Thread by @hjillianh

New #DukeBRAVEKids preprint:
"Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents"
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medrxiv.org/content/10.110…

First off - this was again a big team effort that involved multiple investigators, from the clinical research team to the immunologists! @Duke_Childrens @TheDHVI @MattKellyMD @DebLugoPedsID @AlexRotta @DukeMedSchool @eleanor_semmes @SalliePermar @dukemedicine

Right now, we know that kids become infected with SARS-CoV-2, but the majority don't get very sick Many of the studies focusing on kids (and there are some great ones) have looked at kids hospitalized with #COVID or #MISC
nature.com/articles/s4159…

You should also read this paper from @carlpierce and colleagues:
stm.sciencemag.org/content/12/564…

And this one from Preeti Jaggi's group @EmoryUniversity
pubmed.ncbi.nlm.nih.gov/32879033/

Some of the data from adults with SARS-CoV-2 infection suggest that the severity of infection may impact your immune response, while others don't show an effect.
nature.com/articles/s4200…

Here's another showing differences in immune response based on severity:
frontiersin.org/articles/10.33…

Here's one showing that mild disease elicits memory immune responses from @PepperMarion
sciencedirect.com/science/articl…

And one from @florian_krammer and colleagues showing that there's a. persistent antibody response in most individuals with prior infection:
science.sciencemag.org/content/370/65…

But what does the immune response in kids with mild or asymptomatic infections look like?

We evaluated the antibody response in 69 kids who were enrolled in the #DukeBRAVEKids study when they were acutely infected with SARS-CoV-2 and followed most of them for over 4 months, with check-ins and sample collection at 2 and 4 months after initial diagnosis:

We also worked with our colleagues from @dukemedicine who are running a similar study in adults with SARS-CoV-2 infection. Importantly, all of the participants had mild infections that didn't require medical attention and 20% of the kids were completely asymptomatic

We collected blood at each of the study visits from our participants and checked in to see if they had any lingering symptoms. All of the samples were evaluated for antibodies that bind a panel of different SARS-CoV-2 antigens and neutralizing antibody activity at each timepoint

Here's an overview of the antibodies we see in kids - we can detect SARS-CoV-2-binding IgM, IgG, and IgA at all three timepoints in pretty much every single kid in the cohort:

Here are a couple of SARS-CoV-2 antibodies to show changes over time:

How about neutralizing activity? Here's the ID50 over time and the percent of kids who have neutralizing activity at each timepoint:

So it looks like nearly every kid has a neutralizing antibody response and they all seem to have antibodies of various flavors, but does infection severity matter?

Nope - symptomatic (purple) and asymptomatic (green) kids look pretty much the same. Here we're showing antibody levels and antibody-mediated virus neutralization

How do kids compare to adults? All of the adults included in this study had mild symptoms and weren't hospitalized, and as mentioned before the kids also had mild symptoms or were asymptomatic

If we look at SARS-CoV-2 binding antibody levels and antibody neutralization, kids and adults are pretty comparable (here we just show IgG, but we have other antigens and IgM and IgA levels in the manuscript):

Younger age seems to be somewhat associated with greater neutralizing activity at the 2 month timepoint, so adults may have a slightly more rapid decrease, but there aren't any statistically significant differences by month 4.

So let's wrap it up:

1) Kids with mild or asymptomatic SARS-CoV-2 infections mount what look to be effective immune responses that bind and neutralize virus.

2) Whether or not kids had symptoms didn't seem to effect the robustness or durability of the response - mark this one in the symptoms don't matter column*
*NB: We didn't directly compare to kids with severe disease, so that may not hold true.

3) Adults and kids have about the same degree of antibody response (and kids might look a little better)

A few caveats:
1 - we only looked at kids with mild infection and don't have a direct comparison to severely ill kids and adults, or kids with MISC
2-We should take a look at cellular immunity and memory (see this great paper from @profshanecrotty
science.sciencemag.org/content/371/65…

More caveats:
3-we're only out to 4 months on these kids, but we're still following them!
4-we should see how these antibodies perform against some of the new variants

Overall though, I think these data are pretty encouraging and suggest that kids who do get infected with SARS-CoV-2 develop some immunity that will likely protect them

Given the recent results from the Pfizer vaccine in adolescence, I would bet younger kids have a pretty great response to COVID vaccines, and I'm hoping we can get some shots in arms soon - there's no herd immunity without kids!

As I mentioned before, this was another big team effort, led by the amazing @MattKellyMD (who caved and got a Twitter handle) and Dr. Genevieve Fouda from @TheDHVI and @Duke_Childrens

And as always, much thanks and appreciation to the families who are participating in this study