Cited by 1,419SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesSARS-CoV-2 detection and testing

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

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Seow, Jeffrey, Graham, Carl, Merrick, Blair, Acors, Sam, Pickering, Suzanne, Steel, Kathryn J. A., Hemmings, Oliver, O’Byrne, Aoife, Kouphou, Neophytos, Galao, Rui Pedro, Betancor, Gilberto, Wilson, Harry D., Signell, Adrian W., Winstone, Helena, Kerridge, Claire, Huettner, Isabella, Jimenez-Guardeño, Jose M., Lista, Maria Jose, Temperton, Nigel, Snell, Luke B., Bisnauthsing, Karen, Moore, Amelia, Green, Adrian, Martinez, Lauren, Stokes, Brielle, Honey, Johanna, Izquierdo-Barras, Alba, Arbane, Gill, Patel, Amita, Tan, Mark Kia Ik, O’Connell, Lorcan, O’Hara, Geraldine, MacMahon, Eithne, Douthwaite, Sam, Nebbia, Gaia, Batra, Rahul, Martinez-Nunez, Rocio, Shankar-Hari, Manu, Edgeworth, Jonathan D., Neil, Stuart J. D., Malim, Michael H., Doores, Katie J.·2020·Nature Microbiology

DOI 10.1038/s41564-020-00813-8PMC PMC7610833

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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 (ID 50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID 50 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.

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MethodInfluential
Immunogenicity Characterization of COVID-19 Vaccines: A Systematic Review and Meta-analysis
Vasconcelos, Z. S., Salem, H. A., Veiga, S., de Lima, F. E. B., Gonçalves, C. R. D. S., Santos, E. C. D., Brandão, A. R. J., Couceiro, K. D. N., Guerra, J. A. D. O., & Guerra, M. D. G. V. B. (2023) · Revista da Sociedade Brasileira de Medicina Tropical · doi:10.1590/0037-8682-0661-2022 · Cited by 4
Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques
Galhaut, M., Lundberg, U., Marlin, R., Schlegl, R., Seidel, S., Bartuschka, U., Heindl-Wruss, J., Relouzat, F., Langlois, S., Dereuddre‐Bosquet, N., et al. (2024) · Communications Medicine · doi:10.1038/s43856-024-00488-w · Cited by 6
“…set of analyses indicated that two injections of the 7 AU dose were suf ﬁ cient to induce high levels of SARS-CoV-2 speci ﬁ c antibodies exceeding the levels reported using identical immune-assays in convalescent patients 41,42 and in convalescent macaquesfromourpreviouslyreportedstudies 28,29,43 .”
COVID-19 antibody testing: From hype to immunological reality
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Antibody Response to SARS-CoV-2 in Relation to the Contributing Factors in COVID-19 Patients
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“Other studies also demonstrated that antibodies appeared and were detected in majority of the patients after a week of diagnosis (34,49).”
Probabilistic classification of anti‐SARS‐CoV‐2 antibody responses improves seroprevalence estimates
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Evaluation of Spike Protein Epitopes by Assessing the Dynamics of Humoral Immune Responses in Moderate COVID-19
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Seroprevalence of immunoglobulin G antibodies against SARS-CoV-2 in Cyprus
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COVID‐19: What if immunity wanes?
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Probabilistic approaches for classifying highly variable anti-SARS-CoV-2 antibody responsesPreprint
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People Living with HIV Easily lose their Immune Response to SARS-CoV-2: Result From A Cohort of COVID-19 Cases in Wuhan, ChinaPreprint
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“Through increased levels of viral antigens, there is a more signi cant depletion of lymphocyte [4] and a high positive conversion rate of antibodies in severe disease [31, 32], thus, result in a longer IgG duration in patients with lower lymphocyte counts at onset.”
BackgroundResult
People Living with HIV Easily Lose Their Immune Response to SARS-CoV-2: Result from a Cohort of COVID-19 Cases in Wuhan, ChinaPreprint
Xiao, Y., Wu, S., Marly, G., Ming, F., Wu, M., Tang, W., & Liang, K. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3774187 · Cited by 5
Long-lasting immune response to a mild course of PCR-confirmed SARS-CoV-2 infection: A cohort study
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“disease severity (85) and longevity is expected to vary greatly across SARS-CoV-2 infected individuals”
Background
Omicron Infection Induces Low-Level, Narrow-Range SARS-CoV-2 Neutralizing ActivityPreprint
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Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profilesPreprint
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Modelling the Effect of Vaccination Program and Inter-state Travel in the Spread of COVID-19 in Malaysia
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SARS-CoV-2 Infection or COVID-19 mRNA Vaccination Elicits Partially Different Spike-Reactive Memory B Cell Responses in Naïve Individuals
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SARS-CoV-2 Surveillance between 2020 and 2021 of All Mammalian Species in Two Flemish Zoos (Antwerp Zoo and Planckendael Zoo)
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Standardization of in-house anti-IgG and IgA ELISAs for the detection of COVID-19
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“6% of SARS-CoV-2 infected patients developed IgG, IgA and IgM synchronously at the early stage of infection (less than 14 days POS) [17].”
BackgroundInfluential
COVID-19 Treatments: Then and Now
Mustafa, S. S., Stern, R. A., Patel, P. C., & Chu, D. K. (2023) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2023.07.045 · Cited by 4
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“Following infection, antibodies are produced against SARS-CoV-2 viral proteins, predominantly the Spike (S) and the Nucleocapsid Protein (NP) [4,5].”
BackgroundInfluential
Quantification of SARS-CoV-2 monoclonal IgG mass fraction by isotope dilution mass spectrometry
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Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data
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“Following an infection, systemic immunoglobulins type G (IgG) specific to SARS-CoV-2, including antibodies against the viral spike (S) and nucleocapsid (N) proteins, are detected in the majority of patients within two weeks, with peak concentrations at around three weeks after symptom onset [1–4].”
BackgroundInfluential
SARS-CoV-2-Specific T-Cell as a Potent Therapeutic Strategy against Immune Evasion of Emerging COVID-19 Variants
Im, K.-I., Kim, N., Lee, J.-S., Oh, U.-H., Lee, H. W., Lee, D., Min, G. J., Lee, R., Lee, J., Kim, S., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910512 · Cited by 6
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Background
Induction of Fc-dependent functional antibodies against different variants of SARS-CoV-2 varies by vaccine type and prior infection
Harris, A. W., Kurtovic, L., Nogueira, J., Bouzas, I. C. D. S., Opi, D. H., Wines, B. D., Lee, W. S., Hogarth, P. M., Poumbourios, P., Drummer, H. E., et al. (2024) · Communications Medicine · doi:10.1038/s43856-024-00686-6 · Cited by 4
“The generation of SARS-CoV-2 speci ﬁ c immunoglobulin G (IgG) correlates strongly with vaccine ef ﬁ cacy 7 and protection against severe disease 8,9 .”
SARS-CoV-2 antibody performances: we need better criteria
Galli, C., & Plebani, M. (2020) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2020-1358 · Cited by 4
Neutralizing SARS-CoV-2
Poeschla, E. M. (2020) · eLife · doi:10.7554/elife.64496 · Cited by 4
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What Is the Antibody Response and Role in Conferring Natural Immunity After SARS-CoV-2 Infection? Rapid, Living Practice Points From the American College of Physicians (Version 1)
Qaseem, A., Yost, J., Etxeandia‐Ikobaltzeta, I., Forciea, M. A., Abraham, G. M., Miller, M. C., Obley, A. J., & Humphrey, L. L. (2021) · Annals of Internal Medicine · doi:10.7326/m20-7569 · Cited by 4
“Europe: 22 studies (Austria [37, 64], Belgium [25, 66], Denmark [7], Finland [62], France [13, 14, 60], Greece [44], Iceland [9], Italy [31, 61, 67], Liechtenstein [41], Spain [22, 59], Switzerland [57, 58], and United Kingdom [42, 43, 50])”
BackgroundInfluential
Air Pollution, SARS-CoV-2 and the Wider Implications - An Overview of Recent Events with a Focus on Italy
Madl, P., Arvay, C. G., Gatti, A. M., Giuliani, L., & Lettner, H. (2021) · Aerosol and Air Quality Research · doi:10.4209/aaqr.200438 · Cited by 4
Complexities in Case Definition of SARS-CoV-2 Reinfection: Clinical Evidence and Implications in COVID-19 Surveillance and Diagnosis
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Pre-vaccination immune response to COVID-19 in a population in Northeast Portugal
Duro, M., Duro, I., Rebelo, I., Moreno, F., Pires, M., Jacinto, S., Pimentel, M., & Almeida, C. (2021) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-021-02799-6 · Cited by 4
Healthcare Considerations for Special Populations during the COVID-19 Pandemic: A Review
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Descriptive evaluation of antibody responses to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in plasma and gingival crevicular fluid in a nursing home cohort—Arkansas, June–August 2020
Brown, N. E., Lyons, A. K., Schuh, A. J., Stumpf, M. M., Harcourt, J. L., Tamin, A., Rasheed, M. A. U., Mills, L. A., Lester, S. N., Thornburg, N. J., et al. (2021) · Infection Control and Hospital Epidemiology · doi:10.1017/ice.2021.484 · Cited by 4
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Successful Treatment of Granulomatous-lymphocytic Interstitial Lung Disease in a Patient with CTLA-4 Deficiency
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Background
COVID-19 symptom relationship to antibody response and ACE2 neutralization in recovered health systems employees before and after mRNA BNT162b2 COVID-19 vaccine
Huhn, G. D., Poorbaugh, J., Zhang, L., Beasley, S., Nirula, A., Brothers, J., Welbel, S. F., Wilson, J., Gillani, S., Weber, K. M., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0273323 · Cited by 4
“SARS-CoV-2 spike protein seropositivity is associated with reduced risk of reinfection after SARS-CoV-2 infection [18, 19] and suggests protection to reinfection among the 71% of spike titer-responsive participants within this post-infection timeframe.”
Background
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Evaluating Johnson and Johnson COVID-19 Vaccination Outcomes in a Low-Income Hispanic Population
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“As transplacental transfer begins at approximately 17 weeks of gestation [13] and as a minimal interval of at least 2 weeks is required from vaccination to delivery for maternal antibody production and placental transfer [4], some authors have recommended maternal COVID-19 vaccination in the second trimester [14,15].”
Mathematical assessment of the role of vaccination against COVID-19 in the United States
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To be remembered: B cell memory response against SARS‐CoV ‐2 and its variants in vaccinated and unvaccinated individuals
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“8,9 It is a subject of concern whether we need to be vaccinated repeatedly, as there are instances of recurrence of the infection.”
Background
The intention to get COVID-19 booster vaccination and its association with cognitive and emotional factors: A survey of Chinese COVID-19 infected people in Hong Kong
Yu, Y., Zhang, X., Lau, M. M. C., & Lau, J. T. F. (2023) · Vaccine · doi:10.1016/j.vaccine.2023.12.015 · Cited by 4

Authors: 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., Snell, L. B., Bisnauthsing, K., Moore, A., Green, A., Martinez, L., Stokes, B., Honey, J., Izquierdo-Barras, A., Arbane, G., Patel, A., Tan, M. K. I., O’Connell, L., O’Hara, G., MacMahon, E., Douthwaite, S., Nebbia, G., Batra, R., Martinez-Nunez, R., Shankar-Hari, M., Edgeworth, J. D., Neil, S. J. D., Malim, M. H., & Doores, K. J.
Affiliations: King's College London (GB)
Guy's Hospital (GB)
Medway School of Pharmacy (GB)
Guy's and St Thomas' NHS Foundation Trust (GB)
Corresponding author: Doores, Katie J.
ORCID: Seow, Jeffrey
Merrick, Blair
Acors, Sam
Pickering, Suzanne
Steel, Kathryn J. A.
Hemmings, Oliver
O’Byrne, Aoife
Kouphou, Neophytos
Galao, Rui Pedro
Betancor, Gilberto
Wilson, Harry D.
Signell, Adrian W.
Winstone, Helena
Jimenez-Guardeño, Jose M.
Temperton, Nigel
Snell, Luke B.
Bisnauthsing, Karen
Martinez, Lauren
Stokes, Brielle
Izquierdo-Barras, Alba
Patel, Amita
Tan, Mark Kia Ik
O’Connell, Lorcan
O’Hara, Geraldine
Douthwaite, Sam
Nebbia, Gaia
Batra, Rahul
Shankar-Hari, Manu
Edgeworth, Jonathan D.
Neil, Stuart J. D.
Malim, Michael H.
Doores, Katie J.
Venue: Nature Microbiology
Publisher: Springer Science and Business Media LLC
Published: 2020-10-26
Volume: 5
Issue: 12
Pages: 1598-1607
ISSN: 2058-5276 (ISSN-L)
DOI: 10.1038/s41564-020-00813-8
PMC: PMC7610833
OpenAlex: W3093667122
Cited by: 1,419
References: 62
Citations by year: 2026: 18 · 2025: 44 · 2024: 75 · 2023: 147 · 2022: 311 · 2021: 615 · 2020: 207
FWCI: 41.93
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Microbiology (publishedVersion)
medRxiv (acceptedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion, other-oa)
Kent Academic Repository (University of Kent) (acceptedVersion)
PubMed Central (acceptedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Research Portal (King's College London) (submittedVersion, other-oa)
Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, cc-by-nc-nd)
Funders: RCUK | Medical Research Council (MC/PC/15068, MR/N013700/1, MR/R015643/1, MC/PC/15068, MR/R015643/1, MR/S023747/1)
Huo Family Foundation
Wellcome Trust (WT098049AIA, MR/S023747/1, 106223/Z/14/Z)
Huo Family Foundation King’s Together Rapid COVID-19 Call award
DH | National Institute for Health Research (CS-2016-16-011)
King’s Together Rapid COVID-19 Call award Huo Family Foundation
Fondation Dormeur, Vaduz King’s Together Rapid COVID-19 Call award Huo Family Foundation
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
Keywords: SARS-CoV-2, COVID-19 pandemic, neutralizing antibodies, antibody waning, seroconversion, antibody kinetics, disease severity, infectious dose, reinfection protection, healthcare workers, booster vaccination, serological testing
MeSH terms: Seroconversion, COVID-19, SARS-CoV-2, Adult, Aged, Aged, 80 and over, Antibodies, Viral, Female, Humans, Kinetics, Longitudinal Studies, Male, Middle Aged, Severity of Illness Index, Young Adult, Antibodies, Neutralizing

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

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