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This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson from the Yale School of Medicine.
This week, one of the most headline-generating COVID studies that has come out in a while appeared in the Journal of Pediatrics.
You've probably seen this one in the news. USA Today suggested that healthy kids may be more contagious than sick adults. Kaiser Health News gave it a similar treatment. And Fox News gives us this, for example:
The message from these headlines is pretty clear — but they all contain an error. That error will become clear by the end of this commentary.
Okay, let's walk through the study because there are actually quite a few worthy take-home points here.
Researchers from Massachusetts General Hospital recruited kids who presented to the hospital or urgent care clinic with COVID-like symptoms or high-risk contacts — 192 in total, making this one of the biggest pediatric cohorts to date. But only 49 of those kids were COVID-positive. Another 18 had the multisystem inflammatory syndrome that we are beginning to recognize as a post-COVID complication in kids. The rest had other infections that give you upper respiratory symptoms.
First key takeaway: It was pretty hard to distinguish the acute COVID-infected kids from kids with other infections on the basis of symptoms alone.
Anosmia was more common in COVID, but only 20% of the COVID-positive kids had that symptom. Fever was present in about half of kids regardless. That's probably why they were in urgent care after all. Reading this gave me some real heartburn about what to do when cold and flu season ramps up; there are going to be a lot of kids who seem like they have COVID even if they don't have COVID. And without ubiquitous testing, we won't be able to tell the difference.
But the crux of this study, the thing that generated all those headlines, was a quantitative analysis of viral RNA in infected kids' nasopharyngeal passages.

Yonker LM, et al. J Pediatr. 2020;S0022-3476(20)31023-4. Republished with permission.
What you see here is how much viral RNA was present in the nasal swab compared with a "housekeeping" gene that is expressed at a constant level (this helps account for differences in sample technique and collection volumes). Those circles way at the bottom — 1 on the y-axis — are the undetectable viral loads. But note that the y-axis is on the log scale. Every point higher is a 10-fold increase in viral RNA. Kids (in red) were compared with severely ill adults, and you can see quite clearly that, at least early in the disease, some were shedding 10-, 100-, 1000-fold more viral RNA than the adults were.
Terrifying, right? I mean, are kids just virus factories? Are they weapons of mass dissemination? Does 1000 times more viral RNA mean 1000 times more contagious? Or, the question underneath all of these questions: When schools open, will cases explode?
The study can't tell us that. Note that I keep saying "viral RNA," not "virus." We do not know if these kids were shedding live virus that was actively capable of infecting others. The authors did not do viral cultures or other infectivity assays. So the error in the headlines? The word "contagious." Higher viral load does not necessarily mean more contagious.
Also, remember that these were sick kids, mostly. These were kids who came to medical attention. Even if they are shedding transmissible virus, if only a small number of kids get sick enough to be in a study like this, we might still dodge the bullet. Selection bias is a hell of a drug.
The study gives us a few other nuggets to digest as well. One big question is why kids don't get as sick as adults do when they contract COVID. You'll remember that the receptor that SARS-CoV-2 binds to on epithelial cells is called ACE-2. One hypothesis is that kids have lower ACE-2 levels, which might limit the ability of the virus to replicate. This study pours some cold water on that hypothesis. The COVID-positive kids did have higher ACE-2 expression than COVID-negative kids, suggesting that maybe having lower ACE-2 levels protects against infection.

Yonker LM, et al. J Pediatr. 2020;S0022-3476(20)31023-4. Republished with permission.
But once infected? ACE-2 levels had nothing to do with viral load. Once it's in, it's in. This does not appear to be the explanation for why kids don't get as sick as adults.

Yonker LM, et al. J Pediatr. 2020; S0022-3476(20)31023-4. Republished with permission.
So, what have we learned? This study lends support to the idea that kids have a bit of a tougher time getting infected because of their lower ACE-2 levels. But once infected, it's clear that the virus does quite well in their nasal passages, at least well enough to make a ton of its own RNA. We don't know how that translates to contagiousness.
But I'll admit that this study makes me worried about schools reopening. We can hope that kids aren't quite as easily infected. We can hope that if infected, they aren't as contagious as their viral loads would suggest. But that's a lot of hope in a pandemic that eats hope for breakfast.
There's a lot we still don't know. But in a few months we'll find out.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale's Program of Applied Translational Research. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @methodsmanmd and hosts a repository of his communication work at www.methodsman.com.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Are Kids With COVID More Contagious Than Adults? - Medscape - Aug 26, 2020.
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