NEW THREAD: «Recent endemic coronavirus infection is associated with less severe COVID-19» The thrust of the paper is that if you had previous exposure to endemic coronaviruses (eCoV) and catch SARS-CoV-2, you’re less likely end up in the ICU.
https://www.jci.org/articles/view/143380
You’ve maybe seen this key figure circulating, showing hospitalized COVID-19 patients recently exposed to eCoV and the obvious conclusion from the face value.

The title isn't technically wrong, but I think there is a lot more to the story.
In this study, hospitalized COVID-19 patients previously positive for eCoV were identified based on historical test results using the following kit (detecting a panel of common respiratory pathogens).
This is the product, I believe: https://www.biofiredx.com/products/the-filmarray-panels/filmarrayrp/
I like the idea of this kit but wouldn’t like the price tag (unsuitable for mass testing). I’ve been tested twice (Mar and Sep), both -ve, and I always think ‘what the hell is it then?’.

If you were told what you DO have, testing would be far more interesting.
So the hypothesis is you identify people who've had relatively recent coronavirus infections after they've been hosptalized with SARS-CoV-2 and monitor their progress and see who lands in the ICU.
Some findings:
No difference between eCoV+ and eCoV- in susceptibility to SARS-COV-2 infection. Again we see pre-existing exposure to eCoV not influencing attack rates.

This may be the best data I’ve seen to support this.
Next >> SARS-CoV-2 viral loads are estimated to be similar using one commercial assay, and one in-house-designed qPCR. Kudos for assessing with independent assays, but this sparked my first query. Is this what we expect if there was effective pre-existing T cell immunity?
But the SEVERITY of the disease is claim… and this the key part of this thread...

This sentence got my hackles up. Significant differences in diabetes? In which direction?!

So, off to the supplementary..…
CRITICAL POINT:
eCoV+ (21) and eCoV- (231) in this study were NOT matched for their comorbidities. The eCoV- group has 3.4x more diabetes (highly significant), 3x more cancer (trend), 2x more congestive heart failure (trend) and higher BMI (trend).
In other words, the eCoV- group is on average more diabetic, overweight, have experienced more cancer burden & are more likely to have had congestive heart failure.

I will only focus on the diabetes or I'll have all the 'it's not significant' people after me... ;)
I don’t have the raw data, but it looks like if HALF of the diabetics in BOTH GROUPS end up in ICU, your significance for previous eCoV exposure will entirely disappear. You have 49% of the eCoV- groups who is diabetic. Look at the curve again with the table next to it! :)
Diabetics are considered a 'clinically vulnerable group'. This is an risky difference for the question under investigation in the current study. I can't be sure unless the authors look at the numbers but this is for me a big issue. https://www.diabetes.org.uk/about_us/news/coronavirus
You see what I mean? Please raise your hand if I’ve gone astray!

The title could be “groups of people in which diabetes, obesity, cancer and congestive heart failure are more common are associated with worse outcomes after COVID-driven hositalization”.
The authors normalized for the overall number comorbidities (blue highlights), and mention this in the text...

BUT: it matters for WHICH you normalize. In this case they are not evenly distributed to the point we can be sure the remaining difference is eCoV exposure.
It *could* be that if you remove diabetics from the study that the curves look the same. The possibility is there for the authors to stratify based on tdifferent comorbidities.

Are we confident of that result? I propose the finding would evaporate.
https://doi.org/10.1016/S2213-8587(20)30238-2
The authors measured higher c-reactive protein (CRP) in the eCoV- group, which they hypothesize could be due to eCoV+ group dealing better with the infection.

Is this a stable hypothesis?
Sorry, not convinced. This took me 1 minute to find. SARS-CoV-2 infected diabetics have sky-high CRP, and this study didn't have anything to do with previous eCoV exposure. It's more likely the diabetes that is driving their observation, in my opinion.
I still think that the hypothesis for T cell immunity and cross-reactive T cells is mega-tempting and all that stuff makes sense. I've discussed it elsewhere.

I’m just not convinced yet, and this study (presented in its current form) didn’t move the dial for me at all.
One last thing: These threads take time and effort. It only makes sense for me to invest time in it if we reach people in a serious way, so scroll back up and bang that RT.

Thanks for reading and being interested in immunology.
You can follow @andrew_croxford.
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