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. 2025 Mar:272:110429.
doi: 10.1016/j.clim.2025.110429. Epub 2025 Jan 20.

The immune response to SARS-CoV-2 in COVID-19 as a recall response susceptible to immune imprinting: A prospective cohort study

Daniel Alvarez-Sierra  1 , Mónica Martínez-Gallo  2 , Adrián Sánchez-Montalvá  3 , Marco Fernández-Sanmartín  4 , Roger Colobran  2 , Juan Espinosa-Pereiro  3 , Elísabet Poyatos-Canton  5 , Coral Zurera-Egea  6 , Alex Sánchez-Pla  7 , Concepción Violan  8 , Rafael Parra  9 , Hammad Alzayat  4 , Ana Vivancos  10 , Francisco Morandeira-Rego  5 , Blanca Urban-Vargas  5 , Eva Martínez-Cáceres  11 , Manuel Hernández-González  2 , Jordi Bas-Minguet  5 , Peter D Katsikis  12 , Aina Teniente-Serra  11 , Ricardo Pujol-Borrell  13
Affiliations
Free article

The immune response to SARS-CoV-2 in COVID-19 as a recall response susceptible to immune imprinting: A prospective cohort study

Daniel Alvarez-Sierra et al. Clin Immunol. 2025 Mar.
Free article

Abstract

The antibody response to SARS-CoV-2 does not follow the immunoglobulin isotype pattern of primary responses, conflicting with the current interpretation of COVID-19.

Methods: Prospective cohort study of 191 SARS-CoV-2 infection cases and 44 controls from the second wave of COVID-19. The study stratified patients by severity and analyzed the trajectories of SARS-CoV-2 antibodies and multiple immune variables.

Results: Isotype-specific antibody time course profiles to SARS-CoV-2 revealed a pattern of recall response in 94.2 % of cases. The time course profiles of plasmablasts, B cells, cTfh high-resolution subsets, and cytokines indicated a secondary response. The transcriptomic data showed that this cohort is strictly comparable to contemporary cohorts.

Conclusions: In most cases, the immune response to SARS-CoV-2 is a recall response. This constitutes a favorable scenario for most COVID-19 cases to be subjected to immune imprinting by endemic coronavirus, which, in turn, can influence the immune response to SARS-CoV-2.

Keywords: Antibody-dependent-enhancement; COVID-19; Immune imprinting; Original antigenic sin; Plasmablast; SARS-CoV-2; Spectral flow cytometry; cTfh.

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Conflict of interest statement

Declaration of competing interest All authors declare that they have no conflicts of interest.