosis most of the time; it's a relatively uncommon infection in the US, and the early stages don't have particularly novel signs and symptoms; it's just a nonspecific febrile illness. About 10% of cases can progress to a second and more severe stage, often called Weil's disease. It's important to remember that it can be a water-borne pathogen, as illustrated by these 2 recent reports.

First, this week's MMWR provides us with documentation of the leptospirosis outbreak in Puerto Rico following Hurricane Fiona in 2022. Leptospirosis is endemic in parts of Puerto Rico, and a disruption like flooding due to a hurricane increases its reach and can result in disease spikes. Look at these graphs of weekly rainfall and leptospirosis cases - it certainly fixes in my mind the tie between water and leptospirosis.

The MMWR article has a link to a nice clinician fact sheet.

Similarly, there's a new spike in leptospirosis infections in Thailand, so far just in news reports (you'll need Google translate again).

I first took a deep dive into leptospirosis as a medical student when I came upon a landmark article of detective work surrounding an outbreak in St. Louis. Two of the authors were mentors of mine, and they loved to regale me with (probably augmented) tales of tracking rats through the sewers of St. Louis. I'm sure this contributed to my choice of pediatric infectious diseases as a career, though not to the extent that I've chased sewer rats.

Mixed Messages About Vaccine Protection From Long Covid

A new article reached a different conclusion from several other reports showing that covid vaccination is somewhat protective against long covid, now better termed PASC (Post-Acute Sequelae of COVID-19). The new study is a retrospective cohort study mining an administrative database from a single (large) healthcare system. The bottom line is (of course!) towards the bottom of the table: no real differences in PASC rates based on vaccine status. Also note this was primarily a study of adults.

Is this a flawed study? Are the authors' conclusions wrong? Well, no to both. We will have differences in conclusions from such studies primarily when we are seeing retrospective studies that rely on administrative databases. The authors did a heroic job of attempting to adjust for various errors in how such data is recorded, but it's impossible to account for everything. Thus, we can have errors in diagnosis, diagnostic code assignment, and missing data, among other issues. Couple that with different definitions of PASC and the likely heterogenous pathogenesis of different forms of PASC, and it's a recipe for conflicting study results. I think we likely will have a clearer picture of PASC, including whether covid vaccination can offer some protection, but it will take prospective longitudinal studies which require more time for data collection and analysis. A longer discussion of the science of PASC is reviewed in Nature Medicine. In the meantime, studies like this one help us fine tune future studies.

Shame on CIDRAP

CIDRAP (Center for Infectious Disease and Research Policy at the University of Minnesota) is one of my favorite daily feeds. I think they blew it in mentioning FDA clearance of a new Lyme test; not only is it not newsworthy, but it could lead some individuals to chase harmful Lyme disease testing. I could be guilty of the same by even mentioning it here.

First of all, FDA clearance of diagnostic tests is a relatively low bar to clear. Although I couldn't find any FDA commentary on the test in question (I guess that would require a Freedom of Information Act request), I did link to the criteria that I think likely were used in this setting, because the particular methodology this test utilizes is nothing new. So, I believe the manufacturer would only need to show "substantial equivalence" to existing tests. This is not the same as showing the new test improved diagnostic accuracy or improved healthcare outcomes. Here's the summary of applicable FDA guidance:

"Studies to Demonstrate Substantial Equivalence

The types of studies typically used to demonstrate substantial equivalence may include the following:

In the majority of cases, analytical studies using clinical samples (sometimes supplemented by carefully selected artificial samples) are sufficient.
For some IVDs, the link between analytical performance and clinical performance is not well defined. In these circumstances, clinical information may be warranted.
FDA rarely requires prospective clinical studies for IVDs, but regularly requests clinical samples with sufficient laboratory and/or clinical characterization to allow an assessment of the clinical validity of a new device. This is usually expressed in terms of clinical sensitivity and clinical specificity or agreement."

This new Lyme test is simply an immunoblot, a very common type of test utilized in multiple settings but with the drawback that interpretation is somewhat subjective - a human needs to decide if a band is prominent enough to be considered present.

When I dug deeper to find supporting studies for this particular test, I became more alarmed. While there are some preliminary studies that I think might have used this new immunoblot method, they don't answer any clinical performance questions. More worrisome is that the test will be sold by a California lab called IGeneX, a company that offers many Lyme tests that, in my opinion, have falsely diagnosed many of my patients with Lyme disease. They often rely on their own interpretations of what constitutes a positive test and provide no reliable scientific evidence to suggest their methodology is valid. In fact, the press release for this new test stated that "Results interpretation is based upon new criteria and not CDC criteria."

Even now on their website they steer providers and patients away from the standardized two-tier testing preferred by CDC. Here's a quote from the IGeneX website: "Lyme disease is typically diagnosed by a two-tiered testing (TTT) approach involving an enzyme-linked immunosorbent assay (ELISA) followed by a Western blot test. However, the sensitivity of these commercially available tests is poor, meaning they can miss active infections. Experts advise against this testing technique due to the ambiguity of its results." It's easy to find a so-called expert to say anything. Again, in my opinion, this lab is to be avoided, and you'll notice I didn't provide a link to them. I'm disappointed CIDRAP gave them free publicity.

Lyme disease testing is far from ideal, and it's certainly possible this new test is an improvement, though I doubt it. CDC explains diagnostic testing for Lyme disease, including the recommended two-tiered testing options. I suspect IGeneX might try to claim that their new immunoblot can fulfill CDC recommendations, but I'm concerned that they will use unsubstantiated rules for interpretation of a positive immunoblot result, as they have for similar tests in their lab.

COVID Crystal Ball

Last week my wife and I got our new covid vaccines, more based on upcoming travel plans rather than any immediate concerns about getting covid. In fact, things seem to be winding down. According to the latest CDC clairvoyance, "we estimate that COVID-19 infections are growing or likely growing in 7 states, declining or likely declining in 16 states, and are stable or uncertain in 25 states." (Not a totally reassuring conviction if half the states could be uncertain!)

I couldn't find a separate precise definition of cutoffs for their categories, but from viewing the data it appears that the Stable or Uncertain category is defined as a probability that the epidemic is growing in those states as between 0.5 and 0.75. By comparison, all the Growing states had probabilities of 0.93 and above.

Curmudgeon-in-Residence

I think I've paid my dues long enough to be entitled to curmudgeon status. The new Lyme test thing reminded me of my dismay that some of the children I've seen in my practice over the years were harmed by use of misleading diagnostic tests resulting in prolonged and unnecessary antibiotic use. I wear my Statler and Waldorf credentials proudly. I think I bear more of a resemblance to Statler.

Now, to cool off a bit, I'll take a quick stroll in my (safer) back yard.

One More Time This Summer

Bud WiedermannAugust 25, 2024August 25, 2024Leave a comment

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

Mpox

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

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

Measles Check-In

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

West Nile Virus

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

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

Timing is Everything

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

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

Holding My Breath on Polio

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

Covid

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

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

Wastewater hasn't changed much nationally.

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

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

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

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

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

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

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

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