Thread by @jbloom_lab

I want to flag this important work by @SCOTTeHENSLEY, which is the best study on whether there are pre-existing antibodies to #SARSCoV2 in uninfected people that affect risk of getting #COVID19. (1/7).

https://twitter.com/SCOTTeHENSLEY/status/1326216898812506113

Much recent speculation (eg, NY Times by @ginakolata) on if some people have pre-existing antibodies to #SARSCoV2 (eg, from common-cold CoV) that affect risk to get #COVID19. Hensley paper is a well-designed study that *actually answers* this question (2/7)

They looked at sera collected prior to #SARSCoV2. Most sera didn't have antibodies that bound #SARSCoV2 spike, but some had modest binding, mostly to S2 but a few to RBD. None of these sera were potently neutralizing, and no trend for kids to have more of them. (3/7)

The pre-existing antibodies to #SARSCoV2 correlated with common-cold human *beta*-CoV antibodies, and so were probably elicited by them. Most of this was already sort of known before Hensley work, although Hensley study is best characterization of it. But then... (4/7)

The Hensley study took it a step further by actually testing if these occasional modest titers of pre-existing antibodies that bound to #SARSCoV2 affected how likely people were to subsequently get infected with #SARSCoV2, and how sick they got if infected. (5/7)

There was *NO* association between occasional modest levels of pre-existing antibodies that bind #SARSCoV2 & infection risk or disease severity. In other words, there is a bit of cross-boosting between seasonal beta-CoV & #SARSCoV2, but not enough to affect disease risk. (6/7)

I'm flagging this because we need to pay attention to good studies. So much speculation about how pre-existing antibodies might protect, cause ADE, etc. If you were to design *perfect study* to answer these questions, this is it! So read paper, & @ginakolata, cover this one (7/7)

Adding more Tweets to this chain as several people (eg, @SternLab @chngin_the_wrld @rcr_pereira @LindorffLarsen) have noted contrast between @SCOTTeHENSLEY study & one in @ScienceMagazine (science.sciencemag.org/content/early/…) saying children have pre-existing neut antibodies. (1a/7a)

First, @ScienceMagazine study doesn't say anything about protection: they just look at antibody titers. Only @SCOTTeHENSLEY study looks at protection, and finds none.

Second, there is something very strange about @ScienceMagazine study... (2a/7a)

@ScienceMagazine study performs the pseudovirus neut assays using 293T cells that do *not* express ACE2. Virtually every other paper in field, including work in our lab, has found that 293T cells can't be infected by spike pseudotyped virus unless you express ACE2. But... (3a/7a)

@ScienceMagazine study uses 293T cells w/o ACE2. This fact is buried in methods. But pre-print for that paper (biorxiv.org/content/10.110…), which shows exact same neut data, explicitly says that 293T cells had no ACE2, and that adding ACE2 didn't increase infection! (4a/7a)

The claim that 293T cells are well-infected by spike-pseudotyped virus and adding ACE2 does not increase infection is simply inconsistent with what we & every other paper in field has observed. Therefore I am suspicious of pseudovirus neut assays in @ScienceMagazine paper (5a/7a)

Admittedly, the @ScienceMagazine also reports neut data with live SARS-CoV-2 in VeroE6 cells, where this issue would not apply. Nonetheless, the fact that pre-print used cells w/o ACE2, and Science version shows same data but buries this fact, is strange... (6a/7a)

Therefore, fact that @SCOTTeHENSLEY paper is "only" pre-print whereas other made it past @ScienceMagazine peer review does not alter my scientific view that the Hensley pre-print is better: it is only one that looks at actual protection, & methods seems a lot more solid. (7a/7a)