April 2022 – Pediatric Infection Connection

Omicron’s Lesson in Humility

Bud WiedermannApril 24, 2022November 4, 2024

We've all learned a lot about SARS-CoV-2 in the past 2 years. However, once again I'm reminded about how much we have to learn; the virus continues to surprise us. First, a bit about last week's ACIP meeting.

Number Needed to Vaccinate

I had hoped the ACIP would give a bit more specific advice for individuals to decide about a second booster dose. It seems clear that the potential benefit to those who are generally healthy and under 50 years of age is minimal and probably doesn't warrant widespread second boosting of those individuals. However, not everyone older than 50 has the same risk factors, and ACIP mostly took a pass in advising the public about how to think this through. I think they should have tried a little harder with that.

On the other hand I was very pleased that Dr. Sarah Oliver presented nice graphical information of the relative benefits of primary series and boosters. As you can see below, the biggest bang for the buck is the primary series plus first booster dose. Don't lose track of that. A second booster dose has some benefit, but the returns on that investment are smaller.

The number needed to vaccinate (NNV) basically states how many individuals would need to be vaccinated to prevent one additional adverse outcome of interest. While studies have shown this isn't too effective in communicating risks and benefits to the general public, I find it very useful to assess strategy. Here is Dr. Oliver's NNV calculation from the same presentation, using hospitalization as the outcome of interest:

So, a second booster isn't without benefit, but the incremental benefit is relatively small. From a public health perspective, what this is telling us is that we need to expend our largest efforts in vaccination of those who are unvaccinated or who have not received their first booster. Keep in mind that because our case monitoring is less precise now due to pandemic fatigue/apathy, these estimations are more prone to error. Also, SARS-CoV-2 is a moving target; numbers today may not apply in another week or 2. Which brings us to our next subject.

Another Sublineage Breaks Out of the Pack

The most astonishing development I saw this past week is the rapid increase of the new omicron sublineage BA.2.12.1. Look at how it seems to be taking over in the US:

Once again we will need to recalibrate all our numbers. Clearly BA.2.12.1 has a selective advantage, perhaps rising more quickly than did BA.2. We haven't seen an uptick in hospitalizations yet so maybe it doesn't have enhanced virulence, but it is at least more transmissible. I'm keeping my fingers crossed that BA.2.12.1 won't bring a large increase in severe disease.

In the meantime, I'm going to take a short break on this sunny Sunday in Silver Spring and enjoy a cup of coffee on the patio. Tomorrow is another day in COVIDland.

Something Besides COVID

Bud WiedermannApril 17, 2022Leave a comment

I haven't been keeping up with the lay press this past week, but from my standpoint not much earth-shattering happened with the pandemic. Yes, Pfizer announced they will ask for booster authorization for 5-11 year old children, based on results from 140 children. As usual, I would recommend waiting to see the full data and the FDA appraisal before getting your hopes up. Also, ACIP has a meeting planned for April 20 to discuss and vote on booster dose recommendations. No agenda released yet, but I'm hoping they will provide a more rational and specific approach to replace the current vague 4th dose "get it if you want to" advice for the 50+ year-old crowd.

In the meantime, it's still difficult to know whether the upticks in cases across the country represent just the expected numbers when restrictions are lifted or the beginning of a true BA.2 surge. With pandemic fatigue on both the public and governmental levels, we just don't have accurate case numbers to guide us. We'll need to wait and see whether hospitalization rates start to increase which would be an indication that we're in for another rough stretch.

Depressing News About STDs

CDC reported data from 2020, a time when we were mostly in lockdown everywhere, and it's pretty depressing. Gonorrhea and syphilis increased significantly, chlamydia was about the same. Here is a look at syphilis in newborns and women of childbearing age the past few years:

Certainly my own clinical practice bears this out. Although I don't generally see adolescents for STD issues, my colleagues and I have seen plenty of referrals for congenital syphilis recently. A sad commentary on our public health system, reflecting poor infrastructure in many states dating back generations.

New Fulminant Hepatitis?

Although we don't have much information to go on yet, small clusters of what appears to be acute fulminant hepatitis in young children have been reported in the UK, Spain, and the US (Alabama). A prime suspect is adenovirus 41, usually a run of the mill infection. Investigations are still ongoing, but the clusters do not appear to be associated with the more usual viral causes (hepatitis A through E) nor with any identifiable toxin exposure. The best information comes from Scotland where officials published comprehensive but still inconclusive data on 13 children.

Adenoviruses are well known to be excreted in the nose and/or stool weeks to months following infection, so a positive PCR from these sites may not indicate causation of a current illness.

I suspect this will be figured out soon. In the meantime, frontline pediatric healthcare providers should be aware of this possibility, both to identify cases early as well as to ward off panic from parents if their child with a cold happens to have a multiplex respiratory pathogen panel positive for adenovirus, a very common occurrence. Of course the best way to ward this off is to not order this test in the first place - it isn't necessary for routine illness!

Coffee and COVID 2

Bud WiedermannApril 10, 20222 Comments

Yesterday I made a trip (dare I say pilgrimage?) to my favorite neighborhood coffee place, a coffee roaster only open to the public on weekend mornings. It is tucked away in a small row of establishments mostly consisting of small business headquarters and tiny religious meeting places; not much going on except for the weekend coffee business. When things hit lockdown for the pandemic, the coffee started flowing again after the owner opened a window to the parking lot to make a walk up outdoor order site. I was happy to park and wait for my cappuccino and bag of beans.

I hadn't been there in a few weeks, and now the walkup window is closed. Inside, the already tiny seating area is even smaller with the counter in front of the main prep area shut down. I waited with a group of about 15 people, some masked, some not, and had a chance to catch up with Felix the owner. Looking around, I realized I was witnessing the future of the pandemic.

Tasseography

I didn't spend my wait there trying to read coffee grounds to predict the future, but as I said last week our current ability to predict the future is limited by poor data (less testing, home testing not reported, some states decreasing reporting frequency, etc). Tasseography might be as accurate as anything else. Looking to the UK once again for hints of the future, the reproductive number there is holding steady or maybe drifting down, a good sign. The variant situation is interesting, still with an overwhelming predominance of BA.2 but now with some newer recombinant lineages and even some totally new omicron sublineages (BA.4 and BA.5) detected last week. Nothing to panic about, just keep a watch.

A Befuddled FDA

Last Wednesday the FDA VRBPAC met to discuss the issue of vaccine boosters. I had a busy clinical load that day so could only attend the live meeting intermittently. Also, due to some technical problems, parts of the live meeting and the recording itself are missing audio input, including a key portion that I wanted to hear where members questioned Israeli scientists about 4th doses in older adults. The slides themselves are available though, and do provide a lot of information.

I don't think I've ever seen a group of medical experts struggle more with trying to blaze a path forward, entirely understandable because of the uncertainties of this pandemic particularly in predicting future variant emergence. What is clear, however, is that we need a new strategy available likely by the fall, when cold weather returns and people again move to more frequent indoor gatherings which will facilitate SARS-CoV-2 transmission like the Gridiron Dinner last week. Here are a few of my take-home messages from the meeting.

There isn't enough time to get clinical data on any new variant in time to decide on vaccine composition; if the past is any predictor, by the time the variant appears it's already too late for a variant-specific vaccine to be developed. This is totally different from seasonal influenza where strains seen at the end of the previous season can be reasonable guides for vaccine production for the next season. Things happen much more quickly with SARS-CoV-2. Also, at present and likely for the extended future, we don't have an antibody or other correlate of protection. Even if we did, that could change with the next variant as we've seen so clearly with omicron.

Future vaccines likely will need to bivalent or multivalent, covering more than one strain/variant, or perhaps a new approach targeting a conserved region of the virus like the nucleoprotein will be better. That latter strategy is underway but could take a longer time to develop. I doubt a vaccine targeting just the original omicron strain will cut the mustard for boosters next fall.

We've just witnessed a super spreader event in DC with some big names infected. Given current behaviors, it won't be just my favorite coffee shop that's risky. Each of us will need to weigh our own risk profiles, taking into account both individual risk factors for severe disease as well as risk factors of our close contacts. I interact with immunocompromised and unimmunized children all the time, I'll be playing it very much safe to protect them. I wear N95 masks full time when I'm around them and also when I'm in the grocery store or other indoor settings.

And yes, I wrote this post while sipping a nice cup of coffee made from Colombian beans: "medium body with hints of honey, pear, cardamom & fennel." No, I couldn't really pick out those flavors, but it tasted great.

Optimistic Omens?

Bud WiedermannApril 3, 2022Leave a comment

It's becoming a little tougher to rely on pandemic data now. Reporting from most, if not all, US jurisdictions is infrequent plus misses most of the home test results; we know individuals generally aren't going to report their home rapid test results. Furthermore, testing around the globe is likely worse, driven additionally by lack of testing resources.

So, to satisfy my craving for data I've had to turn to a bit of a jigsaw puzzle strategy to assemble data pieces into a big picture.

Friends Across the Pond, Plus Some CDC Data

Europe, though with different pandemic epidemiologic drivers, has helped to foreshadow events in the US. I turned to England's poop patrol first. The image below is one of many from the UK's excellent reporting system; focus on the blue line depicting England's viral concentration in wastewater through early March.

What you see are viral levels, mostly representing the BA.2 omicron subvariant, coming down to what was seen at the low point last October. I find this particularly encouraging because this downtrend is happening without British healthcare system overload. Furthermore, R value (reproductive number) in the UK also is heading down. (This last link is only for hardcore pandemic geeks, at the website you then need to download a spreadsheet and study the data.)

In the US, it's hard to find much about the pandemic in the lay press, probably a combination of other important news, less data, and overall pandemic fatigue. The screenshot below is from the CDC's variant tracker; note the striking and rapid appearance of BA.2.

Again, what is a hopeful sign is that we have seen BA.2 virtually take over most of the country, but without a rapid rise in healthcare resource strain. The fully assembled puzzle may be showing us that while BA.2 rapidly became the predominant strain, it did not result in a major illness surge. The next few weeks in the US will reveal a clearer picture.

But Wait, There's More

I was super-excited to see the FDA's new industry guidance for COVID-19 vaccination, the first update in about a year. Other than the vaccine industry, I may be the only other person to be thrilled to see this guidance. The press and even most of my healthcare alerts seem to have ignored it. It's pretty dense, boring reading, but the meat is in Appendix 2 on page 21 where the approach to vaccines for new variants is discussed. Although the FDA always has a disclaimer that these are all nonbinding recommendations, you can bet Pfizer, Moderna, and the other vaccine players will be paying close attention to this roadmap for future trials, likely later this year.

I deliberately chose the term "omen" at the top of this post, feeling like I may as well be reading tea leaves or using similar methods to divine the future. Nonetheless, my puzzle work today reminds me to look forward to my summer vacation with our 1000-piece jigsaw puzzle, this one with a bunch of trees that all look alike. If our plans stay intact, we'll have (and need) the whole family working on this one.

Month: April 2022