The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index; none of the 13 sources its claims cite is checked for support yet.
Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2
Open accessPublished version of a preprint
Abstract
The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally 1. It is expected to become dominant in the coming weeks 2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations 3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies 4. This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
The Omicron (B.1.1.529) variant of SARS-CoV-2 shows marked resistance to neutralization by convalescent and vaccinee sera and by most tested monoclonal antibodies, including authorized therapies. The study identifies four spike mutations—S371L, N440K, G446S, and Q493R—that contribute to this antibody escape.
Key findings
- Convalescent sera from 10 individuals showed a >32-fold drop in ID50 against B.1.1.529 versus D614G, with only 2 samples above the limit of detection.
- Vaccinee sera showed substantial losses: >21-fold for BNT162b2 and >8.6-fold for mRNA-1273; all Ad26.COV2.S and ChAdOx1 nCoV-19 samples were below the limit of detection except two Ad26.COV2.S samples from previously infected individuals. Boosted mRNA vaccinees showed a mean 6.5-fold decrease against B.1.1.529.
- Among 19 monoclonal antibodies, 17 lost neutralizing activity completely or partially; class 1 and class 2 RBD antibodies decreased by more than 100-fold, while S309 and Brii-198 were spared. All four combination monoclonal antibody drugs in clinical use lost substantial activity.
- Four previously undescribed mutations—S371L, N440K, G446S, and Q493R—conferred greater antibody resistance; S371L broadly affected neutralization by monoclonal antibodies in all four RBD classes.
Methods
- Serum neutralization was tested using pseudoviruses and authentic SARS-CoV-2 isolates. Convalescent samples were collected in spring 2020 (9–120 days after symptoms); vaccinee samples included BNT162b2, mRNA-1273, Ad26.COV2.S, ChAdOx1 nCoV-19, and boosted mRNA recipients.
- A panel of 19 monoclonal antibodies (17 RBD-directed, 2 NTD-directed) was tested against B.1.1.529 and B.1.1.529+R346K pseudoviruses, and against pseudoviruses carrying each of 34 individual spike mutations.
- Neutralization curves and IC50 values were derived by nonlinear five-parameter dose-response fitting; P values were determined using two-tailed Wilcoxon matched-pairs signed-rank tests.
Limitations
- The paper states that no statistical methods were used to predetermine sample size, experiments were not randomized, and investigators were not blinded to allocation during experiments and outcome assessment.
- The paper notes that for BNT162b2 and mRNA-1273 groups, samples with high titres were specifically chosen so fold changes could be better quantified, and the difference in samples above the limit of detection may therefore be favourably biased.
- Evident from the text: the study reports in vitro neutralization only and does not measure clinical protection, in vivo efficacy, or reinfection/breakthrough outcomes directly.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
31 Own result · 11 Own method · 8 Not checked yet · 7 Own interpretation
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most striking and perhaps unexpected finding was that S371L broadly affected neutralization by monoclonal antibodies in all four RBD classes”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Mutations conferring antibody resistance
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“a significant drop (>32-fold) in 50% infectious dose (ID 50 ) titres was observed against B.1.1.529,with only two samples showing titres above the limit of detection (LOD)”
- Also stated in: § Abstract · plain
“Here we found that B.1.1.529is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Abstract
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- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“previous variants developed resistance to only NTD antibodies and class 1 and class 2 RBD antibodies”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Evolution of SARS-CoV-2 to antibodies
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the two mRNA-based vaccines, BNT162b2 and mRNA-1273, a >21-fold and >8.6-fold decrease in ID 50 was observed, respectively.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The activities of S309 and Brii-198 were spared.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Antibody neutralization of B.1.1.529
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Strikingly, all four combination monoclonal antibody drugs in clinical use lost substantial activity against B.1.1.529”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Antibody neutralization of B.1.1.529
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“nearly all of the currently authorized or approved monoclonal antibody drugs are rendered weak or inactive by B.1.1.529”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Within the Ad26.COV2.S and ChAdOx1 nCOV-19 groups, all of the samples were below the LOD against B.1.1.529,except for two Ad26.COV2.S samples from patients who had a previous history of SARS-CoV-2 infection”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Every sample showed lower activity in neutralizing B.1.1.529,with a mean decrease of 6.5-fold compared with the WT”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 6
- The quote only partly states this claim. 3
- Probably not a substantial claim. 14
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Again, a substantial decrease in the neutralization of B.1.1.529was observed, with mean decreases of >6.0-fold and >4.1-fold for the fully vaccinated group and the boosted group, respectively”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Q493R, which was previously shown to affect binding of CB6 and LY-CoV555 (ref.28 ) as well as polyclonal sera 29 , mediated resistance to CB6 (class 1) as well as to LY-CoV555 and 2-15 (class 2)”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Mutations conferring antibody resistance
What the sources say
- Not checked yetcites [28] Starr, T. N., Greaney, A. J., Dingens, A. S. & Bloom, J. D. Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016. Cell Rep. Med. 2, 100255 (2021). source
- Not checked yetcites [29] Amanat, F. et al. SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2. Cell 184, 3936–3948 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“its spike protein contains an alarming number of mutations (>30) (Fig. 1b and Extended Data Fig. 1), including at least 15 in the receptor-binding domain (RBD)”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Abstract
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“B.1.1.529,with or without R346K, has made a big mutational leap by becoming not only nearly completely resistant to class 1 and class 2 RBD antibodies, but also substantially resistant to both class 3 and class 4 RBD antibodies.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Evolution of SARS-CoV-2 to antibodies
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Key spike mutations found in the viruses isolated in the major lineage of B.1.1.529.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Online content
plain- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neutralization of D614G and B.1.1.529+R346Kpseudoviruses by RBD-directed and NTD-directed monoclonal antibodies.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Online content
plaindirect- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“revealed several mutations that were not previously known to have functional importance to neutralization”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Mutations conferring antibody resistance
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“which is the defining mutation for the B.1.621/Muvariant 27”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Antibody neutralization of B.1.1.529
What the sources say
- Not checked yetcites [27] Uriu, K. et al. Neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine serum. N. Engl. J. Med. 385, 2397–2399 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All viruses were first titrated to normalize the viral input between assays.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No statistical methods were used to predetermine sample size.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Data availability
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Viruses were propagated in Vero-E6-TMPRSS2 cells and the sequence was confirmed by next-generation sequencing before use.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All of the participants provided written informed consent.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Note that, whenever possible, we specifically chose samples with high titres against the WT strain of SARS-CoV-2 such that the loss in activity against B.1.1.529could be better quantified and the titres observed here should therefore be considered in that context.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All collections were conducted under protocols reviewed and approved by the Institutional Review Board of Columbia University.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Data availability
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data represent one out of two independent experiments.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Online content
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cytopathic effects were then scored by plaque assay in a blinded manner.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Q493R, which was previously shown to affect binding of CB6 and LY-CoV555 (ref.28 ) as well as polyclonal sera 29”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Mutations conferring antibody resistance
What the sources say
- Not checked yetcites [28] Starr, T. N., Greaney, A. J., Dingens, A. S. & Bloom, J. D. Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016. Cell Rep. Med. 2, 100255 (2021). source
- Not checked yetcites [29] Amanat, F. et al. SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2. Cell 184, 3936–3948 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“To verify the sequences of variants, next-generation sequencing libraries were prepared according to a low-volume Nextera sequencing protocol 43 and sequenced on the Illumina Miseq platform (single-end mode with 50 bp R1).”
- Also stated in: § Additional information · plain
“The resulting reads alignments were then visualized in the Integrative Genomics Viewer 46 and manually inspected to verify the fidelity of variants.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Also stated in: § Additional information · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells were purchased from authenticated vendors and morphology was confirmed visually before use.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All cell lines tested mycoplasma negative.”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Additional information
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The authors state this as an assumption.
Patients with COVID-19 in spring 2020 were infected with WT SARS-CoV-2.
“who were presumably infected with the wild-type (WT) SARS-CoV-2”
The paper relies on this without support.
In vitro neutralization activity of monoclonal antibodies predicts their clinical efficacy in patients.
“probably abolishing or impairing their efficacy in patients”
The paper relies on this without support.
Neutralizing antibody titres are a correlate of protection against SARS-CoV-2 infection.
“Collectively, these results suggest that individuals who were previously infected or fully vaccinated remain at risk for B.1.1.529infection.”
The authors state this as an assumption.
Convalescent plasma samples were infected by the WT strain of SARS-CoV-2.
“These samples were collected at the beginning of the pandemic in early 2020 at Columbia University Irving Medical Center and are therefore assumed to be infection by the WT strain of SARS-CoV-2 (ref. 4 ).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Similar findings suggest that vaccination with three doses of the mRNA vaccine BNT162b2 may protect against Omicron-mediated COVID-19.407,408”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [407]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > Abstract
“The short doubling time (2-3 days) of Omicron cases suggests that it could soon become dominant 2 .”
§ Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 > References
“Omicron strain spreads with the doubling time of 3.2-3.6 days in South Africa province of Gauteng that achieved herd immunity to Delta variant.”
Citations
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Metadata
- Authors
- Liu, L., Iketani, S., Guo, Y., Chan, J. F.-W., Wang, M., Liu, L., Luo, Y., Chu, H., Huang, Y., Nair, M. S., Yu, J., Chik, K. K.-H., Yuen, T. T.-T., Yoon, C., To, K. K.-W., Chen, H., Yin, M. T., Sobieszczyk, M. E., Huang, Y., Wang, H. H., Sheng, Z., Yuen, K.-Y., & Ho, D. D.
- Affiliations
- Aaron Diamond AIDS Research Center (US)
- University of Hong Kong (HK)
- Columbia University (US)
- Corresponding author
- Ho, David D.
- ORCID
- Venue
- Nature
- Published
- 2021-12-23
- Volume
- 602
- Issue
- 7898
- Pages
- 676-681
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4220904663
- Cited by
- 1,290
- References
- 47
- Citations by year
- 2026: 60 · 2025: 107 · 2024: 179 · 2023: 341 · 2022: 598 · 2021: 5
- FWCI
- 89.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (2032259)
- Bill and Melinda Gates Foundation
- JPB Foundation
- Regeneron Pharmaceuticals
- Irving Medical Center, Columbia University
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- Omicron variant, SARS-CoV-2, antibody escape, neutralizing antibodies, spike protein mutations, vaccine escape, COVID-19 vaccines, monoclonal antibodies, booster vaccination, serum neutralization
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Antibodies, Monoclonal, Antibodies, Viral, Cell Line, Convalescence, Humans, Immune Sera, Models, Molecular, Mutation, Neutralization Tests, Evolution, Molecular, Inhibitory Concentration 50, Immune Evasion, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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