COVID-19 vaccine booster – Page 4 – Pediatric Infection Connection

Calm Before the Storm?

Bud WiedermannOctober 30, 2022October 30, 2022Leave a comment

Frontline pediatric healthcare providers probably wouldn't think things are calm given our current onslaught of RSV and influenza cases crowding physician practices, emergency rooms, and hospitals. However, we are in a bit of calm of sorts for covid. Covid cases actually are decreasing in the UK and the US. Lacking a reliable crystal ball, we'll all need to wait to see whether the next few months will bring a significant rise in covid cases. In the meantime, let's explore a couple areas of interest and confusion.

How Well Do the Bivalent Boosters Work?

More time is needed for the definitive answer on this. The discussion has been going on for months, but this past week we saw posting of 2 preprint articles suggesting, based on immunologic testing, that they may not be much better than the original vaccine used as a booster, at least in terms of preventing illness after infection from some of the newer variants. This is actually what was suspected all along. The bivalent vaccine to stimulate immune response to the spike protein from BA.4/BA.5 was hoped to be a bit more effective to prevent severe disease caused by future virus variants. Carolyn Johnson's explanation of the issue in the Washington Post was excellent, please check it out. It is important to recognize that these 2 studies were based on very few individuals and have not undergone peer review. However, the reports are from generally reliable teams at Columbia University/University of Michigan and Beth Israel Deaconess Medical Center. I don't expect big changes in the results once the peer review is completed.

I want to expand on one concept mentioned as an explanation for the findings in both articles, that of immunologic imprinting. This phenomenon also has been referred to as original antigenic sin.

This imprinting is very different from filial imprinting, like baby ducks following the first thing they see after birth. Original antigenic sin refers to the 60+ year old observation that our immune systems like to use the memory of our response to an infection with an antigen (virus in most cases) when infected at some future time with a variant of that antigen. It could potentially interfere with a more robust immune response to that new variant. Of course, covid didn't exist when it was first described; the main subject was influenza at that time. Scientists developing new vaccines have been well aware of this phenomenon for decades. Covid vaccine development has incorporated this concept.

A key point: although it's possible the bivalent vaccines aren't that much better than the original vaccines when used as boosters, any booster is far better than no booster. Please encourage everyone eligible to be fully vaccinated and boosted for COVID-19.

[I realize I haven't mentioned this in a while, but some may wonder about my frequent use of Wikipedia in my links. For many medical issues, I find Wikipedia to be highly accurate plus a little more understandable to non-medical folks than virtually all other sources.]

Should We Worry About Polio in the US?

In general, no, but anyone lacking full vaccination against polio needs to beware. A few years ago it would have been hard for me to imagine ever saying that, but a combination of war, politics, natural disasters, and apathy make paralytic polio a real possibility now. Wild-type polio transmission was eliminated in the western hemisphere in 1991, and it still is, but failure to eradicate it elsewhere has led to vaccine-derived poliovirus causing paralytic polio across the world, including in the US. (Paralytic disease, the most severe form of polio, develops in less than 1% of infected individuals.)

For those unfamiliar with the disease (few clinicians have seen an active case of paralytic polio, unless they have worked abroad), remember that we have had 2 types of polio vaccine for many years. The live polio vaccine (aka Sabin vaccine, developed in 1961) is a weakened version of the wild virus, given by mouth, and requires viral replication in our bodies to produce immunity. It is particularly helpful in achieving immunity in populations difficult to reach by widespread immunization because the vaccine virus is excreted in stool and can be spread to others. That's mostly a good thing, but sometimes this vaccine-derived strain can undergo transformation to increased virulence and actually cause disease in others. A killed vaccine given by injection (aka Salk vaccine, developed in 1955) also is effective though slightly less so than the live vaccine. The live vaccine has not been used in the US since 2000; all polio immunizations in the US, and in most other developed countries, utilize the killed vaccine.

Even though most of us in the US are immunized and therefore protected against polio, wastewater surveillance in New York City suggests that the vaccine-derived virus is circulating in at least 5 counties, putting un- or under-immunized people at risk for paralytic polio. This situation likely is occurring elsewhere in the US, but so far we lack comprehensive wastewater polio reports. Data from London suggest the problem is widespread.

The pandemic and ongoing anti-vaccine rhetoric has disrupted vaccination programs in the US. Let's hope we don't see more cases of paralytic polio in the US.

Interested readers can learn more about the history of polio from the Global Polio Eradication Initiative.

Treading Water

Bud WiedermannMay 29, 2022Leave a comment

Although schools aren't quite out yet, the weather is warming up and it's about time to think about relaxing in a pool or at the beach somewhere. I feel a little bit like we're treading water with respect to COVID-19 in the US, waiting to see what how our new omicron subvariants behave, how much the holiday weekend will bump up cases, and whether the upcoming FDA review of evidence for vaccines in the under-5 and -6 year-olds will result in the long-awaited authorization for young children.

Two Views of Disease Transmission

Recent lay press statements and comments from some of my colleagues alerted me to the fact that many may not be aware that the CDC has 2 tracking tools for measuring disease activity. Mentioned most often is the COVID-19 Community Level. This is directed at communities to help track if the infection rates are becoming severe enough to strain healthcare resources. It first looks at new cases in the past 7 days, whether below or above 200/100,000 population by county. It then looks at new hospitalizations and percent of staffed inpatient beds occupied by COVID-19 patients, with different cutoffs based on the new case count partition. The numbers are boiled down into Low, Medium, or High levels, though if the new cases are >200/100,000 population the minimum level is Medium. Guidelines for prevention strategies are then provided for individuals, households, and communities based on the Community Level.

Here's the big picture (weak pun intended):

Things don't look great in the DMV region right now, but of course this is a very fluid situation.

Contrast this with CDC's Community Transmission Levels. You can see right away one source of confusion, this term is very close to Community Level above, but it's a different calculation for different purposes. This measurement is targeted specifically to help healthcare facilities, not for the communities at large. Levels are categorized into Low, Moderate, Substantial, and High based on new cases per 100,000 persons in the past 7 days (<10, 10-49.99, 50-99.99, and >100) and percentage of positive nucleic acid amplification tests in the past 7 days (<5%, 5-7.99%, 8-9.99%, and >10%). The higher of the 2 determinations determines the Community Transmission Level:

As you can see the 2 measurements have very different views for how things are going, but neither bode well for our DMV area.

Which Eligible Kids Should Receive Vaccine Now?

This is in part an answer to Michael Schwartz's question to me last week. All frontline pediatric healthcare providers are being asked what to do about vaccinating children now. From my viewpoint, it's a very simple answer, but the sticking point is how to communicate options to parents and children particularly if they aren't accustomed to weighing choices in medical care. From a risk/benefit perspective, one needs to weigh that ratio in 2 scenarios: getting the vaccine versus being infected. For the primary series in all age groups, it's not even a close comparison. The risks associated with vaccine are miniscule compared to being infected, even for a healthy child. The magnitude of those risks is at least 100-fold different. What makes it a little tougher is that the absolute risk of complications from infection is much lower in a healthy child than, say, for an old geezer like me. So, I can see where the hesitation by some parents originates.

The question of a booster dose, now authorized for the 5-11 year-olds, might take a bit more analysis. Again, we have tremendous reassurance about side effects, so it's more about benefits and timing of the booster. With the newest omicron subvariants now dominant in the US, no vaccine is particularly effective against infection itself, but benefit remains (if we can transpose from studies in older populations and in other countries) for prevention of symptomatic disease and need for visit to a healthcare provider. It's important for parents to consider individual circumstances such as high-risk contacts their children might have with grandparents, etc. If these kids are to receive a booster, now is a good time since nothing new is likely to be available until the fall at best.

I might add, in my broken record mode, that the press releases from vaccine manufacturers giving a preliminary vaccine effectiveness number are way too preliminary. The confidence intervals are huge, and also I would not base any decision on partial data reports from an entity with an overwhelming implicit bias in seeing their vaccines authorized.

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.

Tag: COVID-19 vaccine booster