pandemic – Page 4 – Pediatric Infection Connection

Hope Springs Eternal

Bud WiedermannJanuary 29, 2023January 29, 2023Leave a comment

An interesting week with the FDA VRBPAC meeting and release of a few new studies, but still no word from CDC on relaxing covid testing for asymptomatic individuals. Bottom line though, some more reasons to remain optimistic. Let's dive in.

RESP-NET

Trends continue downward overall as well as individually for covid, flu, and RSV in RESP-NET. This bodes well, although in the pandemic era anything seems possible. Of course still worthwhile to get flu and covid vaccines if eligible.

You might be interested to have a peek at the WHO influenza information, what is pictured below is current as of January 8. It is more or less a typical global flu picture.

As you can see, southern hemisphere activity is low for the most part, with a predominance influenza B and A H1N1pdm09 strains rather than the AH3N2 that predominated earlier. This change in strains is typical at the end of a flu season, both the B and H1N1 strains are well covered by this year's vaccine.

Covid Vaccine Horizon

As planned, the FDA VRBPAC did meet last Thursday. I was able to watch most of the day's proceedings. (It was a long day, you can watch a recording of the whole thing if you want!) Presentations by Pfizer, Moderna, Novavax, FDA, CDC, and others were followed by multiple questions and discussions, all very good. Rather than lull you to sleep with too many details, let me try to summarize key points which were all about simplification. First, the VRBPAC members voted unanimously to recommend harmonization of the covid vaccines going forward. By that I mean that each manufacturer will be providing the same vaccine for both primary series and boosters. So, we won't need to worry about whether a monovalent or bivalent vaccine is needed for a particular individual. If the FDA follows these recommendations and CDC/ACIP agrees, only the bivalent vaccines will be used for primary and booster series - we won't be able to access the monovalent mRNA vaccines. I certainly concur with this - we have had so much lost in translation in implementing covid vaccination in the US, it is too confusing for providers and vaccinees - and data are very reassuring that the bivalent mRNA vaccines have an excellent safety profile and at least equivalent efficacy, if not a little better. More on that later.

Not to be forgotten, we have a third vaccine from Novavax also authorized in the US. It is an adjuvanted vaccine that does not involve mRNA technology, and studies have shown excellent safety and efficacy in adults. Pediatric studies have lagged considerably and the company did not present any substantive new data for young children.

What remains confusing still is how individuals with prior infection but no prior vaccination will be treated. Probably one dose of vaccine would suffice, but how do we verify prior infection for an individual? Also, how do we determine exceptions to what could be a recommendation for annual covid vaccination for most people? Those exceptions include elderly, immunocompromised, and perhaps young children. Will some of them be recommended to receive 2 vaccines per year? Although this is a move towards simplicity, none of this is easy, and the devil will be in the details. I hope the CDC and other agencies are up to the communication task.

Expect more updates on timing and composition of vaccines to be available in late summer/early fall. Churning out an mRNA vaccine targeting newer variants takes about 100 days, maybe a little longer for the Novavax vaccine. It looks like the VRBPAC will be meeting again around May. We should all be very thankful for the efforts of VRBPAC staff and committee members.

Advice for Immunocompromised

Speaking of communication (pun intended), CDC has a nice graphic and somewhat clearer guidance for immunocompromised folks.

This definitely helps, but we all know that not all immunocompromise is equal, so the vaccine nuances (especially whether to administer subsequent doses once or twice a year) will be tough to explain for those with milder underlying conditions.

New Studies of Bivalent Covid Vaccines

Last week saw publication of three updates of results of bivalent covid boosters; all were discussed at the FDA meeting. First, a group at the University of North Carolina reported state data suggesting bivalent vaccine efficacy was pretty good against some of the newer omicron variants. The bivalent boosted individuals (study included ages 12 years and up) had better protection against severe infection than did those who received the monovalent booster. However, numbers were small resulting in wide confidence intervals, and as always protection lessened with longer time after boosting.

CDC reported early estimates of bivalent booster protection against BA.5 and XBB/XBB.1.5 sublineage variants in adults. The study had the same caveat about small numbers and wide confidence intervals, but again a suggestion that the bivalent booster might be performing better than the monovalent booster for these newer omicron variants.

Finally, a study just looking at the Pfizer vaccine showed somewhat better serum neutralization activity against the newer variants in adults who received the bivalent booster compared to those who received just the monovalent booster. This is an important study but less helpful since it is looking at a surrogate marker (neutralization levels) rather than true vaccine efficacy.

More Good News About mRNA Vaccines in Children

A large meta-analysis published last week provides more information about the excellent safety and efficacy of covid mRNA vaccines in children in the 5-11-year-old age group. Benefits far outweigh any risks from these vaccines.

Vaccine Conversations: AAP to the Rescue

The American Academy of Pediatrics published a 49-page report on methods for productive discussions of vaccines with families. If you don't have time to wade through that, AAP will have a 1-hour webinar this Thursday, February 2. I don't think you need to be an AAP member to attend.

Hope

The line "hope springs eternal" is buried somewhere in Alexander Pope's poem An Essay on Man. I also learned that it was the title of a 2018 indie film. I'm not planning to look into either Pope's poem or the movie. However, I can recommend the book I'm reading now, Sea of Tranquility by Emily St. John Mandel, especially if you've read any of her earlier books. It's contains a story of a fictional pandemic, but since I haven't finished it I don't know whether the ending is hopeful or not!

Distracting Drama

Bud WiedermannJanuary 8, 2023January 8, 2023Leave a comment

I tried, but not hard enough, to ignore the drama in the House of Representatives this week. At least now we can step back for a bit before we find out what the House looks like when the dust clears. I hope we still have a somewhat functional legislative branch of government.

This past week characteristically is the least reliable in terms of public health epidemiology. This is because our winter holidays naturally result in some delayed data collection and reporting. Even with likely under-reporting, the covid map doesn't look too good. Rather than boring you with unreliable numbers today, instead I will focus on a question about last week's blog.

Flu vs. Covid

Last Monday Michael Schwartz asked 2 questions:

1. Why do we continue to pursue universal testing and recommend isolation for a minimum of 5 days for COVID , but do neither for influenza ?
2. Should we be trying for universal testing and longer isolation for influenza or should we be treating COVID as endemic and treat it like influenza , or some other answer ?

We still have many questions left unanswered, but it may be that covid could become more like influenza in terms of disease management. Influenza and SARS-CoV-2 are both RNA respiratory viruses, but they have significant differences. Still, the history of influenza pandemics might help inform the path forward with covid.

Not much is known about flu pandemics in the 19th century, mostly because the science and reporting wasn't well-developed at that time. Subsequently our flu pandemics all have been influenza A, because it is able to change and "jump" from one species to another. Influenza B does not have an animal reservoir outside humans, plus it is well adapted to us, so it basically behaves like a regular seasonal flu virus rather than causing pandemics which require a large non-immune population. (Note there is an influenza C virus group, but relatively little is known about its epidemiology. Mostly it just doesn't cause problems, which is why most people have never heard of influenza C.)

Everyone knows something about the 1918 flu pandemic, caused by an A H1N1 subtype that jumped from animals to humans. About 40 million deaths occurred worldwide. The next flu pandemic was in 1957 with an H2N2 subtype that had some leftover elements of H1N1 combined with a bird strain of flu. It was a bad time, estimated several million deaths, but not on the order of 1918. With the start of the H2N2 pandemic, circulation of H1N1 flu went away for awhile and just H2N2 persisted as the main seasonal influenza A strain circulating.

Then we experienced an H3N2 pandemic in 1968, but it shared some elements of the 1957 H2N2 strain so not as severe. I have no memory of a pandemic in 1968 even though I was a teenager and thus partially sentient. (Certainly other historical events that year occupied my attention.) H3N2 persisted as seasonal flu, but in the late 1970s H1N1 reappeared as another seasonal A strain. This setting remained until 2009 when we had our most recent flu pandemic of H1N1, a pretty complex reassortment from human, pig, and avian strains. It was actually somewhat similar to the 1918 strain that persisted for a while, so the elderly didn't have as much problem with the 2009 pandemic as might have been expected. Also, folks like me who received the 1976 "swine flu" vaccine (I do remember all that kerfuffle at the time) also had some leftover immunity active against the 2009 H1N1 strain.

All of us should be getting annual flu vaccines, mostly to guard against the common minor changes in circulating flu strains (antigenic drift) as well as to control the relatively uncommon major changes (antigenic shift). SARS-CoV-2 also has minor and major changes ongoing, but the biggest difference is that so far they both occur much more frequently than for influenza. Ergo our moving target or "whack-a-mole" strategies with vaccines and monoclonal antibody treatments the past couple years.

Here are some other comparisons, assuming normal hosts:

	Influenza	SARS-CoV-2
Incubation period	2-3 days	~3 days¹
Reproduction number	1.3-1.7 (seasonal)	?²
Asymptomatic rate	5-30%	>40%³
Duration of contagion	1 day before - 5-7 days post symptom onset	2 days before - > 5 days post symptom onset⁴

All SARS-CoV-2 estimates are highly variable.

¹Varies with viral variant, prior SARS-CoV-2 immune status, age

²Widely variable based on multiple factors

³Varies with age and prior SARS-CoV-2 immunity, still not well established

⁴Varies with multiple factors including disease severity

Lots of footnotes and disclaimers, but perhaps you'll agree there are similarities between flu and covid. If SARS-CoV-2 does progress to behave more like a seasonal respiratory virus, we will be managing it more like we do flu: annual vaccination with composition determined by the most recent variants and (I hope) avoiding school and work attendance when ill, plus lessening of the mandatory testing and quarantine guides still in effect. Of course, if we do veer off to another major variant change that demonstrates increased severity, we are back where we started (except with a now pandemic-exhausted public). Time will tell, but I'm hoping we soon will revert to Michael's second option of settling into an endemic response mode.

More on Invasive Group A Streptococcal Infections (iGAS)

A couple of reports in the online journal Eurosurveillance offer a bit more information. British authorities describe the pattern of iGAS in children over the past few years, clearly showing an increase in absolute numbers. No specific emm types (the gene coding for specific M proteins that could confer enhanced virulence) were identified. The investigators document some association with respiratory viruses such as human metapneumovirus and RSV, but it isn't clear that this is significant since it is the season for both streptococcal infections and many respiratory viruses. In the Netherlands, investigators describe iGAS cases in children, particularly streptococcal toxic shock syndrome and necrotizing fasciitis. The latter showed an association with varicella infection, a known risk factor. Again, no specific emm type jumped out. In retrospect, it seems odd to me that the British study didn't even mention varicella co-infection.

Neither of these studies involved a control group looking at viral co-infections, so it's still hard to know what's behind these trends. The one potentially modifiable factor for prevention is varicella immunization.

1968

If there was a time period that forever changed the type of person I am, it was probably this year. I find it mildly amusing that I have no memory of the flu pandemic, clearly I was distracted by the Tet offensive, the tragic assassinations, the Democratic convention, Smith and Carlos at the olympics, and even the pictures of Earth from Apollo 8. My fascination with infectious diseases was yet to come.

Potpourri

Bud WiedermannDecember 18, 2022December 18, 2022Leave a comment

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!

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.

Happy Thanksgiving, et al 2

Bud WiedermannNovember 20, 2022November 20, 20222 Comments

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

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

Since I Mentioned Variants

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

Maricopa County - More Than Vote Counting

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

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

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

More on Paxlovid Rebound

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

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

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

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

We Should Be Thankful

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

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

Tag: pandemic