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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.

I'm sorry to disappoint those of you expecting an omicron variant update this week. Although we've seen a lot of commentary in the lay press and some preliminary reports from around the world, in fact we still don't have anything substantive to answer our outstanding questions about transmissibility, disease severity, and immune evasion. Maybe next week.

Home for the Holidays with Flu?

At Children's National for the week ending November 28 we had a slight uptick in influenza cases, though not enough to declare our official start of flu season. CDC surveillance suggests the beginning of increases nationally. Conveniently the CDC published a detailed account of a what has been reported across the country: flu outbreaks on college campuses. The December 3 MMWR report was of an outbreak on the University of Michigan campus occurring in October and November. All the isolates were influenza A H3N2 and should be covered by this year's vaccine. However, H3N2 is a bit more troublesome than other strains in that it is more prone to drift as the season progresses. It is somewhat concerning that individuals with positive and negative tests for flu had similar vaccination rates, suggesting not great protection against mild infection, at least in this one relatively small outbreak. Watch out for spikes in flu following holidays as college students and other travelers add fuel to flu season.

COVID-19 Monoclonal Antibody Use in Young Children?

I was caught completely unaware when I learned on December 3 the FDA extended emergency use authorization down to the newborn period for the monoclonal antibody combination of bamlanivimab and etesevimab for children at high risk of developing COVID-19 complications. Previously this combination had EUA only for high risk individuals 12 years and above with weight at least 40 kg. This extension was based on some new data from an open-label (i.e. no control arm) trial looking at treatment effects on viral load as well as some pharmacokinetic data on weight-based dosing for younger age groups. The EUA covers both therapeutic and post-exposure indications. Note also that, for children above age 2 years of age, this is only for outpatient use.

I have one main concern about this EUA related to use in children in the first year of life. First, the notice lists age < 1 year as defining a high risk group, without need for any other risk factors. To my knowledge no study has found this age group to represent high risk for COVID-19 complications. Second, the youngest child in the trial was 10 months and weighed 8.6 kg; only 5 children in the trial were less than 2 years of age. We know that metabolism in newborns and young infants is very different from older children and, coupled with the fact that I can't find evidence that otherwise healthy young infants represent a high risk group, I'm reluctant to sign on to use in otherwise healthy children in the first year of life. Our team at Children's National is looking at the data and will come up with guidelines incorporating this new EUA.

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I know I'm in trouble when I first hear about an infectious disease problem through the lay press. In the case of this year's flu vaccine, it was NPR, about a week ago. It looks like it started turning up on some national news feeds a few days earlier, and the message was that estimates of vaccine efficacy from Australia (the southern hemisphere flu season is winding down) were around 10%.

As is my usual practice, I go to the source data, which in this instance wasn't easy since virtually none of the lay press announcements included a link to that source. I finally traced it back to an online publication from October 26, 2017, and I'm still wondering why it didn't make more a splash back then, rather than 6 weeks later.

Based on interim reports of flu activity in Australia through late September, investigators did determine vaccine efficacy to be 10% (95% confidence interval -16 to 31) for influenza A H3 strains for all age groups; A H3 are the most common strains circulating this season. They used a test-negative study design for flu-positive patients seeking medical attention in sentinel clinics, which is a standard approach for flu vaccine efficacy research. Overall vaccine efficacy against all subtypes of influenza A and B was a more respectable 33% (17 to 46). Efficacy against A H3 strains varied by age. Children under 15 years of age and adults 15-64 years experienced rates of about 15% efficacy, while adults 65 and older having essentially no efficacy for A H3 strains. These numbers, if true, are not unprecedented with A H3 strains and have resulted in heavier flu seasons in the past.

It's too early to tell whether these estimates will hold for Australia once all data are available, and of course it's still too early to make an estimate for the US. A season with lower vaccine efficacy can mean greater risk of serious outcomes in high-risk populations, and this risk will be even greater if news about the lower efficacy results in fewer people seeking immunization this year. For now, it's important to stress that everyone should be immunized for influenza.

You can keep track of influenza season at the CDC and the Maryland Department of Health websites.