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Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS­CoV-2 infection.
Manisty, Charlotte; Treibel, Thomas Alexander; Jensen, Melanie; Semper, Amanda; Joy, George; Gupta, Rishi K; Cutino-Moguel, Teresa; Andiapen, Mervyn; Jones, Jessica; Taylor, Stephen; Otter, Ashley; Pade, Corrina; Gibbons, Joseph; Lee, Jason; Bacon, Joanna; Thomas, Steve; Moon, Chris; Jones, Meleri; Williams, Dylan; Lambourne, Jonathan; Fontana, Marianna; Altmann, Daniel M; Boyton, Rosemary; Maini, Mala; McKnight, Aine; Chain, Benjamin; Noursadeghi, Mahdad; Moon, James C.
  • Manisty C; Institute of Cardiovascular Sciences, University College London, London, UK; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
  • Treibel TA; Institute of Cardiovascular Sciences, University College London, London, UK; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
  • Jensen M; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
  • Semper A; National Infection Service, Public Health England, Porton Down, UK.
  • Joy G; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
  • Gupta RK; Division of Infection and Immunity, University College London, London, UK.
  • Cutino-Moguel T; Department of Virology, Barts Health NHS Trust, London, UK.
  • Andiapen M; Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Jones J; National Infection Service, Public Health England, Porton Down, UK.
  • Taylor S; National Infection Service, Public Health England, Porton Down, UK.
  • Otter A; National Infection Service, Public Health England, Porton Down, UK.
  • Pade C; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Gibbons J; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Lee J; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Bacon J; National Infection Service, Public Health England, Porton Down, UK.
  • Thomas S; National Infection Service, Public Health England, Porton Down, UK.
  • Moon C; National Infection Service, Public Health England, Porton Down, UK.
  • Jones M; Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Williams D; MRC Unit for Lifelong Health and Ageing, University College London, London, UK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Lambourne J; Department of Infection, Barts Health NHS Trust, London, UK.
  • Fontana M; Royal Free London NHS Foundation Trust, London, UK; Division of Medicine, University College London, London, UK.
  • Altmann DM; Department of Immunology and Inflammation, Imperial College London, London, UK.
  • Boyton R; Department of Infectious Disease, Imperial College London, London, UK.
  • Maini M; Division of Infection and Immunity, University College London, London, UK.
  • McKnight A; Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Chain B; Division of Infection and Immunity, University College London, London, UK.
  • Noursadeghi M; Division of Infection and Immunity, University College London, London, UK. Electronic address: m.noursadeghi@ucl.ac.uk.
  • Moon JC; Institute of Cardiovascular Sciences, University College London, London, UK; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
EBioMedicine ; 65: 103259, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1116568
Semantic information from SemMedBD (by NLM)
1. Roche LOCATION_OF Total immunoglobulin measurement
Subject
Roche
Predicate
LOCATION_OF
Object
Total immunoglobulin measurement
2. Assay USES Nucleocapsid Proteins
Subject
Assay
Predicate
USES
Object
Nucleocapsid Proteins
3. Measles Virus Nucleoprotein DISRUPTS Antibody Formation
Subject
Measles Virus Nucleoprotein
Predicate
DISRUPTS
Object
Antibody Formation
4. Assay USES Measles Virus Nucleoprotein
Subject
Assay
Predicate
USES
Object
Measles Virus Nucleoprotein
5. Response process ASSOCIATED_WITH COVID-19
Subject
Response process
Predicate
ASSOCIATED_WITH
Object
COVID-19
6. Roche LOCATION_OF Total immunoglobulin measurement
Subject
Roche
Predicate
LOCATION_OF
Object
Total immunoglobulin measurement
7. Assay USES Nucleocapsid Proteins
Subject
Assay
Predicate
USES
Object
Nucleocapsid Proteins
8. Measles Virus Nucleoprotein DISRUPTS Antibody Formation
Subject
Measles Virus Nucleoprotein
Predicate
DISRUPTS
Object
Antibody Formation
9. Assay USES Measles Virus Nucleoprotein
Subject
Assay
Predicate
USES
Object
Measles Virus Nucleoprotein
10. Response process ASSOCIATED_WITH COVID-19
Subject
Response process
Predicate
ASSOCIATED_WITH
Object
COVID-19
ABSTRACT

BACKGROUND:

SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity.

METHODS:

Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements.

FINDINGS:

A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p<0.0001) but only anti-S1 measurements correlated with near-contemporary pseudovirus neutralising antibody titres (measured at 16-18 weeks, r = 0.57, p<0.0001). By 21 weeks' follow-up, 31/143 (21.7%) anti-S1 and 6/150 (4.0%) anti-NP measurements reverted to negative. Mathematical modelling revealed faster clearance of anti-S1 compared to anti-NP (median half-life of 2.5 weeks versus 4.0 weeks), earlier transition to lower levels of antibody production (median of 8 versus 13 weeks), and greater reductions in relative antibody production rate after the transition (median of 35% versus 50%).

INTERPRETATION:

Mild SARS-CoV-2 infection is associated with heterogeneous serological responses in Euroimmun anti-S1 and Roche anti-NP assays. Anti-S1 responses showed faster rates of clearance, more rapid transition from high to low level production rate and greater reduction in production rate after this transition. In mild infection, anti-S1 serology alone may underestimate incident infections. The mechanisms that underpin faster clearance and lower rates of sustained anti-S1 production may impact on the longevity of humoral immunity.

FUNDING:

Charitable donations via Barts Charity, Wellcome Trust, NIHR.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Diagnostic study / Observational study / Prognostic study / Risk factors Limits: Humans Language: English Journal: EBioMedicine Year: 2021 Document Type: Article Affiliation country: J.ebiom.2021.103259

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / Coronavirus Nucleocapsid Proteins / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Diagnostic study / Observational study / Prognostic study / Risk factors Limits: Humans Language: English Journal: EBioMedicine Year: 2021 Document Type: Article Affiliation country: J.ebiom.2021.103259