COVID-19 Updates: Bonus Pediatric Edition

I thought I would be all done with COVID-19 updates, but with summer coming up and a lot of questions about vaccinating kids and what activities are good for summer, I thought there would be room for one last update with a focus on kids, both from questions about disease risks as well as vaccination risks. We’ll also have a little opportunity to look at the current data on lasting immunity and talk about some good precautions to be taking over the summer.

I think we’re all pretty clear at this point that kids are still at extremely low risk of developing severe disease with COVID-19 infections. As you can see from these CDC charts, while children under the age of 18 have made up about 12.4% of all diagnosed COVID cases in the US, they account for less than 0.2% of all deaths. Given that we’ve probably missed a lot of the cases due to the absence of symptoms, you can probably estimate the infection fatality rate in the pediatric age groups to range somewhere between 0.002% and 0.009%, not taking into account preexisting risk factors.

As I’ve shared in previous updates, there is a very clear biological reason for this; the receptor this virus uses to infect the human body, the ACE2 receptor, is less prevalent in people under the age of 12 or so, which seems to have the effect of reducing the severity of disease as well as reducing how contagious they can be following infection. As near as we can tell, that is still the most logical explanation for why we really don’t see major outbreaks among pediatric populations. This is something is a result of human biology, and doesn’t have a chance of being affected by any mutations the virus is capable of acquiring. I saw the news reporting lately that younger people were constituting a larger percentage of the diagnosed cases now, but I’m sure you’re all aware this is simply a result of the majority of the older population being vaccinated. You can see that effect here in the CDC case trends broken down by age group:

It’s pretty cool to actually see in the demographic data the actual time frame where enough of the high risk population was vaccinated to see a change in the distribution of new diagnosed cases. Of course, there were probably a lot of younger people infected in the beginning of the outbreak a year ago, but we were likely missing the majority of those cases since we weren’t testing most of the asymptomatic cases.

The main issue we’re keeping in mind with the pediatric cases is the childhood multisystem inflammatory syndrome (MIS-C) we’ve seen that arise in a very small percentage of the cases. While it’s difficult to calculate the exact likelihood given we’ve probably missed diagnosing most of the pediatric cases, based on the CDC current numbers of 4000 cases of MIS-C it’s probably somewhere between 0.02% and 0.1%. With 36 deaths reported in the US so far associated with MIS-C, it accounts for maybe 8% of total pediatric deaths associated with SARS-CoV-2. Something of note here, and I’ll revisit this later, is that the majority of these MIS-C cases were in Hispanic and Black children. As I’ve mentioned in previous updates, probably sounding like a broken record by now, that also happens to be the population with the highest incidence of vitamin D deficiency, which certainly raises the question of whether or not vitamin D deficiency plays a role in development of COVID complications.

I have no idea why there isn’t a national, even global, push at this point to get everyone up to sufficient vitamin D levels. Even if it later turns out there was a negligible benefit, the costs of focusing on it are so low that it really doesn’t matter. Make an effort to get plenty of sun this summer.

You can check out this article if you want a description of what to look for when it comes to MIS-C, but in general you want to keep an eye out for fever, abdominal symptoms, bloodshot eyes, and rash appearing about 4 weeks after infection. The type of lab results you’d want to watch out for are elevated C-reactive protein, erythrocyte sedimentation rate, fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase, interleukin 6, elevated neutrophils, reduced lymphocytes and low albumin. Typical treatment protocols I’ve seen are pretty similar to COVID treatments in general; steroids to reduce inflammation and perhaps even anticoagulants to reduce risk of blood clots. Again, the risks for this are extremely low, but there’s no harm in keeping an eye out for the symptoms.

With that perspective on the risks of disease, now we turn to vaccinations for the pediatric population. Currently the FDA has given Pfizer an emergency use authorization status for kids…which is a little strange. There’s been some debate back and forth as to whether such a low chance of serious complications really counts as an “emergency” in the sense that an EUA is supposed to be used. It’s easy to justify it for the older population with a high prevalence of risk factors…it’s harder to justify for kids. The criteria for EUA can be a little subjective, which brings up the question of what the difference is between an EUA and full FDA approval. EUA’s have been thrown around a little haphazardly over the course of this pandemic, most notably the strange EUA given for hydroxychloroquine early on without a single study done in humans or even any dosing recommendation. Meanwhile, FDA approvals have been going out in strange situations as well, with the FDA recently approving Aduhelm for treatment of Alzheimer’s patients without any real proof of efficacy. The data is based on a study population of about 3500 patients that showed Aduhelm reducing the incidence of amyloid beta plaques in neurons…which is one of the proposed causes of Alzheimer’s disease. The plaques could also simply be a byproduct and not a direct cause at all…so there’s that. Either way, this approval was given despite no actual data on the reduction of progression of Alzheimer’s disease in patients…it’s based entirely on the unproven theory that reducing amyloid beta plaques will halt the progression of Alzheimer’s. I guess time will tell whether or not this theory holds water.

Either way, at this point I’m not even sure what the difference EUA and full FDA approval is anymore…I have no idea what the FDA is doing. Fortunately, we don’t need to care about what the FDA says, we can actually look at the published data ourselves for efficacy and safety information, and make our own decisions. And fortunately, we have a lot of great data for these new vaccines showing a great safety profile in all age groups and effectiveness not only in generating antibody response but also in stimulating T Cell, memory cell, and even a more well balanced innate immune system response, which effects not only the SARS-CoV-2 defense but also general immune system modulation effects protecting against cytokine storm responses. It was amusing seeing the antivax crowd going off on how the mRNA vaccines were “reprogramming” the innate immune system, when the reality is that’s literally what all infections and vaccines do. You can check out this article on it if you’re interested in the actual findings, but the “reprogramming” is actually a protective effect that helps modulate the immune system for a more balanced response, making these new mRNA vaccines some of the most effective and beneficial, not to mention safest, vaccines that we’ve ever developed.

For the Pfizer vaccine with ages 12–15, we have data on 1131 vaccinated and 1129 placebo kids age 12–15. With 18 diagnosed COVID-19 cases in the placebo group and none in the vaccinated group, it implies an efficacy of at least 94%. There isn’t much of a surprise here, given the data we had on all the groups above the age of 15 and the data we had on antibody profiles after vaccination, we had every reason to think these vaccines were going to be just as safe and just as effective in this age group. In general there isn’t usually a huge difference in vaccinating adults compared to kids. There are differences for some; hepatitis A and B, for example require a higher dose in adults compared to kids, while diphtheria and pertussis use a lower dose in adults, but those are the kinds of things you identify earlier in the clinical trials.

As far as safety goes, the only issues that have popped for the COVID vaccines in general are extremely rare blood clotting issues and myocarditis issues. From what I’ve seen in the blood clotting examples, they were most prevalent specifically in women that were on birth control, and given that birth control is its own independent risk factor for developing blood clots it’s not clear that the vaccines are really significantly increasing your risk there. We’re talking something on the order of a 1 in a million chance, so not something you usually factor into the decision making process, but it’s something that can arise in the weeks following vaccination. Myocarditis (heart inflammation) is also pretty rare, again somewhere on the order of a few cases per million, and usually don’t result in any significant problems. For these, they were more common in young adult males, and were mostly confined to a few days to a week after the second dose. If you are worried about these side effects, the precautions are pretty simple. The best way to reduce your chances of blood clots is to maintain a healthy level of activity. Don’t sit around on your couch watching Netflix all day; get up, walk around, enjoy the fresh air. For reducing the chance of complications from myocarditis, simply take it easy for a few days to a week after getting your second shot. Instead of going out to run a marathon or overexerting yourself lifting weights at the gym, go for easy, low key walks and activities. Be active, but don’t go crazy…basically just avoid the extremes. Given these complications are so rare, generally none of us are going to know anyone who has them, but they do exist.

This might be a good place to have a little discussion about the VAERS Database. For those of you who aren’t aware, the US has a reporting system for collecting data on adverse events connected with vaccines. It’s a very convenient way of rapidly collecting information that can identify harmful side effects with vaccinations. Unfortunately…there’s a little catch to the whole strategy…literally anyone can report anything they want to the thing…it’s a completely unverified database. I could go to it right now, say I have stomach pain, and claim that it was from my second dose of Moderna I got back in the beginning of April. There would then be an entry in the system associating stomach pain with the Moderna vaccine.

While this system is useful for identifying a specific vaccine manufacturing lot with an issue, it’s pretty useless for trying to extrapolate overall safety data for a vaccine. Whenever you look at the data, you have to ask two questions: are the adverse event reports reliable, and do they represent adverse events that are higher than expected in the average population? Given the…err…passion…to be found in the current antivaccine movement in the US…let’s just say not every data point present in the system is entirely accurate, so that can be a bit of a problem. It’s also true that problems like myocarditis and blood clotting do occur in the general population, and given a frequency of about 1 in a million in vaccinated populations it’s not entirely clear that this represents a significantly higher risk than we would normally see anyway, particularly because we were mostly vaccinating high risk people with a higher prevalence of preexisting medical conditions at first. That’s why it takes so long to analyze the information in the database. Also, this would be a good place to point out that the frequency of these events in vaccinated individuals is still lower than the frequency of these events in people who are naturally infected with SARS-CoV-2, so either way you look at it there is still a protective effect from the vaccines…the current observed benefits far outweigh any observed risks. If I had to make a rough ballpark estimate, I’d say your chance of developing these complications as a result of SARS-CoV-2 infection are about a thousand times higher than your chance of developing them from vaccination, so something to consider.

Speaking of observed benefits: lasting immunity. I know there was a lot of talk recently from CEOs and politician types speculating about annual boosters and things like that, but currently there is nothing in the data that suggests we won’t have lasting immunity from the vaccines that offers sufficient protection against the range of variants that have popped up…claims of needing boosters really fall under the category of speculation at this point. Like I mentioned in an earlier update, these variants really only differ by about 1% or so, which generally isn’t enough to evade the robust, polyclonal immune response we tend to generate from vaccines or infections.

https://science.sciencemag.org/content/371/6529/eabf4063

https://www.nih.gov/news-events/nih-research-matters/lasting-immunity-found-after-recovery-covid-19

https://www.nature.com/articles/d41586-021-01442-9

So far, every study that has followed up recovered patients or vaccinated individuals has told the same story: lasting immunity in the vast majority of subjects. There currently isn’t any evidence to suggest you even need to vaccinate people who already had SARS-CoV-2…the immune responses we’ve followed up to this point suggest that a very small percentage of the population fails to develop lasting protection, and the virus simply isn’t mutating at a fast enough rate to overcome that protection. Incidents of reinfection are extremely rare, and with a few exceptions generally don’t produce noticeable symptoms. Typically they’re only caught with random screenings.

So, the million dollar question, should we vaccinate kids? They really are the lowest risk population, both for contracting and spreading COVID-19, but at the same time the vaccines seem pretty harmless as well…and typically complications from vaccines show up in the month or two following vaccination. If we haven’t spotted any issues yet, we’re probably not going to see any.

However, from a global resource perspective, it really isn’t a logical use of limited resources to be vaccinating the lowest risk population in wealthy countries while the high risk populations in poor countries remain unvaccinated. We don’t exist in a bubble; we’re a global community, and medical resources are used all around the world. Outbreaks of disease in other countries do affect us here, and by nature a pandemic is something that needs to be addressed from a global strategy standpoint, and not an individual country standpoint. If you stop the virus in one country but let it spread uncontrollably in another, eventually it will cause a problem even in the protected country…if for no other reason because it will create a drain on limited health care resources. Given vaccines in the US are no longer supply limited and are now more demand limited, it makes more sense to be focusing our efforts on vaccinating the poorest countries with limited resources than to try using gimmicks to get the low-risk holdouts vaccinated here.

That being said, good luck convincing a parent worried about their kids that they’re better off vaccinating strangers in other countries than making sure their own kids are protected. Not that this is a bad thing, but I just feel like this is a strange time to be using the EUA process for this particular age group. I will say this, however, that the H1N1 flu strain still presents an overall greater risk to the pediatric population than SARS-CoV-2 does, so if you’re worried enough to make sure your kids have the COVID vaccine then you should also make sure you’re getting the flu vaccine as well to cover your bases.

There also is nothing wrong with waiting a little longer to vaccinate your low risk folks if you’re worried about it. We don’t need to get everyone vaccinated to get back to normal. I was teaching class in person all last year before any of us were vaccinated, and we didn’t have any issues. I think the whole year, we had one student in class who came down with COVID-19 and just had to quarantine for a week, and maybe 2 or 3 students out training in clinicals that came down with it and had to quarantine a bit. Every private school I know that had been teaching in person throughout the school year managed to pull it off without any outbreaks or catastrophes. Even if you want to keep masks around, there’s no reason not to have classes in person in the fall. The only school outbreak example I saw last year was a private high school in Fresno that seemed to have about 60% of the school population infected, and that went completely under the radar because no one was looking for it at the time. The only reason it was identified was due to antibody testing afterward; during the time of the outbreak it just looked like a really bad flu season. So, it is possible to have an outbreak at a high school…but pretty unlikely that you’ll actually see serious cases arise from it.

In summary, it isn’t unreasonable whichever way you choose; vaccinating your kids now or waiting a little longer, so don’t give parents a hard time about their decisions either way. No matter what, the risks are extremely low, but I think most parents will find it more convenient to vaccinate their kids just to avoid the hassle of worrying about masks. The risks of coming down with series problems from COVID in kids are really low, but the risks of having problems from the vaccines are even lower. Or if you’re on the fence and you think you might have contracted COVID earlier in the year, go ahead and get yourself an antibody test to see if you test positive for the antibodies. If you do, no need to worry about vaccination for a while.

The other factor to consider is, of course, risk factors for developing complications. Of course Vitamin D is the big one, and also age, followed by obesity and diabetes which both have something like a 2-fold increase in risk of adverse outcomes from infection. There’s been some back and forth on the specific mechanism behind this risk, but it mostly centers on the role of the ACE2 receptor in these conditions. Several medications that are used to treat these conditions have the effect of increasing ACE2 expression in the body, which in theory might make various cells in the body more susceptible to SARS-CoV-2 infection. The subsequent disruption of ACE2 activity might then cause more significant complications in the body, but this is all still mostly in the realm of speculation. Either way, the risks are clearly elevated in those groups and similar conditions, such as elevated blood pressure.

Other factors that you want to watch out for are immunodeficiency issues; anything that impairs your immune system’s ability to fight off viruses. It’s hard to get a good measure of the exact contribution of these risks, given immunosuppressed patients tend to put considerable effort into avoiding getting sick, but it’s a reasonable assumption. Interestingly, it’s been hard to pin down the risks associated with lung conditions like asthma and COPD. While we were originally assuming patients with lung issues would be having major issues with COVID-19, and the CDC still lists them as risk factors on their website, they represent a surprisingly small fraction of the ICU admissions. Several studies have come out showing no additional risks of COVID complications in these groups once you’ve controlled for the other risk factors like age and obesity. We’re not entirely clear if this observation is due to medications these types of patients tend to be on or if it’s something else, but if these conditions do result in increased risk, it’s pretty small relative to the contributions of the other risk factors. Then of course there’s the finding that men tend to have a higher incidence of complications than women, although not by much.

So what does a good summer look like if you haven’t been vaccinated? First of all, be outdoors. Enjoy the fresh air, get some exercise. For good vitamin D levels, make sure you get a good 20 minutes of sun every day. Even if you aren’t vaccinated, the chances of being infected in an outdoor setting are pretty minimal unless you are crammed together in a crowd talking into each other’s faces. Certainly go out and enjoy some summer camps; I myself will be counseling for two weeks at the youth camp that I normally help with. And if it’s outdoors, or the spaces are well ventilated, you really don’t even need masks. The percentage of the vaccinated population is so high, and the risks of the remaining unvaccinated people are so low, that masks really aren’t going to be useful unless your in indoor, crowded areas. Once most of your population is vaccinated, you’re better off focusing on ventilation of indoor spaces and regularly disinfecting surfaces than masking.

I’ve had a lot of questions from people about using masks in the future. A lot of people noticed that our COVID mitigation strategies also had the bonus of greatly reducing seasonal cold and flu infections. Of course they are all respiratory viruses, so they’ll be affected the same way, and I was getting questions about using masks every year during flu season. That can work, the problem is it’s a strategy that really only works if everyone does it together. Masks really don’t protect you from being infected, they limit the number of people an infected person infects when they’re contagious. Given so many people infected with SARS-CoV-2 remained infectious while still being asymptomatic, it was a viable strategy with COVID-19 to just assume everyone was infected and we all wear masks together. As near as we can tell, most masks tended to reduce the spread of infections by the wearer by about 75%. Not perfect, but useful for stopping exponential growth in an outbreak.

I know there was some confusion recently about the whole CDC announcement that immune people no longer need to wear masks. It was a statement that we already suspected was true, which I think was part of what made it confusing. I think what they were doing was just waiting a few more months to see if there were any outbreaks that could be traced to an index patient that had either previously been infected or vaccinated, yet somehow was able to be reinfected and infect others. When we got to the month of May and still hadn’t seen any examples of that, I guess that was enough to make them confident in asserting that people already immune aren’t going to be the source of outbreaks. The question for business and public areas is then whether they want to trust that people will responsibly wear masks if they haven’t yet been vaccinated or if it’s easier to just pretend we’re all still potentially contagious until a larger percentage of the population has been vaccinated. The nice thing about masks is they’re really the easiest, lowest cost mitigation strategy we have, but the downside is they only work if all of your potentially infected people are using them.

If you’re going to get together with people over the summer who aren’t vaccinated and are fed up with masks, the best strategy is to just maximize your time outdoors. Try to avoid jumping back and forth between large crowds of strangers; space out your large gatherings so that you have plenty of days after to look for people coming down with any symptoms, and make sure you communicate with each other if anyone tests positive after. And if you’re vaccinated or previously came down with COVID, there really isn’t any risk for you to worry about; even with the variants around, it’s extremely unlikely for you to contract SARS-CoV-2 or spread it to others, and all the evidence we have up until this point shows that you should have lasting immunity.

And…I do want to make one last point…since I know there’s been a lot of hype about this “Fauci Email Leak” stuff. First of all, these emails weren’t leaked…this guy is a public official, his emails were always available to look at any time. And despite all the hype, all I’ve seen are just normal emails between medical folks that are really just represent the best medical information we had at the time of the writing. People are just picking and choosing the sentences that they want to use to justify the preconceived notions they already have, regardless of the context of the discussion…which I guess is par for the course for the typical response to COVID stuff over the last year and a half anyway.

But I think that’s it for this update, I’m already way over my usual length. Of course, it wouldn’t be a proper COVID-19 update without some thought from the Bible, so I thought it would be nice to wrap up with two complementary proverbs found in the Bible:

Proverbs 22:3 “The prudent sees danger and hides himself, but the simple go on and suffer for it.”

Proverbs 28:1 “The wicked flee when no one pursues, but the righteous are bold as a lion.”

One of the most important things in life is to have a balanced perspective on risks and dangers. On the one hand, we can’t hide in our rooms from every potential danger, but on the other we don’t want to take unnecessary risks if they can be avoided. There’s a warning in these proverbs that foolishness tends to distort our perception of risks, causing us to see danger when there isn’t any while at the same time not recognizing the real danger. I feel like that’s a great description of what we’ve seen over the past year and a half, with some people fighting over toilet paper in the grocery store while others were recklessly gathering for large parties. Of course we take precautions as we need to, but at the same time don’t live your life in total fear of everything around you. Walk the path of humility and wisdom, and allow God to direct your steps. He has a tendency of sending us in the right direction.