Longitudinal serological analysis and neutralizing antibody levels in Coronavirus disease 2019 convalescent patients

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.

N1 - This work was supported by the UK National Health Service and Grants from the National Institutes of Allergy and infectious Diseases R37AI640003 (to PDB) and R01AI078788 (to TH)

PY - 2021/2/1

Y1 - 2021/2/1

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.

AB - 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.

KW - COVID-19

KW - Neutralizing antibodies

KW - SARS-CoV-2

KW - Serology

UR - https://www.scopus.com/pages/publications/85102153147

U2 - 10.1093/infdis/jiaa659

DO - 10.1093/infdis/jiaa659

M3 - Article

C2 - 33140086

SN - 0022-1899

VL - 223

SP - 389

EP - 398

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 3

ER -