Evidence map›Paper›PMID 33831133›Full record

Trial reportPLoS pathogens2021

High-throughput, single-copy sequencing reveals SARS-CoV-2 spike variants coincident with mounting humoral immunity during acute COVID-19.

Sung Hee Ko, Elham Bayat Mokhtari, Prakriti Mudvari, Sydney Stein, Christopher D Stringham, Danielle Wagner, Sabrina Ramelli, Marcos J Ramos-Benitez, Jeffrey R Strich, Richard T Davey and 6 more

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

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  12. Adaptation of SARS-CoV-2 to ACE2Journal of virology · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Sung Hee KoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Elham Bayat MokhtariVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0002-6339-1673
Prakriti MudvariVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Sydney SteinEmerging Pathogens Section, Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland, United States of America.ORCID 0000-0002-0259-4485
Christopher D StringhamVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0003-0487-5157
Danielle WagnerVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0001-5819-1426
Sabrina RamelliEmerging Pathogens Section, Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland, United States of America.
Marcos J Ramos-BenitezEmerging Pathogens Section, Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland, United States of America.ORCID 0000-0001-9445-3294
Jeffrey R StrichEmerging Pathogens Section, Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland, United States of America.
Richard T DaveyLaboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0002-3992-5524
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0002-3935-4637
John MisasiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0001-7169-2639
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0003-3560-232X
Daniel S ChertowEmerging Pathogens Section, Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland, United States of America.
Nancy J SullivanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Eli A BoritzVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0003-4633-4594
National Institutes of Health · USNational Institutes of Health Clinical Center · US

Funding

Influenza and Emerging Infectious DiseasesZIAAI000984 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DAVEY, RICHARD · 2009 to 2025
$44.1M
Mechanisms Of Humoral EvasionZIAAI005023 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$18.6M
mAbs and vaccines against SARS CoV-2ZIAAI005145 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SULLIVAN, NANCY J · 2020 to 2023
$6.2M
Yeast Engineering Technology & Immunobiology CoreZIAAI005142 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SULLIVAN, NANCY J · 2019 to 2022
$2.6M
Persistence and Evolution of SARS-CoV-2ZIAAI005157 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BORITZ, ELI · 2020 to 2025
$1.3M
Clinical and Molecular Features of Coronavirus Disease 2019ZIACL090070 · CLC · CLINICAL CENTER · PI CHERTOW, DANIEL S · 2020 to 2025
$0k
Elucidating the Mechanism of Ebola Virus EnterotoxigenicityFI2GM137804 · NIGMS · U.S. NATIONAL INST ALLERGY & INFECT DIS · PI RAMOS-BENITEZ, MARCOS JAVIER · 2020 to 2020
–
NIGMS NIH HHS FI2 GM137804
6 · The paper itself

Abstract

Tracking evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within infected individuals will help elucidate coronavirus disease 2019 (COVID-19) pathogenesis and inform use of antiviral interventions. In this study, we developed an approach for sequencing the region encoding the SARS-CoV-2 virion surface proteins from large numbers of individual virus RNA genomes per sample. We applied this approach to the WA-1 reference clinical isolate of SARS-CoV-2 passaged in vitro and to upper respiratory samples from 7 study participants with COVID-19. SARS-CoV-2 genomes from cell culture were diverse, including 18 haplotypes with non-synonymous mutations clustered in the spike NH2-terminal domain (NTD) and furin cleavage site regions. By contrast, cross-sectional analysis of samples from participants with COVID-19 showed fewer virus variants, without structural clustering of mutations. However, longitudinal analysis in one individual revealed 4 virus haplotypes bearing 3 independent mutations in a spike NTD epitope targeted by autologous antibodies. These mutations arose coincident with a 6.2-fold rise in serum binding to spike and a transient increase in virus burden. We conclude that SARS-CoV-2 exhibits a capacity for rapid genetic adaptation that becomes detectable in vivo with the onset of humoral immunity, with the potential to contribute to delayed virologic clearance in the acute setting.

Indexed as

COVID-19EpitopesImmunity, HumoralMutationSARS-CoV-2Spike Glycoprotein, CoronavirusCell LineFemaleHigh-Throughput Nucleotide SequencingHumansMaleEpitopesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID33831133
PMCPMC8031304
OpenAlexW3145551965

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.