COVID-19 vaccine – Page 16 – Pediatric Infection Connection

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.

6 More Weeks of Winter

Bud WiedermannFebruary 6, 2022Leave a comment

Apparently Punxsutawney Phil saw his shadow this week, but maybe you didn't know about this important groundhog connection to the world of infectious diseases. Woodchucks (aka groundhogs) are affected by WHV (woodchuck hepatitis virus) and have been used in hepatitis B research. Unfortunately, Phil's forecasting accuracy rate for winter weather duration of 40% might be better than most models of COVID-19 future waves.

Important Conversations at ACIP

I didn't see much about this in the lay press, but the Advisory Committee on Immunization Practices met on February 4, primarily to discuss the recent FDA approval for the Moderna mRNA vaccine that will now be marketed as Spikevax. That all went fine, but I was more interested in the afternoon discussions.

Tracking of vaccine-associated myocarditis continues with further data from both the US and international sites. Although there are no large randomized controlled trials directly comparing the 2 mRNA vaccines, it seems likely that this risk is slightly higher with the Moderna vaccine than with Pfizer's. However, both risk rates are considerably lower in comparison to the risk of myocarditis from natural infection. I think the best way to use this information might be to advise a male adolescent or young adult, the highest myocarditis risk group, to choose the Pfizer vaccine when starting a primary series or considering a booster. The vaccine-associated myocarditis still seems to be very mild with no long-lasting sequelae, but well-designed long term follow-up studies are ongoing.
The other discussion I found very interesting was regarding the interval between first and second doses for a primary mRNA vaccine series. Canada and other countries now have a fair amount of data on this; in the US this has not been well-studied, and in the initial vaccine research trials virtually all of the participants had second doses at around 3 (for Pfizer) or 4 (for Moderna) weeks after the first. Based on the meeting presentations, consensus of ACIP members seemed to lean heavily towards recommending an 8-week interval between the first 2 mRNA vaccine doses, especially in times of low community COVID-19 activity where risk of infection during that more prolonged interval between doses will be less.
Also, stay tuned in the next few days (I think) for more specific and very helpful guidance on immunization of individuals with moderate or severe immunocompromise. This will be very helpful to those patients as well as to providers who advise transplant and other patients on this topic.

Alas, Poor Yorick

I must admit I don't know much about Denmark: it is the origin of the name for epidemic pleurodynia, Bornholm disease, and it is the setting for what is perhaps Shakespeare's best play. Now, Denmark is in the COVID-19 spotlight for 2 reasons.

First, a recent preprint shows us that the new omicron "subvariant," BA.2, has become very prominent in Denmark. The study looked at primary cases of COVID-19 from December 20, 2021, to January 11, 2022, to identify secondary attack rates in those households. Tracking of secondary attack rates ended January 18, and testing of household members was relatively high. From the 8541 primary cases in households, 5702 out of a potential 17,945 exposed household members were infected. When broken down further, the secondary attack rates for BA.1 (the original omicron) and BA.2 were 29% and 39%, respectively. This provides further evidence that BA.2 may be slightly more infectious than BA.1. Vaccination of exposed individuals didn't seem to affect secondary infection rates, but note that this included asymptomatic infections; there was no evidence of increased disease severity of BA.2.

I'm especially interested to watch how this all unfolds in Denmark, both because they are experiencing relatively high percentages of BA.2 and because they have just instituted one of most relaxed mitigation strategies anywhere.

It's hard to guess whether BA.2 has the potential to cause additional new disease surges after BA.1 across the world. Try asking Punxsutawney Phil.

Winter Marches On

Bud WiedermannJanuary 30, 2022Leave a comment

It appears the feared double-whammy of simultaneous COVID-19 and influenza peaks won't happen. The CDC influenza data are a little harder to interpret because of the omicron peak affecting counts of influenza-like illness (ILI); ILI is high, though coming down, but likely most of the numbers are omicron, not influenza. Most of the influenza that is being identified is influenza A H3 which could contain a clade that has a bit of a mismatch with this year's vaccines. CDC's influenza web site is always informative.

More on Vaccine Myocarditis in Adolescents

The New England Journal published brief correspondence from Israel updating Pfizer vaccine-associated myocarditis in teenagers. The latest numbers, looking just at ages 12-15 years, are 1 case per 12,361 second vaccine doses in males and 1 per 144,439 in females. These numbers are in the same ballpark as previously reported in US and Israel. The current data are based on hospitalizations for myocarditis. Note that the illness still looks to be very mild so the Israeli data could be missing cases managed as outpatients.

UK.gov

My new BFF in the world of COVID-19 listservs is from the United Kingdom. I signed up for daily alerts a while back. They come through at around 3 or 4 AM Eastern time and range from 1 to many different updates. All have summaries and links to raw data. Some days I'm almost overwhelmed with new reports. The graphics aren't as attractive as CDC's web site, but in general I think the UK does a better job than CDC in explaining nuances to the general public. I'll highlight 2 reports from this past week. Browse through if you are interested, but it's a definite rabbit hole for COVID nerds.

First is a January 26 report with some interesting mathematical modeling that attempted to determine the numbers of adults who would have tested positive for SARS-CoV-2 antibodies from either vaccination or infection. Not surprisingly, the older age groups with positive testing likely would have been due to vaccination. Another portion of the report looked at children 8 - 15 years of age where of course relatively little of the antibody positivity would have been due to vaccination. This type of analysis is important in understanding new methods to track pandemic/endemic activity.

Friday's report, which generally includes the big picture infection survey for the week, also had a nice report on the BA.2 variant risk assessment; this is the omicron variant getting a fair amount of media attention now. They have a lot of background data elsewhere, but their one-pager is a nice overview comparing the BA.2 variant to BA.1, the original omicron variant. They expressed moderate confidence that there is evidence of community growth advantage for BA.2 in more than one country (Denmark seems to be the country with a lot of BA.2 at the moment). However, they felt only low confidence that increased transmissibility of BA.2 explains this growth advantage. Also with low confidence, they saw no evidence that BA.2 was more able to evade the immune system (i.e. vaccines or monoclonal antibody treatments less effective) compared to BA.1. They had insufficient data to comment on whether infection severity is different. For now, BA.2 is yet another variant to keep an eye on.

Welcome Breathing Room

Bud WiedermannJanuary 23, 2022January 26, 2022Leave a comment

All systems point to the downswing of the omicron wave which is good news for everyone. Risking being labelled a party-pooper, I hasten to add that we cannot let our guard down. Note that we have had 2 variants cause global upheaval in just the second half of 2021 plus still vast portions of the world's population lacking vaccination. It is a question of when, not if, the next variant of concern appears. (I'll rejoice if I'm proven wrong.) We need to accelerate all preventive measures including delivery of vaccines and boosters worldwide.

Continued Evidence That Vaccines Work

Last week saw publication of 4 new studies all showing the benefit of COVID-19 vaccination in protection against serious illness.

A study released by CDC last Wednesday I think got a bit twisted by some press reports into appearing to advocate that being unvaccinated was a good plan. The study looked at surveillance data from California and New York. A summary statement, "By early October, persons who survived a previous infection had lower case rates than persons who were vaccinated alone," was the source of confusion. The confusion can be clarified by a nice graph that unfortunately only appeared as an online supplement to the report, meaning that readers would have had to read through some pretty dense tables of numbers or take an extra mouse click to get a good appreciation of the situation. Here is one of the supplementary figures from New York. Look at the distance between the solid blue line (unvaccinated) and the 3 lines at the bottom. Yes, it is true that vaccinated individuals with no prior infection history had slightly higher hazard rates for lab-confirmed infection, but not that much more compared to the rates of vaccinated or unvaccinated people who had prior infection. Being vaccinated was far better than being unvaccinated regardless of prior infection history. Also, these data are mostly before the omicron surge when everything changed, and it did not look at booster status.

The second study did evaluate booster status and was highly encouraging. The authors, from the CDC, used the familiar test-negative study design and were able to judge the association between 3 doses of either the Pfizer or Moderna vaccine with protection from symptomatic COVID-19 disease against both delta and omicron variants. This study design only permits calculation of odds ratios rather than true relative risks but can be used as an approximation. Comparing 3 doses of an mRNA vaccine to being unvaccinated, odds ratios were 0.33 (95% CI 0.31-0.35) for omicron and 0.065 ((0.059-0.071) for delta, i.e. significantly in favor of vaccination. Similarly, a comparison of 3 versus 2 doses of vaccine showed odds ratios of 0.34 (0.32-0.36) and 0.16 (0.14-0.17) for omicron and delta, respectively. We'll need to see a follow-up to these data since the study extended only through January 1, 2022.
Another study from CDC compared disease incidence and death rates among unvaccinated and fully vaccinated adults, with and without boosters in 25 sites in the US. Significant benefits were demonstrated for the vaccinated and boosted groups, especially for ages 50 years and above.
Also worth noting is a study focused on benefit of third doses in preventing emergency and urgent care visits and hospitalizations in 10 states, covering the August 2021 through some of January 2022. As you might guess by now, the data lend further evidence of the benefit of vaccinations and boosters.

Ten Fingers Ten Days

Only those who have suffered through a clinical rotation with me on the infectious diseases service at Children's National Hospital will recognize the heading above. It is law #5 in Bud's Laws, a list of 10 aphorisms that I've been tweaking the last few decades. It refers to the fact that most antibiotic treatment durations we use are based on little to no evidence. I've maintained that if we were an animal species with 12 fingers we'd be treating everything for 12 days instead of 10.

Enter a new study, the SCOUT-CAP trial. (I won't even mention the origin of such an acronym, it's too long and too forced into forming the acronym itself. Other acronyms in the study are RADAR and DOOR; very cute.) This was a randomized double-blind placebo-controlled trial of 5 versus 10 days of oral antibiotic therapy for outpatient community acquired pneumonia taking place in 8 US cities. It included 380 children 6-71 months of age diagnosed with CAP and initially prescribed one of 3 commonly used regimens (amoxicillin, amoxicillin/clavulanate, or cefdinir) to treat CAP. Children were continued on their original therapy, then randomized to continue that treatment or switch to placebo on days 6-10. (Note that over 90% of the children received amoxicillin originally.) Fewer than 10% of children overall had an inadequate clinical response regardless of treatment assignment, probably indicative of the fact that most children had viral infections and never needed an antibiotic in the first place. However, the 5-day course individuals had better scores for resolution of symptoms and antibiotic-associated side effects, as well as a lower incidence of antibiotic-resistance genes detected in throat swabs obtained in a subset of the participants.

You might have correctly concluded that if the main thing about the study that I'm complaining about is use of acronyms, the study itself is pretty good. It's very difficult to design a study of mild CAP that both applies to real-world practice and has enough safeguards to prevent bias from study design, and this study achieved those goals.

I'm not suggesting we all amputate 5 of our fingers, but please think about shortening courses of antibiotics for outpatient pneumonia in relatively healthy children.

[Note this section was updated January 26 to clarify that this was basically a study of 5 versus 10 days of amoxicillin therapy, too few children received amox/clav or cefdinir to comment.]

Tag: COVID-19 vaccine