paxlovid – Pediatric Infection Connection

Good Will

Bud WiedermannAugust 27, 2023August 27, 2023Leave a comment

This past week I attended an event that led me to reflect on "good will," not necessarily referring to the "peace on earth ...." quote or to the San Antonio chapter of Goodwill Industries where my mother volunteered countless hours in the last century, but a more basic understanding. Its origins may be in the New Testament or in Middle English, but regardless it is pertinent today. More on that later.

Maternal RSV Vaccine Approved by FDA

The approval finally came through, as it turned out on the last day of FDA's deadline to make a decision based on the fast tracking and other priorities assigned to it by the FDA. The FDA advisory committee did not meet again prior to this decision, they had already reviewed the data at a previous meeting in May, and FDA did not release any updated scientific documents. Perhaps lost in the fine print is the important change in the approval. The original trials looked at vaccine administration to pregnant people at 24-36 weeks gestation, but the FDA approval narrows this to 32-36 weeks. This significant change is because of concerns about the vaccine causing premature delivery; the numbers in the published trials were very low, not enough to establish a cause/effect relationship and only answerable but post-marketing surveillance when a much larger number of pregnant people receive the vaccine. However, more concern than usual was expressed because another pharmaceutical company (GSK; the approved vaccine is from Pfizer) stopped their clinical trials in pregnant people for the same reason. Delaying the vaccine administration to 32 weeks gestation is a safety move; even if the vaccine causes a higher but extremely low risk of precipitating premature birth, the clinical consequences at 32+ weeks is small; infants born at that gestational age generally do very well. The down side is that narrowing the window for vaccination creates more logistic difficulties in ensuring pregnant people have the opportunity to receive the vaccine.

Next up will be an important meeting of ACIP/CDC to put together all the recommendations, including how to manage use of maternal vaccine and the long-acting monoclonal antibody to RSV, nirsevimab. Their next scheduled meeting is September 12, but so far the only current agenda item relates to covid vaccines.

A Curmudgeonly Jab at the Lay Press

At my age, what else do I have to do besides complain? I was annoyed by 2 items percolating through the lay press this past week.

BA.2.86

This new but relatively rare covid sublineage is popping up in every news feed there is. I've mentioned it before. Although it is present in only very low numbers, the pattern of mutations it carries suggests that it will be very effective at evading immunity from prior infection or vaccines, perhaps including the new XBB-derived vaccine to be available soon. Biobot helps put this in perspective. First, wastewater covid levels seem to have plateaued in the US and are still well below what we say in winter 2023.

Second, this variant doesn't even appear in wastewater data, although note the graph only reflects sequencing through the week of August 7.

In addition to following wastewater data, the next likely useful piece of information should be some in vitro data on ability of serum from study volunteers who received the new covid vaccine to neutralize newer variants, including BA.2.86. Given how long the assays take, we should see some information in September. A silver lining for all the publicity is that it could speed up the peer-review process for publication so we won't need to rely on non-peer-reviewed data. Look for a research letter in the New England Journal of Medicine relatively soon (just my prediction).

You can see the current CDC risk assessment here.

Tripledemic in Kentucky?

My second gripe is with the reporting on a supposed tripledemic resulting in school closures in Lee County, Kentucky, alleged to be caused by a combination of covid, influenza, and group A streptococcal infections. What seems to be missing in all the reports is how these etiologies were established. It sounds like it was just what parents or school staff were calling covid, flu, or strep, rather than based on careful testing.

It's a little early for influenza in Kentucky, not that it's impossible, but so far CDC data haven't shown it.

I didn't find anything about it on the Kentucky state flu site.

Group A strep infections aren't reliably reported, and the problem with GAS diagnoses is the relatively high carrier rate of the organism, around 10-15% in the pediatric population. So, if someone tests a child with a viral illness (e.g. rhinovirus/enterovirus, which is prominent this time of year), 10-15% will test positive for GAS.

More reliable but less relevant to Kentucky are recent data from England about GAS hospitalizations:

This may reflect changes in epidemiology during and after the pandemic, but I'm still skeptical of the characterization of etiologies for the Kentucky school illnesses. I hope we'll hear more eventually.

Fungus Amongus

I received a COCA Now notice from the CDC nicely summarizing concerning trends in fungal strains causing ringworm and nail infections. It may be that we are in the midst of rising rates of resistance to commonly-used antifungal medications to treat these diseases. A big problem for clinicians is that treatment response may be normally slow, requiring weeks to months of therapy, so it can take a long time to figure out if the infection isn't responding. Keep this in mind if you notice children with poor responses to treatment, and consider culture and susceptibility testing with a qualified lab.

Paxlovid Resistance

No surprise to anyone, but a new report characterizes nirmatrelvir (Paxlovid) resistance in an immunocompromised patient, exactly the sort of setting we'd expect to see for development of resistance. This isn't the first report of Paxlovid resistance, and it won't be the last. I wouldn't worry about it yet, but, like most treatments for infectious diseases, resistance becomes a problem sooner or later.

My Night in a Brewpub

Not one of my usual habitats, but this was for a good cause: a special meeting of the Greater Washington Infectious Diseases Society at a brewpub in Bethesda, MD. You won't find a web link for GWIDS, not because it's a secret society but because no one has gotten around to making one in the few decades of GWIDS' existence. It's a monthly meeting of adult and pediatric infectious diseases training programs in the DC area where fellows in training present challenging and usually obscure infection cases and try to stump the stars in attendance. Basically it is heaven for an infectious diseases nerd.

This meeting was our first in person since the pandemic began. It was special because Dr. Anthony Fauci, an annual speaker usually at the end of the year, was featured in what was supposed to be a fireside chat now transformed into a vatside chat. I moderated the session only because the first 50 or so choices for moderator weren't available. We gathered a list of questions from members prior to the meeting plus opened up for questions from the audience at the end. A good time was had by all, although I myself missed out on the refreshments.

One of the questions I asked, the only one I submitted, was for Dr. Fauci to help us understand the differences between the criticisms he received during the early days of the AIDS pandemic and the terrible threats he now receives from various covid crazies. (Three guys looking very muscular, with receivers in their ears and bulges under their coats, were the only non-GWIDS members present; Fauci came and went in one of those flashing-light black SUVs that disrupt traffic all over the DC area.)

In 1988, Larry Kramer, one of the earliest AIDS activists and a leader in the movement (also an accomplished playwright and author), published letters to Fauci in the Village Voice and the San Francisco Examiner. I read excerpts from those documents, and if you didn't know the context it would be perfectly reasonable to assume they were written recently. Kramer called him a murderer, an idiot, and a liar, among the repeatable epithets. I can't quote Dr. Fauci's response accurately, I wasn't taking notes, but the gist of his reply was that the AIDS and covid personal attacks, while sounding similar, are completely different. The difference boils down to Good Will.

AIDS protesters wanted to work to a solution; they were terribly critical of Fauci as a person as well as of policies of FDA and NIH. The end result was a revamping of the research and approval process for AIDS (and thus other treatments) that resulted in a quicker and more effective benefit to society. According to Fauci, those AIDS activists were motivated by good will and demonstrated willingness to collaborate on a solution. Nothing like that exists in today's Fauci demonization.

Read Tony's NY Times essay on Mr. Kramer and "loving difficult people," and take a little time to practice some good will.

A Dog Named Clytemnestra 2

Bud WiedermannMarch 26, 2023March 26, 20232 Comments

My recent bedtime reading included a mystery by Ruth Rendell, a much-acclaimed British mystery writer. A dog with a name out of Greek mythology appeared in this one, and I was convinced it was a clue to the murderer's identity. Of course it wasn't.

Pediatric Influenza Vaccine Effectiveness (VE)

This study from CDC and its flu VE partners appeared online this week. It provides a good overview of flu VE over 9 flu seasons plus raises some interesting questions. Investigators analyzed data from active flu surveillance at 5 sites around the country (Michigan, Pennsylvania, Texas, Washington, and Wisconsin), the same data that CDC uses to report flu VE every year. None of the numbers are new, but looking at trends and associations over the years was interesting. Note these numbers are from active surveillance rather than collecting data from passive reporting systems like administrative databases; it is much more accurate. Because it is based in outpatient sentinel sites it specifically gives us VE for medically-attended outpatient respiratory illness.

In Figure 1 below the overall VE was 46% - that may not sound that great, but remember this is VE against medically-attended illness, not digging deeper to hospitalization rates which are very high. As you can see, VE varied somewhat with age (younger kids a little bit better effectiveness) and with flu strain.

Influenza A(H3N2) viruses cause more severe illnesses generally and also have had lower VE rates. Figure 2 looks at seasons where H3N2 was the predominant circulating strain and categorizes them as to whether the vaccine that year was either well-matched or mismatched for the strain that was circulating. The advantage for the younger children is more evident in some of these comparisons, especially for the mismatched 2014-15 season.

Why did the 6 to 59 month-old age group show better VE? The authors offer some speculation, including age-related differences in immune response to other factors such as social interactions or characteristics of families with young children that might further protect from infection and doctor visits. Whether this is a difference in immunity or behavior, or a combination, further studies looking into these factors can help inform future preventive measures.

Variants and MIS-C

A group of Kawasaki Disease investigators from several different institutions reported rates of MIS-C categorized by SARS CoV-2 variant periods. Dr. Ashraf Harahsheh, a cardiologist at Children's National Hospital, is a co-author. I had no involvement in the study except as 1 of perhaps a few hundred or so clinicians who helped care for these children at Children's National.

The Table below is a good summary.

Note that the coronary artery row describes dilatation, different from aneurysms. It is certainly reassuring that disease severity declined somewhat during this period, but severe disease still occurred. The declining relative risks of ICU admission from the alpha to omicron eras might be due in part to more comfort of clinicians managing these cases, though that wouldn't explain the concomitant decrease in shock over the same period. One hopes that further study of these patients will lead to discovery of better management for both Kawasaki Disease and MISC-C.

Can Post-Covid Illness Be Prevented?

A couple of studies in adults looked at factors associated with post-covid illness. One investigation was performed in the VA system on a cohort of almost 300,00 individuals. After correcting for many potentially confounding variables, treatment with nirmatrelvir (combined with ritonavir as Paxlovid) did appear to lower risk of persisting illness.

This was a statistically complicated but excellent study. However, what I still hope to see is some post-covid illness study that effectively separates conditions due to direct end-organ damage from the virus versus the fatigue/malaise/dysautonomia/brain fog symptoms. Does an intervention prevent those complications in patients who do not have end-organ damage?

The other study was a systematic review and meta-analysis of 41 studies to identify risk factors for post-covid conditions. They identified female sex, older age (looking only at 18 years and older), higher BMI, and smoking as significant risk factors.

Neither of these studies included pediatric subjects, but still they shed a little more light on this confusing hodgepodge of illnesses. I hope for some tangible breakthroughs in the coming years.

Detective Stories

Much of medical practice, and maybe especially infectious diseases practice, requires good detective work including being observant and asking the right questions. I love Rendell's books. Her characters are often quoting British literature and historical events that I enjoy looking up, but I clearly chased the wrong clues this past week and totally misidentified the perpetrator. I'll keep practicing.

In the Spring, a Young Man’s Fancy Turns to Thoughts of … Ticks?

Bud WiedermannMarch 19, 2023March 19, 2023Leave a comment

OK, I know I'm not a young man, but let me dream a little bit. March 20 is the first day of spring, actually starting at 5:24 PM EDT in the Northern Hemisphere. I was reminded of spring recently when my wife, who spends approximately 86% of her waking hours outdoors, noticed a tick crawling on her arm. In my warped world view I immediately think of tick-borne diseases.

But first, a couple updates.

Paxlovid Poised for Full Approval (for Adults)

FDA's Center for Drug Evaluation and Research Advisory Committee met on March 16 to consider newer data on Paxlovid, the oral combination of nirmatrelvir and ritonavir authorized for SARS-CoV-2 treatment in selected situations. It was no surprise to anyone that data were favorable and likely will lead to full approval for individuals meeting criteria who are 18 years of age or older, but don't expect any new changes for the pediatric population yet. You can view all the documents at the meeting document site. I was more interested in the data on rebound, and the meeting documents (I didn't tune in to the sessions) had a very balanced and nuanced assessment.

First of all, recognize that rebound really involves 2 issues: viral rebound, meaning the amount of virus present drops, then bounces back up; and symptom rebound, meaning symptoms improve and then return. Also, true rebound implies a period of improvement, followed by an increase in virus or symptoms. If there is no improvement, you can't really detect rebound per se.

That all aside, the bottom line (see page 70 of the pdf, slide 59) from all the analysis from FDA was that "...rebound ... is not clearly associated with PAXLOVID treatment, is not associated with severe disease outcomes, and likely reflects natural COVID-19 disease progression and/or technical variability in virology assessments." In other words, although data continue to be collected, for now we can forget about rebound influencing treatment decisions.

The analyses involved 3 different trials including the original trial for authorization plus some trials that were primarily pre- or during omicron circulation. Most importantly, all have shown good efficacy against disease progression and excellent safety profiles, but the numbers from the omicron era (EPIC-SR 2022) are still too small to provide any separate conclusions for current times. That's been a problem with covid all along - by the time we have solid data, we've moved on to a new variant.

For the rebound consideration, here is a summary slide for combined outcomes that gives you an idea of numbers of subjects studied. Note that in the original EPIC-HR trial there was no difference in symptomatic viral RNA rebound.

The meeting site has a ton of other interesting data. I've just highlighted some key aspects.

Also on a slightly related matter, FDA has authorized the Pfizer bivalent vaccine to be used as a booster dose for children ages 6 months through 4 years, joining authorization for the Moderna bivalent vaccine booster for similar ages. It's important to remember that the primary vaccine series for Pfizer is 3 doses and for Moderna is 2 doses, both using the monovalent vaccine. Now we need to wait for CDC/ACIP to weigh in with recommendations.

What we are witnessing is the start of incremental assessments that I hope will lead to use of whatever bi- or multi-valent vaccine might be proposed for next fall, ideally for both primary series and booster doses. If analyses support this change we'll live in a simpler world of covid vaccines for children.

Babesiosis

When was the last time you worried about babesiosis? It's not on the list of commonly encountered infections, but newer CDC data just published should at least put it on our radar. The report covers the years 2011-2019 and shows that the infection is still relatively rare. However, the low numbers might be misleading because the infection is not nationally reportable and often is asymptomatic or self-limited in healthy individuals so can go undetected.

In the 10 states where babesiosis was reportable over this time period (Connecticut, Maine, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Rhode Island, Vermont, and Wisconsin), numbers increased significantly in 8 (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Vermont). Of further interest is that Maine, New Hampshire, and Vermont previously have not been considered to have endemic babesiosis. Clearly we need more states to make babesiosis case reporting mandatory, but I say this knowing that many states are decreasing their public health vigilance generally.

Here's the geographic picture, based on state of residence:

If you aren't too clear about the management of babesiosis, the CDC has excellent resources for healthcare providers and for the lay public. Remember that it is a parasite that infects red blood cells, similar to malaria. Signs and symptoms often are nonspecific (febrile flu-like illness) and thus very difficult to diagnose unless hemolytic anemia develops. Individuals with asplenia, immunodeficiency, and advanced age are at highest risk of severe outcomes.

Peripheral blood smear of Babesia infection:

Another problem with babesiosis management is that some individuals carry this diagnosis falsely, on the basis of unapproved laboratory testing and misguided (or worse) clinicians. I've spent much more of my time disproving Babesia diagnoses than in actually diagnosing and treating true cases. Most of the children and young adults in my practice who were misdiagnosed had prolonged fatigue or other symptoms that weren't suggestive of babesiosis. Consultation with a reputable pediatric infectious diseases specialist is wise if a babesiosis diagnosis is entertained. Avoid so-called practitioners ordering large batteries of non-FDA approved tests for patients with vague symptoms.

Alfred Lord Tennyson

Tennyson is perhaps best-known for his poem, Charge of the Light Brigade, describing the fateful Battle of Balaclava during the Crimean War (1854, not the current Ukraine/Russia war). Thinking about spring allowed me the pleasure of rereading another of his poems, Locksley Hall, first published in 1842. It was even more pleasurable for me because I opened my copy of the slightly more modern (1892) complete and unabridged The Works of Alfred Lord Tennyson printed by Macmillan Standard Library. It's a long poem, but the pertinent passages for spring are:

"In the Spring a fuller crimson comes upon the robin's breast;
In the Spring the wanton lapwing gets himself another crest;

In the Spring a livelier iris changes on the burnish'd dove;
In the Spring a young man's fancy lightly turns to thoughts of love."

I can see robins outside my window as I write this. Take a break, go outside, and enjoy spring. (But watch out for ticks!)

Happy Birthday, Presidents! 2

Bud WiedermannFebruary 19, 2023February 19, 20232 Comments

Presidents' Day, or whatever your state chooses to call it, mostly is observed the third Monday in February. Historically in our house it has been a time for my wife's annual trip to visit relatives in Florida, escaping the snow and ice and usually leaving me behind to work. This year we're both staying at home, and the weather is pretty balmy here. I had the opportunity to learn a bit more about Presidents' Day, and yes I did find a way to tie it to an infectious diseases tidbit.

First let's dive into a bit of current events.

New Vaccine Publications

Last week's New England Journal of Medicine contained 3 new vaccine trial reports, but as is often the case nowadays with vaccine trials, most of the information has already been discussed at various FDA and ACIP meetings. One study concerned the Pfizer covid vaccine performance in young children - I won't comment on that since I was involved in the trial (though not a study author) and likely have some implicit bias. You should note, however, the wide confidence intervals for vaccine efficacy below, a direct byproduct of the low number of infections in both groups.

The other 2 studies were of 2 different RSV vaccines in older individuals, not directly applicable to pediatrics, but the pediatric trials are ongoing. What might be worth your reading, if you have access to the NEJM, is the accompanying perspective by Barney Graham who now is affiliated with Morehouse School of Medicine. No one person can claim all the credit for advances in a particular field of medicine, but Dr. Graham comes the closest when it comes to respiratory virus vaccines. His article traces the history of RSV vaccines from a disastrous clinical trial in the 1960s to a careful, deliberate few decades of research to figure out how this happened and how to avoid problems in the future. He also discusses the link between the mRNA covid vaccine development process, informed by RSV vaccine research. I think we can expect FDA action on the vaccine for adults in the near future, but the timeline for children awaits ongoing trial results.

Also last week, CDC released preliminary data on mRNA vaccine effectiveness for children in the 3 - 5 year old age range, looking at post-marketing data beyond the original research trials. Both the Pfizer and Moderna vaccines showed decent VE against symptomatic infection for at least 4 months after vaccination with monovalent vaccines. This is still very early and evolving information.

It's also important to recognize many limitations of this type of data, such as the fact that Moderna's primary vaccine dosing in the age group requires 2 injections compared to Pfizer's 3; that causes some difficulty in comparing protection numbers between the 2 manufacturers, given that the time intervals of VE measurement then fall at different calendar (and therefore, variant circulation) dates. In total the report details 7 limitations which is typical for CDC's thorough reporting and assessments.

Pegylated Interferon Lambda

Last week I mentioned some encouraging results in treating covid illness with this compound. Dr. Michael Schwartz responded with some comments and questions that I wanted to expand more than just a quick reply to his comment. I will include some of his comments in quotes.

"....I was once invested in this company anticipating these results. Alas , it is a tiny company really dedicated to orphan drugs.
They don’t have the resources to do the studies needed to test this ...."

The company is Eiger Biopharamaceuticals. Although I don't know much about it, I have been aware of them since about a year ago when they announced some encouraging results for this same product in treatment of hepatitis D-infected individuals. Although maybe they are a small company compared to pharmaceutical giants like Pfizer, they certainly aren't naive. They've been working with the FDA for some time now, so I didn't understand the CEO's comments to the press regarding the FDA. Certainly there is more than meets the eye for the situation, but I'm hopeful they already have plans to move forward.

"I can’t understand why we have not had a program to expedite our patient treatments in COVID. Example - my BIG question - does lamda interferon plus Paxlovid avoid Paxlovid rebound? That should be a pretty easy study to do."

That last sentence brought a smile to my face, I don't think there is any such thing as an easy study when it comes to clinical trials. Unfortunately even the simplest require a lot of planning and funding. In one sense, we do have a program to expedite develop of treatments for covid, mostly in the form of regulations like Emergency Use Authorization and with isolated trial structures such as the TOGETHER trial in which interferon lambda was studied. What we don't have, critically, is a dedicated mechanism to test combination therapies like Michael proposes. The main barrier is that pharmaceutical companies have little incentive to invest their own dollars on something like that because the return on investment will be very low.

On the good news side, NIH just announced plans to fund trials for a newer antiviral from Japan, ensitrelvir, that appears effective for adults hospitalized for covid.

Another comment on this topic: note that so-called Paxlovid rebound may not be a real thing. More studies are suggesting this rebound is mostly a phenomenon of covid infection itself rather than something unique to treatment. Last week Lancet Infectious Diseases released a retrospective trial again suggesting this possibility.

The article itself contains more information about different subgroups such as age and vaccination status.

Happy Birthday, John Adams?

Shouldn't Presidents' Day be for all our presidents? Doing my usual digging, I found that George Washington's birthday was the first to be celebrated, soon after his death. In modern times, before Presidents' Day, Washington's birthday was celebrated on February 22, which by some views isn't his actual birthday. It's not at all straightforward to figure out what his real birthday was. He was truly born on February 11, 1731, but that was using the older Julian calendar. Great Britain and its colonies hadn't yet switched to the more modern Gregorian calendar at that time, probably because its origins were in the Catholic church and Great Britain I guess still carried a grudge against that origin. However, they did switch over to the Gregorian calendar in 1752. Not to bore you with more details, but people in Great Britain and colonies who were born before 1752 were told to add 11 days to their birth date. Additionally, those born between January 1 and March 25 (the latter being the start of the new year in the Julian calendar) added one year to their birth year. So, George's birthday shifted from February 11, 1731, to February 22, 1732. Whew!

Well, John Adam's birthday is October 30 (1735; birth date changed from October 19 to October 30, but birth year did not change with adoption of the Gregorian calendar), not even close to February. I've had interest in him ever since I read a terrific book about his wife Abigail (Smith; the book is by Woody Holton, Abigail Adams, ISBN-10 1416546812). Recently I came across some literature about John's experience with smallpox vaccine, of course in the early days of inoculation and marking the start of the anti-vax movement in the US. I copy the relevant parts of his diary here:

"In the Winter of 1764 the Small Pox prevailing in Boston, I went with my Brother into Town and was inocculated under the Direction of Dr. Nathaniel Perkins and Dr. Joseph Warren. This Distemper was very terrible even by Inocculation at that time. My Physicians dreaded it, and prepared me, by a milk Diet and a Course of Mercurial Preparations, till they reduced me very low before they performed the operation. They continued to feed me with Milk and Mercury through the whole Course of it, and salivated me to such a degree, that every tooth in my head became so loose that I believe I could have pulled them all with my Thumb and finger. By such means they conquered the Small Pox, which I had very lightly, but they rendered me incapable with the Aid of another fever at Amsterdam of speaking or eating in my old Age ..."

Mercury poisoning does cause gingival problems, so perhaps he was correct in tying his tooth issues to the vaccination process but not specifically to the vaccine itself. Abigail and their 4 children, John Quincy, Nabby, Charles, and Thomas, did not undergo vaccination until 1776 because Abigail's mother had forbidden it. Her mother, Elizabeth Quincy Smith, died in 1775, clearing the way to move forward presumably. John Quincy, our sixth president, and Nabby showed some reaction. The two youngest children, Charles and Tommy, didn't show signs of a reaction so they were revaccinated which then resulted in Tommy but not Charles developing pustules. Also, Nabby had only developed fever but no pustules, so Abigail requested that she be revaccinated which then resulted in appearance of over 1000 pustules! No mention that I could find of mercury co-medication with Abigail's or the children's vaccination, thank goodness.

Needless to say, all this occurred before we had FDA, VRBPAC, CDC, ACIP, AAP, and a cast of thousands helping us with safety and efficacy of vaccines.

Happy Thanksgiving, et al 2

Bud WiedermannNovember 20, 2022November 20, 20222 Comments

We're hosting a relatively small Thanksgiving gathering this week, but that doesn't mean I won't go crazy with planning and implementation. My goals are to have all of the food on the table, reasonably warm (except for the salads), within 2 hours of the intended sit-down time. A secondary goal is to keep the turkey off the floor during carving.

I suspect most of you are unaware, but this Thanksgiving day also marks the first anniversary of the initial report of the omicron variant appearance in South Africa.

Since I Mentioned Variants

Usually I give the weekly JAMA Medical News section only a cursory glance, but one item last week, written by Rita Rubin, was particularly well done. She effectively summarized a lot of evidence and viewpoints to paint a picture of what a covid winter wave might look like, and why. In addition to addressing the importance of immune-evasion properties of newer subvariants, she also sorts through some of the confusion about variant nomenclature and points out limitations of our standard pandemic tracking data like case numbers and hospitalization rates. It's become a difficult number to grasp now that much of home testing results go unreported, whether positive or negative, and large swaths of the US population have given up testing altogether. Wastewater monitoring probably is our most reliable, although imperfect, early warning indicator for a winter covid wave now.

Maricopa County - More Than Vote Counting

Maricopa County in Arizona features prominently in our news nowadays, mostly as a hotbed of election fraud rumors and innuendo. More significant (IMHO) is the report last week of an autochthonous dengue case (acquired locally rather than during travel to an endemic area). Dengue, a virus transmitted via mosquito bite, is endemic in many parts of the world, and virtually all cases in US residents are acquired via travel to these areas. However, climate change has greatly affected the range of the mosquito vector. Until now, Florida is the only US jurisdiction that has seen autochthonous dengue transmission.

2022 US Dengue cases in US residents as of 11/2/22, all travel-associated except for Florida.

Mosquitoes of the Aedes species (Aedes aegypti is also known as the tiger mosquito) transmit dengue, as well as Zika, chikungunya, and other viruses. Their range now extends across much of the US, including into the DC area.

More on Paxlovid Rebound

We now have an early glimpse via non-peer-reviewed preprint publication of an observational study of the rebound rates of covid positivity and illness following treatment with the oral antiviral agent paxlovid, compared to infection in individuals who did not take paxlovid. This preliminary report contains information on 127 participants who received paxlovid and 43 who did not. It covers the time period from August 4 to November 1, 2022, so all during omicron activity.

Rebound for positive virus testing (these were antigen tests) was 14.2% (18/127) in the paxlovid group versus 9.3% (4/43) in the no treatment group. For clinical symptoms rebound, the rates were 18.9% and 9.3% in paxlovid and no treatment groups, respectively. Another interesting nugget I noticed was that 20% of individuals in both groups still had positive antigen tests on day 10 after first positive test.

This is very preliminary information with a small number of participants, so the exact rates and differences between the 2 groups could change dramatically as more data are analyzed. The observational study design in general (rather than a blinded randomized controlled trial) also has limitations that could skew results.

Note that participants were all 18 years of age or older. Still, this is the start of getting a better ballpark assessment of covid rebound with and without antiviral treatment. For now, in the absence of specific pediatric studies, it remains prudent that covid-infected non-hospitalized children ages 12 years and older with weight at least 40 kg and with the appropriate risks and clinical status should be offered paxlovid treatment.

We Should Be Thankful

RSV, flu, and covid continue to cause a lot of angst in the pediatric medical community, and we know that some of the outcomes of the original Thanksgiving aren't worthy of celebration. But, let's remember to be thankful for the covid vaccines and treatments we do have available. We just need to do a better job of implementing these interventions.

Sunday's Washington Post Food section article on Thanksgiving holiday horrors triggered some post-traumatic stress. I wish I had known they were looking for stories, I would have submitted my greasy drippings jar/glass shards into the gravy pot fiasco from a while back, I'm sure it would have qualified for inclusion. It was a classic too-much-rushing-to-process-the-turkey-pan-drippings-before-the-turkey-turned-cold-drill. We didn't have any turkey gravy that year, but now I've switched to a recipe with roasted turkey wings that I prepare on Wednesday and probably tastes better than the original. So, remember to be thankful for silver linings, and have a safe and happy holiday!

Tag: paxlovid