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Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection

Natalia Sherina, Antonio Piralla, Likun Du, Hui Wan, Makiko Kumagai-Braesh, Juni Andréll, Sten Braesch-Andersen, Irene Cassaniti, Elena Percivalle, Antonella Sarasini, Federica Bergami, Raffaella Di Martino, Marta Colaneri, Marco Vecchia, Margherita Sambo, Valentina Zuccaro, Raffaele Bruno, Tiberio Oggionni, Federica Meloni, Hassan Abolhassani, Federico Bertoglio, Maren Schubert, Miranda Byrne-Steele, Jian Han, Michael Hust, Yintong Xue, Lennart Hammarström, Fausto Baldanti, Harold Marcotte, Qiang Pan-Hammarström
doi: https://doi.org/10.1101/2020.11.06.371617
Natalia Sherina
1Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Antonio Piralla
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Likun Du
1Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Hui Wan
1Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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Makiko Kumagai-Braesh
3Division of Transplantation Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
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Juni Andréll
4Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University
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Sten Braesch-Andersen
5Mabtech AB Research Laboratory, Stockholm, 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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Elena Percivalle
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Antonella Sarasini
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Federica Bergami
2Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Raffaella Di Martino
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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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 Abolhassani
9Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
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Federico Bertoglio
10Institute of Biochemistry, Biotechnology and Bioinformatics; Department of Biotechnology, Technische Universität Braunschweig, Braunschweig, Germany
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Maren Schubert
10Institute of Biochemistry, Biotechnology and Bioinformatics; Department of Biotechnology, Technische Universität Braunschweig, Braunschweig, Germany
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Miranda Byrne-Steele
11HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA
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Jian Han
11HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA
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Michael Hust
10Institute of Biochemistry, Biotechnology and Bioinformatics; Department of Biotechnology, Technische Universität Braunschweig, Braunschweig, Germany
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Yintong Xue
12Department of Immunology, Peking University Health Science Center, Beijing, China
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Lennart Hammarström
9Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Stockholm, 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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Harold Marcotte
9Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
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Qiang Pan-Hammarström
1Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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  • For correspondence: qiang.pan-hammarstrom@ki.se
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Summary

Background The longevity of the immune response against SARS-CoV-2 is currently debated. We thus profiled the serum anti-SARS-CoV-2 antibody levels and virus specific memory B- and T-cell responses over time in convalescent COVID-19 patients.

Methods A cohort of COVID-19 patients from the Lombardy region in Italy who experienced mild to critical disease and Swedish volunteers with mild symptoms, were tested for the presence of elevated anti-spike and anti-receptor binding domain antibody levels over a period of eight months. In addition, specific memory B- and T-cell responses were tested in selected patient samples.

Results Anti-SARS-CoV-2 antibodies were present in 85% samples collected within 4 weeks after onset of symptoms in COVID-19 patients. Levels of specific IgM or IgA antibodies declined after 1 month while levels of specific IgG antibodies remained stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG antibodies were still present, though at a significantly lower level, in 80% samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B- and T-cell responses were developed in vast majority of the patients tested, regardless of disease severity, and remained detectable up to 6-8 months after infection.

Conclusions Although the serum levels of anti-SARS-CoV-2 IgG antibodies started to decline, virus-specific T and/or memory B cell responses increased with time and maintained during the study period (6-8 months after infection).

Funding European Union’s Horizon 2020 research and innovation programme (ATAC), the Italian Ministry of Health, CIMED, the Swedish Research Council and the China Scholarship Council.

Competing Interest Statement

S.B.-A. is a member of the advisory board of Mabtech AB. The other authors declare no competing interests.

Copyright 
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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Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection
Natalia Sherina, Antonio Piralla, Likun Du, Hui Wan, Makiko Kumagai-Braesh, Juni Andréll, Sten Braesch-Andersen, Irene Cassaniti, Elena Percivalle, Antonella Sarasini, Federica Bergami, Raffaella Di Martino, Marta Colaneri, Marco Vecchia, Margherita Sambo, Valentina Zuccaro, Raffaele Bruno, Tiberio Oggionni, Federica Meloni, Hassan Abolhassani, Federico Bertoglio, Maren Schubert, Miranda Byrne-Steele, Jian Han, Michael Hust, Yintong Xue, Lennart Hammarström, Fausto Baldanti, Harold Marcotte, Qiang Pan-Hammarström
bioRxiv 2020.11.06.371617; doi: https://doi.org/10.1101/2020.11.06.371617
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Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection
Natalia Sherina, Antonio Piralla, Likun Du, Hui Wan, Makiko Kumagai-Braesh, Juni Andréll, Sten Braesch-Andersen, Irene Cassaniti, Elena Percivalle, Antonella Sarasini, Federica Bergami, Raffaella Di Martino, Marta Colaneri, Marco Vecchia, Margherita Sambo, Valentina Zuccaro, Raffaele Bruno, Tiberio Oggionni, Federica Meloni, Hassan Abolhassani, Federico Bertoglio, Maren Schubert, Miranda Byrne-Steele, Jian Han, Michael Hust, Yintong Xue, Lennart Hammarström, Fausto Baldanti, Harold Marcotte, Qiang Pan-Hammarström
bioRxiv 2020.11.06.371617; doi: https://doi.org/10.1101/2020.11.06.371617

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