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Immunity to SARS-CoV-2 up to 15 months after infection

Harold Marcotte, Antonio Piralla, Fanglei Zuo, Likun Du, Irene Cassaniti, Hui Wan, Makiko Kumagai-Braesh, Juni Andréll, Elena Percivalle, Josè Camilla Sammartino, Yating Wang, Stelios Vlachiotis, Janine Attevall, Federica Bergami, Alessandro Ferrari, Marta Colaneri, Marco Vecchia, Margherita Sambo, Valentina Zuccaro, Erika Asperges, Raffaele Bruno, Tiberio Oggionni, Federica Meloni, Hassan Abolhassanni, Federico Bertoglio, Maren Schubert, Luigi Calzolai, Luca Varani, Michael Hust, Yintong Xue, Lennart Hammarström, Fausto Baldanti, Qiang Pan-Hammarström
doi: https://doi.org/10.1101/2021.10.08.463699
Harold Marcotte
1Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
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  • For correspondence: harold.marcotte@ki.se
Antonio Piralla
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Fanglei Zuo
3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Likun Du
3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Irene Cassaniti
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Hui Wan
3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Makiko Kumagai-Braesh
4Division of Transplantation Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
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Juni Andréll
5Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University
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Elena Percivalle
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Josè Camilla Sammartino
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Yating Wang
3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Stelios Vlachiotis
3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Janine Attevall
4Division of Transplantation Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
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Federica Bergami
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Alessandro Ferrari
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Marta Colaneri
6Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Italy
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Marco Vecchia
6Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Italy
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Margherita Sambo
6Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Italy
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Valentina Zuccaro
6Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Italy
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Erika Asperges
6Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Italy
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Raffaele Bruno
6Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Italy
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Tiberio Oggionni
7Unit of Respiratory Diseases, Department of Medical Sciences and Infective Diseases IRCCS Policlinico San Matteo Foundation, Pavia, Italy
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Federica Meloni
8Section of Pneumology, Department of Internal Medicine, University of Pavia, Pavia, Italy
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Hassan Abolhassanni
3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Federico Bertoglio
9Technische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics; Department of Biotechnology, Braunschweig, Germany
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Maren Schubert
9Technische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics; Department of Biotechnology, Braunschweig, Germany
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Luigi Calzolai
10European Commission, Joint Research Centre, Ispra, Italy
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Luca Varani
11Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
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Michael Hust
9Technische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics; Department of Biotechnology, Braunschweig, Germany
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Yintong Xue
12Department of Immunology, Peking University Health Science Center, Beijing, China
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Lennart Hammarström
3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Fausto Baldanti
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
13Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy
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Qiang Pan-Hammarström
3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Summary

Background Information concerning the longevity of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in convalescent coronavirus disease-2019 (COVID-19) patients up to 15 months after symptoms onset.

Methods The levels of anti-spike and anti-receptor binding domain antibodies and neutralizing activities were tested in a total of 188 samples from 136 convalescent patients who experience mild to critical COVID-19. Specific memory B and T cell responses were measured in 76 peripheral blood mononuclear cell samples collected from 54 patients. Twenty-three vaccinated individuals were included for comparison.

Findings Following a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8-fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months.

Conclusion The data suggest that antiviral specific immunity especially memory B cells in COVID-19 convalescent patients is long-lasting, but some variants of concern, including the fast-spreading Delta variant, may at least partially escape the neutralizing activity of plasma antibodies.

Funding EU-ATAC consortium, the Italian Ministry of Health, the Swedish Research Council, SciLifeLab, and KAW.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵15 Co-senior authors

  • ↵16 Lead Contact

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 11, 2021.
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Immunity to SARS-CoV-2 up to 15 months after infection
Harold Marcotte, Antonio Piralla, Fanglei Zuo, Likun Du, Irene Cassaniti, Hui Wan, Makiko Kumagai-Braesh, Juni Andréll, Elena Percivalle, Josè Camilla Sammartino, Yating Wang, Stelios Vlachiotis, Janine Attevall, Federica Bergami, Alessandro Ferrari, Marta Colaneri, Marco Vecchia, Margherita Sambo, Valentina Zuccaro, Erika Asperges, Raffaele Bruno, Tiberio Oggionni, Federica Meloni, Hassan Abolhassanni, Federico Bertoglio, Maren Schubert, Luigi Calzolai, Luca Varani, Michael Hust, Yintong Xue, Lennart Hammarström, Fausto Baldanti, Qiang Pan-Hammarström
bioRxiv 2021.10.08.463699; doi: https://doi.org/10.1101/2021.10.08.463699
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Immunity to SARS-CoV-2 up to 15 months after infection
Harold Marcotte, Antonio Piralla, Fanglei Zuo, Likun Du, Irene Cassaniti, Hui Wan, Makiko Kumagai-Braesh, Juni Andréll, Elena Percivalle, Josè Camilla Sammartino, Yating Wang, Stelios Vlachiotis, Janine Attevall, Federica Bergami, Alessandro Ferrari, Marta Colaneri, Marco Vecchia, Margherita Sambo, Valentina Zuccaro, Erika Asperges, Raffaele Bruno, Tiberio Oggionni, Federica Meloni, Hassan Abolhassanni, Federico Bertoglio, Maren Schubert, Luigi Calzolai, Luca Varani, Michael Hust, Yintong Xue, Lennart Hammarström, Fausto Baldanti, Qiang Pan-Hammarström
bioRxiv 2021.10.08.463699; doi: https://doi.org/10.1101/2021.10.08.463699

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