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Tag: omicron variant

Published on Leave a comment on Adventures in My Rabbit Hole

By my rough estimate, I've been in my private rabbit hole of infectious diseases and microbiology for over 50 years. Certainly covid has prolonged my stay. This past week I saw a number of new publications that are worth mentioning, I'll try to be succinct!

Tripledemic Tracking

After pausing for data entry to somewhat catch up after the holiday lull, let's look at the landscape.

Influenza

According to FLUVIEW, the country as a whole is seeing continued decline in flu cases. Remember I'm showing you just the hospitalizations confirmed to be flu, as a most accurate tally. Note that the dashed line is to call attention to the lag in reporting the past few weeks. Let's hope we don't see a rebound.

COVID-19

Percent positivity continues to rise, but a little tougher to determine accurate infection rates given all the nuances we've discussed recently.

The XBB.1.5 variant continues to hold the lion's share of the variant proportion in the US. I was interested to see that, at least so far, this variant is not a big deal in the UK. I expect that to change.

RSV

RSV-NET shows a continued decline in RSV infections, with the caveat that we might still be experiencing delayed reporting from the holidays. I don't expect RSV to trouble us any more this winter.

More on Long Covid

A new analysis from Israel suggests that most symptoms of long covid tend to resolve at 1 year follow-up for those individuals who had mild covid illness originally. This is an analysis from a large database which can have its own misleading reporting issues, but in the past this same database has had a good track record for being correct.

Bivalent Covid Vaccine Boosters No Better Than Monovalent?

Two small studies (here and here) in last week's NEJM suggest this is the case, from comparisons of antibody responses. I first commented on these studies last October when they were only in preprint form. Note these studies did not include children, so we could see some different results when those analyses are performed. The accompanying editorial by Paul Offit is a good read. It is essentially an "I told you so" discussion. Some may recall that he was the only member of the FDA VRBPAC panel last summer who voted against moving forward with the bivalent boosters. His main argument was that we didn't know if they were any better than monovalent boosters against the emerging variants, and these small studies appear to confirm his suspicions.

Please be aware this doesn't mean that bivalent boosters are worse, just that they may be no better than boosting with the monovalent vaccine, at least for now. Stay tuned for what should be a very stimulating discussion of future vaccine plans at the next FDA VRBPAC meeting on January 26.

A Clue to Myocarditis Mechanism Following Covid Vaccine?

Researchers in Boston reported results from 61 adolescents and young adults (16 who developed myocarditis and 45 who did not) who had received either the Pfizer or Moderna mRNA vaccines. They found an association of circulating spike protein in blood samples with the myocarditis group. They also looked at immune and cytokine patterns in the subjects. The discussion portion of the article brings up many possible explanations for how intact spike protein might be involved in the pathogenesis of myocarditis, but this is all very preliminary. Now we need more studies to confirm this association and further explore the immunologic phenomena accompanying it.

Note that nothing in this study changes the bottom line for vaccine advice: benefits of covid vaccination outweigh risks when we are considering myocarditis or any other endpoint for COVID-19.

Everything Old is New Again

No one seems to know definitely who first coined this phrase, but I mention it here to remind all healthcare providers to be on the lookout for those "old" vaccine-preventable diseases such as measles, mumps, rubella, and even diphtheria. This week the CDC gave us figures for vaccination rates in kindergarteners during the 2021-22 school year: not encouraging, but also not surprising. Another publication provided some some explanation for why we see problems with mumps outbreaks even in fully vaccinated adolescents and young adults. (Spoiler alert, it is waning immunity.) If any healthcare provider is a little fuzzy on diagnosis and management of these diseases, please review!

Speaking of old, I found that Alice's Adventures in Wonderland was published in 1865, and Down the Rabbit-Hole is the title of the first chapter. Maybe I'll reread it one of these years.

Published on Leave a comment on Rounding the Corner?

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!

Published on Leave a comment on Potpourri

It's that time of year for various types of potpourri, either simmering on the stove or in dried form. I also realized a need for my own infection potpourri, I have so many topics to catch up on. Here goes.

The "Tripledemic"

You wouldn't know it from the news, but there is reason to be optimistic now even with covid cases surging.

RSV

RSV isn't a reportable disease in the US, so accurate tracking is tough. However, CDC's RSV-NET utilizes active reporting from 58 counties in 12 states (CA, CO, CT, GA, MD, MN, NM, OR, and TN) to give a partial picture:

The above is just one screenshot of many in this interactive display, but note the green bar representing the 2022-2023 season. It confirms what pediatricians in our area have been seeing for the past few weeks - RSV is way down. This needs to be tempered with the fact that current hospitalization rates now are in the same ballpark as peaks in the 2 prepandemic years, so there's still a lot of disease activity.

Although there is no guarantee we won't see another peak later on this winter, I would doubt it. We have probably run through the bulk of susceptible young children, so the remainder will be children born in the next few months. If their mothers were infected in this round, these newborns (except for the extreme prematures) will have benefit of maternal antibody. Also remember that, if studies go well, RSV vaccination for pregnant women and a longer-acting monoclonal antibody preventive treatment may be authorized or approved in 2023. (You can see I'm carried away by optimism today!)

Influenza

Similarly, we might be seeing a break in flu nationally, though like RSV and all other respiratory viruses, the disease activity can vary widely in different parts of the country. FLUVIEW shows us the picture from a few different angles. First is influenza-like illness, which can include other respiratory viruses besides influenza because it has a clinical definition without requiring diagnostic proof of influenza infection:

Note there is a clear downward trend for the (red) 2022-23 season, but also compare with the (green) 2019-20 season with multiple spikes that likely reflected the beginning of covid. However, there is additional evidence to suggest flu is waning when looking at the hospitalization rates for confirmed influenza (also from FLUVIEW).

The slope of red line, which shows cumulative hospitalization rates, is decreasing. Keeping fingers crossed, but still plenty worthwhile to get a flu vaccine for those who have procrastinated. We still have a ways to go with flu this winter.

COVID-19

Poor reporting of at-home test results and general apathy about all things covid mean our data aren't as reliable, but we're certainly seeing a surge this winter which is entirely expected.

The telling parts of the graph above are not only the somewhat tiny blip in weekly cases but more significantly the sharp increase in percentage of positive tests that likely spells at least a modest covid winter.

I'm hoping this winter won't look anything like last winter, but as usual it will depend on the variants.

The omicron subvariants BQ.1, BQ.1.1, and XBB will guide the next few months. They have certain advantages in terms of immune escape and growth but so far do not seem to be causing more severe disease. Human behaviors such as vaccine hesitancy and not restricting activities when having respiratory symptoms also are significant determinants for what the winter holds.

New MIS-C Case Definition

Along the lines of more good news, MIS-C has become increasingly uncommon in the omicron era.

Even last winter, MIS-C was not as common as in previous waves, and this trend is continuing now. The exact reasons aren't clear, likely a combination of previous infection, vaccine immunity, and perhaps genetics of the variants themselves. CDC recently modified the case definition to make it more accurate and easier to report; this will take effect in 2023. Check out a CDC webinar for the graph above and more information about MIS-C.

A More Accurate View of the Global Burden of the Pandemic

So, some degree of good news for covid. However, the overall status still is depressing. WHO estimates the cumulative burden of the pandemic to be almost 15 million excess deaths. Although we've all become somewhat numbed by large numbers, take a moment to let that sink in.

On the good news side, the Commonwealth Fund has estimated tremendous benefits from the first 2 years of covid vaccination in the US:

Covid Vaccine Updates

Speaking of covid vaccines, a few new items appeared recently. CDC released 2 reports showing relatively good efficacy of the bivalent boosters in preventing serious disease in adults. The studies are still preliminary and have a lot of limitations including not being able to control for individual behaviors such as use of therapeutic options like Paxlovid. One study looked at hospitalization rates in those 65 years and older and the other reported emergency department, urgent care, and hospitalization rates in immunocompetent adults.

One study of the Pfizer vaccine documented the benefit of booster dosing in the 5 - 11 year-old age group. This was during the delta and omicron periods but before the bivalent booster appeared.

Now we just need to improve our dismal covid vaccination rates! The AAP provided a guide for busy practices trying to figure out which vials to use for which circumstances, and CDC provided a nice webinar (I learned several things) about discussing vaccine hesitancy. I urge all healthcare providers to look at it.

Happy Birthday Louis!

Whenever I spoke about ancient (i.e. older than 5 years) history of infectious diseases, trainees always assumed I was speaking from personal experience. Let me be clear: Louis Pasteur was not a contemporary of mine. A very happy 200th birthday to Louis on December 27. Several editorials in the December 17 Lancet marked this milestone. The proponent of the germ theory of disease and developer of the first rabies vaccine likely could still teach us a few things about handling today's pandemic.

Also, I can't leave the subject of birthdays without noting my wife's birthday this week. She is considerably younger than Louis. Happy Birthday to Pam!

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Published on 2 Comments on Collateral Damage

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.

Published on Leave a comment on It’s Never Over

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.

DRC = Democratic Republic of Congo; MERS = Middle East respiratory syndrome; SARS = severe acute respiratory syndrome; XDR = extensively drug-resistant

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!

Unless otherwise indicated, the content and opinions expressed on this web site are those of the author(s). They are not endorsed by and do not necessarily reflect the views of the George Washington University.
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