COVID-19 vaccine booster – Page 5 – Pediatric Infection Connection

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!

Roller Coaster Week

Bud WiedermannFebruary 13, 2022Leave a comment

I guess we all should be accustomed to the ups and downs of the pandemic. We continue to see good news with waning of the omicron surge around the world, but parents of children under 5 had a bit of a jolt on Friday with the news that the Pfizer vaccine will not be discussed by the FDA next week as originally planned. We now await ongoing data from the trial which has begun a booster dosing phase. Regular readers of Pediatric Infection Connection will know that I oversee this trial at Children's National Hospital, but I have no knowledge of the data submitted by Pfizer to the FDA so can't provide any independent opinion.

Booster News?

Speaking of boosters, CDC released some important new information about boosters, some of which pertains to children. First, an early release in MMWR highlighted waning of effectiveness of 2- and 3-dose mRNA vaccines. This is sort of a glass half empty or full view, I was actually more encouraged by the continuing effectiveness, particularly for boosted individuals, against severe disease and hospitalization. Just looking specifically at the data from the omicron-dominant time period, vaccine efficacy (VE) in preventing emergency or urgent care visits was 87% 2 months following a third or booster dose though dropped to 66% beyond 5 months (note few data available for this latter estimate). VE in preventing hospitalization was 91% and 78% for those 2 intervals post third dose. This is by no means the final word, lots of limitations in this study and also it looked only at individuals 18 years of age and older and did include a significant number of people with immunocompromise and other risk factors for severe COVID-19 disease. No information about how these risk factors specifically affected VE.

Also, as promised the CDC issued an update to guidance for vaccination of those with moderate or severe immunocompromise to include a fourth dose in some circumstances. This update applies to people down to 12 years of age and provides a good road map for vaccination of those individuals.

Variant Viewing

I'd definitely be happier stargazing or watching butterflies and bees in season, but lately I've been keeping an eye on the BA.2 subvariant of omicron. It has started to appear in our CDC data (after clicking on this link, choose Variants and Genomic Surveillance, then Variant Proportions from the left-side menu). BA.2 now comprises 3.6% of isolates as of Feb 5 compared to 96.4% omicron BA.1) and similarly has increased slightly in the UK. As I indicated last week, it is more transmissible than the original omicron variant, but it isn't clear whether prior infection with omicron BA.1 confers some immunity against BA.2. That is probably the key factor in determining if we will see another surge due to BA.2.

I also note some encouraging news in the UK that the reproductive number is now estimated at 0.8 to 1.0, a milestone that signals flattening or decrease in the pandemic. Of course it could be just another ride on the roller coaster but I choose to take this as a further good sign.

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.]

Olio of Omicron 2

Bud WiedermannJanuary 2, 20222 Comments

The omicron stew is simmering with a variety of reports, none of which are particularly definitive.

Severity of illness - It's almost like you can decide what you want to believe and then find a study that supports your view. If you want to visit South Africa, you'd be pleased to find predictions that omicron causes relatively mild disease. Alternatively, looking at the UK gives you the opposite view. Which is correct? It is likely they both are, serving to point out that multiple variables impact how severity of disease is determined. Population age and risk factor distribution, season of the year, vaccination rates, prior natural infection experience (and with which variant), testing frequency, individual risk behavior .... I could go on and on. We need a little more time to see how things will fare in the US.
Vaccine efficacy - It is very clear that no current vaccines are particularly effective in preventing infection, but some are more likely to protect against severe illness and death. A recent letter in the New England Journal of Medicine is noteworthy. Investigators at Rockefeller University measured neutralizing antibody titers from 47 individuals previously vaccinated and/or infected and found significant immune escape in all. On a more positive note, they found that a third mRNA vaccine dose or infection followed by mRNA vaccination results in significantly better protection.
Testing - Well, the biggest problem here is test availability. You may have heard that FDA reported that antigen tests are less sensitive for detection of omicron compared to other variants. Note that this statement is based on testing inactivated specimens and, as the FDA cautions, does not replace clinical studies to document true sensitivity and specificity. Antigen tests are known to be less sensitive than PCR testing anyway, and this FDA report is likely true though not quantified. Bottom line, a negative rapid antigen test doesn't mean an individual is not infected. Still, some testing is better than none right now.
How long will the omicron surge last and when will it peak? Get out your crystal ball, or if you want to delve deeper look at the modeling report from the University of Texas COVID-19 consortium. I can't even begin to understand the mathematical formulas used, but it gives a number of outcomes depending on which set of initial assumptions one uses. Again, suffice to say we'll need to wait and see what really happens.
The new CDC quarantine and isolation media release and interim guidance for ending isolation - Talk about confusion, here we are! Note that this is a media release, not an actual formal guidance. I understand and agree with the need to balance safety with trying to keep necessary infrastructure (e.g. healthcare, transportation, schools) available by decreasing staff outages due to exposure or infection, but know that this is a calculated risk. More pertinent to healthcare providers and pediatric settings in particular, I am unable to find any significant data that inform duration of infectivity of children infected with omicron. The guidelines are for use for the general public and do not specifically address precautions to be taken for patients in clinics or inpatient settings. Only my personal opinion, but I would not relax any precautions for pediatric healthcare settings and still follow the prior recommendations for quarantine and isolation for children coming to a healthcare setting. Note that CDC does have new guidance on contact tracing in schools.
NPI - At least we still have nonpharmaceutical interventions that help, if we would only use them. If you can, use a NIOSH-approved N95 of KN95 mask.

Whirlwind Week

Bud WiedermannDecember 19, 2021Leave a comment

Somebody pushed the reset button this past week. Although we don't yet have the weekly variant reports from CDC (they are published on Tuesdays) it is very clear from just my small world at Children's National Hospital that omicron has hit with a vengeance. I was speaking in the hallway on Friday with my longtime friend and esteemed colleague Dr. Larry D'Angelo who likened what we are seeing to the early situation in South Africa where omicron increased exponentially even while delta was still very much present. An important caveat, however: it's risky to make too much out of day-to-day data, many factors affect case rates and sometimes we can be misled by "hot off the presses" numbers.

A Triple Whammy Ahead?

Most winters in pre-pandemic times I kept my fingers crossed that we would not have our RSV and influenza seasons occur concurrently; the few years we had a double whammy like that it really strained our resources. This winter could be worse. The good news is that although RSV is still around it seems to be on a downward trend. However, influenza A numbers have been increasing both at Children's National and nationally, suggesting we will hit full-blown flu season soon. The second and third components of the trifecta are delta and omicron. If we see all 3 of these viruses causing infections in large numbers at the same time it will be very tough. One silver lining of the omicron era is that it may stimulate more individuals to seek out primary series and booster vaccinations. Also, with school winter break and perhaps a bit more caution on the part of the public, we might have less viral circulation the next couple of weeks. We'll see.

For now clinicians should remember we have two effective influenza antiviral medications, oseltamivir (Tamiflu) and baloxivir marboxil (Xofluza), available. From a treatment perspective we don't have a lot of choices for outpatient therapy for pediatric SARS-CoV-2 infections, and the monoclonal antibody combination bamlanivimab and etesivimab just authorized for use down to newborn ages but isn't likely to be effective against omicron. (Note that currently Children's National is not using age under 1 year as an independent risk factor for use of this combination.) NIH has a nice web site to check the latest on effects of different therapeutics for SARS-CoV2 variants, much based on in vitro data rather than solid efficacy studies because it's just too soon in the omicron wave for reliable analysis.

Setback and Hope for Pediatric COVID-19 Management

On December 17 we all learned via a press release that the Pfizer vaccine trial failed to reach the pre-established noninferiority margin for children 2 - 4 years of age, although that goal was reached in the 6 - 23 month old age group. As you know I am an investigator in that trial, at the time of this writing still waiting to hear specific plans for modification of the trial presumably to administer third doses to those children.

Also on December 17, CDC released reports of 2 studies of the "Test to Stay" (TTS) strategy for managing school attendance with positive covid cases, one from Los Angeles County, CA, and the other from Lake County, IL. A lot of us have been waiting for high-quality published data on this approach. The basic approach to TTS is described on the CDC web site, suffice to say ready access to testing must be available as well as compliance with masking and other prevention methods. We of course do not have data available for TTS efficacy in the omicron era but at the moment this seems to be a reasonable approach.

Bottom line for all of this, we are entering another worrisome time for COVID-19, no reason to panic but be careful and stay abreast of new developments. Please encourage everyone to get their influenza and COVID-19 vaccinations, including boosters for the latter.

Tag: COVID-19 vaccine booster