The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers
Sheila Lumley, Jia Wei, Denise O’Donnell, Nicole Stoesser, Philippa C. Matthews, Alison Howarth, Stephanie B. Hatch, Brian D. Marsden, Stuart Cox, Tim James, Liam J Peck, Thomas Ritter, Zoe de Toledo, Richard J. Cornall, E. Yvonne Jones, David I. Stuart, Gavin Screaton, Daniel Ebner, Sarah Hoosdally, Derrick W. Crook, Christopher P. Conlon, Koen B. Pouwels, A. Sarah Walker, Tim Peto, A Sarah Walker, Katie Jeffery, David W. Eyre, Molly Abbott, Roxanna E. Abhari, Hibatullah Abuelgasim, Tariq Ahmed-Firani, Ahmed Alhussni, Isobel L.A. Argles, Rebecca Ashworth, Francesca Back, Susannah Black, Isabelle Brennan, Lottie Cansdale, Triya Chakravorty, Zahra Choudhury, Helen Clay, Rebecca Conway-Jones, Aisling Curtis, Joseph Cutteridge, Hannah Danbury, Hettie Davies, Lucy Denly, Julie Dequaire, Stoyan Dimitrov, Ella Dunlop, Polly Dunn, Cameron East, Ben Eastwood, Chantal Edwardes, Meirian Evans, Charlotte Fields, Sarah Jane Flaherty, Thomas Foord, Rosie Freer, Hannah E. Fuchs, Alexander Grassam-Rowe, Lewis Greenan-Barrett, James Gunnell, Callum Harries, Edward Harris, Elizabeth Hatton, Conor Hennessy, Christian Holland, Ben Holloway, Gregory Howgego, Isaac Jarratt Barnham, Síle A. Johnson, Thomas Johnson, Daniela Johnstone, Rebecca Jurdon, Gabriella Kelly, Sven Kerneis, Beinn Khulusi, Annabel Killen, Stefan Kourdov, Mary Kumarendran, Hannah Laurenson-Schafer, Ruby Lawrence, Charlotte Lee, Angus Livingstone, Rosie Lynch, Tara Madsen, Ali Manji, James J. Marsh, Chris Mason, Angus McCance, Euan J McGivern, Ailsa Mckinlay, Alexandra Mighiu, Lancelot Jamie Millar, Yethrib Mohamed, Kenzo Motohashi, Myat San, Andrey Nezhentsev, Katherine O’Byrne
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.