RSV

Keeping Busy

Bud WiedermannApril 9, 2023April 9, 2023Leave a comment

I knew my week would be busy with some holiday event planning, but it got busier with a lot of infectious diseases happenings to keep track of. Let's dive in.

CDC provided a summary of RSV seasonality over the past few years. It's a nice look at how the pandemic affected circulation of this common respiratory virus and perhaps gives us a glimpse of the future. The graph below depicts the seasons based on percent PCR sampling positivity.

The 2019-2020 season was a typical one, peaking well before covid pandemic practices kicked in. Look at the 2020-21 season, with the winter RSV season completely gone but then a very atypical rise starting in May/June and contributing to an early but blunted summer and fall season for 2021-22. The solid black line for 2022-23 looks like a more typical season with a bit of an early peak as masking and social distancing disappeared. Next year should continue with a more standard RSV season unless we have some dire new covid variant that results in a return to masking and other nonpharmaceutical measures to reduce illness.

I was initially hopeful that the online publication of the Pfizer RSV vaccine trial for pregnant women would include results from the most recent RSV season, but alas it did not. I mentioned this topic in my February 26 posting, and now those data appear in a peer-reviewed publication. The trial enrollment was stopped last September because efficacy was demonstrated for one of the primary outcomes, but women and their newborns already enrolled will continue to be followed. I hope data from this past RSV-intense season will be analyzed and released soon.

Severe Group A Streptococcal Disease

Last week saw 2 new studies published, with slightly different focus and different findings. A group from the Netherlands focused on GAS meningitis, studying CSF isolates from 1982 to mid-March 2023. The study included all ages. They found that a particular subtype, M1_UK was more dominant during the recent uptick in severe GAS infections.

A group in Houston looked just at a pediatric population for all invasive GAS disease, finding a different subtype over-represented recently (emm12 versus emm1 previously). The saga continues.

Marburg Virus

Haven't heard of it? It's another in the hemorrhagic fever group of viruses, like Ebola, and it is now bubbling up in parts of Africa (Equatorial Guinea and Tanzania) resulting in a Health Alert from the CDC. A recent timely editorial, written before the Tanzanian cases appeared, provides a little background. Be sure to get a good history from returning international travelers, plus warn any of your patients planning travel to these areas.

Covid

We all know covid isn't going away, and the past couple weeks provided a bit more confusion that we didn't need. First, we saw another publication about SARS-CoV-2 origin, interesting but not at all definitive. A sad report of 2 cases of severe neurologic manifestations in young infants, probably linked to in utero infection, describes in detail various clinical, histologic, and virologic features. It is this type of basic research that will expand our understanding and perhaps lead to more effective interventions.

Last but certainly not least, I want to address an important question posed by Dr. Hilary Deutsch: "What did you think about WHO not recommending Covid vax because there were “only” 17,000 pediatric deaths from Covid worldwide?" The news report commented briefly about this, importantly stating "The low priority group includes healthy children and adolescents aged 6 months to 17 years. Primary and booster doses are safe and effective in children and adolescents. However, considering the low burden of disease, SAGE urges countries considering vaccination of this age group to base their decisions on contextual factors, such as the disease burden, cost effectiveness, and other health or programmatic priorities and opportunity costs."

Digging a little deeper, you can view the agenda for the entire meeting and access various slide presentations by downloading it and opening in Adobe Acrobat. The covid session is entitled "Roadmap for COVID-19 Vaccination in the era of Omicron" and consists of 75 slides; it is a very complete analysis. The bottom line comes down to the quotation from the news release in the previous paragraph. WHO needs to provide global guidance, and situations in different countries are very different of course. So, this is an attempt to help health officials make a judgment that best suits their particular setting. This is not just an issue for countries with severe resource constraints. For example, the United Kingdom recently proposed targeting "clinically vulnerable" 6-month to 4-year-old children for their vaccination program. They do not advise vaccinating healthy children in this age group.

Comparatively speaking, healthy children and adolescents are a low-risk population for serious outcomes from covid. From a public health view, especially if resources are limited, it may be best to direct priorities to higher risk groups. From a personal or family perspective, it is still clear that covid vaccination versus no vaccination is the better choice to avoid serious outcomes, even in low risk individuals. I would still maintain that the "contextual factors" in the US still favor recommending covid vaccination for all, including healthy children starting at 6 months of age.

So Much for Retirement

I thought I had retired from clinical practice several months ago, but now I've been cajoled out of my bliss to help with some new subspecialty ID consultations at regional hospitals in DC, Maryland, and Virginia. So, I've unretired for now with new permanent retirement delayed somewhat. Any resemblance of my situation to Tom Brady's is purely coincidental (obviously).

A Noisy Week

Bud WiedermannFebruary 26, 2023February 26, 2023Leave a comment

Lots of pediatric infection-related meetings and reports this week, but actionable items for front-line care providers were sparse. It's not that the information wasn't interesting, but when all was said and done I couldn't come up with anything to change clinical practice. That type of noise is good, but I'll be more excited a few months from now when we might have actionable events from ongoing studies.

A 3-Day CDC Advisory Council on Immunization Practices (ACIP) Meeting

This ACIP meeting covered a lot of vaccine topics including vaccines for mpox, influenza, pneumococcus, meningococcus, polio, RSV (both pediatric/maternal and elderly adults), chikungunya, dengue, varicella, and our old friend covid. I wasn't able to view the sessions live but have reviewed many of the slides that were posted. The only vote at the meeting was to continue use of mpox vaccination pretty much as before; the rest of the meeting primarily consisted of updates. In the next few months we should be approaching some decisions particularly for RSV immunization of pregnant people to protect their newborns, long-acting monoclonal antibody treatment to prevent RSV in high-risk and/or all infants, 20-valent pneumococcal vaccines for children, and more.

With regard to RSV prevention, in the past I was struck by ACIP wording about anti-RSV monoclonal antibody therapy being labelled a "vaccine" when it really is a therapy. I now understand that the vaccine label would have made it easier to provide the intervention through the Vaccines for Children program; if it is a therapy, some infants will fall through the cracks in terms of access. AAP had a nice summary of these issues.

Pfizer presented data that they have submitted to FDA for maternal RSV immunization during pregnancy to prevent RSV in their newborns, but I won't show that data since it was only from the pharmaceutical company without separate analysis by ACIP or CDC. FDA/VRBPAC will discuss RSV vaccines for people 60 years of age and older (this also was discussed at the ACIP meeting) on February 28 and March 1, but it doesn't look like they will cover any pediatric issues at this meeting. However, if studies look good it is possible we will have new interventions to prevent RSV in young infants prior to next winter's RSV season.

Post-Acute Sequelae of COVID-19 (PASC)

I did attend a February 23 webinar on PASC in children and adolescents hoping to see some new data, but ultimately I was disappointed. That's not to say that progress hasn't been made, but the session was mainly a review of previous data and guidelines. I did learn that risk factors for PASC in children and adolescents include age greater than 12 years, unvaccinated status, and history of allergic disease. PASC symptoms were less common in vaccinated individuals than in the unvaccinated. Here's a peek at main symptom frequencies:

It was a good review session of general evaluation and treatment options, check out the complete slide deck.

PASC is really a tough issue, likely because it is still a mixture of at least 2 different processes. One includes all the end-organ damage from the infection itself, while the other comprises more vague manifestations such as brain fog, fatigue, and dysautonomia symptoms. I've been seeing children with these conditions long before the covid era, seemingly following a wide variety of otherwise run of the mill infections. I'm hoping the intense research focused on PASC will yield something useful for the larger body of individuals affected with what has been called myalgic encephalomyelitis/chronic fatigue syndrome. I dislike that term, it still sounds somewhat pejorative to my ears. Of note, the National Academies of Science, Engineering and Medicine is planning a series of workshops to better characterize a working definition for Long COVID.

We Still Have a Failure to Communicate

Just a quick mention of a study that reviewed US state and territory public health sites for readability and accessibility of their covid treatment information. Broadly speaking, most sites fell short of effective communication - wording too technical or at a high reading level, not helpful for individuals with communication barriers, etc. South Dakota was the best site, followed by Maine and Tennessee (would you have guessed these states coming out on top?). You might want to look at where your state scored. I'm hoping public health units see this article and work to improve their sites.

Enough Ivermectin Already?

Well, yet another study has shown no benefit of ivermectin as a covid therapy, this time using a higher dose. I was more enthralled with one of the accompanying editorials about the ethical principle of equipoise in performing clinical trials to deal with uncertainty in medicine. Simply put, it's a good idea to perform clinical trials to deal with uncertainty, but given that we always have uncertainty in medicine, when should we call it quits for these trials? Specifically, when does it become unethical to perform studies of ivermectin for covid in the hopes of finding some small niche where there might be benefit? That question has no easy answer. Ivermectin became a political pawn early in the pandemic; I fear the end result of that conflict is now wasted resources and unnecessary risks for trial subjects.

Better Data on Paxlovid Rebound

We were just talking about this last week, and now we have results of a prospective study that gives us perhaps even better data. Both viral and symptom rebound were slightly higher in the Paxlovid group compared to controls, but pretty much still in the same ballpark. For example, symptom rebound was about 14% in the treatment group and 9% in the controls. The prospective design of the study is more likely than retrospective studies to give "truer" numbers, and I think what we are seeing is that rebound is more common in untreated people than originally thought. From my viewpoint, the slight increase in rebound from Paxlovid is far outweighed by the benefit of treatment in preventing complications in high-risk individuals.

White Noise

Speaking of noise, this past week my wife and I watched Noah Bambach's adaptation of Don DeLillo's novel, White Noise. Buried somewhere in the few hundred books in our house is a copy of the novel, but neither of us could remember plot details. Fifteen minutes into the movie, we realized neither of us had ever read it!

It's an understatement to say that reviews of the movie were mixed; in fact, many were at the extremes of love or hate. This isn't surprising for a book that was said to be impossible to translate to the screen. Yes, the movie had its dragging and confusing moments, but I loved it so much that I decided to read the book. I'm almost done with it, and it's very interesting for me to see what elements Baumbach left out or changed substantially, versus other parts taken nearly verbatim from the book.

The book, written in 1985 and dealing with fears of mortality, a college professor and his family, and an "airborne toxic event," sadly translates very well to today's chaotic world. The movie was mostly true to the book's central themes, and the song and dance ending, a backdrop to the closing credits, made me smile. I'd recommend both the novel and the movie to folks who might enjoy a quirky, reflective view of modern life and be able to put up with some unevenness in presentation.

Death Valley Days

Bud WiedermannFebruary 5, 2023February 5, 2023Leave a comment

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

Winter Virus Update

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

Covid Immunologic Insights

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

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

More Measles Mess

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

20 Mule Team Borax

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

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

Another Week in the ID World

Bud WiedermannJanuary 22, 2023January 22, 2023Leave a comment

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

Tripledemic Receding

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

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

Vaccine Coverage

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

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

A Brief Word on Variants

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

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

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

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

Wastewater

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

Is My Spice Rack Going to Kill Me?

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

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

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

Fear the Snail

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

Looking Forward to This Week

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

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

Rounding the Corner?

Bud WiedermannJanuary 1, 2023January 2, 2023Leave a comment

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!

Tag: RSV