omicron variant – Page 10 – Pediatric Infection Connection

It’s been a long time comin’

Bud WiedermannJune 19, 2022Leave a comment

Readers of my generation will recognize the opening line of the Crosby, Stills & Nash song "Long Time Gone." Of course I'm co-opting the phrase to mark our entry into the era of COVID-19 vaccines available for children as young as 6 months. I caught most of last week's FDA VRBPAC and CDC/ACIP meetings plus studied I don't know how many pages of documents, so today I will devote the entire posting to summarizing the data. Unfortunately, as of mid-day June 19 CDC has still not posted specific recommendations, so what you see below are tentative recommendations.

Note that CDC still has not issued official recommendations for Moderna vaccine for children and young adults 6-17 years of age, although FDA has authorized its use for this age group. ACIP is meeting June 23 to discuss that. Furthermore, a very important FDA meeting will take place June 28 to plan for potential vaccine composition and doses next fall.

NOTE THAT THE FOLLOWING INFORMATION SUMMARIZES THE JUNE 17-18 CDC/ACIP MEETINGS BUT IS NOT YET AN OFFICIAL RECOMMENDATION.

The Process

CDC and ACIP followed a standardized process to assess raw data from the Pfizer and Moderna trials. Representatives from these companies presented data at this meeting, as they did at the FDA/VRBPAC meeting, but in general I find this less helpful. Pharmaceutical companies naturally want to put their products in the best light possible, but sometimes I feel these presentations obscure the key points. So, I will be presenting information only from the CDC. I found it to be high-quality, non-biased assessments. For those who wish to dig deeper, you can access all the presentation from both days at the ACIP web site. The key documents in my opinion are from CDC's Drs. Sara Oliver and Elisha Hall.

Basis for Recommendations

The primary basis for recommending these vaccines down to 6 months of age is from antibody levels, which was the original primary objective of the trials. Two doses of the Moderna vaccine and three doses of the Pfizer vaccine achieved neutralizing antibody titers similar to the titers seen in 16 (or 18 for Moderna) through 25 year-old trial participants who were protected from infection at that level, albeit well before the omicron era. Additionally, the Moderna trial was able to accumulate enough SARS-CoV-2 cases to provide some assessment of vaccine efficacy for symptomatic infection during the omicron era: VE point estimate was 37.8%, but the confidence interval was relatively wide at 20.9-51.1%. Note that CIs are merely a reflection of how large the number of events is; as time goes on and more cases accumulate, they may be able to report new data with a more precise VE and smaller CI. For Pfizer, just ignore any VE number you might have heard from the manufacturer. The number of cases so far are too small to make any prediction from that data alone. However, extrapolating to older children and adults using the neutralizing antibody data alone, we should expect similar VE. The problem is our moving target as the virus changes. Neutralizing titers and VE in the omicron era are lower, and we don't even have data yet on the rapidly emerging BA.4 and BA.5 subvariants.

Another way to look at this is using Number Needed to Vaccinate (NNV). Using a range of possibilities for VE, CDC estimated for mRNA COVID vaccines that 1660-3320 vaccinations would be needed to prevent 1 hospitalization for COVID-19 disease in children 6 months-4 years of age. This compares with influenza vaccination where the NNV is 1030-6890. (This is all contained in Dr. Oliver's presentation starting with slide 64.)

We do have good safety data with no significant concerns in either the Moderna or Pfizer trials. Of course, rare reactions would not be expected to be seen in trials that combined have about 8000 participants. However, note that just in the US alone around 600 million doses of mRNA vaccines have been administered, surrounded by the most intense reporting system for vaccine side effects ever seen. This should be very reassuring to everyone that these vaccines are very safe and orders of magnitude safer than SARS-CoV-2 infection itself.

Which Vaccine to Choose?

Well, it depends on who is asking. If it is a healthcare provider, go with the product that is easier to implement in your practice. You want to be able to continue providing your high quality care to all patients, and minimizing disruption will help. It may boil down to storage and packaging, with screens shots as below:

For example, you can see that the Pfizer product requires diluent whereas Moderna does not. Neither vaccine requires ultra-low freezer use for everyday practice. CDC should have more guidance available on their website soon.

If, however, it is the parent asking which to receive, that's a different consideration. The principal difference is the need for 2 doses for Moderna versus 3 for Pfizer, although note it is very likely Moderna will need a 3rd dose anyway. Still, a family who is anxious to get the best protection the fastest might want to go with Moderna. The side effects from the Moderna vaccine are a bit higher, more children with fever and lymphadenopathy, so this is the tradeoff.

Vaccine Interchangeability and Coadministration

We have no studies of mixing the Pfizer and Moderna vaccine administration for the same patient, nor any studies of administering these vaccines simultaneously with other childhood vaccines in these age groups. CDC likely will advise to use the same vaccine product throughout the primary series and to allow coadministration with other vaccines.

What are the Recommended Regimens?

As I stated at the top, CDC has not yet published the recommendations online. However, I can show you Dr. Oliver's slide 128 since it is part of the public record. Just be advised to check the official recommendations before administering any vaccine to this age group. Watch for CDC announcements; they also plan to provide all kinds of examples of specific situations such as those involving inadvertent interchangeability.

The interval range between doses 1 and 2 for immunocompetent young children reflects studies in older children and adults suggesting better response with the 8-week intervals; studies in this younger age group have not been performed.

Parting Shot

C, S & N also said, "The darkest hour is always/Always just before the dawn." I don't think that is exactly accurate, but please recognize we are at a new dawn in managing this pandemic. We still have a bumpy road ahead, but we also have much better tools to protect our children.

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.

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.

Tag: omicron variant