Long COVID-19 autoantibodies and their potential effect on fertility
Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-...
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| Published in | Frontiers in immunology Vol. 16; p. 1540341 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Switzerland
Frontiers
27.05.2025
Frontiers Media S.A |
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| Abstract | Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-2 infection on male fertility and determine the potential reasons leading to impaired male reproductive functions. In silico approach identified ~60 amino acid sequences containing at least five continuous residues shared by SARS-CoV-2 Spike glycoprotein and spermatogenesis-linked proteins. Four synthetic peptides were tested with sera from independent cohorts of patients with acute and long COVID-19 syndrome (LCS), and naïve vaccinated subjects. Immunogenicity and pathogenicity studies were performed by immunizing mice with two selected peptides and testing the antigenicity of induced antibodies. While none of four peptides were recognized by antibodies from vaccinated people, infected patients exhibited high reactivity to peptide 4, and LCS patients, especially women, showed elevated antibody levels against peptide 2. Women with LCS and chronic fatigue syndrome had higher levels of peptide 2–reacting antibodies than those with idiopathic chronic fatigue syndrome. Noteworthy, peptide 2 antibodies showed, in in vitro experiment, a specific interaction with mouse testicular tissue antigens. These findings raise the possibility that cross-reactive epitopes between SARS-CoV-2 Spike protein and spermatogenesis-related antigens may affect infected patients’ fertility, suggesting a potential for autoimmune responses with human consequences. |
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| AbstractList | Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-2 infection on male fertility and determine the potential reasons leading to impaired male reproductive functions. In silico approach identified ~60 amino acid sequences containing at least five continuous residues shared by SARS-CoV-2 Spike glycoprotein and spermatogenesis-linked proteins. Four synthetic peptides were tested with sera from independent cohorts of patients with acute and long COVID-19 syndrome (LCS), and naïve vaccinated subjects. Immunogenicity and pathogenicity studies were performed by immunizing mice with two selected peptides and testing the antigenicity of induced antibodies. While none of four peptides were recognized by antibodies from vaccinated people, infected patients exhibited high reactivity to peptide 4, and LCS patients, especially women, showed elevated antibody levels against peptide 2. Women with LCS and chronic fatigue syndrome had higher levels of peptide 2-reacting antibodies than those with idiopathic chronic fatigue syndrome. Noteworthy, peptide 2 antibodies showed, in in vitro experiment, a specific interaction with mouse testicular tissue antigens. These findings raise the possibility that cross-reactive epitopes between SARS-CoV-2 Spike protein and spermatogenesis-related antigens may affect infected patients' fertility, suggesting a potential for autoimmune responses with human consequences.Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-2 infection on male fertility and determine the potential reasons leading to impaired male reproductive functions. In silico approach identified ~60 amino acid sequences containing at least five continuous residues shared by SARS-CoV-2 Spike glycoprotein and spermatogenesis-linked proteins. Four synthetic peptides were tested with sera from independent cohorts of patients with acute and long COVID-19 syndrome (LCS), and naïve vaccinated subjects. Immunogenicity and pathogenicity studies were performed by immunizing mice with two selected peptides and testing the antigenicity of induced antibodies. While none of four peptides were recognized by antibodies from vaccinated people, infected patients exhibited high reactivity to peptide 4, and LCS patients, especially women, showed elevated antibody levels against peptide 2. Women with LCS and chronic fatigue syndrome had higher levels of peptide 2-reacting antibodies than those with idiopathic chronic fatigue syndrome. Noteworthy, peptide 2 antibodies showed, in in vitro experiment, a specific interaction with mouse testicular tissue antigens. These findings raise the possibility that cross-reactive epitopes between SARS-CoV-2 Spike protein and spermatogenesis-related antigens may affect infected patients' fertility, suggesting a potential for autoimmune responses with human consequences. Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-2 infection on male fertility and determine the potential reasons leading to impaired male reproductive functions. In silico approach identified ~60 amino acid sequences containing at least five continuous residues shared by SARS-CoV-2 Spike glycoprotein and spermatogenesis-linked proteins. Four synthetic peptides were tested with sera from independent cohorts of patients with acute and long COVID-19 syndrome (LCS), and naïve vaccinated subjects. Immunogenicity and pathogenicity studies were performed by immunizing mice with two selected peptides and testing the antigenicity of induced antibodies. While none of four peptides were recognized by antibodies from vaccinated people, infected patients exhibited high reactivity to peptide 4, and LCS patients, especially women, showed elevated antibody levels against peptide 2. Women with LCS and chronic fatigue syndrome had higher levels of peptide 2–reacting antibodies than those with idiopathic chronic fatigue syndrome. Noteworthy, peptide 2 antibodies showed, in in vitro experiment, a specific interaction with mouse testicular tissue antigens. These findings raise the possibility that cross-reactive epitopes between SARS-CoV-2 Spike protein and spermatogenesis-related antigens may affect infected patients’ fertility, suggesting a potential for autoimmune responses with human consequences. Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-2 infection on male fertility and determine the potential reasons leading to impaired male reproductive functions. approach identified ~60 amino acid sequences containing at least five continuous residues shared by SARS-CoV-2 Spike glycoprotein and spermatogenesis-linked proteins. Four synthetic peptides were tested with sera from independent cohorts of patients with acute and long COVID-19 syndrome (LCS), and naïve vaccinated subjects. Immunogenicity and pathogenicity studies were performed by immunizing mice with two selected peptides and testing the antigenicity of induced antibodies. While none of four peptides were recognized by antibodies from vaccinated people, infected patients exhibited high reactivity to peptide 4, and LCS patients, especially women, showed elevated antibody levels against peptide 2. Women with LCS and chronic fatigue syndrome had higher levels of peptide 2-reacting antibodies than those with idiopathic chronic fatigue syndrome. Noteworthy, peptide 2 antibodies showed, in experiment, a specific interaction with mouse testicular tissue antigens. These findings raise the possibility that cross-reactive epitopes between SARS-CoV-2 Spike protein and spermatogenesis-related antigens may affect infected patients' fertility, suggesting a potential for autoimmune responses with human consequences. Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-2 infection on male fertility and determine the potential reasons leading to impaired male reproductive functions. In silico approach identified ~60 amino acid sequences containing at least five continuous residues shared by SARS-CoV-2 Spike glycoprotein and spermatogenesis-linked proteins. Four synthetic peptides were tested with sera from independent cohorts of patients with acute and long COVID-19 syndrome (LCS), and naïve vaccinated subjects. Immunogenicity and pathogenicity studies were performed by immunizing mice with two selected peptides and testing the antigenicity of induced antibodies. While none of four peptides were recognized by antibodies from vaccinated people, infected patients exhibited high reactivity to peptide 4, and LCS patients, especially women, showed elevated antibody levels against peptide 2. Women with LCS and chronic fatigue syndrome had higher levels of peptide 2–reacting antibodies than those with idiopathic chronic fatigue syndrome. Noteworthy, peptide 2 antibodies showed, in in vitro experiment, a specific interaction with mouse testicular tissue antigens. These findings raise the possibility that cross-reactive epitopes between SARS-CoV-2 Spike protein and spermatogenesis-related antigens may affect infected patients’ fertility, suggesting a potential for autoimmune responses with human consequences. |
| Author | Filgueiras, Igor Salerno Meroni, Pier Luigi Verdot, Cindy Ryabkova, Varvara A. Ng, Lisa F.P. Gavrilova, Natalia Y. Young, Barnaby E. Fonseca, Dennyson Leandro M. Chaloin, Olivier Fong, Siew-Wai Lensch, Christian Lozano, José Manuel Borghi, Maria Orietta Muller, Sylviane Kanduc, Darja Rénia, Laurent Halpert, Gilad Talamini, Laura Cabral-Marques, Otávio Thurner, Lorenz Galmiche, Christian Dotan, Arad Lye, David Chien Churilov, Leonid P. Shoenfeld, Yehuda |
| AuthorAffiliation | 20 Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore 22 Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN) , São Paulo , Brazil 7 Department of Immunology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil 12 Research Institute of Phthisiopulmonology , Saint-Petersburg , Russia 11 Pavlov First Saint Petersburg State Medical University , Saint-Petersburg , Russia 9 Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico , Milano , Italy 26 Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo School of Medicine , São Paulo , Brazil 8 Department of Clinical Sciences and Community Health, University of Milan , Milano , Italy 24 Instituto D’Or de Ensino e Pesquisa , São Paulo , Brazil 2 Inter |
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| Copyright | Copyright © 2025 Talamini, Fonseca, Kanduc, Chaloin, Verdot, Galmiche, Dotan, Filgueiras, Borghi, Meroni, Gavrilova, Ryabkova, Churilov, Halpert, Lensch, Thurner, Fong, Ng, Rénia, Young, Lye, Lozano, Cabral-Marques, Shoenfeld and Muller. Distributed under a Creative Commons Attribution 4.0 International License Copyright © 2025 Talamini, Fonseca, Kanduc, Chaloin, Verdot, Galmiche, Dotan, Filgueiras, Borghi, Meroni, Gavrilova, Ryabkova, Churilov, Halpert, Lensch, Thurner, Fong, Ng, Rénia, Young, Lye, Lozano, Cabral-Marques, Shoenfeld and Muller 2025 Talamini, Fonseca, Kanduc, Chaloin, Verdot, Galmiche, Dotan, Filgueiras, Borghi, Meroni, Gavrilova, Ryabkova, Churilov, Halpert, Lensch, Thurner, Fong, Ng, Rénia, Young, Lye, Lozano, Cabral-Marques, Shoenfeld and Muller |
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| Keywords | coronavirus infection peptide sequence identity autoantibodies post-COVID-19 condition male reproductive system autoantibodies peptide sequence identity male reproductive system coronavirus infection post-COVID-19 condition |
| Language | English |
| License | Copyright © 2025 Talamini, Fonseca, Kanduc, Chaloin, Verdot, Galmiche, Dotan, Filgueiras, Borghi, Meroni, Gavrilova, Ryabkova, Churilov, Halpert, Lensch, Thurner, Fong, Ng, Rénia, Young, Lye, Lozano, Cabral-Marques, Shoenfeld and Muller. Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Xingwang Li, First Affiliated Hospital of Xi’an Jiaotong University, China Reviewed by: Angela Ostuni, University of Basilicata, Italy Edited by: Allen Jay Rosenspire, Wayne State University, United States Yaping Sun, Yale University, United States |
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| Title | Long COVID-19 autoantibodies and their potential effect on fertility |
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