omicron variant – Page 9 – Pediatric Infection Connection

Collateral Damage 2

Bud WiedermannDecember 4, 2022December 4, 20222 Comments

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

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

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

The Mother of All Flu Seasons?

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

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

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

Be on the Lookout for Previously Rare Vaccine-Preventable Diseases

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

You Can Limit Collateral Damage

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

It’s Never Over

Bud WiedermannNovember 27, 2022November 27, 2022Leave a comment

I co-opted the title above from last week's New England Journal of Medicine perspective article by Dr. Anthony Fauci. It's 3 pages, read it if you have a chance. Mostly by virtue of working in the same infectious diseases community as Fauci for the past few decades, I've been privileged to interact with him on a number of occasions both formal and informal. He is a true genius but also a warm and caring person.

His timeline of emerging infectious diseases, copied below, particularly spoke to me as it coincided with my entry into the pediatric infectious diseases subspecialty. Because my practice was located in an area of high international travel, I had to respond very quickly to possibilities of new infectious diseases. Each time I felt exhilaration with a tinge of fear.

I also note that, of the 21 infectious diseases listed, I've only directly cared for children who truly had 10 of them. However, I was prepared and did evaluate children for all of them. I suspect all infectious diseases clinicians are accustomed to working in hyperdrive at the slightest hint of something new appearing.

Overdiagnosis of Penicillin Allergy

Most healthcare providers know that penicillin and other drug allergies are over-diagnosed. Also, drug allergy is not a lifelong condition but rather is very dynamic. That amoxicillin "allergy" in an infant, even if a true type 1 hypersensitivity reaction, often resolves in later life. Penicillin allergy is a real problem in pediatric healthcare; I long ago lost track of the number of children I've seen who were hospitalized with a serious infection and treated with broad spectrum antibiotics chosen because of a penicillin allergy history. With further probing, it was readily clear that the original so-called allergic event was poorly documented, making it difficult to remove that label in real time. Virtually none of the children had ever been referred to an allergist to sort out the penicillin allergy label. The unnecessary use of broad spectrum therapy contributes to antimicrobial resistance.

This brings us to a recent systematic review and meta-analysis of studies of adult and pediatric patients referred to non-allergists for de-labelling of penicillin allergy. After an extensive systematic literature review of over 11,000 articles, the authors from the UK selected 69 that were of sufficient quality to include in the analysis based on pre-established quality criteria. [Note, this winnowing of articles from 11,000 down to 69 isn't unusual. It's another way of saying that most published articles add little to our understanding of medical management, probably a by-product of "publish or perish" pressure in academic medicine that sometimes rewards quantity over quality.]

Meta-analyses require some of the most sophisticated statistical evaluation in all of medicine; these authors did follow fairly standard methodology in their approach. What's interesting to me are the bottom line numbers. Looking at just the studies that had complete data listed for the proportion of patients tested who were de-labelled, 5072 were tested of which 4698 (92.6%) were de-labelled and 76 (1.5%) were harmed. None of those harmed had serious reactions. Digging a little deeper, 14% of 4350 patients assessed by history alone, 98% of 4207 patients assessed by drug provocation, and 41% of 2890 assessed by skin testing followed by drug provocation were de-labelled.

The take-home points I see from this study are: 1) most subjects labelled as penicillin-allergic aren't truly allergic; 2) front-line healthcare providers need to carefully document possible drug reactions, i.e. don't just record "rash" but rather a complete description of the event in the patient's medical record; 3) for those with possible type-1 hypersensitivity reactions, re-evaluate those patients at the next well visit and consider referral to a provider who can assess for true allergy if needed; and 4) don't let that patient languish for years with a penicillin (or other drug allergy) label. Reassess at every well-child visit and consider a de-labelling process before many years have passed.

COVID-19 Cutaneous Findings

Another group of primarily UK researchers reported findings of cutaneous symptoms from 348,691 participants in an ongoing self-reporting system for COVID-19 symptoms. This is essentially a retrospective case series study. The time period covers both delta and omicron variant waves. They found that skin findings were reported more commonly during the delta time period, 17% versus 11% during omicron, and that cutaneous findings rarely (<2%) were the initial or only findings of infection. The most prominent cutaneous features were unusual hair loss and rashes described as burning, acral, erythematopapular, or urticarial. Skin findings lasted slightly longer in the delta period compared to omicron, and both were shorter than what was reported from the onset of the pandemic with the ancestral strain. Vaccination status didn't seem to have a bearing on cutaneous findings with the exception that vaccinated individuals were less likely to report a burning rash.

Last year some of these same authors developed a nice website to view these cutaneous findings of COVID-19 illness. I look forward to seeing updates of this study as we see new variants and waves.

The Doctor's Dilemma

Fauci referred to an older article by Robert Petersdorf, an early infectious diseases giant, titled The Doctor's Dilemma. That in turn referred to the play by George Bernard Shaw which has been one of my favorites for many years. It is a satire and critique of the medical profession and expresses strong anti-vivisectionist viewpoints. I strongly disagree with some of the tenets presented while agreeing with others, but overall it is very entertaining. If you're looking for some high-quality escapist reading, try it!

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!

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.

Calm Before the Storm?

Bud WiedermannOctober 30, 2022October 30, 2022Leave a comment

Frontline pediatric healthcare providers probably wouldn't think things are calm given our current onslaught of RSV and influenza cases crowding physician practices, emergency rooms, and hospitals. However, we are in a bit of calm of sorts for covid. Covid cases actually are decreasing in the UK and the US. Lacking a reliable crystal ball, we'll all need to wait to see whether the next few months will bring a significant rise in covid cases. In the meantime, let's explore a couple areas of interest and confusion.

How Well Do the Bivalent Boosters Work?

More time is needed for the definitive answer on this. The discussion has been going on for months, but this past week we saw posting of 2 preprint articles suggesting, based on immunologic testing, that they may not be much better than the original vaccine used as a booster, at least in terms of preventing illness after infection from some of the newer variants. This is actually what was suspected all along. The bivalent vaccine to stimulate immune response to the spike protein from BA.4/BA.5 was hoped to be a bit more effective to prevent severe disease caused by future virus variants. Carolyn Johnson's explanation of the issue in the Washington Post was excellent, please check it out. It is important to recognize that these 2 studies were based on very few individuals and have not undergone peer review. However, the reports are from generally reliable teams at Columbia University/University of Michigan and Beth Israel Deaconess Medical Center. I don't expect big changes in the results once the peer review is completed.

I want to expand on one concept mentioned as an explanation for the findings in both articles, that of immunologic imprinting. This phenomenon also has been referred to as original antigenic sin.

This imprinting is very different from filial imprinting, like baby ducks following the first thing they see after birth. Original antigenic sin refers to the 60+ year old observation that our immune systems like to use the memory of our response to an infection with an antigen (virus in most cases) when infected at some future time with a variant of that antigen. It could potentially interfere with a more robust immune response to that new variant. Of course, covid didn't exist when it was first described; the main subject was influenza at that time. Scientists developing new vaccines have been well aware of this phenomenon for decades. Covid vaccine development has incorporated this concept.

A key point: although it's possible the bivalent vaccines aren't that much better than the original vaccines when used as boosters, any booster is far better than no booster. Please encourage everyone eligible to be fully vaccinated and boosted for COVID-19.

[I realize I haven't mentioned this in a while, but some may wonder about my frequent use of Wikipedia in my links. For many medical issues, I find Wikipedia to be highly accurate plus a little more understandable to non-medical folks than virtually all other sources.]

Should We Worry About Polio in the US?

In general, no, but anyone lacking full vaccination against polio needs to beware. A few years ago it would have been hard for me to imagine ever saying that, but a combination of war, politics, natural disasters, and apathy make paralytic polio a real possibility now. Wild-type polio transmission was eliminated in the western hemisphere in 1991, and it still is, but failure to eradicate it elsewhere has led to vaccine-derived poliovirus causing paralytic polio across the world, including in the US. (Paralytic disease, the most severe form of polio, develops in less than 1% of infected individuals.)

For those unfamiliar with the disease (few clinicians have seen an active case of paralytic polio, unless they have worked abroad), remember that we have had 2 types of polio vaccine for many years. The live polio vaccine (aka Sabin vaccine, developed in 1961) is a weakened version of the wild virus, given by mouth, and requires viral replication in our bodies to produce immunity. It is particularly helpful in achieving immunity in populations difficult to reach by widespread immunization because the vaccine virus is excreted in stool and can be spread to others. That's mostly a good thing, but sometimes this vaccine-derived strain can undergo transformation to increased virulence and actually cause disease in others. A killed vaccine given by injection (aka Salk vaccine, developed in 1955) also is effective though slightly less so than the live vaccine. The live vaccine has not been used in the US since 2000; all polio immunizations in the US, and in most other developed countries, utilize the killed vaccine.

Even though most of us in the US are immunized and therefore protected against polio, wastewater surveillance in New York City suggests that the vaccine-derived virus is circulating in at least 5 counties, putting un- or under-immunized people at risk for paralytic polio. This situation likely is occurring elsewhere in the US, but so far we lack comprehensive wastewater polio reports. Data from London suggest the problem is widespread.

The pandemic and ongoing anti-vaccine rhetoric has disrupted vaccination programs in the US. Let's hope we don't see more cases of paralytic polio in the US.

Interested readers can learn more about the history of polio from the Global Polio Eradication Initiative.

Tag: omicron variant