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Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients.
J Immunol. 2020 11 01; 205(9):2437-2446.JI

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific Abs are typically a major predictor of protective immunity, yet human B cell and Ab responses during COVID-19 are not fully understood. In this study, we analyzed Ab-secreting cell and Ab responses in 20 hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19 and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific Ab-secreting cells in all 20 COVID-19 patients using a multicolor FluoroSpot Assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing Abs by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG, and IgM Ab levels positively correlated with SARS-CoV-2-neutralizing Ab titers, suggesting that SARS-CoV-2-specific Ab levels may reflect the titers of neutralizing Abs in COVID-19 patients during the acute phase of infection. Last, we showed that IL-6 and C-reactive protein serum concentrations were higher in patients who were hospitalized for longer, supporting the recent observations that IL-6 and C-reactive protein could be used as markers for COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in 20 COVID-19 patients, with a focus on B cell and Ab responses, and describes tools to study immune responses to SARS-CoV-2 infection and vaccination.

Authors+Show Affiliations

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.Department of Infectious Diseases, Karolinska University Hospital, 141 86 Stockholm, Sweden. Department of Medicine Solna, Karolinska Institutet, 171 76 Stockholm, Sweden.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.Public Health Agency of Sweden, 171 65 Solna, Sweden.Department of Infectious Diseases, Karolinska University Hospital, 141 86 Stockholm, Sweden. Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden; and.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden. Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden; and.Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, 141 52 Stockholm, Sweden.Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, 141 52 Stockholm, Sweden.Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, 141 52 Stockholm, Sweden.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden. Public Health Agency of Sweden, 171 65 Solna, Sweden.Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden; sara.gredmark.russ@ki.se. Department of Infectious Diseases, Karolinska University Hospital, 141 86 Stockholm, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32878912

Citation

Varnaitė, Renata, et al. "Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients." Journal of Immunology (Baltimore, Md. : 1950), vol. 205, no. 9, 2020, pp. 2437-2446.
Varnaitė R, García M, Glans H, et al. Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients. J Immunol. 2020;205(9):2437-2446.
Varnaitė, R., García, M., Glans, H., Maleki, K. T., Sandberg, J. T., Tynell, J., Christ, W., Lagerqvist, N., Asgeirsson, H., Ljunggren, H. G., Ahlén, G., Frelin, L., Sällberg, M., Blom, K., Klingström, J., & Gredmark-Russ, S. (2020). Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients. Journal of Immunology (Baltimore, Md. : 1950), 205(9), 2437-2446. https://doi.org/10.4049/jimmunol.2000717
Varnaitė R, et al. Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients. J Immunol. 2020 11 1;205(9):2437-2446. PubMed PMID: 32878912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients. AU - Varnaitė,Renata, AU - García,Marina, AU - Glans,Hedvig, AU - Maleki,Kimia T, AU - Sandberg,John Tyler, AU - Tynell,Janne, AU - Christ,Wanda, AU - Lagerqvist,Nina, AU - Asgeirsson,Hilmir, AU - Ljunggren,Hans-Gustaf, AU - Ahlén,Gustaf, AU - Frelin,Lars, AU - Sällberg,Matti, AU - Blom,Kim, AU - Klingström,Jonas, AU - Gredmark-Russ,Sara, Y1 - 2020/09/02/ PY - 2020/06/15/received PY - 2020/08/20/accepted PY - 2020/9/4/pubmed PY - 2020/10/28/medline PY - 2020/9/4/entrez SP - 2437 EP - 2446 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 205 IS - 9 N2 - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific Abs are typically a major predictor of protective immunity, yet human B cell and Ab responses during COVID-19 are not fully understood. In this study, we analyzed Ab-secreting cell and Ab responses in 20 hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19 and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific Ab-secreting cells in all 20 COVID-19 patients using a multicolor FluoroSpot Assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing Abs by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG, and IgM Ab levels positively correlated with SARS-CoV-2-neutralizing Ab titers, suggesting that SARS-CoV-2-specific Ab levels may reflect the titers of neutralizing Abs in COVID-19 patients during the acute phase of infection. Last, we showed that IL-6 and C-reactive protein serum concentrations were higher in patients who were hospitalized for longer, supporting the recent observations that IL-6 and C-reactive protein could be used as markers for COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in 20 COVID-19 patients, with a focus on B cell and Ab responses, and describes tools to study immune responses to SARS-CoV-2 infection and vaccination. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/32878912/Expansion_of_SARS_CoV_2_Specific_Antibody_Secreting_Cells_and_Generation_of_Neutralizing_Antibodies_in_Hospitalized_COVID_19_Patients_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=32878912 DB - PRIME DP - Unbound Medicine ER -