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I've had a wonderful week, just returned from a west coast swing to visit a son and also do some hiking in Death Valley. In the meantime, the infectious disease world soldiers on.

Winter Virus Update

We continue to see good news from RESP-NET, though again with the concern particularly with covid that we don't have accurate case tracking, likely resulting in underreporting. XBB.1.5, as expected, appears to be sweeping westward across the country and is by far the dominant variant east of the Mississippi.

Covid Immunologic Insights

A couple of articles released recently bring up some interesting findings. First, researchers at WHO and multiple other academic institutions around the world performed a systematic review and meta-regression looking at protection from prior infection with or without vaccination against omicron infection. Not surprisingly, protection against infection itself waned very rapidly, but hybrid immunity (combination of prior infection plus vaccination) was relatively long-lasting for protection against severe disease and hospitalization: better than 90% at 12 months following last vaccination or infection. This is somewhat supportive of the proposal for annual covid vaccine boosters, although in practice it will be exceptionally impractical to determine individual prior infection status.

The other article was a detailed analysis of clonal T-cell responses to asymptomatic or mild covid infection, comparing adults and children. It is highly technical, mostly of interest to basic scientists, but I was intrigued by the finding that children did not develop effective adaptive immune responses compared to adults. This has important ramifications for future vaccine development.

More Measles Mess

We are already seeing measles outbreaks around the country, mostly isolated/contained, but given the pandemic-associated drop in childhood vaccination coverage we should prepare to see more. Now, researchers at U. Penn have reported relatively high rates of negative measles serologic testing in parturient patients at 2 Philadelphia hospitals. About 20% lacked protective antibodies to measles, an important finding not only for these patients but also for their newborns. For the babies, it's a bit of mixed news because maternal antibody will block response to measles vaccine in the first 6 months of life but also means that these infants could be unprotected very early in life. The main caveat for interpretation is that measles antibody is only a surrogate of protection from infection and thus we can't assume directly that the 20% rate corresponds to true lack of protection.

20 Mule Team Borax

I have vague memories of a television show, Death Valley Days, from my early childhood. Or, should I say what I do remember are the commercials for 20 Mule Team Borax, a laundry detergent still available today. Its main ingredient is sodium tetraborate, very toxic if taken internally or even used as a topical soak/bath. It's a sad state of affairs that I wasn't surprised that borax is yet another toxic compound advocated for use in the covid era, this time by anti-vaxxers as a bath component to reverse the effects of covid vaccination. Bad idea.

Of course, kicking up the trail dust in Death Valley, I couldn't help but think about health risks and not just from tumbling 5000 feet down the Dante's View trail. Death Valley is coccidioidomycosis territory, so if I develop a respiratory illness within the incubation period (1-3 weeks), I'll remind my physician to keep it in the differential diagnosis!

A few interesting items last week. I also enjoyed the CDC COCA call on Saturday - not much new stuff, but a nice summary of issues surrounding covid variants and immune escape among other topics. The recording should be posted soon. It was mostly geared towards adult care.

Tripledemic Receding

I made a great (for me) discovery of RESP-NET - I'm not sure if it is new or if I just wasn't aware of its existence, but it tracks the 3 viruses of interest all on one page. Here is the most recent view:

This is an interactive graph, note on the left side and at the top there are multiple views. The age group 5-17 years is selected here and you can see that downward trends are present for combined respiratory virus-associated hospitalizations as well as for influenza and RSV. Covid doesn't have a consistent downward trend but the recent data (which may be affected by reporting delays) also is heading down. Let's hope so.

Vaccine Coverage

CDC just started reporting covid vaccine rates for children under 5 years of age. It's not pretty and is similar for all ages.

Again, this is an interactive graph, so you can look at rates by sex and age.

A Brief Word on Variants

Here is the latest. Also, I may not have mentioned this before, but if you look at the top right the NOWCAST designation for the past 3 weeks indicates this is a forecast, not based on data collected those specific weeks. The variant data always have a lag time to allow time for sequencing to be performed. For example, the latest actual data we have on this graph is for the week ending December 31, 2022.

Are you starting to get too confused about variant nomenclature? I am. As a quick review, the original omicron variant that appeared in 2021 was BA.1. In January 2022 it was mostly replaced by BA.2. Subsequently we've seen new omicron lineage variants labelled BA.3, BA.4, BA.5, and XE.

The variants taking over in the US now are labelled XBB and BQ.1 and are descended from the BA.5 sublineage. (XBB is a recombinant of BA.2.10.1 and BA.2.75 sublineages, not to confuse you more.) XBB has a high level of immune escape (i.e. immunity from vaccines and prior infection is lessened and current monoclonal antibody therapies are less effective) and also probably enhanced binding to the ACE2 receptor on our cells.

On the other hand, it appears that BF.7 is circulating now in China - this is a sublineage of BA.5 that hasn't taken off in the rest of the world so far.

Wastewater

Wastewater is a very important source of data on what variants are active and when we might see covid surges. Unfortunately I don't think the CDC data presentations for wastewater are very helpful, and the data sources are scattered sporadically throughout the country. This is because reporting has been on a voluntary basis; if you live in a blue state area, you have a better chance of early alerts from wastewater testing. Several national agencies are working on a better network for wastewater testing, but the legal and ethical issues are significant. For example, one could also choose to test collection sites for drugs of abuse and then target police actions to a specific region - those working on a better process want to restrict wastewater testing to just public health uses that do not stigmatize or otherwise target communities for other reasons. I attended a nice summary of the situation provided by the National Academies of Sciences, Engineering, and Medicine (NASEM) which is studying the issue and has produced a preliminary report.

Is My Spice Rack Going to Kill Me?

No, but the closest I come to hoarding behavior is my spice armamentarium. I did a quick count and noted 105 unique spices in my kitchen cupboard, and that doesn't count the maybe 40 or so extra large bags plus maybe 6 different kinds of salt I have on hand.

Last week the lay press picked up on a study that first appeared last September. It looked at contamination rates for people making turkey patties and lettuce salad. The participants were told they were evaluating new recipes, but in fact the turkey meat was laced with a harmless bacteriophage that was then tracked to see where it ended up after the food preparation. It turned out the spice jars were a prime source of contamination. The study didn't seem to address the amount of contamination, but at least it should serve as a good reminder that hand and dish washing during food preparation should be thorough.

I don't plan to wash all of my spice jars, as you might imagine I'm a stickler for food hygiene when I'm cooking!

Fear the Snail

Well, not really. But a recent issue of the Journal of Infectious Diseases reported new trematodes found to be carried by snails in California and elsewhere. These agents have the potential to infect humans, with transmission most likely in a manner seen with angiostrongyliasis in Hawaii. Bottom line, don't eat raw snails on a dare (yes, some people have done this and become infected), and make sure your produce is washed well - you never know when a snail has slimed its way across that piece of lettuce.

Looking Forward to This Week

CDC will release new guidelines for covid testing that will likely de-emphasize routine screening of asymptomatic individuals. The draft is being reviewed now, so expect something fairly soon, perhaps this week.

Also, FDA/VRBPAC will meet on January 26 to start planning covid vaccine strategy going forward. As of today (January 22) the agenda still has not been posted but "the discussion will include consideration of the composition and schedule of the primary series and booster vaccinations" for covid vaccines. I plan to listen in though I don't expect any final decision to be made at this meeting.

First, some of you may notice I'm posting unusually late for my regular Sunday routine. I wish I could say it was because I was out all night partying New Year's Eve, but anyone who knows me would realize that's a total fabrication. The truth of the matter is that I've been locked out of my blog account all day and unable to reach anyone at GWU to help me, but now all of a sudden my access reappeared. So, I'm writing this at night in case the Gods of Blog decide to exile me again tomorrow.

We have definitely entered a new phase of the pandemic. I know this because the "A" section of the January 1, 2023 Washington Post (yes, I still get the home-delivered version of our local newspaper) had no original news articles about anything related to medical aspects of covid or the other respiratory viruses circulating. The only acknowledgement that this could still be newsworthy was an editorial bemoaning the situation in China.

Let's dive in.

Tripledemic Tracking

RSV

Continued good news from RSV-NET, further definite decrease in RSV activity nationally.

As you can see from the green line, things appear to be coming down to less drastic levels this year.

Influenza

FLUVIEW also has good news.

We have a very definite downward trend on the red line for this year, very encouraging.

COVID-19

The news is not as good with our old friend covid.

The weekly cases don't show a surge, but percent positivity continues to rise.

In the meantime, a new variant appears to be taking over, particularly in the northeast and mid-Atlantic US.

Those big blue pieces of pie represent XBB.1.5, a subvariant in the omicron BA.2 lineage. It has exploded in the last couple of weeks. It likely has similar immune evasion properties as other recent subvariants, but too early to determine if it has increased ability to cause more severe disease.

What does all of this mean for the future of the tripledemic? That again would require an accurate crystal ball, but hey it's a new year, so why not stick my neck out? With the consistent downward trends in RSV and influenza, I think the tripledemic is over. I do not expect a rebound for either flu or RSV this winter because it's already run through most of the susceptibles who now have considerable immunity. I can't say the same for covid, however, because changing variants are still able to infect those who have been recently infected or immunized. The good news is that pre-existing infection and/or vaccination with boosting likely protects somewhat against severe disease, at least for a number of months, but not so much against new infection. So, I think covid will continue to increase though I doubt at levels we saw last winter, unless a more formidable variant appears.

Long Covid News

We still know very little about long covid, but what is increasingly apparent is that we need to have adequate control groups of uninfected people and people infected with other viruses for comparison. A recent example is an article just accepted for publication in Clinical Infectious Diseases. Long covid is likely a mixture of symptoms resulting from direct organ damage from the virus, such as severe pneumonia or cardiac or renal disease, along with some more poorly understood entities such as "brain fog" and other "myalgic encephalitis" symptoms that are known to follow multiple different types of infections. I am hopeful that the many longitudinal studies that are ongoing will shed more light on this confusing grab-bag of illnesses.

Another Effective Oral Anti-Covid Drug?

I was encouraged by the NEJM article showing non-inferiority of VV116 to Paxlovid, with fewer side effects. Development of resistance to antiviral agents is an ongoing concern for any antiviral treatment, so having more options is always preferable. Let's hope more studies support its efficacy.

It Could Have Been Worse

I came across a somewhat uplifting presentation about Epidemics That Didn't Happen. Take a few minutes to look at it; public health principles, when followed, actually work!

If You'll Be Rounding the Corner With Me, How About Doing It With a Silly Walk?

Every year at this time I enjoy reading the Christmas issue of the BMJ which contains some real but tongue-in-cheek research studies. I was particularly drawn to the study alleging to show the health benefits of the "silly walk" shown in the Monty Python skit in 1970. Try it out - it will bring a smile to your face, and we could all use more of that in 2023.

I wish everyone a safe, healthy, and fun 2023!

Whether you celebrate Christmas, Hanukkah, Kwanzaa, or any number of winter solstice/festival of light ceremonies like Saturnalia, Dong Zhi, Sah-e Yalda, or Shalako (the list of holidays this time of year is quite long), or choose to celebrate nothing at all, I hope you will take advantage of a few days away from work to relax and reflect.

Tripledemic Tracking

Let's check the latest stats from CDC.

RSV

The hospitalization rate graph looks pretty similar to last week on RSV-NET, the final endpoint is for data ending December 17. As indicated in the inset, recent data likely suffer from reporting lag. Still, overall good news.

I'm hoping our community of RSV-susceptible individuals is very low now, such that we won't see a rebound later. Note that we usually have 2 strains of RSV circulating every year, RSV A and RSV B, so in theory it is possible to be infected twice in a season. In the past this has occurred only rarely.

Influenza

Influenza likewise continues to decline nationally as per FLUVIEW, though still at a high level.

The lay press has a lot of buzz about flu increasing because of holiday travel, but I'd remind folks that sometimes with early flu seasons in the past, we've actually seen a big decline in infections because kids are out of school. Again, still plenty of flu around, and with 3 strains circulating still important and not at all too late to get vaccinated.

COVID-19

The CDC's weekly data update is on holiday, but daily updates occurred last on December 23 and I could access a graph similar to last week that tracked through December 21.

Rates continue to increase in general. If you aren't already, indoor masking would be prudent now. I continue to be appalled by the low booster vaccination rates in people who have already received the primary covid vaccine series.

Invasive Group A Streptococcal (iGAS) Infection

I've been following this topic in my myriad of listservs since early reports appeared from the Netherlands last spring, but now the lay press has raised an alarm likely in response to CDC weighing in. The problem is still very uncommon and only sporadically cropping up, but it's worth reviewing what's going on.

CDC issued a Health Alert Advisory (HAN) on December 22 documenting increased reporting of iGAS cases this fall; these include entities such as scarlet fever, cellulitis and necrotizing fasciitis, mastoiditis and sinusitis, retropharyngeal abscess, pneumonia/empyema, and streptococcal toxic shock syndrome. What isn't clear is whether this is something unusual or just the expected number during streptococcal season in a year when we are back to mostly "full contact" among people in our communities. Certainly the large number of respiratory viral infections bear some blame; iGAS is well known to follow viral infections. A few clinical caveats for healthcare providers as well as parents:

A biphasic illness, meaning a respiratory infection/fever followed by a few days of relative well-being and then return of illness with high fever and other symptoms, is a classic red flag for bacterial superinfection following viral illness. That is a time to seek care and pay close attention to consideration of iGAS.

Streptococcal skin infections occur much less frequently since the advent of varicella vaccine. But, given the drop-off in regular childhood vaccines, we likely have a much larger group of children non-immune to varicella. Beware iGAS superimposed on varicella.

Group A streptococcal pneumonia and empyema can be severe. Back in my days as inpatient teaching attending I referred to this as Henson's disease (not to be confused with Hansen's disease, aka leprosy) because this is what killed puppeteer Jim Henson. (I note that his Wikipedia entry has a confusing entry about his final illness, including blaming Disney negotiations for his illness!)

Necrotizing fasciitis is especially dangerous. It is a deeper skin and soft tissue infection than is simple cellulitis and can progress very rapidly to cause extensive tissue destruction and death. One possible clinical clue for healthcare providers is that the degree of pain at the site seems out of proportion to the skin appearance. Quick intervention with both antibiotic therapy and surgical resection can be life-saving.

Speaking of antibiotics, pediatric healthcare providers are aware of the amoxicillin suspension shortage nationwide, ongoing for many months now. AAP has a nice list of alternatives.

Cherish Diversity

Too often recently, the cultural and other differences among us are used instead as excuses for persecution. Wouldn't it be nice if we could all just cherish our diversity and use it to build rather than tear down communities? Have a wonderful holiday of your choice!

It's that time of year for various types of potpourri, either simmering on the stove or in dried form. I also realized a need for my own infection potpourri, I have so many topics to catch up on. Here goes.

The "Tripledemic"

You wouldn't know it from the news, but there is reason to be optimistic now even with covid cases surging.

RSV

RSV isn't a reportable disease in the US, so accurate tracking is tough. However, CDC's RSV-NET utilizes active reporting from 58 counties in 12 states (CA, CO, CT, GA, MD, MN, NM, OR, and TN) to give a partial picture:

The above is just one screenshot of many in this interactive display, but note the green bar representing the 2022-2023 season. It confirms what pediatricians in our area have been seeing for the past few weeks - RSV is way down. This needs to be tempered with the fact that current hospitalization rates now are in the same ballpark as peaks in the 2 prepandemic years, so there's still a lot of disease activity.

Although there is no guarantee we won't see another peak later on this winter, I would doubt it. We have probably run through the bulk of susceptible young children, so the remainder will be children born in the next few months. If their mothers were infected in this round, these newborns (except for the extreme prematures) will have benefit of maternal antibody. Also remember that, if studies go well, RSV vaccination for pregnant women and a longer-acting monoclonal antibody preventive treatment may be authorized or approved in 2023. (You can see I'm carried away by optimism today!)

Influenza

Similarly, we might be seeing a break in flu nationally, though like RSV and all other respiratory viruses, the disease activity can vary widely in different parts of the country. FLUVIEW shows us the picture from a few different angles. First is influenza-like illness, which can include other respiratory viruses besides influenza because it has a clinical definition without requiring diagnostic proof of influenza infection:

Note there is a clear downward trend for the (red) 2022-23 season, but also compare with the (green) 2019-20 season with multiple spikes that likely reflected the beginning of covid. However, there is additional evidence to suggest flu is waning when looking at the hospitalization rates for confirmed influenza (also from FLUVIEW).

The slope of red line, which shows cumulative hospitalization rates, is decreasing. Keeping fingers crossed, but still plenty worthwhile to get a flu vaccine for those who have procrastinated. We still have a ways to go with flu this winter.

COVID-19

Poor reporting of at-home test results and general apathy about all things covid mean our data aren't as reliable, but we're certainly seeing a surge this winter which is entirely expected.

The telling parts of the graph above are not only the somewhat tiny blip in weekly cases but more significantly the sharp increase in percentage of positive tests that likely spells at least a modest covid winter.

I'm hoping this winter won't look anything like last winter, but as usual it will depend on the variants.

The omicron subvariants BQ.1, BQ.1.1, and XBB will guide the next few months. They have certain advantages in terms of immune escape and growth but so far do not seem to be causing more severe disease. Human behaviors such as vaccine hesitancy and not restricting activities when having respiratory symptoms also are significant determinants for what the winter holds.

New MIS-C Case Definition

Along the lines of more good news, MIS-C has become increasingly uncommon in the omicron era.

Even last winter, MIS-C was not as common as in previous waves, and this trend is continuing now. The exact reasons aren't clear, likely a combination of previous infection, vaccine immunity, and perhaps genetics of the variants themselves. CDC recently modified the case definition to make it more accurate and easier to report; this will take effect in 2023. Check out a CDC webinar for the graph above and more information about MIS-C.

A More Accurate View of the Global Burden of the Pandemic

So, some degree of good news for covid. However, the overall status still is depressing. WHO estimates the cumulative burden of the pandemic to be almost 15 million excess deaths. Although we've all become somewhat numbed by large numbers, take a moment to let that sink in.

On the good news side, the Commonwealth Fund has estimated tremendous benefits from the first 2 years of covid vaccination in the US:

Covid Vaccine Updates

Speaking of covid vaccines, a few new items appeared recently. CDC released 2 reports showing relatively good efficacy of the bivalent boosters in preventing serious disease in adults. The studies are still preliminary and have a lot of limitations including not being able to control for individual behaviors such as use of therapeutic options like Paxlovid. One study looked at hospitalization rates in those 65 years and older and the other reported emergency department, urgent care, and hospitalization rates in immunocompetent adults.

One study of the Pfizer vaccine documented the benefit of booster dosing in the 5 - 11 year-old age group. This was during the delta and omicron periods but before the bivalent booster appeared.

Now we just need to improve our dismal covid vaccination rates! The AAP provided a guide for busy practices trying to figure out which vials to use for which circumstances, and CDC provided a nice webinar (I learned several things) about discussing vaccine hesitancy. I urge all healthcare providers to look at it.

Happy Birthday Louis!

Whenever I spoke about ancient (i.e. older than 5 years) history of infectious diseases, trainees always assumed I was speaking from personal experience. Let me be clear: Louis Pasteur was not a contemporary of mine. A very happy 200th birthday to Louis on December 27. Several editorials in the December 17 Lancet marked this milestone. The proponent of the germ theory of disease and developer of the first rabies vaccine likely could still teach us a few things about handling today's pandemic.

Also, I can't leave the subject of birthdays without noting my wife's birthday this week. She is considerably younger than Louis. Happy Birthday to Pam!