tetano
Editor, Senior Moderator
Front Immunol
. 2025 Oct 2:16:1670324.
doi: 10.3389/fimmu.2025.1670324. eCollection 2025. Post-COVID syndrome patients show reduced anti-Spike antibodies compared to COVID-recovered controls, but enhanced IgG4/IgG1 switch after the third vaccine dose
Nineth Rossi[SUP] #[/SUP][SUP] 1 [/SUP], Javier Benítez-Cruz[SUP] #[/SUP][SUP] 1 [/SUP], Patricia Marín-García[SUP] 2 [/SUP], Isabel G Azcárate[SUP] 3 [/SUP], Alba González-Escalada[SUP] 3 [/SUP], Oscar G Hervás[SUP] 1 [/SUP], Balbino Alarcón[SUP] 4 [/SUP], José R Regueiro[SUP] 1 5 [/SUP], José M Bautista[SUP] 6 7 [/SUP], Narcisa Martinez-Quiles[SUP] 1 [/SUP]
Affiliations
Introduction: Long COVID and post-COVID syndromes represent a significant global health crisis and a substantial societal challenge. Although an altered immunological response has been suggested as a possible underlying mechanism, the antibody response to vaccination and infection of the patients remains unclear.
Methods: We studied a post-COVID syndrome cohort compared to a COVID-recovered cohort. Initially, we established the risk factors and the evolution of symptoms. Then, we analyzed the antibody response, focusing on immunoglobulin subclasses. Apart from determining immunoglobulin G (IgG) against the Nucleocapsid, which is a marker of infection, we analyzed IgG and its subclasses against the full-length Spike, and against the receptor-binding domain (RBD). Additionally, we examined the switch to IgG4, which can be promoted by repeated antigen exposure.
Results: We show the major risk factors for developing post-COVID syndrome, such as infection before vaccination and comorbidities. Furthermore, we describe the evolution of the post-COVID symptoms, which agrees with previous reports. Regarding the antibody response, we found that compared to COVID-recovered individuals, post-COVID patients present readily detectable anti-Nucleocapsid IgG but low quantities of anti-Spike antibodies. Nevertheless, the anti-RBD IgG1 levels are similar between post-COVID and COVID samples. Interestingly, post-COVID patients with three vaccine doses, who were infected before vaccination by the Wuhan strain and subsequently reinfected post-Omicron, show decreased Spike response but intensified anti-RBD IgG4/IgG1 switch, compared to their non-reinfected post-COVID counterparts.
Discussion: Our results support a differential antibody response in post-COVID versus COVID-recovered patients, which might be relevant for post-COVID syndrome treatment, including appropriate recall vaccination strategies for the still-circulating SARS-CoV-2.
Keywords: IgG subclass; IgG4; SARS-CoV-2; Spike protein; antibody response; post-COVID; reinfection; vaccination.
. 2025 Oct 2:16:1670324.
doi: 10.3389/fimmu.2025.1670324. eCollection 2025. Post-COVID syndrome patients show reduced anti-Spike antibodies compared to COVID-recovered controls, but enhanced IgG4/IgG1 switch after the third vaccine dose
Nineth Rossi[SUP] #[/SUP][SUP] 1 [/SUP], Javier Benítez-Cruz[SUP] #[/SUP][SUP] 1 [/SUP], Patricia Marín-García[SUP] 2 [/SUP], Isabel G Azcárate[SUP] 3 [/SUP], Alba González-Escalada[SUP] 3 [/SUP], Oscar G Hervás[SUP] 1 [/SUP], Balbino Alarcón[SUP] 4 [/SUP], José R Regueiro[SUP] 1 5 [/SUP], José M Bautista[SUP] 6 7 [/SUP], Narcisa Martinez-Quiles[SUP] 1 [/SUP]
Affiliations
- PMID: 41112288
- PMCID: PMC12528128
- DOI: 10.3389/fimmu.2025.1670324
Introduction: Long COVID and post-COVID syndromes represent a significant global health crisis and a substantial societal challenge. Although an altered immunological response has been suggested as a possible underlying mechanism, the antibody response to vaccination and infection of the patients remains unclear.
Methods: We studied a post-COVID syndrome cohort compared to a COVID-recovered cohort. Initially, we established the risk factors and the evolution of symptoms. Then, we analyzed the antibody response, focusing on immunoglobulin subclasses. Apart from determining immunoglobulin G (IgG) against the Nucleocapsid, which is a marker of infection, we analyzed IgG and its subclasses against the full-length Spike, and against the receptor-binding domain (RBD). Additionally, we examined the switch to IgG4, which can be promoted by repeated antigen exposure.
Results: We show the major risk factors for developing post-COVID syndrome, such as infection before vaccination and comorbidities. Furthermore, we describe the evolution of the post-COVID symptoms, which agrees with previous reports. Regarding the antibody response, we found that compared to COVID-recovered individuals, post-COVID patients present readily detectable anti-Nucleocapsid IgG but low quantities of anti-Spike antibodies. Nevertheless, the anti-RBD IgG1 levels are similar between post-COVID and COVID samples. Interestingly, post-COVID patients with three vaccine doses, who were infected before vaccination by the Wuhan strain and subsequently reinfected post-Omicron, show decreased Spike response but intensified anti-RBD IgG4/IgG1 switch, compared to their non-reinfected post-COVID counterparts.
Discussion: Our results support a differential antibody response in post-COVID versus COVID-recovered patients, which might be relevant for post-COVID syndrome treatment, including appropriate recall vaccination strategies for the still-circulating SARS-CoV-2.
Keywords: IgG subclass; IgG4; SARS-CoV-2; Spike protein; antibody response; post-COVID; reinfection; vaccination.