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Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients.
J Infect Dis. 2021 02 13; 223(3):389-398.JI

Abstract

BACKGROUND

Understanding the longitudinal trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is crucial for diagnosis of prior infection and predicting future immunity.

METHODS

We conducted a longitudinal analysis of coronavirus disease 2019 convalescent patients, with neutralizing antibody assays and SARS-CoV-2 serological assay platforms using SARS-CoV-2 spike (S) or nucleocapsid (N) antigens.

RESULTS

Sensitivities of serological assays in diagnosing prior SARS-CoV-2 infection changed with time. One widely used commercial platform that had an initial sensitivity of >95% declined to 71% at 81-100 days after diagnosis. The trajectories of median binding antibody titers measured over approximately 3-4 months were not dependent on the use of SARS-CoV-2 N or S proteins as antigen. The median neutralization titer decreased by approximately 45% per month. Each serological assay gave quantitative antibody titers that were correlated with SARS-CoV-2 neutralization titers, but S-based serological assay measurements better predicted neutralization potency. Correlation between S-binding and neutralization titers deteriorated with time, and decreases in neutralization titers were not predicted by changes in S-binding antibody titers.

CONCLUSIONS

Different SARS-CoV-2 serological assays are more or less well suited for surveillance versus prediction of serum neutralization potency. Extended follow-up should facilitate the establishment of appropriate serological correlates of protection against SARS-CoV-2 reinfection.

Authors+Show Affiliations

Laboratory of Retrovirology, The Rockefeller University, New York, New York, USA.Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, Scotland.Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, Scotland.Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, Scotland.Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, Scotland.University Hospital Monklands, NHS Lanarkshire, Airdrie, Scotland.University Hospital Monklands, NHS Lanarkshire, Airdrie, Scotland.University Hospital Monklands, NHS Lanarkshire, Airdrie, Scotland.Ninewells Hospital and Medical School, NHS Tayside, Dundee, Scotland.Ninewells Hospital and Medical School, NHS Tayside, Dundee, Scotland.Ninewells Hospital and Medical School, NHS Tayside, Dundee, Scotland.Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, Scotland.Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.Laboratory of Retrovirology, The Rockefeller University, New York, New York, USA.Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, Scotland.Laboratory of Retrovirology, The Rockefeller University, New York, New York, USA. Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

33140086

Citation

Muecksch, Frauke, et al. "Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients." The Journal of Infectious Diseases, vol. 223, no. 3, 2021, pp. 389-398.
Muecksch F, Wise H, Batchelor B, et al. Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients. J Infect Dis. 2021;223(3):389-398.
Muecksch, F., Wise, H., Batchelor, B., Squires, M., Semple, E., Richardson, C., McGuire, J., Clearly, S., Furrie, E., Greig, N., Hay, G., Templeton, K., Lorenzi, J. C. C., Hatziioannou, T., Jenks, S., & Bieniasz, P. D. (2021). Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients. The Journal of Infectious Diseases, 223(3), 389-398. https://doi.org/10.1093/infdis/jiaa659
Muecksch F, et al. Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients. J Infect Dis. 2021 02 13;223(3):389-398. PubMed PMID: 33140086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients. AU - Muecksch,Frauke, AU - Wise,Helen, AU - Batchelor,Becky, AU - Squires,Maria, AU - Semple,Elizabeth, AU - Richardson,Claire, AU - McGuire,Jacqueline, AU - Clearly,Sarah, AU - Furrie,Elizabeth, AU - Greig,Neil, AU - Hay,Gordon, AU - Templeton,Kate, AU - Lorenzi,Julio C C, AU - Hatziioannou,Theodora, AU - Jenks,Sara, AU - Bieniasz,Paul D, PY - 2020/08/10/received PY - 2020/10/15/accepted PY - 2020/11/4/pubmed PY - 2021/3/3/medline PY - 2020/11/3/entrez KW - COVID-19 KW - Neutralizing antibodies KW - SARS-CoV-2 KW - Serology SP - 389 EP - 398 JF - The Journal of infectious diseases JO - J Infect Dis VL - 223 IS - 3 N2 - BACKGROUND: Understanding the longitudinal trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is crucial for diagnosis of prior infection and predicting future immunity. METHODS: We conducted a longitudinal analysis of coronavirus disease 2019 convalescent patients, with neutralizing antibody assays and SARS-CoV-2 serological assay platforms using SARS-CoV-2 spike (S) or nucleocapsid (N) antigens. RESULTS: Sensitivities of serological assays in diagnosing prior SARS-CoV-2 infection changed with time. One widely used commercial platform that had an initial sensitivity of >95% declined to 71% at 81-100 days after diagnosis. The trajectories of median binding antibody titers measured over approximately 3-4 months were not dependent on the use of SARS-CoV-2 N or S proteins as antigen. The median neutralization titer decreased by approximately 45% per month. Each serological assay gave quantitative antibody titers that were correlated with SARS-CoV-2 neutralization titers, but S-based serological assay measurements better predicted neutralization potency. Correlation between S-binding and neutralization titers deteriorated with time, and decreases in neutralization titers were not predicted by changes in S-binding antibody titers. CONCLUSIONS: Different SARS-CoV-2 serological assays are more or less well suited for surveillance versus prediction of serum neutralization potency. Extended follow-up should facilitate the establishment of appropriate serological correlates of protection against SARS-CoV-2 reinfection. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/33140086/Longitudinal_Serological_Analysis_and_Neutralizing_Antibody_Levels_in_Coronavirus_Disease_2019_Convalescent_Patients_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiaa659 DB - PRIME DP - Unbound Medicine ER -