SARS-CoV2 – Page 3 – Pediatric Infection Connection

Try to See It From Grendel’s Perspective

Bud WiedermannJuly 2, 2023July 2, 2023Leave a comment

Ever read Beowulf? Me neither. Nor do I plan to ever read this epic poem consisting of 3182 lines of alliterative verse. Recently I did read Grendel by John Gardner. Grendel is the monster who was killed by Beowulf in the famous poem. Gardner's book is told entirely from Grendel's perspective, very different from how Beowulf and the other humans saw things of course.

Malaria Season

Practicing in the Washington, DC, area for almost 40 years meant that I had a steady diet of malaria. Our "malaria season" was towards the end of summer when vacationing families returned home after visiting relatives in malaria-endemic countries. This seasonality abated a bit during the pandemic when international travel was scarce, then came back with a vengeance. Now, however, autochthonous malaria has been reported in Florida and Texas.

Autochthonous, from the Greek autokhthon meaning "sprung from the land itself," in this instance refers to malaria acquired without visiting a malaria-endemic country. I didn't mention the initial CDC report a couple weeks ago, but now that a second state is involved and CDC issued a health alert advisory, I'll attempt to summarize what's happening.

We still have virtually no clinical details about any of the 5 cases, but CDC implied they are all due to Plasmodium vivax which is not as severe/deadly as P. falciparum. Autochthonous malaria in the US was common in the old days, but since effective mosquito control programs in the 1950s it has been scarce. Prior to the current reports, we hadn't seen autochthonous malaria since 2003. High risk areas in the US are those that have high population density, plenty of Anopheles mosquitoes (including favorable conditions for their reproduction), and a source of people who have recently traveled from malaria-endemic areas. So, it's not surprising that Florida and Texas are points of origin now.

Speaking of mosquitoes, climate change has greatly increased the range of various insect vectors of disease; for example, Lyme disease risk has expanded geographically in recent years as deer ticks broaden their range. Anopheles mosquitoes are present in virtually the entire US.

For frontline providers, malaria shouldn't be the first thing to suspect in a child with fever in the US, but recognize that in cases of prolonged fever it is a consideration even without a history of international travel. Look at the CDC's malaria website for more details, and read this article if you want to see a longer discussion of (prepandemic) autochthonous malaria.

Foodborne Disease is Back

Another sign that the pandemic is lifting is this CDC report of 2022 data. Certain foodborne illnesses such as Shiga toxin-producing Escherichia coli, Yersinia, Vibrio, and Cyclospora infections increased compared to 2016–2018 data; Campylobacter, Salmonella, Shigella, and Listeria incidences didn't change much. Although they didn't show the data in this report, foodborne diseases decreased in the 2020-2021 time period.

I was a bit disappointed that, although the report did mention increased use of culture-independent diagnostic testing rather than culture, it did not mention the fact that the highly sensitive CIDT methods can be more prone to false positives. This makes it difficult to compare trends across time periods.

Ideally one would perform a backup culture test for bacterial pathogens particularly to detect antimicrobial resistance; CIDT can not test for this.

Can We Shorten Treatment Duration for Pediatric Urinary Tract Infection?

The short answer is yes, but the more difficult question is how to decide which patients are appropriate for shortened therapy. Even this randomized controlled trial couldn't answer that question. The study compared 5 versus 10 days of therapy for UTI in children 2 months to 10 years of age. Children who showed clinical improvement at 5 days treatment were then randomized to another 5 days of antibiotic versus placebo. Failure rate in the 10-day treatment group was 0.6% versus 4.2% in the 5-day group.

Ultimately I think the details of study design doomed this trial to leave this question mostly unanswered. In particular the duration of followup after stopping antibiotic was too short for the 10-day group (which would have skewed results to a falsely low failure rate). Fundamentally the problem with UTI treatment in children is trying to determine which children have pyelonephritis versus just cystitis, much more difficult in children than in adults. Pyelonephritis likely requires more than 5 days of treatment.

This study definitely adds to our understanding of pediatric UTI but I don't think is immediately transferrable to clinical practice. The accompanying editorial offers some ideas in this regard.

'Demic Doldrums

We continue to enjoy relief from covid from the standpoint of no evidence of major surges around the world, just continued pockets of upswings in disease activity (tempered by the knowledge that we aren't tracking it very well now). Of course, the number of total cases in this WHO graph, as of June 28, is pretty depressing overall.

According to WHO, confirmed covid deaths now number 6,947,192.

Blood Group and Covid

I have blood group A positive. Should I be worried? It's been known for a while that individuals with type A blood have a slightly higher risk of SARS-CoV-2 infection, and this recent article lends some credence to these observations by supplying a biologic explanation. The A blood group antigen is very attractive to the receptor binding domain of the virus, including omicron variants. But no, I'm not concerned. The increase in infection risk attributable to blood group is very small, paling in comparison to other risk factors.

Whatever Happened to Wastewater Monitoring?

In the US, wastewater monitoring for viruses like SARS-CoV-2 has great potential but is ineffective because it involves voluntary reporting by states. Most people in the US live in areas that don't monitor wastewater. Our northern neighbors in Canada, specifically Peel, Ontario, provide evidence that wastewater monitoring truly can be an early warning for increased infections. Investigators reported that wastewater levels predicted very reliably 1 day before the rise in infections and 4 days before a rise in hospitalizations during the omicron period of November 2021 to June 2022. At this point I'm not sure if the US has the resources to implement wastewater virus monitoring on a larger scale.

Better Evidence for MIS-C Treatment

The multi-system inflammatory syndrome in children is still difficult to diagnose precisely. Thankfully MIS-C seems less common in today's covid era with omicron dominance and high levels of antibody in the population. Now we have some better guidance for immunomodulatory therapy for MIS-C. This meta-analysis suggests that the combination of intravenous immunoglobulin plus glucocorticoid therapy improved cardiovascular dysfunction better than either agent alone. The study was very well done but had to rely heavily on nonrandomized cohort studies which introduces a great degree of bias in the results. We missed a chance by not conducting large RCTs of MIS-C treatment early in the pandemic.

Understanding Grendel

I needed to consult Wikipedia and other Cliff Notes-like versions of Beowulf to understand Gardner's book. As with everything I read, I think about what, if anything, might apply to me. With Grendel and Beowulf it was relatively easy. When faced with dramatically different perspectives, say for example pandemic deniers or anti-vaxxers (Grendel) versus traditional science and medicine (Beowulf), it's a good idea to try to see things from the opposing perspective. If one can do this without resorting to raised voices or worse, it's possible to have a meaningful dialog and even occasionally change minds, even my own! Next time you see me, look for Grendel perched on my shoulder. For those less prone to wild fantasies I recognize this is quite a stretch, but regular readers are accustomed to my tangents.

What Next?

Bud WiedermannMay 14, 2023May 14, 2023Leave a comment

We are definitely in a new era now. If you need evidence of that, just look at CDC's most recent listserv message:

For the future, look to the CDC's revised covid data tracking site:

What's mainly missing are the covid community levels. Combined with the knowledge that all jurisdictions have stepped down their level of disease monitoring resulting in significantly fewer data points means we aren't anywhere near the level of infection tracking we had previously, though even that varied with jurisdiction. Wastewater monitoring is likely to be the most reliable early warning of a resurgence in the US, but note that this monitoring is done on a voluntary basis, covering about 40% of the US population but very skewed geographically. Here's the latest CDC wastewater map looking at variant analysis:

Increasingly I will be turning to the World Health Organization to look at what's going on elsewhere. Current "hot spots" include the SE Asia and Western Pacific regions.

I was also reminded of changes more locally for me. My phone told me this week that I would no longer receive notifications from Virginia's COVIDWISE app to tell me if I had been exposed to anyone with covid. Since I never received any notifications anyway, I wonder how effective it was. I probably set it up incorrectly.

My Book Report - Preliminary Thoughts

As promised last week, I've been working on my first book report since elementary school. However, when I took a break to actually find out what a book report is, I'd say what I've done is more like a book review. The book is Lessons from the Covid War,: An Investigative Report, ISBN-10 1541703804, authored by "The Covid Crisis Group" but principally written by University of Virginia history professor Philip Zelikow. I picked up my copy on April 27 and took my time reading it. I wanted both to see what they had to say but also to determine potential sources of bias in the report. The Crisis Group compiled the report given that there is still no federal commission planned to officially dissect the pandemic response. I purposely haven't read other reviews of the book, though I recall from one TV news report that the reviewer felt they were too soft on criticizing the Trump administration.

First, let's drill down on the potential sources of bias, particularly important with a highly charged political topic. Dr. Zelikow certainly is well qualified for the project having served as executive director of the federal 9/11 Commission. He has held several jobs in both Democratic and Republican administrations. The other 33 members of the crisis group include some involved in politics (again from both sides of the aisle) as well as physicians, scientists, and public health specialists. Notably missing from the group was anyone heading the response from either the Trump or Biden administrations, perhaps a good thing though leaving a gap in verifying circumstances or allowing rebuttal. The report itself has a thorough listing of individual and organizational sources of interviews and other materials, as well as 25 pages of fine-print notes for specific statements in the text.

Another potential source of bias is funding source. Four foundations sponsored the group: Schmidt Futures, the Rockefeller Foundation, the Skoll Foundation, and Stand Together. After reviewing their web sites and other commentaries, my best guess is that 3 are slightly left-leaning and 1 is tilted more towards the conservative side. All have excellent records of interest and accomplishments in various international efforts including disaster evaluation and relief. The foundations contributed equal funds and had no role in drafting or writing the report.

So, my final gestalt is that this is about as non-biased a report as can be expected for the topic. I think the only people who could conceivably have major concerns with it would be those who do not accept the scientific method or specific source documentation.

The report itself is well-written, with explanations making it accessible to those without a scientific or medical background. I was a little put-off by the near constant comparisons to war and military strategies, although the comparison of Operation Warp Speed for vaccine development to the 1940s Manhattan Project to develop the atomic bomb was convincing.

The Meat of the Report

Here are some of the points I thought were helpful.

Clearly the Group felt that we were doomed in our response from the start by the state of our public health system in the US, little changed from the late 19th century in their opinion. They describe 3 main cultures in governance: program and process, research and investigation, and operations. We were lacking in all 3 prior to the pandemic, resulting in much higher loss of life and interruption of daily activities than would have occurred if we had invested in this infrastructure previously. They allude to investing billions to save trillions, and this principle still holds.

I learned that the "Communicable Disease Center," precursor of the CDC, wasn't established until 1946. Atlanta supposedly was chosen as the site because more malaria was present in the South, though this tidbit didn't have a footnote so I'm not sure if that is accurate. The Group clearly feels that the decentralization of public health (we have 2800 local public health departments varying widely in expertise, technology access, and operational guidance) needs overhaul in order to have an effective response to wide-scale emergencies. Essentially, we do not have a national public health service, "all operational responsibility [is] at the state, local, territorial, and tribal levels." (page 71).

I somehow missed or didn't remember that the White House Council of Economic Advisors issued a report in September 2019 estimating that a pandemic would cost trillions and kill more than 500,000 people in the US. It was based more on influenza and sadly turned out to be an underestimate. I was also unaware of Crimson Contagion, a pandemic exercise conducted in early 2019 that identified many coordination problems in responding to an influenza-like pandemic. The death toll in the exercise was in the hundreds of thousands.

Regardless of our preparedness prior to the pandemic, it is clear that our responses once it started contributed to greater hardship and loss of life. Early in 2020, so many mistakes were made it would almost be comic without the tragic results. Virtually everyone in the US failed to realize key differences between an influenza pandemic and covid (or coronaviruses in general). These include the presence of asymptomatic infection with effective human transmission from those individuals, the nature of aerosol spread and use of mask, social distancing, etc., the ability of the virus to rapidly produce variants resulting in multiple disease waves, poor development and deployment of resources and distribution systems, and, critically, effective communications.

Operation Warp Speed is one of the few successes of the US response. Prior to reading this report, I had credited the government of China with posting the genomic sequence of the virus early in January, 2020, but I learned that the sequence was posted by a Chinese scientist without government permission. This sequence was a necessary precursor for covid vaccine and test research. Thankfully, investment in basic research in coronaviruses and mRNA technology allowed for a rapid response to produce effective vaccines in record time. Still, we failed miserably in vaccine distribution and communications about benefits and risks to the general public.

Needless to say, it is the communication issues where the Trump administration, the president in particular, derailed effective vaccine uptake early on and continues to contribute to the anti-vax movement and almost total covid vaccine refusal in some groups. Any chance at herd immunity was lost fairly early in the pandemic. In April and May 2020 "Trump poured acid on the strained bonds" (p. 209) trying to hold together all the different parts of the US pandemic response, effectively eroding trust and confidence in public health.

The US also did not have a system to detect variants quickly. Instead, we relied on Israel, Denmark, the United Kingdom, and later South Africa to give us early warning. The Report also is critical of President Biden and his administration, especially in 2021; no one gets off cleanly.

The good guys for pandemic response globally appear to be South Korea and Germany; the Group implies we can learn a great deal from them.

It isn't until page 253 of the 288-page Report that we start to see concrete considerations for going forward. As you might expect, it takes money, authorized by Congress on a multi-year basis, to start to prepare for the next pandemic. This holds whether it be covid, another coronavirus, influenza, or something we haven't yet identified. We also need to partner globally; we've all seen how closely tied together we are with fellow world citizens, not only with pandemics but with localized outbreaks (remember Ebola?) that can spill into other parts of the world very easily. Today, the Middle East has no covid vaccine manufacturing sites. Sub-Saharan Africa has only one. Abandoning the World Health Organization and adopting the America First strategy early in the Trump Administration really hurt the pandemic response.

I counted 13 different lessons from the final chapter. (I was disappointed that the Report was almost devoid of tables and graphs, so I made my own.)

Develop systems to govern highly risky biologic research
Build worldwide early warning systems for early threats
Develop systems for ongoing evidence gathering during a crisis
Develop basic vaccine designs for each category of potential pandemic agents and create vaccine libraries with resources to manufacture and distribute vaccines at high scale
Plan similarly for development, distribution, and use of diagnostic tests
Ditto for therapeutics
Advance investment and access to emergency funding
Plan for proactive partnerships with private industry to meet public needs
Create effective global coalitions
Develop effective non-medical interventions to buy time early in health emergencies
Crisis communication - need I say more?
Develop a "coherent national health security enterprise" (p. 284)
Perhaps not a separate point, but I think very important. The White House should not be the center of crisis management (corollary: the President is not the central guide for large operation management); we need a new structure as in #12.

I realize I've now detailed only about 1/3 of the underlinings, highlights, and margin notes I made in my copy of the Report. I won't bore you with all that. Suffice to say that I highly recommend reading this Report if you want a better understanding of the US role in the pandemic. It's certainly not the final word, but I hope Congress and high-ranking officials in the federal government pay attention to it.

And, to be fair, it's not like the feds are doing nothing. As I mentioned last week, CDC has a planned overhaul, though maybe at risk with a change in leadership. HHS just announced a new plan. FDA is trying to evolve based on pandemic lessons learned. All we need now is political consensus and funding!

Thanks for putting up with my long-winded book report/review. Now I can dig into "Maigret in Retirement."

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.

A Few Good Reads This Week

Bud WiedermannNovember 13, 2022November 13, 2022Leave a comment

I love to read. However, I've got a long ways to go to match comedian Mel Brooks's literary appetite. In a recent NY Times interview (sorry, subscription only), his past reading list is prolific. I suppose he could be exaggerating to pull our collective legs, but I doubt it.

Compared to the previous week, it wasn't difficult to find new articles to talk about this week. I'll just pick a few.

A mAb-Less Winter

I stole this phrase from Dr. William Werbel, an adult infectious diseases physician and researcher at Johns Hopkins, speaking at a CDC/IDSA Clinician Call webinar on November 12. It's a great sound bite of how variants are changing our prophylactic and therapeutic landscape for COVID-19 particularly with regard to use of monoclonal antibody products.

It's getting tough to keep track of all the variants going around, but keep in mind we are seeing exclusively omicron subvariants. We haven't had a major change in variant type since omicron appeared almost a year ago. Here's the latest picture from the CDC:

What you can see most recently is the decrease in proportion of BA.5 accompanied mainly by increases in BQ.1, BQ.1.1, and a little of BF.7. It's still a bit early to understand all of the clinical implications of these newer sublineages, but the main concern is that they appear to have specific mutations that limit the effectiveness of current monoclonal antibody preparations we have come to rely upon.

Bebtelovimab is the only monoclonal antibody effective for treatment currently, but laboratory studies strongly suggest that it loses significant potency with mutations in the 444 region; BQ.1 and BQ.1.1 have the K444T mutation. Similarly, Evusheld (combination of tixagevimab and cilgavimab) is an important agent for prophylaxis of SARS-CoV-2 infection, long-acting and widely recommended (though underutilized) for individuals with immune compromise. Evusheld loses potency against viruses with mutations in either the 444 or 346 regions. BQ.1 has the K444T mutation only, BF.7 has the R346T mutation only, and BQ.1.1 has both mutations, Together, these 3 subvariants comprise over half of the circulating viruses in the US and are rising. Thus the concern that this winter will leave us stranded without effective monoclonal antibody products for treatment and prevention. Of course research is ongoing to develop new monoclonal antibody preparations, and we still have antiviral agents like ritonavir-boosted nirmatrelvir (Paxlovid), remdesivir (Veklury), and molnupiravir (Lagevrio) that appear to retain activity against new subvariants.

For the most part, monoclonal antibodies exert their effects by providing neutralizing antibody against the viruses. However, vaccines go a bit further to stimulate not only neutralizing antibody production in the recipient but also to activate other parts of the immune system to lower risks of infection and severe disease. I'll play the broken record again: everyone eligible should be vaccinated and boosted against COVID-19.

Covid and Kids

Two recent reports of covid and young children are helpful. One, from the CDC, was widely publicized. The other, from the UK, was not, at least not in the US that I could appreciate. Whenever I see data drawn from administrative databases I worry about drawing too many conclusions, because clinical details often are lacking or inaccurate. However, we do have some more refined clinical details in both of these studies.

The CDC report focuses on infants under 6 months of age during the time period June 2021 through August 2022 (first half mostly delta variant, second half omicron). What struck me most were the risk factors for hospitalization which did not change during the study period. Overall almost a quarter of all hospitalized infants had at least one risk factor for severe disease, with prematurity being most common. The proportion of infants with risk factors generally increased with age. This is clearly an alarm to promote immunization of pregnant people to protect not only themselves but their infants as well.

The UK study looked at deaths in children and young adults less than 20 years of age; having a national health system makes this data collection much more accurate than we can provide in the US. Over 13 million individuals comprise this UK age group, and the investigators identified almost 3 million covid infections during the study period of March 2020 through December 2021 (almost all pre-omicron). They found 185 deaths within 100 days of a positive SARS-CoV-2 test and then dug deeper with clinical questionnaires. Ultimately they concluded that 81 of the deaths were caused by covid with the remainder attributed to other causes. With this small number it's tough to break this down further, but about half of the non-covid death subjects had no comorbidities compared to about a quarter of the covid deaths. Within the covid death group, severe neurodisability was particularly striking to me at about one-third of that group. Note that during the study time period, covid vaccines were not available to the under 12-year-old population.

School Masking Works

This might be a case of closing the barn door after the horses have escaped, but we now have further evidence that masking works. The study from multiple institutions in Boston looked at covid incidence before and after school masking mandates were lifted and, although this was an observational study rather than a prospective randomized trial, it did confirm that masking can help prevent infection and illness. This should be useful should we encounter a severe upswing in covid cases in the future; masking could mitigate students missing school. Another important feature of this article is that schools with poor ventilation and higher rates of students with language barriers, disabilities, and low-income families are at highest risk of infection. The discussion portion of the article should be required reading for school administrators and policy experts.

My Homework Just Increased

But back to Mel Brooks, one of my all-time favorite entertainers and personalities. In the Times interview, he mentioned over 20 books/authors, plus 9 pieces of music and 4 entertainers, in a wide-ranging commentary on life influences. I think my reading list just doubled. I was totally taken aback when, asked about the best book he ever received as a gift, he mentioned Gogol's "Dead Souls" as a "life-changing gift" that he reads annually. I'll be searching for a copy in my area used bookstores.

A Failure to Communicate

Bud WiedermannOctober 17, 2022October 17, 2022Leave a comment

Regular blog readers know I've taken a few months respite from posting to get my newly retired status figured out (still working on that) and deciding whether to continue blogging (affirmative, as indicated by this posting).

Even before the COVID-19 pandemic I was struck by how poorly we healthcare providers communicate risks, benefits, and management choices to each other and to our patients. We haven't done a good job of communicating the uncertainties inherent in medical science and practice; for multiple reasons, the pandemic has transformed this communication gap into a wide chasm. I'll be trying harder to be an effective communicator, not only to pediatric healthcare providers as before but also to patients, families, and the public in general.

The title of this post comes from the 1967 movie "Cool Hand Luke" starring Paul Newman and depicting the lives of jailers and inmates in the Deep South shortly after World War II. Having never watched the movie in its entirety before, I forced myself to do so recently. More on that later.

Bivalent COVID-19 Vaccines for 5-year-olds and Up

I hope all pediatric healthcare providers are now well aware that both Pfizer-BioNTech (ages 5 and up) and Moderna (ages 6 and up) bivalent vaccines are authorized for booster doses. Note that the bivalent part of the terminology just means it contains proteins from both the original strain of the SARS-CoV-2 virus that appeared in late 2019 as well that from the more recent omicron variants BA.4 and BA.5 that have some ability to evade the immune protection of the original vaccine.

Although we don't yet have peer-reviewed publications of the data leading to this authorization, know that it was based primarily on safety and antibody data, rather than a prolonged trial looking at how effective the boosters are in preventing severe COVID-19 disease in children - that information will take many more months to accumulate, and studies are ongoing as are studies in younger children.

At this point in the pandemic, the scientific data on the benefits of vaccination are clear. Compared to outcomes of natural infection with the SARS-CoV-2 virus, vaccines come out ahead for all age groups and risk factors, including for children. Of course, the magnitude of the benefit (bang for the buck) is greater for older individuals and those with underlying conditions leaving them at higher risk for COVID-19 complications. Risk for a poor outcome in a healthy child with COVID-19 disease is much lower than in an old geezer like me, for example. Still, it's a slam dunk from my perspective: every child eligible for vaccination should receive the primary series and available boosters. Reliable information is available from the CDC website. Vaccine Recipient Information also is available. 'Nuff said.

Variations on a Theme

Regardless of what COVID-19 variants are up to, we are in for a tough winter of respiratory virus illness, including for children. Our usual seasonal patterns have changed since the pandemic started, but maybe this season will be more normalized. We have already had a very busy enteroviral illness season; this virus usually peaks in August/September and came back with a vengeance recently. Influenza is ramping up mostly in the southern US but will soon involve the entire country, and respiratory syncytial virus (RSV) activity is already up - usually RSV is a late fall/winter virus. In the days before the pandemic every winter I (selfishly) hoped that RSV season would taper off before flu season started; if they came at the same time, we'd all be working overtime. Now, we're layering COVID-19 on top of all this. I strongly recommend annual influenza vaccine for everyone who is eligible.

Everything so far is pointing to an increase in COVID-19 cases this winter season. For example, cases in the United Kingdom and elsewhere in Europe are already rising, and with so many unvaccinated children out there all going back to school, we can expect a lot of SARS-CoV-2 transmission. How much, and how severe, are unanswered questions so far. In part this depends on the behavior of the so-called virus variants.

The graph at the right depicts the most recent CDC data for circulating variants of SARS-CoV-2, as of October 15, 2022. First, the good news. These are all subvariants of the omicron variant; this has been the case for several months (remember the delta variant?). Omicron seems to be a variant that causes less severe illness in general.

Now for the bad news. Some of these subvariants show early indications that they are resistant to some of the therapies now very helpful in managing or preventing infections. Secondly, some of those now increasing, like the dark blue BA.4.6, may not be prevented by the original COVID-19 vaccines. That's why there was a big push to produce the bivalent vaccines that include components that could be more effective for these newer subvariants. Again, everyone eligible for the bivalent COVID-19 booster should receive it.

The real concern is that we are waiting for the next major change in the virus that could portend something that could evade our existing treatments and vaccines and cause more severe disease. As long as we have humans being infected, this virus will continue to mutate; the more infections, the more mutations and the more likely we'll see a worse version of the virus come to the forefront.

But enough of this doom and gloom! Sometime, maybe about a year ago when it became clear that SARS-CoV-2 had incredible ability to produce new variants, I was reminded of the Goldberg Variations, a set of keyboard pieces written by J. S. Bach. Johann Gottlieb Goldberg studied under Bach and likely was the first person to perform Bach's variations. My favorite pianist playing these variations (not that I've sampled all the recordings) is Glenn Gould. It is my never-fail stress reliever, especially needed during pandemic times.

Cool Hand Luke

Retirement has given me more freedom to go down rabbit holes, and when I found out the "failure to communicate" quote came from this movie (though not present in the book from which it was adapted) I had to watch the full movie. I said at the start of this post that I had to force myself to watch the entire movie; the emotional and physical brutality depicted was a bit tough for me. However, I enjoyed performances of all the lead actors plus a few "hey, doesn't he look like ..." moments that I discovered were younger versions of future stars, their names buried in a long list of cast credits.

The quote itself, delivered by the great character actor Strother Martin in his role as prison warden, is: "What we've got here is failure to communicate." (It is #11 on the American Film Institute's list of 100 greatest American movie quotes.)

Tag: SARS-CoV2