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A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics.
J Infect Dis. 2021 07 15; 224(2):218-228.JI

Abstract

BACKGROUND

Primary diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is based on detection of virus RNA in nasopharyngeal swab samples. In addition, analysis of humoral immunity against SARS-CoV-2 has an important role in viral diagnostics and seroprevalence estimates.

METHODS

We developed and optimized an enzyme immunoassays (EIA) using SARS-CoV-2 nucleoprotein (N), S1 and receptor binding domain (RBD) of the viral spike protein, and N proteins from SARS, Middle East respiratory syndrome (MERS), and 4 low-pathogenic human CoVs. Neutralizing antibody activity was compared with SARS-CoV-2 IgG, IgA, and IgM EIA results.

RESULTS

The sensitivity of EIA for detecting immune response in COVID-19 patients (n = 101) was 77% in the acute phase and 100% in the convalescent phase of SARS-CoV-2 infection when N and RBD were used as antigens in IgG and IgA specific EIAs. SARS-CoV-2 infection significantly increased humoral immune responses against the 229E and NL63 N proteins. S1 and RBD-based EIA results had a strong correlation with microneutralization test results.

CONCLUSIONS

The data indicate a combination of SARS-CoV-2 S1 or RBD and N proteins and analysis of IgG and IgA immunoglobulin classes in sera provide an excellent basis for specific and sensitive serological diagnostics of COVID-19.

Authors+Show Affiliations

Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Department of Physiology, Biomedicum, University of Helsinki, Helsinki, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland. Finnish Institute for Health and Welfare, Helsinki, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Department of Physiology, Biomedicum, University of Helsinki, Helsinki, Finland. School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden. Nordic SARS Response AB, Stockholm, Sweden.Department of Physiology, Biomedicum, University of Helsinki, Helsinki, Finland.Finnish Institute for Health and Welfare, Helsinki, Finland.Finnish Institute for Health and Welfare, Helsinki, Finland.Department of Virology, University of Helsinki, Helsinki, Finland.HUS Diagnostic Center, HUSLAB, Clinical Microbiology, University of Helsinki and Helsinki University Hospital, Finland.HUS Diagnostic Center, HUSLAB, Clinical Microbiology, University of Helsinki and Helsinki University Hospital, Finland.HUS Diagnostic Center, HUSLAB, Clinical Microbiology, University of Helsinki and Helsinki University Hospital, Finland.Turku University Hospital, Clinical Microbiology, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland. Turku University Hospital, Clinical Microbiology, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland. Turku University Hospital, Clinical Microbiology, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland. Turku University Hospital, Clinical Microbiology, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Department of Physiology, Biomedicum, University of Helsinki, Helsinki, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland.Institute of Biomedicine, Infections and Immunology Unit, University of Turku, Turku, Finland. Turku University Hospital, Clinical Microbiology, Turku, Finland.

Pub Type(s)

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

Language

eng

PubMed ID

33905505

Citation

Jalkanen, Pinja, et al. "A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics." The Journal of Infectious Diseases, vol. 224, no. 2, 2021, pp. 218-228.
Jalkanen P, Pasternack A, Maljanen S, et al. A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics. J Infect Dis. 2021;224(2):218-228.
Jalkanen, P., Pasternack, A., Maljanen, S., Melén, K., Kolehmainen, P., Huttunen, M., Lundberg, R., Tripathi, L., Khan, H., Ritvos, M. A., Naves, R., Haveri, A., Österlund, P., Kuivanen, S., Jääskeläinen, A. J., Kurkela, S., Lappalainen, M., Rantasärkkä, K., Vuorinen, T., ... Julkunen, I. (2021). A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics. The Journal of Infectious Diseases, 224(2), 218-228. https://doi.org/10.1093/infdis/jiab222
Jalkanen P, et al. A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics. J Infect Dis. 2021 07 15;224(2):218-228. PubMed PMID: 33905505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics. AU - Jalkanen,Pinja, AU - Pasternack,Arja, AU - Maljanen,Sari, AU - Melén,Krister, AU - Kolehmainen,Pekka, AU - Huttunen,Moona, AU - Lundberg,Rickard, AU - Tripathi,Lav, AU - Khan,Hira, AU - Ritvos,Mikael A, AU - Naves,Rauno, AU - Haveri,Anu, AU - Österlund,Pamela, AU - Kuivanen,Suvi, AU - Jääskeläinen,Anne J, AU - Kurkela,Satu, AU - Lappalainen,Maija, AU - Rantasärkkä,Kaisa, AU - Vuorinen,Tytti, AU - Hytönen,Jukka, AU - Waris,Matti, AU - Tauriainen,Sisko, AU - Ritvos,Olli, AU - Kakkola,Laura, AU - Julkunen,Ilkka, PY - 2021/01/09/received PY - 2021/04/21/accepted PY - 2021/4/28/pubmed PY - 2021/7/23/medline PY - 2021/4/27/entrez KW - COVID-19 KW - SARS-CoV-2 KW - antibodies KW - coronavirus proteins KW - enzyme immunoassay KW - neutralizing antibodies KW - respiratory infection KW - serology SP - 218 EP - 228 JF - The Journal of infectious diseases JO - J Infect Dis VL - 224 IS - 2 N2 - BACKGROUND: Primary diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is based on detection of virus RNA in nasopharyngeal swab samples. In addition, analysis of humoral immunity against SARS-CoV-2 has an important role in viral diagnostics and seroprevalence estimates. METHODS: We developed and optimized an enzyme immunoassays (EIA) using SARS-CoV-2 nucleoprotein (N), S1 and receptor binding domain (RBD) of the viral spike protein, and N proteins from SARS, Middle East respiratory syndrome (MERS), and 4 low-pathogenic human CoVs. Neutralizing antibody activity was compared with SARS-CoV-2 IgG, IgA, and IgM EIA results. RESULTS: The sensitivity of EIA for detecting immune response in COVID-19 patients (n = 101) was 77% in the acute phase and 100% in the convalescent phase of SARS-CoV-2 infection when N and RBD were used as antigens in IgG and IgA specific EIAs. SARS-CoV-2 infection significantly increased humoral immune responses against the 229E and NL63 N proteins. S1 and RBD-based EIA results had a strong correlation with microneutralization test results. CONCLUSIONS: The data indicate a combination of SARS-CoV-2 S1 or RBD and N proteins and analysis of IgG and IgA immunoglobulin classes in sera provide an excellent basis for specific and sensitive serological diagnostics of COVID-19. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/33905505/A_Combination_of_N_and_S_Antigens_With_IgA_and_IgG_Measurement_Strengthens_the_Accuracy_of_SARS_CoV_2_Serodiagnostics_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiab222 DB - PRIME DP - Unbound Medicine ER -