Journal Article

Cytokine and Antibody Isotype Responses in Vaccinated Healthcare Workers with SARS-CoV-2 Breakthrough Infections

Salazar, Ana María, Hinojosa, Juan Pablo Ramírez, Ávila, Guillermina, Chávez-Vargas, Mariana, Plett-Torres, Tanya, Mendlovic, Fela, Fernández-Rojas, Miguel Ángel, Ostrosky-Wegman, Patricia, Cruz-Rivera, Mayra, Sordo, Monserrat, Coeto Ángeles, Cesar Josué, Romero-Valdovinos, Mirza, Flisser, Ana, Santiago-Olivares, Carlos, Maravilla, Pablo

2025

Overview

Background: Healthcare workers (HCWs) are at high risk of breakthrough SARS-CoV-2 infections despite complete vaccination schedules. There are gaps in our understanding of the specific antibody isotypes and cytokine profiles produced during an infection following vaccination. In this study, we evaluated SARS-CoV-2−specific antibody isotypes and their association with cytokine production in HCWs with breakthrough infections. Methods: Serum samples from 114 HCWs were analyzed for antibody isotypes against the nucleoprotein (NCP) and the receptor binding domain (RBD) of the spike protein, as well as for a panel of 13 cytokines. Results: Vaccinated SARS-CoV-2+ HCWs showed a higher prevalence of anti-SARS-CoV-2 antibodies against NCP (IgM = 93.8%, IgG = 93.8%, IgA = 28.1%) and RBD (IgM = 46.9%, IgG = 100%, IgA = 90.6%). A specific IgM response to NCP was more frequent in vaccinated SARS-CoV-2+ individuals, whereas IgA responses were predominantly specific for RBD. Both pro- and anti-inflammatory cytokines were elevated in vaccinated HCWs with breakthrough infections compared with unvaccinated and uninfected individuals. Interestingly, infected IgG+ HCWs with IgM specific for both NCP and RBD exhibited significantly higher IL-8, IL-6, TNF-α, IFN-γ, IL-2, IL-10, and TGF-β concentrations. Conclusion. Our data show that breakthrough infections in vaccinated HCWs induce a robust pro-and anti-inflammatory cytokine profile, which is associated with a broader IgM response directed against both NCP and RBD.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Adult / Analysis / Antibodies / Antibodies, Viral - blood / Antibodies, Viral - immunology / BNT162b2 vaccine / Breakthrough Infections / Coronavirus Nucleocapsid Proteins - immunology / COVID-19 / COVID-19 - blood / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 vaccines / COVID-19 Vaccines - administration & dosage / COVID-19 Vaccines - immunology / Cytokines / Cytokines - blood / Cytokines - immunology / Diabetes / Female / Health care / Health Personnel / healthcare workers / Hospitals / Humans / Hypertension / Immune response / Immunoglobulin A / Immunoglobulin A - blood / Immunoglobulin G / Immunoglobulin G - blood / immunoglobulin isotypes / Immunoglobulin Isotypes - blood / Immunoglobulin Isotypes - immunology / Immunoglobulin M / Immunoglobulin M - blood / Infections / Inflammation / Interleukins / Isotypes / Male / Medical personnel / Medical research / Middle Aged / Obesity / Overweight / Practice / Proteins / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - immunology / Spike protein / Testing / Transforming growth factor-b / Tumor necrosis factor-α / Vaccination / Viral antibodies / Young Adult / γ-Interferon