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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!

I couldn't help thinking, as I channel-surfed through various college football, golf, and other sporting events on Saturday, that COVID-19 disease rates will see another significant spike in the coming weeks. I hope I'm wrong. Hand-wringing aside, I wanted to mention a couple issues that you might have missed this past week.

MISC-C Long-term Followup

I fall into the glass half full crowd when I read this report on 1 year follow-up data for 68 children in England. No deaths occurred and only 2 children required critical care readmission. Fourteen of 19 children with coronary aneurysms had resolution and all 39 with abnormal function but no aneurysms had returned to normal echocardiograms. Yes, I know it's just a few patients, but given how sick most of these kids are at the start I'm encouraged.

The Rule of 3's

This month could see data submitted to FDA requesting authorization for COVID-19 vaccines for children under 12 years of age. Because these trials are "immunobridging" studies, the key data in addition to safety are whether the immunologic responses are similar to those seen in adolescents and young adults who showed protection from infection in the larger efficacy trials.

Speaking of safety, you all have probably heard that FDA requested additional children ages 5 through 11 years to be enrolled in the mRNA trials. I was puzzled by this because the myopericarditis rates seen so far are pretty low, about 10 excess cases per million vaccine doses in a recent article. It would require an impossibly large number of children in a research trial to detect this, so I was even more surprised to hear FDA's Peter Marks state that the FDA was following the rule of 3's in trying to assess safety of these vaccines for serious adverse events. This rule is explained in an oldie but goodie review article in JAMA stating that, if no events occurred in n subjects we can be 95% confident that the highest chance of this event is 3/n. The number of subjects in these current trials are in the few thousands, so if the logic behind adding a few more is to satisfy cardiac inflammatory risk concerns the addition of a couple thousand more subjects probably won't answer the question. It may allow some reassurance that the rate isn't substantially higher than what is being seen in adolescents and young adults.