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I tried, but not hard enough, to ignore the drama in the House of Representatives this week. At least now we can step back for a bit before we find out what the House looks like when the dust clears. I hope we still have a somewhat functional legislative branch of government.

This past week characteristically is the least reliable in terms of public health epidemiology. This is because our winter holidays naturally result in some delayed data collection and reporting. Even with likely under-reporting, the covid map doesn't look too good. Rather than boring you with unreliable numbers today, instead I will focus on a question about last week's blog.

Flu vs. Covid

Last Monday Michael Schwartz asked 2 questions:

1. Why do we continue to pursue universal testing and recommend isolation for a minimum of 5 days for COVID , but do neither for influenza ?
2. Should we be trying for universal testing and longer isolation for influenza or should we be treating COVID as endemic and treat it like influenza , or some other answer ?

We still have many questions left unanswered, but it may be that covid could become more like influenza in terms of disease management. Influenza and SARS-CoV-2 are both RNA respiratory viruses, but they have significant differences. Still, the history of influenza pandemics might help inform the path forward with covid.

Not much is known about flu pandemics in the 19th century, mostly because the science and reporting wasn't well-developed at that time. Subsequently our flu pandemics all have been influenza A, because it is able to change and "jump" from one species to another. Influenza B does not have an animal reservoir outside humans, plus it is well adapted to us, so it basically behaves like a regular seasonal flu virus rather than causing pandemics which require a large non-immune population. (Note there is an influenza C virus group, but relatively little is known about its epidemiology. Mostly it just doesn't cause problems, which is why most people have never heard of influenza C.)

Everyone knows something about the 1918 flu pandemic, caused by an A H1N1 subtype that jumped from animals to humans. About 40 million deaths occurred worldwide. The next flu pandemic was in 1957 with an H2N2 subtype that had some leftover elements of H1N1 combined with a bird strain of flu. It was a bad time, estimated several million deaths, but not on the order of 1918. With the start of the H2N2 pandemic, circulation of H1N1 flu went away for awhile and just H2N2 persisted as the main seasonal influenza A strain circulating.

Then we experienced an H3N2 pandemic in 1968, but it shared some elements of the 1957 H2N2 strain so not as severe. I have no memory of a pandemic in 1968 even though I was a teenager and thus partially sentient. (Certainly other historical events that year occupied my attention.) H3N2 persisted as seasonal flu, but in the late 1970s H1N1 reappeared as another seasonal A strain. This setting remained until 2009 when we had our most recent flu pandemic of H1N1, a pretty complex reassortment from human, pig, and avian strains. It was actually somewhat similar to the 1918 strain that persisted for a while, so the elderly didn't have as much problem with the 2009 pandemic as might have been expected. Also, folks like me who received the 1976 "swine flu" vaccine (I do remember all that kerfuffle at the time) also had some leftover immunity active against the 2009 H1N1 strain.

All of us should be getting annual flu vaccines, mostly to guard against the common minor changes in circulating flu strains (antigenic drift) as well as to control the relatively uncommon major changes (antigenic shift). SARS-CoV-2 also has minor and major changes ongoing, but the biggest difference is that so far they both occur much more frequently than for influenza. Ergo our moving target or "whack-a-mole" strategies with vaccines and monoclonal antibody treatments the past couple years.

Here are some other comparisons, assuming normal hosts:

InfluenzaSARS-CoV-2
Incubation period2-3 days~3 days1
Reproduction number1.3-1.7 (seasonal)?2
Asymptomatic rate5-30%>40%3
Duration of contagion1 day before -
5-7 days post symptom onset
2 days before -
> 5 days post symptom onset4
All SARS-CoV-2 estimates are highly variable.

1Varies with viral variant, prior SARS-CoV-2 immune status, age

2Widely variable based on multiple factors

3Varies with age and prior SARS-CoV-2 immunity, still not well established

4Varies with multiple factors including disease severity

Lots of footnotes and disclaimers, but perhaps you'll agree there are similarities between flu and covid. If SARS-CoV-2 does progress to behave more like a seasonal respiratory virus, we will be managing it more like we do flu: annual vaccination with composition determined by the most recent variants and (I hope) avoiding school and work attendance when ill, plus lessening of the mandatory testing and quarantine guides still in effect. Of course, if we do veer off to another major variant change that demonstrates increased severity, we are back where we started (except with a now pandemic-exhausted public). Time will tell, but I'm hoping we soon will revert to Michael's second option of settling into an endemic response mode.

More on Invasive Group A Streptococcal Infections (iGAS)

A couple of reports in the online journal Eurosurveillance offer a bit more information. British authorities describe the pattern of iGAS in children over the past few years, clearly showing an increase in absolute numbers. No specific emm types (the gene coding for specific M proteins that could confer enhanced virulence) were identified. The investigators document some association with respiratory viruses such as human metapneumovirus and RSV, but it isn't clear that this is significant since it is the season for both streptococcal infections and many respiratory viruses. In the Netherlands, investigators describe iGAS cases in children, particularly streptococcal toxic shock syndrome and necrotizing fasciitis. The latter showed an association with varicella infection, a known risk factor. Again, no specific emm type jumped out. In retrospect, it seems odd to me that the British study didn't even mention varicella co-infection.

Neither of these studies involved a control group looking at viral co-infections, so it's still hard to know what's behind these trends. The one potentially modifiable factor for prevention is varicella immunization.

1968

If there was a time period that forever changed the type of person I am, it was probably this year. I find it mildly amusing that I have no memory of the flu pandemic, clearly I was distracted by the Tet offensive, the tragic assassinations, the Democratic convention, Smith and Carlos at the olympics, and even the pictures of Earth from Apollo 8. My fascination with infectious diseases was yet to come.

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!

2

Of course covid hasn't gone away, we are entering a period of increased activity in the US now. (Note that reported new cases showed a slight decline, but hospitalizations are up; this likely reflects poor reporting of new infections.) If no new significantly different variants emerge, I don't think we'll see anything like last winter's covid surge. Individuals can now report home test results anonymously; if used extensively it would provide better understanding of disease activity.

Unfortunately immunocompromised and other high-risk individuals will need to weather this covid winter without much help from monoclonal antibody treatment and prevention strategies. Bebtelovimab is now unavailable for treatment due to poor neutralizing activity against current variants. Tixagevimab/cilgavimab (Evusheld) still is available for preventive management in very high-risk people due to lack of any other effective pharmacologic preventive measures, but Evusheld also is likely to be ineffective for the current variants.

Increasingly now our attention should also focus on what I call collateral damage, mainly through 2 mechanisms. First, the pandemic disrupted other respiratory virus transmission during its peak, meaning a lot of young children haven't seen our common respiratory viruses in their lifetimes. Also, a number of factors combined to lower general immunization rates across the globe. So, we have a large collection of non-immune people, including young children, at risk not only for covid but also for both common and previously rare (in high resource countries) infectious diseases.

The Mother of All Flu Seasons?

Well, no, but it's been tough and may last a bit longer. I haven't seen a flu map this bad in a long time (late October 2009, our pandemic year, is in the neighborhood; you can scroll back to see it at the same weblink).

Note that this map represents "influenza-like illness" activity, so likely includes some RSV and other respiratory infections as well.

Most of the influenza cases currently are H3N2 which is well-matched by this year's vaccine. It's still wise to provide flu vaccine to unimmunized children even if they have already had a documented influenza infection because both the 2009 pandemic strain of H1N1 as well as influenza B strains also are circulating and likely will increase later in the season. Olsetamivir is helpful for treatment of high-risk children with flu.

Be on the Lookout for Previously Rare Vaccine-Preventable Diseases

Measles probably represents our biggest risks for outbreaks and deaths worldwide, because of high transmission rate and severity of disease. It won't take much to see outbreaks in the US. Also, did you know England has already seen a diphtheria outbreak this year? The US is at risk as well. Pertussis is always around and could be more severe in the coming months; also watch out for more cases of otitis media (if poor pneumococcal vaccine rates), tetanus, and, as we've already seen, polio.

You Can Limit Collateral Damage

Pandemics and other times of upheaval have always affected immunization rates. However, I am struck by the degree of anti-vaccination campaigns and general misinformation we've seen in what should be an era of enlightenment and celebration of vaccine successes in the US. Frontline healthcare providers are an important countermeasure against this collateral damage. Don't miss an opportunity to reinforce this with your patients and families.