March 2022 – Pediatric Infection Connection

Holding My Breath

Bud WiedermannMarch 27, 2022Leave a comment

Breath holding has a lot of uses during a pandemic spread via the respiratory route. I suspect many parents of young children are holding their breaths after Moderna's press release that their COVID-19 vaccine trial met its primary endpoint in children 6 months to under 6 years of age. A problem is that this endpoint of neutralizing antibody response has less practical meaning in the omicron era. The statement contained slightly more numbers than did Pfizer's press release for their vaccine trial in young children last December, but still too little to make much sense of it. I'll stick to my policy of mostly ignoring Big Pharma press releases and focus on actual data reviewed by impartial experts. I'm hopeful, but this will take time and certainly I can't hold my breath that long.

Variant Alphabet Soup

The Greek alphabet was nice while it lasted, but now with subvariants we're back to more letters and numbers. Some pundits have made a big deal of the new "deltacron" strain, a recombination of delta and omicron variants. However, know that this recombination of variants has been happening since day 1 of the pandemic. Any time a host, human or animal, has more than 1 strain circulating in their body at a time, the possibility for recombination exists. Coinfection is an uncommon occurrence but when in the current pandemic happens often enough to reach detection. Usually these new strains are clinically insignificant with no advantage in transmissibility or virulence, and they just die out. Again I have turned to my friends in the UK for good explanations. A news release covers this in lay language but also has a link to the hard data if you're interested. As always, we'll need to wait a while to know if/when a new variant of concern arises.

The most important practical point to all this is that the FDA now has limited use of the monoclonal antibody sotrovimab in some jurisdictions due to likely poor effectiveness against the BA.2 subvariant that is rapidly becoming dominant in the US. If you live in HHS Region 1 (CT, ME, MA, NH, RI, VT) or Region 2 (NJ, NY, PR, VI)* you won't be able to obtain sotrovimab for treatment because BA.2 predominates. Expect this list to expand in the coming weeks.

*You might ask how Puerto Rico and the Virgin Islands ended up in the same region as New Jersey and New York. I couldn't find an official answer, I think they just needed some region to pigeon-hole those far-flung geographic places, not necessarily thinking about transmissible disease analysis.

Potpourri

I made a trip to my favorite neighborhood public library for the first time in years. I was pleased to see a table with free COVID-19 rapid antigen tests and N95 masks and yes, I helped myself. Also in the realm of new things, CDC has a nice COVID-19 Isolation and Quarantine Calculator. This makes it much easier to figure out what everyone needs to do depending on local circumstances.

Speaking of holding one's breath, sewers are at the forefront these days. Pre-pandemic if someone mentioned sewers I thought of 3 things. First is the classic exploration of the London cholera epidemic of the mid-19th century by John Snow. Second is an important article about a leptospirosis in people linked to their immunized pet dogs who cavorted with sewer rats. It is especially memorable to me because one of my mentors, Ralph Feigin, loved to regale trainees with his (embellished, I suspect) tales of sewer expeditions to collect samples for the report. Lastly, The Third Man, a noir movie of old, has a great scene in the sewers of Vienna.

All that aside, sewers are a valuable predictor of what to expect for the pandemic in the coming days and weeks. The CDC has continued to ramp up their SARS-CoV-2 RNA wastewater tracking with an interactive page. You can type in any jurisdiction and see the latest, assuming they are providing data (most Maryland counties show no data from the last 15-day period). Poop patrol isn't limited to just your evening dog walks.

Happy Vernal Equinox!

Bud WiedermannMarch 20, 2022Leave a comment

Yes, the first official day of spring is today, Sunday, March 20. To be more precise it occurs at 11:33 AM EDT. (Note, after reading last Sunday's Washington Post comics section, I realized I erroneously referred to EDT as Daylight Savings Time, rather than Daylight Saving Time, in last week's posting.) While we await further results for COVID-19 vaccine trials in younger children as well as possible EUAs for 4th doses of vaccine for adults, let's see what else spring has to offer.

COVID-19 Hospitalization Rates in 0 - 4 yo Children

CDC released new data on March 15 confirming what everyone working in a children's hospital already knew: the omicron surge was bad news for young children, even though overall the variant did not appear to be more virulent than its predecessors. Hospitalization rates were higher in young children than at any time during the pandemic. One picture says it all.

Meanwhile, I remain focused on Europe as a possible harbinger of things to come for the US. Certainly as COVID-19 restrictions relax across the world we can expect an uptick in cases, but the real question I have is whether the uptick now in Europe is simply that or represents another surge due to the BA.2 subvariant. I am closely following my daily reports from uk.gov and have noticed a drifting up of the weekly reproductive number. At the last update a few days ago, the R value is estimated at 1.1-1.4. As explained in their helpful report, " An R value of 1 means that on average every person who is infected will infect 1 other person, meaning the total number of infections is stable. If R is 2, on average, each infected person infects 2 more people. If R is 0.5 then on average for each 2 infected people, there will be only 1 new infection. If R is greater than 1 the epidemic is growing, if R is less than 1 the epidemic is shrinking. The higher R is above 1, the more people 1 infected person infects and so the faster the epidemic grows." Note this week's number really represents transmission that happened 2-3 weeks ago, it takes time for reporting and tracking to be reflected in R values. In my opinion, this currently reported R rate is consistent with just relaxing of restrictions, but if it goes much higher it probably means we're headed for a more significant surge that might call for going back to masking and other nonpharmaceutical interventions.

Remember Tickborne Diseases?

Yes, it's hard to think about anything but COVID sometimes, but spring also brings us into tick season. (Note that climate change increasingly allows for tick survival throughout the year, but there will be more of them around now, for the next several months.) In the DC area of course we need to continue to be on the watch for Lyme disease; providers should make use of excellent guidelines for management.

Recently another tickborne disease appeared in the news as Heartland virus, aka HRTV, was detected in lone star ticks (Amblyomma americanum) in Georgia. HRTV is still rare, only about 40 cases reported in the US since first described in 2009, but it is serious. Clinically it is a hemorrhagic fever with thrombocytopenia syndrome with a high fatality rate, though the rate is probably falsely elevated a little bit because milder cases would not have resulted in detailed investigation for causes.

While we are on the subject, keep in mind Bourbon virus, named for the county in Kansas where it was first discovered in 2014. It isn't as severe as HRTV and has not been reported in the DC area.

Remember to advise your patients and their families about prevention and management of tick bites. However, don't let this keep anyone from enjoying the outdoors!

Happy Daylight Savings Time (and official 2nd anniversary of the pandemic)

Bud WiedermannMarch 13, 2022Leave a comment

I finished setting all my clocks and outdoor light timers to DST this morning for our annual spring ritual, but I realize that I might not be doing this for much longer. Congress continues to look into abolishing these switches due to growing data suggesting it is bad for our health, now awaiting an analysis from the Department of Transportation. I'm not holding my breath.

In the meantime, I will mention a couple of CDC reports from last week.

BNT162b2 Vaccine Effectiveness for 5-15 year-olds

In case you don't recognize the code, BNT162b2 is the Pfizer/BioNTech COVID-19 vaccine. CDC now has a new analysis of how it has worked in this age group, covering the time period from July, 25, 2021 through February 12, 2022. Bottom line: adjusting for various confounders like health information, mask use, local virus circulation, and other factors, VE was higher for 12-15 year olds compared to the 5-11 age group. It was better against delta than omicron variants. They don't yet have information to break down asymptomatic versus symptomatic infections.

The CDC generally is pretty thorough in stating data limitations, and they did a good job here. The 2 take-home points I see from the data are: 1) VE, while it wanes with time after vaccination and is lower with younger children, is still pretty good; and 2) this situation is fluid. I'm not so focused on the exact numbers reported now, especially with wide confidence intervals. We'll have new analyses as time goes by (apologies to Dooley Wilson).

Influenza Vaccine Effectiveness 2021-22 Season

As they generally do this time of year, CDC released an interim analysis of influenza VE for this season. It didn't look good; the vaccine did not appear to be effective against H3N2 infections that predominate so far this year. This wasn't too surprising, see my December 5, 2021 posting first raising concern about a mismatch of this year's vaccine. However, we are in an unusual flu season with brief heightened activity in some parts of the country and little to no activity elsewhere. Given that NPI (non-pharmaceutical interventions) for COVID-19 are lifting, we'll see what happens to our flu season. I would still recommend influenza vaccine for everyone eligible.

I well remember being on call as a pediatric resident during the spring forward to DST and rejoicing that I had 1 less hour to work. I definitely try not to count my work hours now, not something to dwell on! Maybe I'll find time to watch an old movie today.

Take a Deep Breath

Bud WiedermannMarch 6, 2022Leave a comment

Data continue to look encouraging in terms of case rates, hospital bed availability, and other pandemic tracking across the country, notably with exceptions and still at substantial transmission levels in many areas. Let's look today at some slightly conflicting reports of vaccine effectiveness (VE) and a bit of reflection 2 years after the start of all this.

Which Numbers are Correct?

The answer, of course, is that both are likely correct, within the imperfect data analyzed. Last Monday, February 28, the New York State Department of Health posted a pre-print (non-peer reviewed) study that showed low rates of VE in children 5-11 years of age compared to 12 years and older who received a higher dose of the Pfizer mRNA vaccine. I had questions about the accuracy of the data in the study, a problem with all studies like this one that uses administrative databases. If the authors can answer those questions satisfactorily when it is peer-reviewed, it did indicate that VE wanes faster in the children who received the lower dose.

Then on March 1 the CDC released their own data looking at the same question. It also is based on administrative datasets but has the advantage of being more established and more likely to be free of serious errors. Also, getting through the CDC review process is a bit more like peer-review, though most of the peers are CDC personnel which could introduce unintentional bias. I'll focus on the CDC numbers because I think they are more reliable. Here is the bottom line for VE against laboratory-confirmed COVID-19-associated emergency department (ED) and urgent care (UC) clinical encounters and hospitalizations (H). Note that time after vaccination varies because the younger age group was authorized for vaccine only recently. Also, some estimates have very wide confidence intervals (CI) because the number of events is too small to be more precise.

	Age Group/Vaccine Status	VE (95% CI)
ED/UC*	5-11 yo, 2 vaccine doses 14-67 days earlier	51 (30 - 65)
	12-15 yo, 2 doses 14-149 days earlier	45 (30 - 57)
	12-15 yo, 2 doses > 150 days earlier	-2 (-35 - 95)
H**	5-11 yo, 2 doses 14-67 days earlier	74 (-35 - 95)
	12-15 yo, 2 doses 14-149 days earlier	92 (79 - 97)
	12-15 yo, 2 doses > 150 days earlier	73 (43 - 88)

*omicron period only; **combined delta and omicron periods

VE is similar relatively soon after receiving 2 doses of vaccine, suggesting less of an effect from the vaccine dose itself. Remember that 5-11 year-olds received 10 mcg doses compared to 30 mcg in the 12-15 age group. The numbers of events for these children receiving a third dose was too low to calculate anything, but in the 16-17 year-olds a third dose seemed to produce a terrific rise in VE. Undoubtedly we'll see more reports about this from other jurisdictions as we have more time elapsed to observe VE.

Learning Now to Prepare for the Future

I'll close with a quick plug for 2 opinion items I read in the last few days. First is journalist Joel Achenbach's article in the Sunday Washington Post Magazine about 10 lessons learned so far from the pandemic. I especially noted #7: pandemics end psychologically before they do biologically. How true. Let's not get too complacent yet.

Second is a piece released this week in the New England Journal of Medicine talking about the need to develop capabilities to produce a vaccine within 100 days of the start of a new pandemic. The authors note that it took 326 days from the SARS-CoV-2 genetic sequence release in January 2020 to the emergency use authorization of the first COVID-19 vaccine. I've said before that this speed approached miracle status, so proposing lowering that to 100 days will take a bit of work. Let's hope we don't repeat past behavior and lose our research momentum when this pandemic calms down.

Month: March 2022