Evidence map›Paper›PMID 37892220›Full record

ArticleBiomolecules2023

Treatment-Emergent Cilgavimab Resistance Was Uncommon in Vaccinated Omicron BA.4/5 Outpatients.

Cesare Ernesto Maria Gruber, Fabio Giovanni Tucci, Martina Rueca, Valentina Mazzotta, Giulia Gramigna, Alessandra Vergori, Lavinia Fabeni, Giulia Berno, Emanuela Giombini, Ornella Butera and 8 more

Open access · goldAbstract read
In one paragraph

Article in Biomolecules, 2023. 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
0.4field-weighted citation impact, top 39% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  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

18 authors at 2 institutions in 1 country.

Cesare Ernesto Maria GruberLaboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.ORCID 0000-0002-8831-3380
Fabio Giovanni TucciLaboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Martina RuecaLaboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.ORCID 0000-0001-5162-046X
Valentina MazzottaClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.ORCID 0000-0002-0240-7504
Giulia GramignaLaboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Alessandra VergoriClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.ORCID 0000-0001-6944-0686
Lavinia FabeniLaboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Giulia BernoLaboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.ORCID 0000-0003-0331-2627
Emanuela GiombiniLaboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Ornella ButeraLaboratory of Microbiology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Daniele FocosiNorth-Western Tuscany Blood Bank, Pisa University Hospital, 56124 Pisa, Italy.
Ingrid Guarnetti PrandiDepartment for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), University of Tuscia, Via S. Camillo de Lellis s.n.c, 01100 Viterbo, Italy.
Giovanni ChillemiDepartment for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), University of Tuscia, Via S. Camillo de Lellis s.n.c, 01100 Viterbo, Italy.ORCID 0000-0003-3901-6926
Emanuele NicastriClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.ORCID 0000-0002-5606-8712
Francesco VaiaGeneral Direction, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Enrico GirardiScientific Direction, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.ORCID 0000-0001-8182-5896
Andrea AntinoriClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.ORCID 0000-0003-2121-4684
Fabrizio MaggiLaboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani · ITUniversità degli Studi della Tuscia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutations in the SARS-CoV-2 Spike glycoprotein can affect monoclonal antibody efficacy. Recent findings report the occurrence of resistant mutations in immunocompromised patients after tixagevimab/cilgavimab treatment. More recently, the Food and Drug Agency revoked the authorization for tixagevimab/cilgavimab, while this monoclonal antibody cocktail is currently recommended by the European Medical Agency. We retrospectively reviewed 22 immunocompetent patients at high risk for disease progression who received intramuscular tixagevimab/cilgavimab as early COVID-19 treatment and presented a prolonged high viral load. Complete SARS-CoV-2 genome sequences were obtained for a deep investigation of mutation frequencies in Spike protein before and during treatment. At seven days, only one patient showed evidence of treatment-emergent cilgavimab resistance. Quasispecies analysis revealed two different deletions on the Spike protein (S:del138-144 or S:del141-145) in combination with the resistance S:K444N mutation. The structural and dynamic impact of the two quasispecies was characterized by using molecular dynamics simulations, showing the conservation of the principal functional movements in the mutated systems and their capabilities to alter the structure and dynamics of the RBD, responsible for the interaction with the ACE2 human receptor. Our study underlines the importance of prompting an early virological investigation to prevent drug resistance or clinical failures in immunocompetent patients.

Indexed as

OutpatientsSpike Glycoprotein, CoronavirusAntibodies, MonoclonalCOVID-19 Drug TreatmentHumansRetrospective StudiesAntibodies, MonoclonalcilgavimabSpike Glycoprotein, CoronaviruscilgavimabdeletionmAbsmutationsquasispeciesSARS-CoV-2Spiketixagevimab

Identifiers

PMID37892220
PMCPMC10605390
OpenAlexW4387744106

What OpenQuestion 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 OpenQuestion graph.