The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers
Author:
Lumley Sheila F12, Wei Jia32, O’Donnell Denise2, Stoesser Nicole E245, Matthews Philippa C245, Howarth Alison2, Hatch Stephanie B2, Marsden Brian D26, Cox Stuart1, James Tim1, Peck Liam J7, Ritter Thomas G7, de Toledo Zoe7, Cornall Richard J2, Jones E Yvonne2, Stuart David I2, Screaton Gavin2, Ebner Daniel28, Hoosdally Sarah245, Crook Derrick W245, Conlon Christopher P2, Pouwels Koen B59, Walker A Sarah245, Peto Tim E A245, Walker Timothy M210, Jeffery Katie1, Eyre David W34511, Abbott Molly, Abhari Roxanna, Abuelgasim Hibatullah, Ahmed-Firani Tariq, Alhussni Ahmed, Argles Isobel, Ashworth Rebecca, Back Francesca, Black Susannah, Brennan Isabelle, Cansdale Lottie, Chakravorty Triya, Choudhury Zahra, Clay Helen, Conway-Jones Rebecca, Curtis Aisling, Cutteridge Joseph, Danbury Hannah, Davies Hettie, Denly Lucy, Dequaire Julie, Dimitrov Stoyan, Dunlop Ella, Dunn Polly, East Cameron, Eastwood Ben, Edwardes Chantal, Evans Meirian, Fields Charlotte, Flaherty Sarah, Foord Thomas, Freer Rosie, Fuchs Hannah, Grassam-Rowe Alexander, Greenan-Barrett Lewis, Gunnell James, Harries Callum, Harris Edward, Hatton Elizabeth, Hennessy Conor, Holland Christian, Holloway Ben, Howgego Gregory, Barnham Isaac Jarratt, Johnson Síle, Johnson Thomas, Johnstone Daniela, Jurdon Rebecca, Kelly Gabriella, Kerneis Sven, Khulusi Beinn, Killen Annabel, Kourdov Stefan, Kumarendran Mary, Laurenson-Schafer Hannah, Lawrence Ruby, Lee Charlotte, Livingstone Angus, Lynch Rosie, Madsen Tara, Manji Ali, Marsh James, Mason Chris, Mccance Angus, Mcgivern Euan, Mckinlay Ailsa, Mighiu Alexandra, Millar Lancelot, Mohamed Yethrib, Motohashi Kenzo, Myat San, Nezhentsev Andrey, O’Byrne Katherine, Okuwoga Temitope, Oliver Madeleine, Pattenden Saxon, Perera Vimukthi, Petit Yva, Pickles Florence, Pikoula Maria, Randhawa Govind, Ravi Krupa, Reed Lara, Rigler Caitlin, Robinson Charlotte, Rothwell Evie, Santos-Paulo Stephanie, Savva Constantinos, Scharmeli Alice, Scott Samuel, Shabir Zamin, Sharma Ishta, Sheehan Remarez, Shibu Afrah, Somanathan Arun, Sussmes Samuel, Sweeney Owen, Swift Emily, Tadikamalla Gayatri, Tamblyn Morwenna, Taylor Adan, Naudé Rebecca Te Water, Thomas Sarah, Thompson Connor, Till Lottie, Toward Ross, Virgo Charis, Vorley Imogen, Waite Seren, Ward Harry, Ward Jocelyn, Watson Adam, Watson Lily, Wedlich Matthew, Wilkins Laura, Wilson Jack, Wilson Joseph, Wong William, Young Rebecca, Doherty George, Kavanagh James, Chau Kevin K, Fowler Philip W, Swann Jeremy, Volk Denis, Yang-Turner Fan, Skelly Donal, Karpe Fredrik, Neville Matt J, Ferreira Lucas Martins, Christott Thomas, Rodger Gillian, Pickford Hayleah, Cameron Sarah, Tamblin-Hopper Phoebe, Amini Ali, Andersson Monique, Anson Karen, Aston Lisa, Axten David, Barot Simran, Bellinger Trisha, Bialek Adrian, Bodo Noemi, Brent Andrew, Campbell Mark, Cox Vanessa, Cronin Tammy, Davies Timothy, Deales Alessio, Downs Louise, Drennan Philip, Dudareva Maria, Gates Laura, Gates Michelle, Georgiou Dominique, Gergely Bernadett, Holland Louise, Jones Nicola, Jones Sarah, Kerr Sharon, Lawson Elaine, Looms Stacy, Luciw Michael, Martins Diva, Mcknight Mary, Mentzer Alexander, Millard Rebecca, Mitchell Tracey, Morgan Lisa, Morrow Jordan, Mortimore Emma, Mullins Harriet, Nevard Heather, O’Donnell Anne-Marie, Patel Kaisha, Peto Leon, Philips Jane, Ponting Jessica, Ray Roshni, Robles Maria, Rughani Sonam, Sande Nellia, Shaw Robert, Simons Emma-Jane, Sims Elizabeth, Smit Kyla, Smith Lucianne, Szczurkowska Justyna, Thompson Zoe, Turford Rachel, Vilca Kim, Vogt Alexander, Warren Fiona, Warren Laura, Wharton Vicki, Whitty Alison, Woodley Heather, Wozniak Barbara, Young Bernadette, Justice Anita, Jesuthasan Gerald, Wareing Susan, Fadzillah Nurul Huda Mohamad, Cann Kathryn, Kirton Richard, Sutton Claire, Salvagno Claudia, D’Amato Gabriella, Pill Gemma, Butcher Lisa, Rylance-Knight Lydia, Tabirao Merline, Moroney Ruth, Wright Sarah,
Affiliation:
1. Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom 2. Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom 3. Big Data Institute, University of Oxford, Oxford, United Kingdom 4. National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom 5. NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford in partnership with Public Health England, Oxford, United Kingdom 6. Kennedy Institute of Rheumatology Research, University of Oxford, United Kingdom 7. Medical School, University of Oxford, Oxford, United Kingdom 8. Target Discovery Institute, University of Oxford, Oxford, United Kingdom 9. Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom 10. Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam 11. Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Abstract
Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary.
Methods
We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare workers (HCWs). Serial measurements of SARS-CoV-2 anti-nucleocapsid and anti-spike IgG were obtained. Interval censored survival analysis was used to investigate the duration of detectable responses. Additionally, Bayesian mixed linear models were used to investigate anti-nucleocapsid waning.
Results
Anti-spike IgG levels remained stably detected after a positive result, for example, in 94% (95% credibility interval [CrI] 91–96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% CrI 19–31) days post first polymerase chain reaction (PCR)-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titer, the mean estimated antibody half-life was 85 (95% CrI 81–90) days. Higher maximum observed anti-nucleocapsid titers were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity, and prior self-reported symptoms were independently associated with higher maximum anti-nucleocapsid levels and increasing age and a positive PCR test undertaken for symptoms with longer anti-nucleocapsid half-lives.
Conclusions
SARS-CoV-2 anti-nucleocapsid antibodies wane within months and fall faster in younger adults and those without symptoms. However, anti-spike IgG remains stably detected. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.
Funder
UK Government’s Department of Health and Social Care NIHR Public Health England Medical Research Council Canada Foundation for Innovation Genome Canada Ontario Genomics Institute Innovative Medicines Initiative São Paulo Research Foundation Kennedy Trust for Rheumatology Research
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
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