Early functional maturation of anti-Spike antibodies predicts efficient SARS-CoV-2 RNA clearance
7 affiliations
- 1Laboratório de Biologia de Linfócitos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , , ,
- 2Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro , , ,
- 3Centro de Ciências Exatas e Tecnologia, Universidade Federal do Estado do Rio de Janeiro , , ,
- 4Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro , , ,
- 5Núcleo de Enfrentamento e Estudos de Doenças Infecciosas Emergentes e Reemergentes, Universidade Federal do Rio de Janeiro , , ,
- 6Laboratório de Biotecnologia e Bioengenharia Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , , ,
- 7Laboratório de Engenharia de Cultivos Celulares, Programa de Engenharia Química, COPPE, Universidade Federal do Rio de Janeiro , , ,
Abstract
Introduction: Viral RNA clearance following mild SARS-CoV-2 infection varies considerably among individuals, but the early humoral immune features underlying this heterogeneity remain incompletely understood.
Methods: We investigated whether the kinetics and functional maturation of the antibody response were associated with viral RNA clearance in a longitudinal study of 78 healthcare professionals infected with the ancestral Wuhan SARS-CoV-2 strain and followed for up to three years. Participants were stratified according to viral RNA clearance kinetics as nonpersistent (≤21 days) or persistent (>21 days). Humoral responses were longitudinally characterized by seroconversion kinetics, antibody isotypes and IgG subclasses, affinity, cross-variant recognition, and neutralizing activity.
Results: Nonpersistent individuals exhibited accelerated seroconversion to Spike and receptor-binding domain antigens within the first 11 days after symptom onset, accompanied by significantly greater neutralizing activity against the ancestral strain. In contrast, persistent individuals displayed delayed seroconversion, prolonged IgM responses, and reduced coordination among IgG subclasses during acute infection, consistent with delayed early humoral maturation. Total immunoglobulin levels did not distinguish the groups, whereas cross-variant antibody recognition during acute infection remained limited and predominantly strain-focused in both groups. During convalescence, durable anti-Spike IgG responses were maintained independently of persistence status, without significant differences in cross-variant breadth. Vaccination robustly enhanced antibody titers, variant recognition, and ACE2-blocking responses in both groups.
Discussion: Accelerated functional maturation of the early anti-Spike antibody response, rather than overall antibody magnitude, was associated with efficient SARS-CoV-2 RNA clearance. These findings identify early functional maturation of the humoral response as an immunological correlate of efficient viral clearance and provide mechanistic insight into the immune processes underlying heterogeneous SARS-CoV-2 RNA clearance during mild infection.
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BibTeX
@article{rodrigues2026early,
title = {{Early functional maturation of anti-Spike antibodies predicts efficient SARS-CoV-2 RNA clearance}},
author = {Danielle A. S. Rodrigues and Barbara Gabrielle de Araujo and Julia Pestana and Layla de Freitas and Brenda N. Ramos and Lendel C. da Costa and Matheus V. Andrade and Letícia M. Raposo and Vicente B. T. Bozza and Luciana Conde and Elena Montes-Cobos and Andreza M.D.S. Gama and Vinicius M. Vidal and Rafael M Galliez and Amilcar Tanuri and Orlando D. C. Ferreira and Marcus Vinicius de Mattos Silva and Ronaldo Mohana-Borges and Leda R. Castilho and Juliana Echevarria-Lima and Luiza M. Higa and Terezinha M. Castineiras and Marcelo T. Bozza and André M. Vale},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1948045},
url = {https://europepmc.org/article/PMC/PMC13672549},
note = {CC BY},
}
RIS
TY - JOUR
TI - Early functional maturation of anti-Spike antibodies predicts efficient SARS-CoV-2 RNA clearance
AU - Danielle A. S. Rodrigues
AU - Barbara Gabrielle de Araujo
AU - Julia Pestana
AU - Layla de Freitas
AU - Brenda N. Ramos
AU - Lendel C. da Costa
AU - Matheus V. Andrade
AU - Letícia M. Raposo
AU - Vicente B. T. Bozza
AU - Luciana Conde
AU - Elena Montes-Cobos
AU - Andreza M.D.S. Gama
AU - Vinicius M. Vidal
AU - Rafael M Galliez
AU - Amilcar Tanuri
AU - Orlando D. C. Ferreira
AU - Marcus Vinicius de Mattos Silva
AU - Ronaldo Mohana-Borges
AU - Leda R. Castilho
AU - Juliana Echevarria-Lima
AU - Luiza M. Higa
AU - Terezinha M. Castineiras
AU - Marcelo T. Bozza
AU - André M. Vale
PY - 2026
DA - 2026/10/02
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1948045
UR - https://europepmc.org/article/PMC/PMC13672549
AB - Introduction: Viral RNA clearance following mild SARS-CoV-2 infection varies considerably among individuals, but the early humoral immune features underlying this heterogeneity remain incompletely understood. Methods: We investigated whether the kinetics and functional maturation of the antibody response were associated with viral RNA clearance in a longitudinal study of 78 healthcare professionals infected with the ancestral Wuhan SARS-CoV-2 strain and followed for up to three years. Participants were stratified according to viral RNA clearance kinetics as nonpersistent (≤21 days) or persistent (>21 days). Humoral responses were longitudinally characterized by seroconversion kinetics, antibody isotypes and IgG subclasses, affinity, cross-variant recognition, and neutralizing activity. Results: Nonpersistent individuals exhibited accelerated seroconversion to Spike and receptor-binding domain antigens within the first 11 days after symptom onset, accompanied by significantly greater neutralizing activity against the ancestral strain. In contrast, persistent individuals displayed delayed seroconversion, prolonged IgM responses, and reduced coordination among IgG subclasses during acute infection, consistent with delayed early humoral maturation. Total immunoglobulin levels did not distinguish the groups, whereas cross-variant antibody recognition during acute infection remained limited and predominantly strain-focused in both groups. During convalescence, durable anti-Spike IgG responses were maintained independently of persistence status, without significant differences in cross-variant breadth. Vaccination robustly enhanced antibody titers, variant recognition, and ACE2-blocking responses in both groups. Discussion: Accelerated functional maturation of the early anti-Spike antibody response, rather than overall antibody magnitude, was associated with efficient SARS-CoV-2 RNA clearance. These findings identify early functional maturation of the humoral response as an immunological correlate of efficient viral clearance and provide mechanistic insight into the immune processes underlying heterogeneous SARS-CoV-2 RNA clearance during mild infection.
SN - 1664-3224
ER -