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The title above is one of several great turns of phrase in the book I just finished reading, Edith Wharton's Age of Innocence. It refers to an episode where the protagonist was at a loss for words during a poignant encounter and presumably only later thought of something better to have said. I've been there.

Next Round for Covid Vaccine

The FDA's Vaccine and Related Biological Products Advisory Committee finally had their meeting last week; it had been postponed to give a little more time to see which way the new SARS-CoV-2 variants were headed. I was able to listen in on most of the meeting and have reviewed all the documents. The vote was unanimous to choose a monovalent JN.1-based vaccine for the next iteration, no surprise and in agreement with the recent WHO decision I discussed recently. (For those interested, there is quite a bit of international collaboration on these types of decisions. See the ICMRA posting about covid vaccines.) Still, there were some interesting updates on covid in general. I'll try to distill this down into the main takeaways.

The Latest on Epidemiology (from Thornburg FDA presentation)

Current circulation of SARS-CoV-2 is relatively low. Although our reporting is not as reliable these days, looking just at percentage of positive covid tests in orange you can see we are in a lull now, though perhaps with a hint of an uptick. This is pretty similar to last summer when we saw a bit of a surge in summer into fall and winter. SARS-CoV-2 still has not come around to a winter seasonality seen with other coronaviruses of with influenza, making predictions for surges and vaccine composition very tough.

JN.1 lineages replaced XBB.1.5 lineages during winter 2023-2024. I like the depiction below because it's looking at normalized numbers of positive tests rather than a percentage of positive tests due to different variants. This gives a better appreciation of numbers of cases and shows that we are still talking about relatively low numbers compared to 2022.

Here's a closeup of the most recent part of the above slide showing that KP.2-like, KP.3, and other JN.1 derivatives are starting to take over, though still all at very low numbers.

The recent subvariants have very few differences from other JN.1-derived strains and antigenically are very similar. This has important meaning for vaccine choice - should it be the original JN.1 variant or one of these newer KP.2 or KP.3 type subvariants, currently at extremely low numbers? Look at the last 2 rows in the table below, showing that these newer subvariants have very few mutation differences from the earlier JN.1-like variants.

In a totally new and as yet unpublished CDC analysis, severity of JN.1 infections does not appear to be worse than earlier lineages. The trend was towards milder illness, though not statistically significantly different. Note these numbers are just for adults.

Vaccine Effectiveness in Children (from Link-Gelles FDA presentation)

This it tough to estimate because children generally have milder disease, plus so few children are vaccinated. Adult data is pretty favorable for VE; SGT failure is a faster method of testing and correlates will with JN.1 lineage strains. 2023-2024 VE drops a little with these strains compared to effectiveness against XBB lineage strains.

On the pediatric side, it's important to remember that the vast majority of US children have been infected with SARS-CoV-2 at some time in their lives - this has been apparent since late 2022.

So, it's important to determine any VE now in light of prior infection and vaccination. We can't rely on older estimates. Here's the best and latest estimates for VE in children who received vaccine in the past year. Confidence intervals are relatively wide, reflecting the small numbers able to be studied, but do show benefit in prevention of ED or urgent care use. VE wanes with time after vaccination as it does with all age groups, but there is clear benefit for covid vaccination of children.

David Wentworth, representing WHO, delivered a wonderful explanation of the complexities in choosing among current subvariants for vaccine inclusion. He had this great quote: "... antigenic evolution just speeds up waning immunity." The variant evolution we're seeing now is parallel, i.e. lots of different subvariants evolving on their own, in parallel, rather than one subvariant evolving into another, and then into another, etc. Parallel evolution is what XBB lineages did previously, and we're seeing it now in the JN.1 groups. The slide below demonstrates this process with a timeline on the X axis.

The dilemma in choosing composition of the next vaccine is that no one knows which way the very new subvariants will evolve in terms of antigenic similarity to earlier JN.1 strains. Currently, KP.2, KP.3, and JN.1.23 are within what is thought to be close proximity to JN.1 in terms of antigenic similarity and therefore a vaccine based on any of those likely will have cross-reactivity with one another, enough to provide protection. However, as illustrated by the arrows, it just isn't known how the offspring of the newer subvariants will evolve - will it be farther away from JN.1 and each other, or will it remain relatively stable?

No one can predict what next fall's or winter's subvariants will look like. Once they appear, new lab testing would need to be done, ideally using human serum containing antibody to the newer strains, which Wentworth stated would take about a month to produce. So, it's not something that can be turned around quickly.

Also, it bears mentioning that virtually all of the immunity studies involve neutralizing antibody. Antibody does correlate well with VE, but T-cell immunity also is important. We don't see as much data about this arm of the immune system because the studies are more difficult.

All 3 US vaccine manufacturers, Moderna, Pfizer, and Novavax, presented their new data at the meeting. They are developing and testing new vaccines "at risk," meaning the companies are making vaccines without funding currently, risking their own research and development dollars, hoping whatever they are working on will be recommended for the next covid vaccine rounds and allow them to recoup their investment. Moderna and Pfizer have both developed JN.1- and KP.2-based mRNA vaccines. Novavax, the adjuvanted protein-based vaccine, only developed a JN.1-based vaccine. The protein vaccine takes much longer to construct than do mRNA vaccines, about 6 months to get good data in all. So, if a KP.2 or other vaccine were recommended, Novavax would need to start over and wouldn't be ready until about December.

I don't usually like to use pharma slides to illustrate points, but this one from Pfizer isn't biased in favor of their product and I think nicely shows the current situation, including how closely related the newer subvariants are to JN.1.

In the discussion after the vote to have a monovalent JN.1-based vaccine, which could mean one based on KP.2, the majority of the group felt that using the JN.1 variant rather than KP.2 or another subvariant was the best route, both to allow Novavax to be ready this fall but also not to take a chance that fall and winter predominant subvariants might be more antigenically removed from KP.2 antigenically. All in all I felt this was the right choice, though I probably wouldn't have let Novavax's problems affect the decision; very few US residents have received Novavax in the past, though it is nice to have an alternative to mRNA vaccines available.

On June 7 the FDA formally recommended sticking with the JN.1 strain for this next vaccine round. Next step with be the CDC's Advisory Council on Immunization Practices meeting the end of this month, where the official seal of approval will be issued. I'm sure Moderna, Pfizer, and Novavax already are ramping up production.

NASEM Long Covid Report Available

Long covid remains a quagmire, lots of different symptoms, many of which are vague, and still no definite light shed on diagnosis and treatment of what is likely a heterogenous group of conditions requiring different approaches. The National Academies of Science, Engineering, and Medicine published their full report, available free online. I haven't gotten through all of it, it's pretty long, but it is of interest to those practitioners who see these patients. Most of the evidence is from adults, but it appears that pediatric patients tend to have a better prognosis, especially if improvements are occurring in the first year after onset. Note that a positive covid test is not required for diagnosis testing may not have been done at the time of the triggering infection and antigen or PCR tests will have reverted to negative by the time a long covid diagnosis is considered.

Doxycycline for Post-Exposure Prophylaxis of STIs

The official guidelines appeared this past week, although the gist of the recommendations had been floated previously. Particularly high risk groups are gay, bisexual, and other men who have sex with men and transgender women. The summary is very helpful for practitioners who may want to print out and post Box 1 and Box 2 in their workspaces. Note that the recommendations apply just to those high risk groups.

Summer Bugs!

Bugs in the sense of both insects and microbes. We now have more details about a new rickettsial agent, termed species C6269, that caused a Rocky Mountain Spotted Fever-like illness in 2 individuals in northern California last summer. Both had severe disease, were hospitalized and treated with doxycycline, and survived. As always, keep RMSF and other tick-borne diseases in mind during our warm months.

Speaking of bugs, our dog came down with a skin abscess, expertly debrided by her veterinarian. She is now enjoying chewable amoxicillin/clavulanate but is less thrilled with her "cone of shame." The vet had another bug concern, however. She didn't want the dog to spend much time outside - apparently it is also maggot season, and they love open dog wounds. The vet doesn't know I'm an ID doctor, and I was trying to come up with some clever comment on maggots but failed at that moment - belated eloquence of the inarticulate!

Courtesy of Wikipedia. Hope you aren't eating as you read this.

I've been a Super Bowl addict I think from Super Bowl I, persisting in spite of the fact that the NFL has done very little to limit head trauma and chronic traumatic encephalopathy. I'm usually tied to the Super Bowl screen almost continuously because I like to pay particular attention to the national anthem (more on that later) and to all the commercials. For Super Bowl LVIII I'll unfortunately need to grimace and grit my teeth when the Kansas City fans do their insensitive tomahawk chopping and war hooping.

As I rush to finish my long list of chores for today I somehow need to cull through this week's list of 16 blog topic ideas to post something with low soporific properties. Here goes.

I'm Beginning to Really Worry About Measles

It's difficult to find a central, accurate source of data, but it seems to me that an unprecedented level of sites around the world are experiencing high numbers of measles cases. Coupled with robust international travel, declining vaccine rates, and very high contagion, the US population could have a major resurgence.

An editorial in the BMJ last week (unfortunately freely available only to those with a subscription) re-sounded the alarm. The impetus was a new outbreak in the West Midlands, but really the problem has been sweeping Europe for at least a year. They quote other sources citing over 42,000 cases in European Union countries from January to November 2023, with 5 fatalities. Ireland, which had only a few measles cases in 2022 and 2023, reported the death of a middle-aged man who had visited Birmingham; no further details such as underlying risk factors are available presently. Our northern neighbors in Montreal report a measles case in an unimmunized child, likely acquired on a trip to Africa. The child's age isn't mentioned but he was apparently school-aged since a school is one of multiple sites where health authorities are trying to track down contacts.

I came across an updated measles website from the Infectious Diseases Society of America that I think is pretty helpful, including several links to other sites. Look at the Facts link for a good discussion of common measles misconceptions. And, please, please, please make sure all your eligible pediatric patients are immunized.

Speaking of Vaccine-Preventable Diseases

Diphtheria has killed 130 Somali children in the last 3 months, according to a news report. Antitoxin availability in the country is very limited. Diphtheria continues to pop up in resource-poor countries with ever-present risk of imported and then locally-acquired cases appearing in the US.

"Silent" ARF

A new study carried out in Sudan informed me about the existence of "silent" acute rheumatic fever. The investigators performed handheld echocardiography testing on 400 febrile children 3-18 years of age who did not have a definite etiology for their fever. Of 281 children who had no clinical features of ARF, 44 had evidence of rheumatic heart disease on echocardiogram. This is an interesting diagnostic intervention that could prove practical for use in high risk ARF countries, but costs and training could be significant barriers.

Thankfully we don't have much of a rheumatic fever problem in the US, likely because most endemic US group A streptococcal strains are unlikely to trigger ARF. However, imported strains certainly pose a risk, and evaluation of any suspected ARF case should take into account travel history/country of origin.

More on Treatment of Hearing Loss in Congenital CMV Infection

Last week I mentioned a small phase 2 study of late, short course treatment for children with hearing loss likely due to congenital CMV infection; it didn't work. Now this week we have a report of a small phase 3 study in the Netherlands. It was an unusual circumstance where a randomized trial was converted to a non-randomized trial because the original trial floundered due to lack of enrollment; most parents wanted their children to receive treatment. In the new study, children with hearing loss but otherwise clinically silent congenital CMV infection received either 6 weeks of oral valganciclovir (n=25) or no treatment (n=15). They were followed until 18-22 months of age, and the treatment group had less hearing deterioration than did the control group. Not the cleanest study but a better design overall than was the US study, and it did find evidence of benefit. This also points out the great difficulty in conducting these trials; even though congenital CMV infection is very common and virtually all US infants are screened for hearing loss, it's very difficult to enroll and follow-up these children in randomized double-blind placebo-controlled trials. We still don't have a definitive answer on treatment benefits for isolated hearing loss in congenital CMV, but I hope the investigators don't give up trying.

Alaskapox

No, I didn't make up that word, it's a real orthopoxvirus that can rarely infect humans mostly in, you guessed it, Alaska. Only 7 human cases are known to exist, but the most recent one, in an immunocompromised man, was fatal. The report also is striking for how long it took to diagnose him. The virus mainly infects small mammals (voles, shrews) with no known human-to-human transmission so far. However, there is no reason it wouldn't be spread from another human, just like other viruses (smallpox, cowpox, Mpox) in the same family.

Photo from https://health.alaska.gov/dph/Epi/id/SiteAssets/Pages/Alaskapox/Alaskapox-FAQ.pdf.

New Syphilis Testing Guidance

CDC released new recommendations for laboratory testing for syphilis, good timing given our terrible syphilis epidemic in the US. It is highly technical, so mostly of interest to laboratorians and syphilis geeks like me. Some of the illustrations and graphs are useful for everyone. Here is a nice quick view of lab test results in various syphilis stages:

And an explanation of the prozone effect, very important and something that I've found not all hospital clinical lab personnel understand. It appears mostly with RPR testing, where very high antibody levels cause a false negative result unless the assay is run at higher dilutions.

WRIS

Not a whole lot new with the Winter Respiratory Infection Season.

Investigators in France reported that rhinovirus infection in infants was a major contributor to bronchiolitis hospitalizations pre- and during the pandemic. Here's an example of ventilator use for RSV and rhinovirus during 2019 - 2020.

From a practical standpoint we have a tough time sorting this out with commercially-available testing. PCR testing for rhinovirus uses primers that include most enteroviruses, so you will always see these results combined as rhinovirus/enterovirus with no way to separate out which is which. The problem is compounded because most enteroviruses normally persist in the body and in nasal secretions weeks to months after the clinical illness resolves. So, a positive rhino/enterovirus test might reflect an infection that a) occurred months previously, and b) could have been asymptomatic (90+% of enteroviral infections are asymptomatic). Often we can guess rhinoviruses are active if we see a mid-winter bump in rhino/entero positivity, since the usual enterovirus epidemic peak is late summer/early fall.

Of note, the French investigators did not provide details of the PCR assay used in their study, so we are left trusting the journal editors that it did reliably distinguish rhinoviruses from enteroviruses.

RSV is pretty clearly on the way out, though still causing a lot of illness nationwide. The decline is present in all 7 monitoring sites.

Influenza also is declining, with a couple caveats.

First, we are starting to see a higher percentage of influenza B isolates now. This typically happens near the end of flu season, but it could also produce a secondary bump in infections. Second, local and regional flu levels are quite variable - what's true for Maryland is completely different in New Mexico. Also, I've never been a fan of presenting city-level (NYC, DC) data in the same context as state data - a classic apples and oranges comparison.

Covid wastewater data continue to be encouraging.

We also have a few new updates on the covid scene. The UK released their spring vaccine recommendations which are to offer vaccine (usually mRNA XBB.1.5 vaccine unless not suitable for an individual) to adults 75 years of age and older, residents in adult care homes for older people, and anyone 6 months of age or older fulfilling their definition of immunosuppression.

I was pleased to see an update on trying to get a handle on Postacute Sequelae of SARS-CoV-2 in Children (PASC), though as I read through it I still felt it was a difficult jumble of clinical syndromes that make it hard to develop practical management advice anytime soon. Here's an overview of their conceptual model:

I applaud the investigators for continuing to slog through this and I do expect to see concrete advice sometime in the future, not only for PASC but perhaps for all those other post-infections syndromes currently lumped into the myalgic encephalomyelitis/chronic fatigue syndrome wastebasket.

Birdhouse Update

I'm sure everyone has been waiting to hear the latest update in my birdhouse squirrel-proofing adventures. I'm happy to say the birds are back, but so far no squirrels are stealing the birdseed! I did notice one dastardly Scurius representative sitting on the large branch from which the birdhouse was suspended, but it never made an attempt to jump. We'll see how long this holds up.

White-breasted nuthatch enjoying the sun and safflower seeds, unmolested by squirrels.

Super Bowl VIII

Yes, I'm aware it's now LVIII, but much of my Super Bowl roots go back to the one 50 years ago where I happened to be employed selling beer in the stands. I didn't make much money; I was assigned to the Vikings side of the stadium, and they got blown out by the Dolphins and quit buying. I also didn't see much of the game itself due to walking up and down the stands, yelling "cold beer" and looking for raised hands.

I was required to show up several hours before kickoff time, and the stadium was virtually empty. One person on the field that morning happened to be one of my personal heroes, the country singer Charley Pride. (As an ironic note to me, he died of covid complications at age 86, in the first year of the pandemic and before vaccine availability.)

Pride was really the only Black person to have broken through as a country music star at the time, and he was practicing singing the national anthem which he would do at the start of the game. When he finished practicing I walked down to the field level and he was kind enough to chat with me a few minutes. He autographed my flimsy paper vender tag, now lost somewhere during my many moves.

As you can tell, I haven't lost that 50-year-old wonderful memory. Kiss an angel good mornin' if you have a chance. 😉

4

I'm only mildly ashamed to admit that when I saw a recent publication of a randomized controlled trial of symbiotic therapy for post-acute COVID-19 syndrome (PACS), I had no idea what the term meant. Now I know more, and the study brings up some intriguing thoughts but no direct answers.

First, let's talk about a couple other issues.

Winter Respiratory Illness Season

I'm inventing a new acronym, WRIS, just because I can. CDC went so far as to issue a Health Alert Network posting reminding all of us about the low vaccination rates for covid, influenza, and RSV as well as the availability of treatments for the first 2 infections. So far, flu vaccine coverage in the pediatric age range (6 months to 17 years) is about 36%, pretty poor. The post has a lot of good information throughout, but if you're pressed for time please at least take a look at Table 2 with its links for suggestions for discussions with the unimmunized.

Looking at CDC's weekly viral report page, respiratory illnesses continue to increase. Nationally, emergency department visits for WRIS continue to rise, driven largely by influenza. RSV may be past its peak.

RSV hospitalizations might be coming down, though the data are preliminary:

Influenza-like illness remains high in many states in the South:

Lastly, covid is till out there with high levels in wastewater suggesting we'll see a bigger bump in illness soon.

Although I've presented the national picture, be aware that many of these sites have the ability to display findings by state and other jurisdictions, so you can see what's going on in your area.

Is Pediatric Omicron Infection More Contagious Than We Thought?

That's certainly the implication of a recent study looking at duration of viral shedding in infected children over a 90-day period in early 2022. It's important to note that the study looked only at duration of positivity of PCR at high levels thought to link to infectivity, and also at rapid antigen test (RAT) positivity over time. So, it wasn't a direct measure of whether these children actually transmitted infection at home or in school. With this caveat in mind, they found that 25% of children still had presumed infectious viral loads by day 7 of illness, a bit longer than guidelines recommend for isolation. RAT positivity was a mixed bag as usual (the watermark in the graph just denotes "accepted manuscript" as this paper was published for early online access).

This article shouldn't change practice per se. Looking back at publications of covid spread from children, the results are highly variable with some studies suggesting children have little role in spread. With this much variation in study results, likely the issue is multifactorial, making it difficult to come to any broad generalizations that apply across ages, settings, and time.

Meningococcal B Vaccine and Shared Clinical Decision Making

A few weeks ago I mentioned that healthcare providers don't have enough information at their fingertips to allow parents and patients to truly participate in decisions about vaccination. A new publication about meningococcal serogroup B disease rates helps inform the discussion for meningococcal B vaccine. As you may recall, the ACIP and AAP recently updated meningococcal B vaccination information with the approval of a new pentavalent vaccine. Meningococcal B disease in the US is relatively rare, making risks pretty low overall regardless of vaccination status.

The authors looked at rates of meningococcal disease in persons 18-24 years of age in the years 2014-2017, so not altered by any pandemic considerations. They found 229 confirmed or probable meningococcal disease reports, for an overall rate of 0.18 per 100,000 person years. 120 of the 226 cases for which they had college status were undergraduates, the group at highest risk of meningococcal B infection in the US and the main target for any vaccine intervention. Of those 120 students, 89 had infection with serogroup B.

Students attending 2-year colleges did not have an increased risk of infection compared to non-college students. Only 4-year college attendees had increased risk, and the risk was higher among first-year students and among "Greek life" participants, probably because those groups have a bit more crowding and sharing of beverages, etc.

The authors had some excellent advice in their discussion:

"These findings might be useful for patients, parents, and clinicians when discussing whether to vaccinate adolescents against serogroup B before they go to college. Adolescents planning to live on campus at a 4-year college, particularly ones planning to engage in Greek life or attend schools known for their social life, may benefit more from vaccination. Immunity from MenB vaccines is known to wane quickly, but concentration of risk among first year college students means there is an opportunity to prevent relatively more disease by vaccinating students shortly before they go to college so that the timing of maximum protection overlaps with the highest period of risk."

"Requiring or recommending vaccination against serogroup B disease might not be a tenable policy decision for all colleges, but our findings suggest that 4-year colleges with large numbers of students participating in Greek life or with a high party school ranking might be most likely to benefit from such policies, as these schools were significantly more likely to experience serogroup B cases or outbreaks."

Did you catch that party school mention? Another aid for parents referenced in the study was a ranking of party schools. Those with high rankings presumably represent higher risk for meningococcal B disease. No surprise to me, my undergraduate school didn't make the list.

What I really wanted to know was the Number Needed to Vaccinate (NNV), i.e. how many students would need to be vaccinated to prevent 1 additional case of meningococcal B disease. I knew it would be high because this is such a rare event. It took a little work because I needed a denominator - I knew the number of cases, but I didn't know how many were in the risk group. I had to go to a supplementary table in the article, then look at web links to try to choose a reasonable denominator. I settled on the number of full-time students in undergraduate schools in 2017; it included both 2-year and 4-year colleges. That number, from the National Center for Education Statistics, was 12,085,000. Let's assume the MenB vaccines are 100% effective (they are not, but all are pretty close and I got tired of calculations) and that none of those 89 students in the study were vaccinated (the authors couldn't determine precisely the vaccination rates in their study). NNV is the reciprocal of the absolute risk reduction, which is the rate of infection in the control group (89/12,085,000) minus the rate in the experimental (vaccine) group, which we are assuming to be zero. Crunching those numbers gives us an NNV of 135,786. That is to say, we would need to vaccinate that number of students entering full-time college with a meningococcal B vaccine to prevent 1 additional infection. That NNV number is astronomical and orders of magnitude above NNV for other recommended vaccines. If we were doing a cost-benefit analysis of meningococcal B vaccine, it wouldn't jive at all, but what isn't taken into account is the panic that develops when a case of meningococcal disease occurs on a college campus. Also, I made a lot of assumptions in coming to that number, so it's really just a very rough ballpark. Any decision would need to balance vaccine risks (virtually zero; anaphylaxis from vaccination found 33 cases in 25,173,965 vaccination events in one study, a similar ballpark to the rate of meningococcal B disease above.) This all goes to show that using absolute risk reduction can be more informative than looking at relative risks, which are ratios. For example, in the meningococcal B rates study, participation in Greek life carried a 9.8-fold increase in infection risk compared to other students - a high number that doesn't convey the extremely low infection rates. News stories invariably talk about relative risks rather than absolute risks - bigger numbers sell more papers/advertisements.

So, you can see why those quoted discussion points from the authors are so important. If a parent/potential college student asked me about meningococcal B vaccine, I'd start with saying meningococcal disease is very rare but also very dangerous, with a high fatality rate if one is infected. The risk of getting the infection is very low, about equal to risk of having a life-threatening allergic reaction to any vaccine, both being very rare. [The provider could insert in here if they've ever seen in case of anaphylaxis with a vaccine.] If the plan is to attend a 4-year college, live in a dormitory or fraternity/sorority, and have an active "party" life, the risks for infection are higher though still rare. Some people might value having some more piece of mind and choose to receive vaccination; others may not. Regardless, if at school one hears that you have been exposed to someone with meningococcal infection, you need to follow specific guidance from the local health department or student health team without delay - antibiotic and/or vaccination might be life-saving.

What I Learned About Synbiotics

I'm exhausted after too much number crunching, let's look at a new study that certainly is food (pun intended) for thought. A few definitions first:

Prebiotic - a nondigestible food ingredient that promotes the growth of beneficial microorganisms in the gut

Probiotic - live microorganisms ingested to improve the gut microbiome

Synbiotic - a combination of prebiotic and probiotic substances

The randomized, double-blind, placebo-controlled study looked at 463 adult patients in Hong Kong who were previously diagnosed with covid and fulfilled a standard definition of PACS. The experimental group received twice daily oral doses ("sachets") consisting of 3 probiotic bacteria and 3 prebiotic compounds; the control group received vitamin C with inert additives such that the packets of oral doses were identical in appearance, smell, and weight. The choice of synbiotic elements was based specifically on prior Hong Kong microbiome studies that suggested beneficial elements. The main outcome of interest was change in PACS symptoms at 6 months.

Although there was no difference in quality of life or physical activity between the 2 groups, the treatment did seem to have a beneficial effect on several symptoms and was correlated with favorable microbiome changes.

Maybe some progress, we'll need to see more studies on synbiotic therapy for long covid, hopefully expanded to many different populations. I think I'll go get some yogurt for lunch.

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!