Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Jeffrey Seow; Carl Graham; Blair Merrick; Sam Acors; Suzanne Pickering; Kathryn J. A. Steel; Oliver Hemmings; Aoife O’Byrne; Neophytos Kouphou; Rui Pedro Galao; Gilberto Betancor; Harry D. Wilson; Adrian W. Signell; Helena Winstone; Claire Kerridge; Isabella Huettner; Jose M. Jimenez-Guardeño; Maria Jose Lista; Nigel Temperton; Luke B. Snell; Karen Bisnauthsing; Amelia Moore; Adrian Green; Lauren Martinez; Brielle Stokes; Johanna Honey; Alba Izquierdo-Barras; Gill Arbane; Amita Patel; Mark Kia Ik Tan; Lorcan O’Connell; Geraldine O’Hara; Eithne MacMahon; Sam Douthwaite; Gaia Nebbia; Rahul Batra; Rocio Martinez-Nunez; Manu Shankar-Hari; Jonathan D. Edgeworth; Stuart J. D. Neil; Michael H. Malim; Katie J. Doores

doi:10.1038/s41564-020-00813-8

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Jeffrey Seow, Carl Graham, Blair Merrick, Sam Acors, Suzanne Pickering, Kathryn J. A. Steel, Oliver Hemmings, Aoife O’Byrne, Neophytos Kouphou, Rui Pedro Galao, Gilberto Betancor, Harry D. Wilson, Adrian W. Signell, Helena Winstone, Claire Kerridge, Isabella Huettner, Jose M. Jimenez-Guardeño, Maria Jose Lista, Nigel Temperton, Luke B. SnellKaren Bisnauthsing, Amelia Moore, Adrian Green, Lauren Martinez, Brielle Stokes, Johanna Honey, Alba Izquierdo-Barras, Gill Arbane, Amita Patel, Mark Kia Ik Tan, Lorcan O’Connell, Geraldine O’Hara, Eithne MacMahon, Sam Douthwaite, Gaia Nebbia, Rahul Batra, Rocio Martinez-Nunez, Manu Shankar-Hari, Jonathan D. Edgeworth, Stuart J. D. Neil, Michael H. Malim, Katie J. Doores

Research output: Contribution to journal › Article › peer-review

647 Citations (Scopus)

47 Downloads (Pure)

Abstract

Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.

Original language	English
Pages (from-to)	1598-1607
Number of pages	10
Journal	Nature Microbiology
Volume	5
Issue number	12
Early online date	26 Oct 2020
DOIs	https://doi.org/10.1038/s41564-020-00813-8
Publication status	Published - 1 Dec 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41564-020-00813-8

Longitudinal observation and decline of neutralizing_DOORES_Publishedonline26October2020_GREEN AAMAccepted author manuscript, 701 KB

Cite this

Seow, J., Graham, C., Merrick, B., Acors, S., Pickering, S., Steel, K. J. A., Hemmings, O., O’Byrne, A., Kouphou, N., Galao, R. P., Betancor, G., Wilson, H. D., Signell, A. W., Winstone, H., Kerridge, C., Huettner, I., Jimenez-Guardeño, J. M., Lista, M. J., Temperton, N., ... Doores, K. J. (2020). Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nature Microbiology, 5(12), 1598-1607. https://doi.org/10.1038/s41564-020-00813-8

@article{04053a71ef4f43668e7c8b407e90fddb,

title = "Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans",

abstract = "Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.",

author = "Jeffrey Seow and Carl Graham and Blair Merrick and Sam Acors and Suzanne Pickering and Steel, {Kathryn J. A.} and Oliver Hemmings and Aoife O{\textquoteright}Byrne and Neophytos Kouphou and Galao, {Rui Pedro} and Gilberto Betancor and Wilson, {Harry D.} and Signell, {Adrian W.} and Helena Winstone and Claire Kerridge and Isabella Huettner and Jimenez-Guarde{\~n}o, {Jose M.} and Lista, {Maria Jose} and Nigel Temperton and Snell, {Luke B.} and Karen Bisnauthsing and Amelia Moore and Adrian Green and Lauren Martinez and Brielle Stokes and Johanna Honey and Alba Izquierdo-Barras and Gill Arbane and Amita Patel and Tan, {Mark Kia Ik} and Lorcan O{\textquoteright}Connell and Geraldine O{\textquoteright}Hara and Eithne MacMahon and Sam Douthwaite and Gaia Nebbia and Rahul Batra and Rocio Martinez-Nunez and Manu Shankar-Hari and Edgeworth, {Jonathan D.} and Neil, {Stuart J. D.} and Malim, {Michael H.} and Doores, {Katie J.}",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41564-020-00813-8",

language = "English",

volume = "5",

pages = "1598--1607",

journal = "Nature Microbiology",

issn = "2058-5276",

publisher = "Nature Publishing Group",

number = "12",

}

Seow, J , Graham, C , Merrick, B , Acors, S , Pickering, S , Steel, KJA , Hemmings, O, O’Byrne, A, Kouphou, N , Galao, RP, Betancor, G, Wilson, HD , Signell, AW , Winstone, H , Kerridge, C , Huettner, I , Jimenez-Guardeño, JM, Lista, MJ, Temperton, N, Snell, LB, Bisnauthsing, K, Moore, A, Green, A, Martinez, L, Stokes, B, Honey, J, Izquierdo-Barras, A, Arbane, G, Patel, A, Tan, MKI, O’Connell, L, O’Hara, G, MacMahon, E, Douthwaite, S, Nebbia, G, Batra, R, Martinez-Nunez, R , Shankar-Hari, M , Edgeworth, JD , Neil, SJD , Malim, MH & Doores, KJ 2020, 'Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans', Nature Microbiology, vol. 5, no. 12, pp. 1598-1607. https://doi.org/10.1038/s41564-020-00813-8

TY - JOUR

T1 - Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

AU - Seow, Jeffrey

AU - Graham, Carl

AU - Merrick, Blair

AU - Acors, Sam

AU - Pickering, Suzanne

AU - Steel, Kathryn J. A.

AU - Hemmings, Oliver

AU - O’Byrne, Aoife

AU - Kouphou, Neophytos

AU - Galao, Rui Pedro

AU - Betancor, Gilberto

AU - Wilson, Harry D.

AU - Signell, Adrian W.

AU - Winstone, Helena

AU - Kerridge, Claire

AU - Huettner, Isabella

AU - Jimenez-Guardeño, Jose M.

AU - Lista, Maria Jose

AU - Temperton, Nigel

AU - Snell, Luke B.

AU - Bisnauthsing, Karen

AU - Moore, Amelia

AU - Green, Adrian

AU - Martinez, Lauren

AU - Stokes, Brielle

AU - Honey, Johanna

AU - Izquierdo-Barras, Alba

AU - Arbane, Gill

AU - Patel, Amita

AU - Tan, Mark Kia Ik

AU - O’Connell, Lorcan

AU - O’Hara, Geraldine

AU - MacMahon, Eithne

AU - Douthwaite, Sam

AU - Nebbia, Gaia

AU - Batra, Rahul

AU - Martinez-Nunez, Rocio

AU - Shankar-Hari, Manu

AU - Edgeworth, Jonathan D.

AU - Neil, Stuart J. D.

AU - Malim, Michael H.

AU - Doores, Katie J.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.

AB - Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.

UR - http://www.scopus.com/inward/record.url?scp=85094166805&partnerID=8YFLogxK

U2 - 10.1038/s41564-020-00813-8

DO - 10.1038/s41564-020-00813-8

M3 - Article

SN - 2058-5276

VL - 5

SP - 1598

EP - 1607

JO - Nature Microbiology

JF - Nature Microbiology

IS - 12

ER -

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this