The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers
Authors: Lumley Sheila F , Wei Jia , O’Donnell Denise , Stoesser Nicole E , Matthews Philippa C , Howarth Alison , Hatch Stephanie B , Marsden Brian D , Cox Stuart , James Tim , Peck Liam J , Ritter Thomas G , de Toledo Zoe , Cornall Richard J , Jones E Yvonne , Stuart David I , Screaton Gavin , Ebner Daniel , Hoosdally Sarah , Crook Derrick W , Conlon Christopher P , Pouwels Koen B , Walker A Sarah , Peto Tim E A , Walker Timothy M , Jeffery Katie , Eyre David W ,   Oxford University Hospitals Staff Testing Group, 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 
Published: January 2021

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.