Evidence map›Paper›PMID 41729079›Full record

ArticleJCI insight2026

SARS-CoV-2 antibody-dependent enhancement of infection depends on antibody binding to both ACE2 and Fc receptors.

Natalia A Kuzmina, Sivakumar Periasamy, Kritika Kedarinath, Keziah Hernandez, Caroline Atyeo, S Moses Dennison, Kan Li, Daniel Bedinger, Sharon L Schendel, Georgia D Tomaras and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Natalia A KuzminaDepartment of Pathology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.
Sivakumar PeriasamyDepartment of Pathology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.
Kritika KedarinathDepartment of Pathology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.
Keziah HernandezDepartment of Pathology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.
Caroline AtyeoRagon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
S Moses DennisonCenter for Human Systems Immunology, Departments of Surgery, Immunology, and Molecular Genetics and Microbiology and Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
Kan LiCenter for Human Systems Immunology, Departments of Surgery, Immunology, and Molecular Genetics and Microbiology and Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
Daniel BedingerCarterra Inc. Salt Lake City, Utah, USA.
Sharon L SchendelCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA.
Georgia D TomarasCenter for Human Systems Immunology, Departments of Surgery, Immunology, and Molecular Genetics and Microbiology and Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
Hanif AliQuadrucept Bio Ltd, Kemp House, London, United Kingdom.
Galit AlterRagon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
Erica Ollmann SaphireCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA.
Alexander BukreyevDepartment of Pathology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.

Funding

Specific and Broadly Active Monoclonal Antibody Therapeutics Against The FilovirusesU19AI142790 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI SAPHIRE, ERICA OLLMANN · 2019 to 2023
$40.0M
NIAID NIH HHS U19 AI142790
6 · The paper itself

Abstract

Antibody-dependent enhancement (ADE) of infection is a well-described phenomenon for several viruses, including dengue, Ebola, respiratory syncytial virus, and HIV. ADE occurs when virus-antibody complexes engage Fc receptors (FcRs) and virus-specific receptors, enhancing infection under conditions of incomplete neutralization. The Coronavirus Immunotherapeutic Consortium (CoVIC) assembled a comprehensive dataset of functional properties for over 400 mAbs, enabling direct comparison of neutralization, Fc-mediated functions, receptor binding, and infection of immune cells. Infection rates in most primary human immune cell types were low, with modest increases observed for some mAbs. In contrast, macrophages were more susceptible to SARS-CoV-2 and exhibited substantial ADE with select mAbs. ADE was completely inhibited by FcR blockade and significantly reduced by antibody- or ceftazidime-mediated blocking of angiotensin-converting enzyme 2 (ACE2). Neutralization potency did not correlate with ADE, as both strongly and weakly neutralizing antibodies induced enhancement. Instead, ADE magnitude depended on an antibody's ability to block spike protein binding to ACE2. Importantly, ADE resulted in productive infection with release of infectious virus. Evaluation of antibodies against the BA.1 (Omicron) variant revealed reduced or lost ADE for most mAbs, with increased ADE observed for several mAbs relative to the USA-WA1/2020 strain.

Indexed as

Angiotensin-Converting Enzyme 2Antibodies, ViralAntibody-Dependent EnhancementCOVID-19Receptors, FcSARS-CoV-2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingHumansSpike Glycoprotein, CoronavirusACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralReceptors, FcSpike Glycoprotein, CoronavirusAdaptive immunityCOVID-19ImmunoglobulinsImmunologyVirology

Identifiers

PMID41729079
PMCPMC12956010

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.