Detectable SARS-CoV-2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection.

Memory T cells play an important role in mediating long-lasting adaptive immune responses to viral infections, such as SARS-CoV-2. In the context of the latter, much of our current knowledge stems from studies in vaccinated individuals or repeatedly infected individuals. However, limited knowledge i...

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Main Authors: Nikolas Weigl, Claire Pleimelding, Leonard Gilberg, Duc Huynh, Isabel Brand, Jan Bruger, Jonathan Frese, Tabea M Eser, Mohamed I M Ahmed, Jessica M Guggenbuehl-Noller, Renate Stirner, Michael Hoelscher, Michael Pritsch, Christof Geldmacher, Sebastian Kobold, Julia Roider, KoCo19-/ORCHESTRA-study group
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0325923
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author Nikolas Weigl
Claire Pleimelding
Leonard Gilberg
Duc Huynh
Isabel Brand
Jan Bruger
Jonathan Frese
Tabea M Eser
Mohamed I M Ahmed
Jessica M Guggenbuehl-Noller
Renate Stirner
Michael Hoelscher
Michael Pritsch
Christof Geldmacher
Sebastian Kobold
Julia Roider
KoCo19-/ORCHESTRA-study group
author_facet Nikolas Weigl
Claire Pleimelding
Leonard Gilberg
Duc Huynh
Isabel Brand
Jan Bruger
Jonathan Frese
Tabea M Eser
Mohamed I M Ahmed
Jessica M Guggenbuehl-Noller
Renate Stirner
Michael Hoelscher
Michael Pritsch
Christof Geldmacher
Sebastian Kobold
Julia Roider
KoCo19-/ORCHESTRA-study group
author_sort Nikolas Weigl
collection DOAJ
description Memory T cells play an important role in mediating long-lasting adaptive immune responses to viral infections, such as SARS-CoV-2. In the context of the latter, much of our current knowledge stems from studies in vaccinated individuals or repeatedly infected individuals. However, limited knowledge is available on these responses in fully naive individuals in German communities. We performed immunophenotyping of a previously naive SARS-CoV-2 cohort in convalescent individuals after asymptomatic to moderate COVID-19. The samples were collected median 250 days post infection during the first wave of the COVID pandemic in Germany (March - May 2020). In this cohort of 174 individuals, we phenotyped different leukocyte cell populations in peripheral blood (B, T and Natural Killer cells). We then assessed the serostatus against the SARS-CoV-2 antigens Nucleocapsid (N) and Spike subunit (S1) with its receptor binding domain (RBD), as these are important correlates of protection, by testing for presence of immunoglobulin G (IgG) antibodies. We also measured IgG antibody responses against the N antigen of the common cold coronaviruses HCoV-OC43, HCoV-HKU1, HCoV-NL63 and HCoV-229E, to determine possible cross-reactivity. In a subset of the cohort (n = 76), we performed intracellular staining assays (ICS) after stimulation with SARS-CoV-2 and HCoV antigens. Key findings are significant differences in frequency of CD4+ memory T cell populations, notably CD4+ TEM and CD4+ TEMRA cells, between the group of SARS-CoV-2 positive individuals and the control group. These differences correlated with cytokine production (TNFα, IFNγ) after stimulation with SARS-CoV-2 peptides, indicating a specific T cell immune response. In conclusion, a clear memory T cell and humoral response can be detected up to 250 days post mild to moderate COVID-19 disease. Our results underline findings reported by others indicating a lasting cellular immune response even in a population which previously had not been exposed to SARS-CoV-2.
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spelling doaj-art-6e0fa1fc4e634205a0c75b2e27de4c5a2025-08-20T03:32:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01206e032592310.1371/journal.pone.0325923Detectable SARS-CoV-2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection.Nikolas WeiglClaire PleimeldingLeonard GilbergDuc HuynhIsabel BrandJan BrugerJonathan FreseTabea M EserMohamed I M AhmedJessica M Guggenbuehl-NollerRenate StirnerMichael HoelscherMichael PritschChristof GeldmacherSebastian KoboldJulia RoiderKoCo19-/ORCHESTRA-study groupMemory T cells play an important role in mediating long-lasting adaptive immune responses to viral infections, such as SARS-CoV-2. In the context of the latter, much of our current knowledge stems from studies in vaccinated individuals or repeatedly infected individuals. However, limited knowledge is available on these responses in fully naive individuals in German communities. We performed immunophenotyping of a previously naive SARS-CoV-2 cohort in convalescent individuals after asymptomatic to moderate COVID-19. The samples were collected median 250 days post infection during the first wave of the COVID pandemic in Germany (March - May 2020). In this cohort of 174 individuals, we phenotyped different leukocyte cell populations in peripheral blood (B, T and Natural Killer cells). We then assessed the serostatus against the SARS-CoV-2 antigens Nucleocapsid (N) and Spike subunit (S1) with its receptor binding domain (RBD), as these are important correlates of protection, by testing for presence of immunoglobulin G (IgG) antibodies. We also measured IgG antibody responses against the N antigen of the common cold coronaviruses HCoV-OC43, HCoV-HKU1, HCoV-NL63 and HCoV-229E, to determine possible cross-reactivity. In a subset of the cohort (n = 76), we performed intracellular staining assays (ICS) after stimulation with SARS-CoV-2 and HCoV antigens. Key findings are significant differences in frequency of CD4+ memory T cell populations, notably CD4+ TEM and CD4+ TEMRA cells, between the group of SARS-CoV-2 positive individuals and the control group. These differences correlated with cytokine production (TNFα, IFNγ) after stimulation with SARS-CoV-2 peptides, indicating a specific T cell immune response. In conclusion, a clear memory T cell and humoral response can be detected up to 250 days post mild to moderate COVID-19 disease. Our results underline findings reported by others indicating a lasting cellular immune response even in a population which previously had not been exposed to SARS-CoV-2.https://doi.org/10.1371/journal.pone.0325923
spellingShingle Nikolas Weigl
Claire Pleimelding
Leonard Gilberg
Duc Huynh
Isabel Brand
Jan Bruger
Jonathan Frese
Tabea M Eser
Mohamed I M Ahmed
Jessica M Guggenbuehl-Noller
Renate Stirner
Michael Hoelscher
Michael Pritsch
Christof Geldmacher
Sebastian Kobold
Julia Roider
KoCo19-/ORCHESTRA-study group
Detectable SARS-CoV-2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection.
PLoS ONE
title Detectable SARS-CoV-2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection.
title_full Detectable SARS-CoV-2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection.
title_fullStr Detectable SARS-CoV-2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection.
title_full_unstemmed Detectable SARS-CoV-2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection.
title_short Detectable SARS-CoV-2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection.
title_sort detectable sars cov 2 specific immune responses in recovered unvaccinated individuals 250 days post wild type infection
url https://doi.org/10.1371/journal.pone.0325923
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