The DOI matches its Crossref record; 281 of the 281 references it cites were found in a registry or an index; 24 of the 147 sources its claims cite were checked for support.
The biological and clinical significance of emerging SARS-CoV-2 variants
Open accessAbstract
The past several months have witnessed the emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic. These variants can increase rates of virus transmission and/or increase the risk of reinfection and reduce the protection afforded by neutralizing monoclonal antibodies and vaccination. These variants can therefore enable SARS-CoV-2 to continue its spread in the face of rising population immunity while maintaining or increasing its replication fitness. The identification of four rapidly expanding virus lineages since December 2020, designated variants of concern, has ushered in a new stage of the pandemic. The four variants of concern, the Alpha variant (originally identified in the UK), the Beta variant (originally identified in South Africa), the Gamma variant (originally identified in Brazil) and the Delta variant (originally identified in India), share several mutations with one another as well as with an increasing number of other recently identified SARS-CoV-2 variants. Collectively, these SARS-CoV-2 variants complicate the COVID-19 research agenda and necessitate additional avenues of laboratory, epidemiological and clinical research. In this Review, the authors describe our latest understanding of the emergence and properties of SARS-CoV-2 genetic variants, particularly those designated as WHO (World Health Organization) ‘variants of concern’. They focus on the consequences of these variants for antibody-mediated virus neutralization, with important implications for reinfection risk and for vaccine effectiveness.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review synthesizes SARS-CoV-2 evolution, spike structure and the biological/clinical significance of the four WHO variants of concern as of June 2021: Alpha, Beta, Gamma and Delta. It shows that recurrent spike mutations increase transmissibility and immune evasion, reducing neutralization by monoclonal antibodies and vaccinee plasma, and calls for integrated genomic, neutralization and vaccine-efficacy surveillance.
Key findings
- Four VOCs emerged independently: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). Alpha was estimated to be ~50% more transmissible than prior UK variants and associated with an estimated 50% increased mortality; Beta was estimated to be 50% more transmissible than preceding lineages; Gamma was estimated to cause 3–4 times higher virus levels and 1.1-fold to 1.8-fold higher mortality; Delta spread to 54 countries and replaced Alpha in the UK and USA.
- Neutralization escape varied by variant. Beta showed 3-fold to 10-fold reduced susceptibility to 46% and >10-fold reduced susceptibility to 22% of convalescent plasma samples; mRNA vaccinee plasma showed 45% with 3-fold to 10-fold and 30% with >10-fold reduced Beta neutralization. Delta showed 3-fold to 10-fold reduced susceptibility to 45% and >10-fold to 5% of convalescent plasma samples, while ~15% of BNT162b vaccinee plasma had 3-fold to 10-fold reduced Delta neutralization. Alpha was rarely associated with reduced convalescent plasma susceptibility but showed 3-fold to 10-fold reduced susceptibility to ~15% of mRNA vaccinee plasma samples.
- Vaccine efficacy against VOCs was reduced in several studies: BNT162b retained >90% efficacy against Alpha in Israel and Qatar; Beta efficacy was 72% in a Qatar cohort and 75% in a test-negative case-control study; Delta efficacy was ~85% for BNT162b and ~60% for AZD1222 in UK case-control studies. In trials, AZD1222 efficacy against Beta was 10% in South Africa, and NVX-CoV2373 efficacy was 49% against Beta and 86.3% against Alpha versus 96.4% against non-Alpha variants.
- Key mutations include D614G, which rose to near 100% global prevalence by June 2020; N501Y, which increases ACE2 affinity; E484K, which reduces susceptibility to several monoclonal antibodies and plasma; and non-spike mutations that antagonize innate immunity, with Alpha and Beta showing mean 112-fold and 8-fold reduced susceptibility to type I interferons, respectively, compared with an early pandemic virus.
Methods
- Narrative review creating a framework for SARS-CoV-2 variants by describing evolution, spike protein structure/function, laboratory characterization methods, biological and epidemiological properties of VOCs/VOIs, and required research responses; data summarized as of June 2021.
- Synthesizes genomic surveillance data from more than two million partially or fully sequenced virus isolates, in vitro selection and neutralization experiments using pseudotyped viruses, VSV-based chimeric viruses, full-length recombinant SARS-CoV-2 and cultured isolates, deep mutational scanning, and vaccine efficacy trials, test-negative case-control studies and cohort studies.
- Neutralization results were pooled in the Stanford University Coronavirus Antiviral & Resistance Database and summarized as <3-fold, 3–10-fold and >10-fold reductions compared with control viruses.
Limitations
- The paper states that as of June 2021 it is uncertain whether current lineage-based variant classification will be sustainable, and that classifying variants by component mutations may become challenging if recurrent mutations increase.
- The paper notes unresolved questions, including whether neutralizing antibodies are the most important protective mechanism versus memory B cells, Fc-effector functions and T cell immunity, and whether updated immunogens can broaden responses in animal models more predictive of humans.
- Evident from the text: this is a synthesis as of June 2021, so later variants and data are not included; neutralization estimates pool results across pseudotyped, chimeric and infectious virus assays, and some distributions are approximate because they include results reported only as aggregate mean fold reductions.
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Claims the paper makes
67 Not checked yet · 10 Own interpretation · 9 Partly supported · 3 No basis given · 1 Mixed support · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Among plasma samples obtained from recipients of the BNT162b vaccine, approximately 15% displayed 3-fold to 10-fold reduced neutralizing activity against the Delta variant 100,118,214 (fIg.5).”
What the sources say
- Partly supportedcites [100] Liu, C. et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell 184, 4220–4336 (2021). sourceExperimental — accuracy not yet measured
The Results section ('Protection from B.1.617.1 and B.1.617.2 by vaccine serum'; page not provided) reports reduced neutralization of Delta (B.1.617.2) by serum from BNT162b2 recipients. It gives a 2.5-fold reduction in geometric mean titer across 25 samples, but does not report that approximately 15% of samples had 3-fold to 10-fold reductions. (LLM, conf=0.88)
- Disputedcites [118] Liu, J. et al. BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants. Nature 596, 273–275 (2021). sourceExperimental — accuracy not yet measured
The Article (p. 2) reports a geometric mean titre of 502 against wild-type virus and 355 against B.1.617.2 (Delta), describing the reduction as modest. The individual results in Extended Data Table 1 (p. 8) show no Delta titre 3- to 10-fold lower than its paired wild-type titre, contrary to the claimed 15% of samples. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
- Partly supportedcites [214] Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276–280 (2021). sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports that antibodies elicited by the Pfizer and AstraZeneca vaccines were about three- to fivefold less potent against Delta than Alpha. The section ‘Sensitivity of Delta to sera from vaccinated individuals’ (page unavailable) reports that 13% of Pfizer recipients’ sera neutralized Delta after one dose, not that approximately 15% showed a three- to tenfold reduction. The claimed sample proportion and full reduction range are not supported. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, in three other studies, the median reduction in neutralizing activity was between onefold and threefold 102,214,215 .”
What the sources say
- Partly supportedcites [102] Supasa, P. et al. Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera. Cell 184, 2201–2211 (2021). sourceExperimental — accuracy not yet measured
The Results section ('Neutralization activity of convalescent plasma and vaccine sera'; page not provided) reports a 2.9-fold reduction for convalescent plasma and 2.1- and 2.5-fold reductions for AstraZeneca vaccine sera, all within the claimed range. These are geometric means, not medians, and the reported Pfizer vaccine-serum reduction is 3.3-fold, outside that range. This source cannot establish the results of the other two cited studies. (LLM, conf=0.85)
- Supportedcites [214] Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276–280 (2021). source
In “Sensitivity of Delta to convalescent sera” (page unavailable), the paper reports median neutralization titres and says Delta titres were fourfold lower than Alpha titres and sixfold lower than D614G titres. Those comparisons imply an approximately 1.5-fold reduction for Alpha relative to D614G, within the claimed onefold-to-threefold range. This paper is one of the three studies cited; it need not itself report the other two. (LLM, conf=0.84)
- Not checked yetcites [215] Mlcochova, P. et al. SARS-CoV-2 B.1.617.2 Delta variant emergence and vaccine breakthrough. Preprint at Research Square https://www.researchsquare.com/article/rs-637724/v1 (2021).
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of plasma samples obtained from persons receiving one of the mRNA vaccines, 45% had 3-fold to 10-fold and 30% had >10-fold reduced Beta variant neutralizing activity 97,104,117,121,151,204,208,209,222,223 (fIg.5).”
What the sources say
- Not checked yetcites [97] Chen, X. et al. Neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination: a systematic review and pooled meta-analysis. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciab646 (2021). This paper presents a systematic review and meta-analysis of in vitro neutralization studies of SARS-CoV-2 variants by convalescent and vaccinee plasma. source
- Partly supportedcites [104] Zhou, D. et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera. Cell 184, 2348–2361 (2021). sourceExperimental — accuracy not yet measured
The Results section, “Neutralization of B.1.351 by vaccinee serum” (page unavailable), reports that serum from Pfizer-BioNTech vaccine recipients had a 7.6-fold lower geometric mean neutralization titer against B.1.351 than against Victoria. It does not report that 45% of mRNA-vaccine samples had a 3- to 10-fold reduction or that 30% had a greater-than-10-fold reduction. (LLM, conf=0.88)
- Partly supportedcites [117] Chen, R. E. et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 27, 717–726 (2021). sourceExperimental — accuracy not yet measured
The Results report reduced neutralization of the Beta (B.1.351) variant by sera from BNT162b2 mRNA-vaccine recipients: a 10-fold reduction in geometric mean activity in one assay and a 6- to 9-fold reduction in another. They do not report the claimed distribution of samples—45% with 3- to 10-fold reductions and 30% with reductions greater than 10-fold—or results from more than one mRNA vaccine. (LLM, conf=0.88)
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.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“By contrast, among plasma samples obtained from recipients of the AZD1222 vaccine, higher proportions displayed reduced neutralizing activity against this variant 100,209,214 .”
What the sources say
- Partly supportedcites [100] Liu, C. et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell 184, 4220–4336 (2021). sourceExperimental — accuracy not yet measured
The Results section, “Protection from B.1.617.1 and B.1.617.2 by vaccine serum” (page unavailable), reports that neutralization titers in serum from Oxford-AstraZeneca (AZD1222) recipients were 4.3-fold lower against B.1.617.2 (Delta) than against the Victoria strain. That supports reduced neutralizing activity, but the passage reports a reduction in the group's geometric mean titer, not a higher proportion of individual samples showing reduced activity. (LLM, conf=0.83)
- Partly supportedcites [209] Wall, E. C. et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet 397, 2331–2333 (2021). sourceExperimental — accuracy not yet measured
The main text (page not given; appendix p. 2 cited) reports that a higher proportion of samples from BNT162b2 recipients had low neutralising titres against B.1.617.2 (Delta) than against wild-type virus. It does not report this result for AZD1222 recipients; searches for AZD1222 and ChAdOx1 found no such analysis in our copy. (LLM, conf=0.86)
- Partly supportedcites [214] Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276–280 (2021). sourceExperimental — accuracy not yet measured
In “Sensitivity of Delta to sera from vaccinated individuals,” the paper reports that after one AstraZeneca (AZD1222) dose, only 9% of recipients’ sera neutralized Delta, compared with 74% for D614G and 61% for Alpha. The claim omits the dose qualification: four weeks after a second dose, sera from 95–100% of AstraZeneca recipients neutralized all four strains. The paper tested sera, rather than describing the samples as plasma. (LLM, conf=0.86)
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
None of the sources cited for this claim have been checked yet.
In the paper
“The past several months have witnessed the emergence of four SArS-cov-2 variants of concern (Alpha, beta, Gamma and Delta)”
- Also stated in: § SARS-CoV-2 evolution · plain
“The four variants of concern, the Alpha variant (originally identified in the UK), the Beta variant (originally identified in South Africa), the Gamma variant (originally identified in Brazil) and the Delta variant (originally identified in India)”
What the sources say
- Not checked yetcites [27] Rambaut, A. et al. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. Virological https://virological.org/t/563 (2020).
- Not checked yetcites [16] Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592, 438–443 (2021). This molecular epidemiological study charts the spread of the beta variant in South Africa and shows that it resulted from selective evolutionary forces. source
- Not checked yetcites [19] Faria, N. R. et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 372, 815–821 (2021). This paper presents an analysis showing that the Gamma variant is about twofold more transmissible than previous variants in Manaus, Brazil, and that it poses an increased risk of reinfection compared with previous variants. source
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.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § SARS-CoV-2 evolution · plain
A conclusion the paper draws from its own results — 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 increasing number of SArS-cov-2 variants share a repertoire of mutations that is enabling the virus to spread despite rising population immunity while maintaining or increasing its replication fitness.”
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.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“In a post-hoc analysis of a NVX-CoV2373 clinical trial, vaccine efficacy was 86.3% against Alpha variants compared with 96.4% against non-Alpha variants 212 (TABLe 2).”
What the sources say
- Not checked yetcites [212] Heath, P. T. et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2107659 (2021). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“By the second quarter of 2021, the Alpha variant accounted for the majority of infections in the USA and many European countries 23,196 .”
What the sources say
- Not checked yetcites [23] Hodcroft, E. CoVariants: SARS-CoV-2 mutations and variants of interest (NextStrain). CoVariants https://covariants.org/ (2021).
- Not checked yetcites [196] Mullen, J. L. et al. Outbreak.info https://outbreak.info/citation (2020).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“It was also associated with threefold to eightfold higher upper-airway levels [199][200][201]”
What the sources say
- Not checked yetcites [199] Golubchik, T. et al. Early analysis of a potential link between viral load and the N501Y mutation in the SARS-COV-2 spike protein. Preprint at bioRxiv https://doi.org/10.1101/2021.01.12.20249080 (2021). source
- Not checked yetcites [200] Kidd, M. et al. S-variant SARS-CoV-2 lineage B1.1.7 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-qPCR. J. Infect. Dis. 223, 1666–1670 (2021). source
- Not checked yetcites [201] Borges, V. et al. Tracking SARS-CoV-2 lineage B.1.1.7 dissemination: insights from nationwide spike gene target failure (SGTF) and spike gene late detection (SGTL) data, Portugal, week 49 2020 to week 3 2021. Eur. Surveill. 26, 2100131 (2021). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“and an estimated 50% increased mortality 194,195,202 .”
What the sources say
- Not checked yetcites [194] Davies, N. G. et al. Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature 593, 270–274 (2021). source
- Not checked yetcites [195] Challen, R. et al. Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study. BMJ 372, n579 (2021). source
- Not checked yetcites [202] Grint, D. J. et al. Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February. Eur. Surveill. 26, 2100256 (2021). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 33
- Probably not a substantial claim. 8
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“E484K has resulted in 3-fold to 10-fold reduced susceptibility to about 30% and >10-fold reduced susceptibility to about 10% of convalescent plasma samples”
What the sources say
- Partly supportedcites [121] Wang, P. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130–135 (2021). This paper presents a comprehensive analysis of the effects of Alpha and Beta variant mutations on antibody neutralization. sourceExperimental — accuracy not yet measured
The Discussion’s E484K row in Fig. 3b reports more than 10-fold reduced neutralization for 2 of 20 convalescent plasma samples (10%), as claimed. But 12 of 20 samples (60%), not about 30%, show reductions between 3-fold and 10-fold. (LLM, conf=0.88)
- Partly supportedcites [130] Greaney, A. J. et al. Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition. Cell Host Microbe 29, 44–57.e9 (2021). sourceExperimental — accuracy not yet measured
The Results section, “Functional and Evolutionary Constraint on Antibody-Escape Mutations” (page unavailable), says mutations at site 484 have been reported to escape polyclonal sera. It does not give the claimed 3- to 10-fold or >10-fold reductions, the percentages of convalescent plasma samples, or those findings specifically for E484K. (LLM, conf=0.82)
- Not checked yetcites [160] Liu, Z. et al. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. Cell Host Microbe 29, 477–488.e4 (2021). source
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of 34 convalescent plasma samples from persons infected with the Alpha variant, 59% had 3-fold to 10-fold reduced neutralizing activity and 18% had >10-fold reduced neutralizing activity to the Beta variant 99,104,221 .”
What the sources say
- Partly supportedcites [99] Faulkner, N. et al. Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains. Elife 10, e69317 (2021). sourceExperimental — accuracy not yet measured
The Results and Discussion report reduced neutralisation of B.1.351 (Beta) by B.1.1.7 (Alpha) sera, with a 7.7-fold change and a range of 3.4- to 17.9-fold. They do not report the claimed breakdown of 59% and 18%; the Materials and methods describe 29 patients with B.1.1.7 infection, not 34. (LLM, conf=0.88)
- Partly supportedcites [104] Zhou, D. et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera. Cell 184, 2348–2361 (2021). sourceExperimental — accuracy not yet measured
The Results section reports reduced neutralization of Beta (B.1.351), but the 34 convalescent samples were collected before Alpha (B.1.1.7) emerged. The paper reports a separate Alpha-infected group of 13 patients, not 34, and does not report the claimed 59% and 18% breakdown for that group. Page numbers are unavailable in our copy. (LLM, conf=0.86)
- Partly supportedcites [221] McCallum, M. et al. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science 373, 648–654 (2021). sourceExperimental — accuracy not yet measured
The Results section (page unavailable) reports reduced neutralization of the Beta variant (B.1.351) by convalescent plasma. But its nine donors were likely infected with Wuhan-1 or a related virus, not Alpha, and it does not report the claimed 34 samples or the 59% and 18% breakdowns. (LLM, conf=0.84)
plaindirectn = 34- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“By June 2021, the Gamma variant accounted for a high proportion of infections in several South American and Caribbean countries 196 and 10% of US infections 33 .”
What the sources say
- Not checked yetcites [196] Mullen, J. L. et al. Outbreak.info https://outbreak.info/citation (2020).
- Partly supportedcites [33] Bolze, A. et al. Rapid displacement of SARS-CoV-2 variant B.1.1.7 by B.1.617.2 and P.1 in the United States. Preprint at medRxiv https://doi.org/10.1101/2021.06.20.21259195 (2021). sourceExperimental — accuracy not yet measured
The Results (page not available) report that Gamma reached 15% of sequenced US samples by May 28–June 3, 2021. This supports a substantial US presence around June, but not the cited figure of 10% of infections. The South American and Caribbean statement carries a different citation and is not assessed here. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As the Gamma variant was associated with a surge of infections in a region of Brazil estimated to have achieved a high infection rate, it is suspected of being able to infect and cause illness in persons previously infected with other variants 19,29,30 .”
What the sources say
- Supportedcites [19] Faria, N. R. et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 372, 815–821 (2021). This paper presents an analysis showing that the Gamma variant is about twofold more transmissible than previous variants in Manaus, Brazil, and that it poses an increased risk of reinfection compared with previous variants. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [29] Buss, L. F. et al. Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic. Science 371, 288–292 (2021). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [30] Sabino, E. C. et al. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet 397, 452–455 (2021). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition, the mRNA vaccines appear to often elicit memory B cells that undergo somatic hypermutation, which should broaden the response to viruses with variant spike proteins 239,240 .”
What the sources say
- Partly supportedcites [239] Wang, Z. et al. Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature 595, 426–431 (2021). sourceExperimental — accuracy not yet measured
The Memory B cells section reports continued somatic hypermutation after infection, and the Discussion says mRNA vaccination enhances memory B-cell responses and likely protects vaccinated convalescent individuals against variants (page not specified). But the paper says vaccine-driven expansion of persistent memory clones does not accumulate large numbers of additional mutations. It does not establish that mRNA vaccines often elicit this mutation-driven broadening in people without prior infection. (LLM, conf=0.88)
- Partly supportedcites [240] Turner, J. S. et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature https://doi.org/10.1038/s41586-021-03738-2 (2021). sourceExperimental — accuracy not yet measured
The paper reports persistent germinal-centre responses after mRNA vaccination and finds that a small fraction of cross-reactive B-cell clones had higher somatic hypermutation, suggesting a pre-existing memory B-cell origin (Abstract; page not provided). It does not show that vaccination often elicits memory B cells that undergo new somatic hypermutation, or establish that this process broadens responses to variant SARS-CoV-2 spike proteins. (LLM, conf=0.85)
hedgedconditional- 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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of convalescent plasma samples, about 40% had 3-fold to 10-fold and 15% had >10-fold reduced neutralizing activity 100,122,234 .”
What the sources say
- Partly supportedcites [100] Liu, C. et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell 184, 4220–4336 (2021). sourceExperimental — accuracy not yet measured
The Results section, ‘Neutralization of B.1.617.1 by convalescent serum’ (page unavailable), reports reduced neutralization of the Kappa variant in convalescent samples, including a 3.9-fold reduction in geometric mean titer for B.1.617.1-B. It does not report that about 40% of samples had 3- to 10-fold reductions or that 15% had reductions greater than 10-fold; a group mean cannot establish those sample-level proportions. (LLM, conf=0.84)
- Partly supportedcites [122] Edara, V. V. et al. Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants. N. Engl. J. Med. 385, 664–666 (2021) sourceExperimental — accuracy not yet measured
The paper’s main text (page unavailable) reports reduced neutralizing activity against B.1.617.1 (Kappa) in convalescent serum, including a lower geometric mean titer than against WA1/2020. It does not report that about 40% of samples had a 3- to 10-fold reduction or that 15% had a greater-than-10-fold reduction. (LLM, conf=0.86)
- Partly supportedcites [234] Hoffmann, M. et al. SARS-CoV-2 variant B.1.617 is resistant to bamlanivimab and evades antibodies induced by infection and vaccination. Cell Rep. 36, 109415 (2021). sourceExperimental — accuracy not yet measured
The Results section ('Diminished neutralization by plasma from COVID-19 convalescent patients'; page unavailable) reports reduced neutralization of B.1.617 by plasma from 15 patients, averaging about 2-fold. It does not report that about 40% of samples had 3- to 10-fold reductions or that 15% had reductions greater than 10-fold. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
None of the sources cited for this claim have been checked yet.
In the paper
“The Alpha variant is susceptible to neutralization by most neutralizing mAbs as well as by most plasma samples from previously infected persons 97,102,121,149,159,[203][204][205][206] (fIg.5).”
What the sources say
- Not checked yetcites [97] Chen, X. et al. Neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination: a systematic review and pooled meta-analysis. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciab646 (2021). This paper presents a systematic review and meta-analysis of in vitro neutralization studies of SARS-CoV-2 variants by convalescent and vaccinee plasma. source
- Not checked yetcites [102] Supasa, P. et al. Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera. Cell 184, 2201–2211 (2021). source
- Not checked yetcites [121] Wang, P. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130–135 (2021). This paper presents a comprehensive analysis of the effects of Alpha and Beta variant mutations on antibody neutralization. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The fact that the Alpha variant is rarely associated with reduced susceptibility to convalescent plasma is consistent with it not being associated with an increased risk of reinfection 207 .”
What the sources say
- Not checked yetcites [207] Graham, M. S. et al. Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study. Lancet Public Health 6, e335–e345 (2021). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“associated with increased transmissibility, increased risk of reinfection and/or reduced vaccine efficacy”
plaincorrelational- 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
“The Beta variant is associated with reduced susceptibility to many mAbs because E484K interferes with binding of several RBM class 1 and 2 mAbs and K417N interferes with the binding of several RBM class 1 mAbs 104,117,121,163,217 .”
What the sources say
- Not checked yetcites [104] Zhou, D. et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera. Cell 184, 2348–2361 (2021). source
- Not checked yetcites [117] Chen, R. E. et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 27, 717–726 (2021). source
- Not checked yetcites [121] Wang, P. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130–135 (2021). This paper presents a comprehensive analysis of the effects of Alpha and Beta variant mutations on antibody neutralization. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The Alpha variant also contains several non-spike mutations including nsp6:Δ106-108 and the nucleocapsid mutations D3L, R203K and G204R, which may increase transmission by antagonizing innate immunity 25,[185][186][187] .”
What the sources say
- Not checked yetcites [25] Martin, D. P. et al. The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape. Preprint at medRxiv https://doi.org/10.1101/2021.02.23.21252268 (2021). source
- Not checked yetcites [185] Thorne, L. G. et al. Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant. Preprint at bioRxiv https://doi.org/10.1101/2021.06.06.446826 (2021). This systems biology study shows that in contrast to earlier SARS-CoV-2 variants, the alpha variant may owe its increased transmissibility and virulence to its antagonism of cellular innate immunity. source
- Not checked yetcites [186] Jiang, H. et al. SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70. Cell Mol. Immunol. 17, 998–1000 (2020). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“N501Y increases ACE2 affinity 128,146,147 and increases virus replication in human upper-airway cells and in the upper respiratory tracts of hamsters 127”
What the sources say
- Not checked yetcites [128] Starr, T. N. et al. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 182, 1295–1310.e20 (2020). source
- Not checked yetcites [146] Zhu, X. et al. Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. PLoS Biol. 19, e3001237 (2021).
- Not checked yetcites [127] Liu, Y. et al. The N501Y spike substitution enhances SARS-CoV-2 transmission. Preprint at bioRxiv https://doi.org/10.1101/2021.03.08.434499 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the previously cited Qatar cohort study, the efficacy of BNT162b against the Beta variant was estimated to be 72%, which was 15% lower than that for the Alpha variant 211 .”
What the sources say
- Not checked yetcites [211] Abu-Raddad, L. J., Chemaitelly, H. & Butt, A. A. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N. Engl. J. Med. 385, 187-189 (2021). source
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Even though E484Q is more likely than T478K to evade antibody neutralization 48,100,165 , only the Delta variant has demonstrated increased transmissibility, spreading to 54 countries and rapidly replacing the Alpha variant in the UK 32,35 and the USA 33 .”
What the sources say
- Not checked yetcites [48] Weisblum, Y. et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. eLife 9, e61312 (2020). source
- Not checked yetcites [100] Liu, C. et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell 184, 4220–4336 (2021). source
- Not checked yetcites [165] Ferreira, I. et al. SARS-CoV-2 B.1.617 mutations L452 and E484Q are not synergistic for antibody evasion. J. Infect. Dis. https://doi.org/10.1093/infdis/jiab368 (2021). source
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“It also contains five NTD mutations, of which L18F has been shown to interfere with the binding of NTD-targeting neutralizing antibodies 51 .”
What the sources say
- Not checked yetcites [51] McCallum, M. et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 184, 2332–2347.e16 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“It was estimated to result in virus levels 3-4 times higher than earlier variants and to be responsible for an estimated 1.1-fold to 1.8-fold higher mortality 19 .”
What the sources say
- Not checked yetcites [19] Faria, N. R. et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 372, 815–821 (2021). This paper presents an analysis showing that the Gamma variant is about twofold more transmissible than previous variants in Manaus, Brazil, and that it poses an increased risk of reinfection compared with previous variants. source
hedgeddirect- 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
“Of the five FDA EUA-approved mAbs, bamlanivimab, etesevimab and casirivimab are largely inactive against B.1.351whereas imdevimab and sotrovimab, which bind to the RBD core, retain neutralizing activity 104,109,117,175,204 (TABLe 1).”
What the sources say
- Not checked yetcites [104] Zhou, D. et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera. Cell 184, 2348–2361 (2021). source
- Not checked yetcites [109] Copin, R. et al. The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies. Cell 184, 3949–3961 (2021). source
- Not checked yetcites [117] Chen, R. E. et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 27, 717–726 (2021). source
plain- 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
“Of convalescent plasma samples, about 40% display 3-fold to 10-fold and 10% display >10-fold reduced Iota variant neutralizing activity 166,235 .”
What the sources say
- Not checked yetcites [166] Zhang, L. et al. Comparison of 10 emerging SARS-CoV-2 variants: infectivity, animal tropism, and antibody neutralization. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-492659/v1 (2021). source
- Not checked yetcites [235] Zhou, H. et al. B.1.526 SARS-CoV-2 variants identified in new york city are neutralized by vaccine-elicited and therapeutic monoclonal antibodies. mBio https://doi.org/10.1128/mBio.01386-21 (2021). source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although SARS-CoV-2 variants differ in their transmission rates, disease severity and risk of reinfection, there is no evidence that they are differentially affected by non-pharmaceutical public health measures such as social distancing and the use of personal protective equipment, or that they will respond differently to most antiviral therapies.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The Zeta variant was common in Brazil in late 2020 and early 2021 (ref. 157 ), but appears to be decreasing in prevalence.”
What the sources say
- Not checked yetcites [157] Ferrareze, P. A. G. et al. E484K as an innovative phylogenetic event for viral evolution: genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil. Infect. Genet. Evol. 93, 104941 (2021). source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — 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 two most recently approved mAb preparations, casirivimab/imdevimab and sotrovimab, retain activity against all VOCs and VOIs, in part because imdevimab and sotrovimab target the RBD core whereas the most prevalent immune escape mutations are in the RBD RBM.”
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
“The Theta variant was first reported in March 2021 in the Philippines.It contains 13 lineage-defining mutations including N501Y, E484K, P681H and the NTD deletion at positions 141-143 (refs 155,156 ).”
What the sources say
- Not checked yetcites [155] Bascos, N. A. D., Mirano-Bascos, D. & Saloma, C. P. Structural analysis of spike protein mutations in an emergent SARS-CoV-2 variant from the Philippines. Preprint at bioRxiv https://doi.org/10.1101/2021.03.06.434059 (2021). source
- Not checked yetcites [156] Tablizo, F. A. et al. Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines. Preprint at bioRxiv https://doi.org/10.1101/2021.03.03.21252812 (2021). source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“Of plasma samples from recipients of an mRNA vaccine, approximately 55% had 3-fold to 10-fold and 5% had >10-fold reduced neutralizing activity 100,118,122,234 .”
What the sources say
- Not checked yetcites [100] Liu, C. et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell 184, 4220–4336 (2021). source
- Not checked yetcites [118] Liu, J. et al. BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants. Nature 596, 273–275 (2021). source
- Not checked yetcites [122] Edara, V. V. et al. Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants. N. Engl. J. Med. 385, 664–666 (2021) source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The Iota variant was first identified in New York state.In June 2021, it had a prevalence of 5-10% in the USA but remained rare outside the USA 154 .”
What the sources say
- Not checked yetcites [154] Annavajhala, M. K. et al. A novel SARS-CoV-2 variant of concern, B.1.526, identified in New York. Preprint at bioRxiv https://doi.org/10.1101/2021.02.23.21252259 (2021). source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — 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 Beta and Gamma variants are each associated with increased transmissibility because of their ability to evade humoral immunity and cause reinfections.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“AY.1 and AY.2 are recently reported sub-lineages of the Delta variant that have developed additional mutations including the RBD mutation K417N (ref. 196 ).”
What the sources say
- Not checked yetcites [196] Mullen, J. L. et al. Outbreak.info https://outbreak.info/citation (2020).
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.
In the paper
“It is highly prevalent in several South American countries and is associated with reduced susceptibility to the locally used CoronaVac vaccine 238 .”
What the sources say
- Not checked yetcites [238] Acevedo, M. L. et al. Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda. Preprint at medRxiv https://doi.org/10.1101/2021.06.28.21259673 (2021). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In case-control studies from the UK, the BNT162b vaccine was approximately 85% effective for the Delta variant whereas the AZD1222 vaccine was approximately 60% effective 232,233 .”
What the sources say
- Not checked yetcites [232] Bernal, J. L. et al. Effectiveness of COVID-19 vaccines against the B.1.617.2 variant. N. Engl. J. Med. 385, 585–594 (2021). source
- Not checked yetcites [233] Sheikh, A., McMenamin, J., Taylor, B. & Robertson, C. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 397, 2461–2462 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“It was estimated to be about 20% more transmissible than co-circulating lineages and to be associated with twofold higher upper-airway virus levels 123,192 .”
What the sources say
- Not checked yetcites [123] Deng, X. et al. Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant. Cell 184, 3426–3437.e8 (2021). source
- Not checked yetcites [192] Peng, J. et al. Estimation of secondary household attack rates for emergent spike L452R SARS-CoV-2 variants detected by genomic surveillance at a community-based testing site in San Francisco. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciab283 (2021). source
hedgedcorrelational- 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
“The levels of neutralizing mAbs elicited by the mRNA vaccines has been high and in most persons are likely to be maintained for many months above the levels required for protection against even the most resistant circulating variants 164,239,240 .”
What the sources say
- Not checked yetcites [164] Greaney, A. J. et al. Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. Sci. Transl Med. 13, eabi9915 (2021). source
- Not checked yetcites [239] Wang, Z. et al. Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature 595, 426–431 (2021). source
- Not checked yetcites [240] Turner, J. S. et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature https://doi.org/10.1038/s41586-021-03738-2 (2021). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The Eta variant is present at low levels in many countries, with Nigeria having the highest proportion of infections 236 .”
What the sources say
- Not checked yetcites [236] Ozer, E. A. et al. High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.525 lineage in Oyo State, Nigeria. Preprint at medRxiv https://doi.org/10.1101/2021.04.09.21255206 (2021). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It results in approximately 3-fold to 10-fold reduced susceptibility to 45% and >10-fold reduced susceptibility to 5% of convalescent plasma samples 100,118,214,215,231 (fIg.5).”
What the sources say
- Not checked yetcites [100] Liu, C. et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell 184, 4220–4336 (2021). source
- Not checked yetcites [118] Liu, J. et al. BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants. Nature 596, 273–275 (2021). source
- Not checked yetcites [214] Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276–280 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — 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 Alpha and Delta variants are each associated with increased transmissibility and greater disease severity because of immune evasion, and potentially because of higher virus levels resulting from the antagonism of innate immunity.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“This paper presents a meta-analysis showing that the level of neutralizing antibodies elicited by a vaccine is strongly correlated with its efficacy.”
What the sources say
- Not checked yetcites Khoury, D. S. et al.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This post-hoc analysis of a clinical trial shows that the beta variant was frequently responsible for reinfections in South Africa.”
What the sources say
- Not checked yetcites Shinde, V. et al.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This study demonstrates the likely importance of SARS-CoV-2 neutralizing mAb Fc-effector functions in an animal model.”
What the sources say
- Not checked yetcites Schäfer, A. et al.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This post-hoc analysis of a clinical trial shows that AZD1222 appeared ineffective at preventing infection with the beta variant.”
What the sources say
- Not checked yetcites Madhi, S. A. et al.
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This experimental study shows that the plasma from persons infected with the beta variant can usually neutralize pre-variant viruses.”
What the sources say
- Not checked yetcites Moyo-Gwete, T. et al.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This systems biology study shows that in contrast to earlier SARS-CoV-2 variants, the alpha variant may owe its increased transmissibility and virulence to its antagonism of cellular innate immunity.”
What the sources say
- Not checked yetcites Thorne, L. G. et al.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This paper demonstrates that a high proportion of neutralizing antibodies elicited by SARS-CoV-2 infection will bind poorly to epitopes containing the spike RBD mutation E484K.”
What the sources say
- Not checked yetcites Greaney, A. J. et al.
boostedcorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“These VOCs exhibit increased transmissibility and/or immune evasion, traits that have been linked to mutations in the viral spike (S) protein”
From The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic (2022) · cites this paper as Tao et al., 2021
Citations
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“As expected and heavily warned, SARS-CoV-2 mutated, and now a myriad of variants, including rapidly expanding virus lineages since December 2020, designated variants of concern (VOCs) were identified in distinct populations (Tao et al., 2021).”
Puligedda, R. D., Al‐Saleem, F. H., Wirblich, C., Kattala, C. D., Jović, M., Geiszler, L., Devabhaktuni, H., Feuerstein, G., Schnell, M. J., Sack, M., et al. (2021) · Diagnostics · doi:10.3390/diagnostics11112092 · Cited by 10
“The efforts to control SARS-CoV-2 have been challenged by the emergence of variant strains that have important implications for clinical and epidemiological decision making [1,2].”
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“Currently, there are four variants of concern, the Alpha, Beta, Gamma and Delta variants, which were originally identified in the UK, South Africa, Brazil and India, respectively, as well as with an increasing number of other recently identified SARS-CoV-2 variants (Tao et al. 2021).”
BackgroundAkingbola, A., Adewole, O., Adegbesan, A., Peters, F., Odukoya, T., Aremu, O., Adeleke, O., Idris, A., Owolabi, A., & Aiyenuro, A. (2025) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2025.2485840 · Cited by 7
“26,27 Following the emergence of JN.1 SARS-CoV-2 in December 2023, the omicron variant KP.2 (JN.1.11.1.2) was discovered in early January 2024.”
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Preventing future zoonosis: SARS-CoV-2 mutations enhance human–animal cross-transmission
Wee, J., Chen, J., & Wei, G. (2024) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2024.109101 · Cited by 7
Wastewater Surveillance of SARS-CoV-2 in Zambia: An Early Warning Tool
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“Understanding the predominant variants is very critical in guiding mitigation strategies to address COVID-19 [66,67].”
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“Towards the end of the second wave, when high vaccination rates among the adult Italian population had raised hopes of a return to pre-pandemic life, a newly identified variant of SARS-CoV-2, named the Delta variant, led to a resurgence in COVID-19 infections [7].”
BackgroundBroad-spectrum coronavirus inhibitors discovered by modeling viral fusion dynamics
Reilly, C. B., Moore, J., Lightbown, S. L., Paul, A., Bernier, S. G., Carlson, K. E., & Ingber, D. E. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1575747 · Cited by 9
“…most of these drugs targeted sites on the external surface of the S protein to interfere with its binding to the host membrane ACE2 receptor (Tao et al., 2021; Lieber et al., 2022), and virtually all of the approved therapeutic antibodies target this same interaction site (Taylor et al.,…”
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“For example, in mid-2020, single mutations in the spike protein distinguished different clades of the virus [8].”
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“SARS-CoV-2 infections continue to have a significant impact on public health worldwide (2) with emergence of multiple variants (12, 44, 45) reducing the effectiveness of vaccines and monoclonal antibody therapy (46–48).”
BackgroundSubacute thyroiditis following COVID-19 vaccination: Case presentation
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“The emergence of new SARS-CoV-2 variants which possess higher infectivity and stronger resistance towards currently available vaccines only further worsen the situation [28].”
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“34 Genomic mutations arise that define phylogenetic lineages, alter virus properties, and have 35 functional consequences of clinical significance (1).”
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“In addition, the heterogeneity is further enhanced by the rapid mutation of the virus giving rise to different clades and variants that caused varying pathologies over the course of the pandemic (3).”
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Pathogenic Mechanism and Multi-omics Analysis of Oral Manifestations in COVID-19
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“Despite these historic successes, SARS-CoV-2 continues to surge across the world, generating variants that threaten the effectiveness of existing vaccines (Tao et al., 2021).”
Changing Dynamics of SARS-CoV-2: A Global Challenge
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“The P681H mutation near the furin site slightly increases the S1/S2 cleavage [52] (Figures 2b and 3i).”
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Misidentification of the SARS-CoV-2 Mu variant using commercial mutation screening assays
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“Genomic surveillance of the pandemic has allowed rapid identification of emerging new variants, which could represent a risk of increased transmission, higher virulence, or escape from immune response or vaccination [2].”
BackgroundNanoagent-based theranostic strategies against human coronaviruses
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“This, along with immune evasion by Delta, could contribute to the increased disease severity seen (9).”
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“Many individuals infected with SARS-CoV-2 develop antibodies that neutralize multiple variants; however, the breadth and potency of antibody repertoires vary across human individuals 3,4 .”
DEVELOPMENT OF A POTENT MONOCLONAL ANTIBODY FOR TREATMENT OF HUMAN METAPNEUMOVIRUS INFECTIONS
Harris, E. D., McGovern, M., Pernikoff, S., Ikeda, R., Kipnis, L., Hannon, W. W., Sobolik, E. B., Gray, M., Greninger, A. L., He, S.-J., et al. (2025) · bioRxiv · doi:10.1101/2025.06.09.657676 · Cited by 6
Intranasal liposomal remdesivir induces SARS-CoV-2 clearance in K18-hACE2 mice and ensures survival.
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Amentoflavone from Selaginella tamariscina inhibits SARS-CoV-2 RNA-dependent RNA polymerase
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“SARS-CoV-2 is an RNA virus, and the RNA virus tends to evolve into new mutant forms due to its low fidelity of RNA polymerase [1,2].”
Basic implications on three pathways associated with SARS-CoV-2
Lee, J., Sergi, C. M., Kast, R. E., Kanwar, B. A., Bourbeau, J., Oh, S.-S., Sohn, M.-G., Lee, C. J., & Coleman, M. D. (2024) · Biomedical Journal · doi:10.1016/j.bj.2024.100766 · Cited by 6
“Like other RNA viruses, SARS-CoV-2 undergoes genetic evolution and develops mutations over time, resulting in the emergence of multiple variants that may have different characteristics than their ancestral strains [77,78].”
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Divergent pathogenetic outcomes in BALB/c mice following Omicron subvariant infection
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“…new evolutionary patterns emerged that were associated with mutations that enhanced escape from circulating neutralizing antibodies (Zamorano Cuervo and Grandvaux, 2020; Tao et al., 2021; Zahradnik et al., 2021; Roemer et al., 2023; Corman et al., 2018; Eckerle et al., 2010; Eguia et al., 2021).”
BackgroundAbassi, L., Bertoglio, F., Šafranko, Ž. M., Schirrmann, T., Greweling‐Pils, M. C., Seifert, O., Khan, F., Katzmarzyk, M., Jacobsen, H., Gödecke, N., et al. (2023) · Viruses · doi:10.3390/v15112153 · Cited by 5
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Roper, K. J., Thomas, J., Albalawi, W. O., Maddocks, E., Dobson, S. L., Alshehri, A. A., Barone, F. G., Baltazar, M., Semple, M. G., Ho, A. Y. W., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-41928-2 · Cited by 6
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“7), which was flagged as a particular concern [38,39].”
BackgroundPlikusienė, I., Mačiulis, V., Juciutė, S., Ramanavičius, A., & Ramanavičienė, A. (2023) · Biosensors · doi:10.3390/bios13080784 · Cited by 6
“It has been related to considerable immune evasion following vaccination and spontaneous infection, as well as lowered sensitivity to numerous monoclonal antibodies (mAbs) [30].”
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Rapid screening of SARS-CoV-2 variants, a key tool for pandemic surveillance
Muñoz-Gallego, I., Carmona, M. Á. M., Higuera, C. M., Viedma, E., Delgado, R., & Folgueira, M. D. (2023) · Scientific Reports · doi:10.1038/s41598-023-37866-8 · Cited by 6
Duong‐Quy, S., Huynh-Truong-Anh, D., Nguyen-Thi-Kim, T., Nguyen-Quang, T., Tran-Ngoc-Anh, T., Nguyen-Van-Hoai, N., Do-Thi-Thu, M., Nguyen-Chi, T., Nguyen-Van, T., Tang-Thi-Thao, T., et al. (2023) · Pulmonary Therapy · doi:10.1007/s41030-023-00231-1 · Cited by 6
A Trim-RBD-GEM vaccine candidate protects mice from SARS-CoV-2
Su, R., Shi, Z.-Z., Li, E., Zhu, M., Li, D., Liu, X., Sun, Y., Feng, N., Wang, J., Wang, T.-C., et al. (2023) · Virology · doi:10.1016/j.virol.2023.06.005 · Cited by 6
“In the variants of SARS-CoV-2, some mutations have developed in this protein and possibly influenced the antigenicity of the virus (Tao et al., 2021).”
Muthusami, R., & Saritha, K. (2023) · Proceedings of the Indian National Science Academy · doi:10.1007/s43538-023-00176-8 · Cited by 7
“Due to the rarity of sequences, it has also been uncommon to observe S-protein genetic changes in the RBD sequence of the enzyme that interacts with ACE2 (Tao et al.”
BackgroundAmorim, V. M. D. F., de Souza, R. F., Guzzo, C., & de Souza, A. D. (2023) · COVID · doi:10.20944/preprints202304.0012.v1 · Cited by 6
Hognon, C., Bignon, E., Monari, A., Marazzi, M., & García-Iriepa, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032517 · Cited by 6
“Since the beginning of the pandemic, in the late 2019, different variants have emerged [5,6].”
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Zhang, G. F., Meng, W., Chen, L., Ding, L., Sun, S., Wang, X., Huang, Y., Guo, H., & Gao, S. (2022) · Journal of Medical Virology · doi:10.1002/jmv.28437 · Cited by 9
“However, in cells that express a lower level of ACE2 protein, other entry‐related factors might partially compensate for its function in SARS‐CoV‐2 infection, which could provide VOCs with broader tropism and higher transmissibility.(41,46) Consistent with the observed broader infectivity, VOCs also manifest wider pat…”
BackgroundHu, W., Wen, J., Yang, Y., Liu, H., Wang, S., Ding, X., Zhou, C., & Zhang, X. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1036208 · Cited by 8
Berry, N. J., Ferguson, D., Kempster, S. L., Hall, J., Ham, C., Jenkins, A., Rannow, V., Giles, E., Leahy, R., Goulding, S., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-23339-x · Cited by 4
Predicting the Trajectory of Replacements of SARS-CoV-2 Variants Using Relative Reproduction Numbers
Piantham, C., & Ito, K. (2022) · Viruses · doi:10.3390/v14112556 · Cited by 6
“As a result, the average transmissibility in the viral population increases over time [1].”
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Mendes, D., Chapman, R., Gal, P., Atwell, J. E., Nguyen, J. L., Hamson, L., Fusco, M. D., Czudek, C., & Yang, J. (2022) · Journal of Medical Economics · doi:10.1080/13696998.2022.2111935 · Cited by 6
“Furthermore, emerging SARS-CoV-2 variants had been thought to increase the likelihood of reinfection and reduce vaccine-derived protection.(15) The Delta variant (B.”
BackgroundMapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens
de Souza, M. O., Madan, B., Teng, I., Huang, A., Liu, L., Fahad, A. S., Acevedo, S. N. L., Pan, X., Sastry, M., Gutiérrez-González, M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.977064 · Cited by 7
“The emergence of genetic changes has resulted in drastic phenotypic differences in transmission rates, virulence, and viral susceptibility to targeted biologic interventions including monoclonal antibody therapies and vaccines (15, 16).”
BackgroundZhou, Z., Du, P. F., Li, N., Xiong, X., Tang, S., Dai, Q., Wang, T., Yu, M., Man, M., Lam, K., et al. (2022) · MedComm · doi:10.1002/mco2.143 · Cited by 12
“The following criteria were used for fusion: (1) Fused cells increased in size by at least twofold, and (2) the intensity of fluorescence in the fused cells was reduced.”
MethodClinical characteristics, risk factors, and rate of severity of a nationwide COVID-19 Saudi cohort
Al-Numair, N., Alyounes, B., Al-Saud, H., Halwani, R., & Al-Muhsen, S. (2022) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2022.103315 · Cited by 6
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Scope of SARS-CoV-2 variants, mutations, and vaccine technologies
Wambani, J., & OKOTH, P. K. (2022) · The Egyptian Journal of Internal Medicine · doi:10.1186/s43162-022-00121-z · Cited by 9
“K417N mutations are more common in the Beta strain, whereas K417T mutations are more common in the Gamma variants [29, 50, 51].”
BackgroundInfluentialMapping Data to Deep Understanding: Making the Most of the Deluge of SARS-CoV-2 Genome Sequences
Sokhansanj, B. A., & ROSEN, G. L. (2022) · mSystems · doi:10.1128/msystems.00035-22 · Cited by 9
“As mutations recur, revert, and proliferate, taxonomy hits its limits of utility (11).”
BackgroundRaj, R., Uppuluri, R., Parambil, B. C., Dhariwal, N., Totadri, S., Mathew, L. G., Radhakrishnan, V. S., Charan, A., Yadav, S. P., Mahajan, A., et al. (2022) · Pediatric Hematology Oncology Journal · doi:10.1016/j.phoj.2022.03.002 · Cited by 6
“The latter was reported to be more virulent resulting in a higher mortality [5].”
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“Our current understanding of SARS-CoV-2 mutations principally comes from studies on 12 the spike protein given its central role in mediating the entry into the host cells and serving as the 13 primary target for neutralizing antibodies (15-17).”
BackgroundTransmission of SARS-CoV-2 Indoor and Outdoor Environments
Xu, X., Zhang, J., Zhu, L., & Huang, Q. (2021) · Atmosphere · doi:10.3390/atmos12121640 · Cited by 7
“2 (surged in India in early 2021, Delta variant) [98].”
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“Another significant limitation is the fact that the data of the COVID-19 population analyzed in this study were obtained during the initial wild-type (Wuhan-Hu-1) phase in the United States and before the emergence of variants of concern that later replaced the wild-type virus, namely Alpha, Delta, and Omicron, that h…”
Inferring variant-specific effective reproduction numbers from combined case and sequencing dataPreprint
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“As SARS- CoV-2 evolves, variants may emerge that increase in their ability to transmit and escape acquired immunity ( Tao et al., 2021 ).”
Natural Alkaloids as Antiviral Agents Against RNA Viruses: A Comprehensive and Mechanistic Review
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“The virus continues to undergo mutations, resulting in variants that exhibit increased transmissibility and reduced susceptibility to vaccine-induced protection [1,2].”
SARS-CoV-2 mutant spectrum complexity is an epidemiologically evolvable trait
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“Several variants of concern have been identified by the World Health Organization since 2020 (https://www.who.int/en/activities/ tracking - SARS - CoV - 2 - variants/ ) ( 19 ).”
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Advances in Genotyping Detection of Fragmented Nucleic Acids
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“The COVID-19 pandemic caused by SARS-CoV-2 has underscored the significance of viral genomic variations, which continue to influence the transmissibility, pathogenicity, and immune evasion capabilities of the virus [2,10].”
BackgroundAnti-SARS-CoV-2 gapmer antisense oligonucleotides targeting the main protease region of viral RNA
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Concerns regarding SARS-CoV-2 JN.1 mutations should be raised
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Gerashchenko, G. V., Hryshchenko, N. V., Melnichuk, N., Marchyshak, T., Chernushyn, S. Y., Demchyshina, I. V., Chernenko, L. M., Kuzin, I., Tkachuk, Z. Y., Kashuba, V. I., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25618 · Cited by 7
“These three VOC strains were the cause of the three powerful epidemic waves of COVID-19 in the world as well [19,31,32].”
Background
Metadata
- Authors
- Tao, K., Tzou, P. L., Nouhin, J., Gupta, R. K., de Oliveira, T., Kosakovsky Pond, S. L., Fera, D., & Shafer, R. W.
- Affiliations
- Stanford Medicine (US)
- University of Cambridge (GB)
- Swarthmore College (US)
- Corresponding author
- Shafer, Robert W.
- Venue
- Nature Reviews Genetics
- Published
- 2021-09-17
- Volume
- 22
- Issue
- 12
- Pages
- 757-773
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- PMC
- PMC8447121
- OpenAlex
- W3199849883
- Cited by
- 1,009
- References
- 281
- Citations by year
- 2026: 43 · 2025: 90 · 2024: 170 · 2023: 251 · 2022: 415 · 2021: 38
- FWCI
- 25.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Reviews Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Works - Scholarship, Research, & Creative Expression (Swarthmore College) (submittedVersion)
- Funders
- University of Washington
- National Institute of Allergy and Infectious Diseases (R24AI136618)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- SARS-CoV-2, COVID-19 variants of concern, spike protein mutations, Alpha variant, Beta variant, Gamma variant, Delta variant, virus transmission, reinfection risk, neutralizing antibodies, vaccine effectiveness, herd immunity, viral replication fitness
- MeSH terms
- COVID-19, SARS-CoV-2, Epitopes, Biological Evolution, Humans, Mutation, Spike Glycoprotein, Coronavirus
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