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18 Mar, 10 tweets, 6 min read
I agree w @Ayjchan’s analysis of @undarkmag article (undark.org/2021/03/17/lab…) by @schmidtwriting on #SARSCoV2 origins, which has thoughtful comments by experts like @ras_nielsen & David Relman. We need objective discussion of possibilities, including accidental lab leak. (1/9)
There are divergent opinions, as always for scientific questions w little evidence. But that’s point: there’s incomplete evidence either way. So like @mbeisen (), I’m astonished about certainty professed given current evidence. (2/9)
Central to being a good scientist is keeping an open mind when evidence is sparse, and as a “virus expert” who has followed this topic closely: it’s clear in any objective assessment that both natural origins and accidental lab leak are plausible. (3/9)
Furthermore, regardless of your opinion on origins, we should all be able to agree as scientists that there is a need for greater transparency about the SARS-related coronaviruses being studied in Wuhan prior to the pandemic. (4/9)
Hallmark of #SARSCoV2 research has been sharing data. But addendum to Shi Zhengli paper (nature.com/articles/s4158…) says closest #SARSCoV2 relative, RaTG13, just 1 of 9 SARS-like CoVs from mine where miners got respiratory disease. Full sequences of other 8 still not shared! (5/9)
This despite fact presentations have shown trees & alignments that seem to include more than short RdRp fragments of these Mojiang mine viruses that have been published. See: & & (6/9)
So regardless of opinion on plausibility of natural origins vs lab escape, all scientists should agree there needs to be full sharing of sequences of SARS-related viruses studied in Wuhan, including from Mojiang mines where closest known relative of #SARSCoV2 was found. (7/9)
That’s the first step towards enabling an objective scientific discussion. (8/9)
And that's why I was disappointed to hear @PeterDaszak say WHO team didn't even *ask* Wuhan Institute of Virology to see database of virus sequences because *he* knows it doesn't have anything relevant (). Science is sharing data, not assertions. (9/9)
Someone pointed out to me that link to Daszak interview about database referenced in Tweet immediately above has become inaccessible. Here is new link: (10/9)

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More from @jbloom_lab

Bloom Lab Profile picture
18 Mar
In new work led by @AllieGreaney, we analyze mutational escape of #SARSCoV2 from monoclonal & polyclonal antibodies in terms of RBD epitope classes (biorxiv.org/content/10.110…). Provides useful framework for conceptualizing effects of individual and combined mutations. (1/n)
Specifically, @cobarnes27 @bjorkmanlab classified potent neutralizing anti-RBD antibodies in 3 classes using structural analyses (nature.com/articles/s4158…). These classes (1, 2, 3) shown below (also 4th class of less potent antibodies that bind further from ACE2 interface). (2/n) Image
@AllieGreaney used deep mutational scanning to map all mutations that escape binding to yeast-displayed RBD by antibodies of each class (from @NussenzweigL). Below are escape maps. Escape mutations usually at antibody contact sites, but not all contact site mutations escape (3/n) Image
Read 11 tweets
Bloom Lab Profile picture
23 Feb
We have completely mapped #SARS_CoV_2 mutations that escape binding by LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) both alone & in cocktail with LY-CoV016 in a new study led by @tylernstarr w/ @AllieGreaney & @AdamDingens: biorxiv.org/content/10.110… (1/n)
We corroborate recent work showing LY-CoV555 and its cocktail with LY-CoV016 is escaped by mutations in B.1.351 and P.1 viral lineages (E484K and K417N/T, respectively), and also show that LY-CoV555 is affected by the L452R mutation in B.1.429. (2/n)
Specifically, we used complete mapping approach we had previously applied to antibodies in REGN-COV2 (science.sciencemag.org/content/371/65…) to also determine how all RBD mutations affect LY-CoV555 binding. Below are maps of how mutations affect binding (big letter = escape from binding) (3/n)
Read 7 tweets
Bloom Lab Profile picture
9 Feb
Our complete mapping of mutations to #SARSCoV2 RBD that reduce binding by convalescent human plasma is out in @cellhostmicrobe (cell.com/cell-host-micr…). Right now E484K getting lot of attention, but I want to emphasize what our results suggest to keep eyes on in *future* (1/n)
To recap, we measured how all mutations to RBD reduce binding by antibodies in convalescent plasma. Lots of person-to-person variation in effects of mutations, but mutations at E484 have biggest effect. My old summary from early Jan: (2/n)
That summary was written just as E484K-containing 501Y.V2 (B.1.351) & 501Y.V3 (P.1) lineages were being reported & focused on E484 as most important site of mutations. Since then, many labs have characterized these lineages to confirm E484K is major antigenic change. (3/n)
Read 7 tweets
Bloom Lab Profile picture
25 Jan
Our study mapping #SARSCoV2 mutations that escape key therapeutic monoclonal antibodies is out in @ScienceMagazine. The study also shows that some of these escape mutations arise in a persistently infected patient treated with REGN-CoV-2: science.sciencemag.org/content/early/… (1/n)
I previously summarized the pre-print (), so in this thread I'll just update on new insights since we posted the pre-print in late November. (2/n)
In the study, we mapped all mutations to #SARSCoV2 RBD that escape binding by recombinant forms of antibodies in REGN-CoV2 cocktail (Regeneron) and LY-CoV016 antibody (Eli Lilly). These maps are useful because some of these mutations are appearing in new viral lineages (3/n).
Read 10 tweets
Bloom Lab Profile picture
13 Jan
In this short thread, I am going to plot some experimental data in a way that provides perspective on concerns that #SARSCoV2 mutation E484K will completely abolish immunity. (Thanks @profshanecrotty @apoorva_nyc for inspiring this post.) (1/n)
Last week, we posted a study describing how some #SARSCoV2 mutations, especially at site E484, reduce binding & neutralization (). This study (& similar ones by other) have drawn a lot of interest since E484K is in B.1.351 viral lineage. (2/n)
However, E484 mutations *reduced* neutralization, they did not ablate it. The plot below shows how E484 reduces neutralization titers for 16 sera. The dashed orange line shows titers against unmutated virus (measured by Pfizer) after 1 dose of BNTB162 vaccine. (3/n)
Read 11 tweets
Bloom Lab Profile picture
5 Jan
Here's plot of how mutating RBD sites affects average serum binding (y-axis) vs frequency of mutations (x-axis). E484K in S African lineage most worrying. But others affect some serum to various degrees & no such thing as "average" human when it comes to serum specificity (13/n) Image
Importantly, we only looked at RBD muts, since majority of neut activity of most sera from RBD antibodies (2nd tweet of thread). But NTD muts also important; see @10queues @mccarthy_kr @GuptaR_lab @e_andreano @McLellan_Lab: biorxiv.org/content/10.110…, medrxiv.org/content/10.110… (14/n)
This relative role of RBD & NTD mutations consistent w historical evolution of common-cold CoV-229E, where mutations concentrated in receptor-binding loops of RBD, but also in parts of NTD. Here is plot of mutational variability in CoV-229E spike: (15/n)
Read 16 tweets

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