The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers

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

BACKGROUND: SARS-CoV-2 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, e.g., in 94% (95% credibility interval, CrI, 91-96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post first PCR-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. Higher maximum observed anti-nucleocapsid titres 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. CONCLUSION: SARS-CoV-2 anti-nucleocapsid antibodies wane within months, and 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.