Long-Term Persistence of Spike Protein Antibody and Predictive Modeling of Antibody Dynamics After Infection With Severe Acute Respiratory Syndrome Coronavirus 2
Authors: Grandjean Louis , Saso Anja , Torres Ortiz Arturo , Lam Tanya , Hatcher James , Thistlethwayte Rosie , Harris Mark , Best Timothy , Johnson Marina , Wagstaffe Helen , Ralph Elizabeth , Mai Annabelle , Colijn Caroline , Breuer Judith , Buckland Matthew , Gilmour Kimberly , Goldblatt David ,   COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) team, Mirambe-Korsah Dorcas , Torrente Fernanda Fenn , Wyszynski Jakub , Gander Victoria , Leonard Amy , Myers Louise , Vallot Aimee , Paillas Camille , Fitzgerald Rose , Twigg Adam , Manaf Rabia , Gibbons Lois , Powell Hollie , Nar-Dorh Richard , Gray Ally , Fernandez Elias , Minja Aline , Beech Emily , Girshab Waffa , Chia Pei Shi , Webb Kate , Nakrani Malti , Gardiner Kim , Karaluka Valerija , Ryan Karen , Groves Dorothy Lee Katie , Khan Hamad , Nsubuga Shamime , Rosie-Wilkinson Olivia , Spires Julia , Sanchez-Clemente Nuria , Kaur Sapriya , Carroll Natasha , Efford Jemma , Bredin Gabriel , Dos Santos Domingues Celma Marisa , Foxall Sophie , Ashton Helen , Afzal Abbey , Mainland Sally , Crumpler Kate , Dawson Lucinda , Smith Claire , Tabbu Maria , Chiverton Laura , Sugars Jade , Mooney Jordan , Chikusu Dorothy , Tahami Fariba , Samy Baratth , Begum Shomona , Patel Dhimple , Wiltshire Philippa , Susay Annie , Ryan Anna , Lancaster Luke , Thind Kavita , Speller Kate , Sterling Rachel , Tugulu Connor , Ghurburrun Sandhya , Gray Steffi , Mugas Joy , Kishma Moe , Akpokomua Kathleen , White Sophie , Pieri Eleana , Shamsad Sabina , Alexandrou Demi , Aguele Odera , Miles Katherine , Jain Anamika , Gautam Subishma , Simms Oliver , Goff Rachel , Shams Zarif , Chirinda Tinya , Nur Aaliya , Rahman Tarekur 
Published: July 2021

Abstract

Background
Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to neutralize the virus in vitro and prevent disease in animal challenge models on reexposure. However, the current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting.

Methods
The COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike protein (S), receptor-binding domain, and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for a maximum of 7 months with the Meso Scale Discovery Assay. Survival analysis determined the proportion of seroreversion, while 2 hierarchical gamma models predicted the upper and lower bounds of long-term antibody trajectory.

Results
A total of 1163 monthly samples were provided from 349 seropositive participants. At 200 days after symptoms, &gt;95% of participants had detectable S antibodies, compared with 75% with detectable N antibodies. S antibody was predicted to remain detectable in 95% of participants until 465 days (95% confidence interval, 370–575 days) using a “continuous-decay” model and indefinitely using a “decay-to-plateau” model to account for antibody secretion by long-lived plasma cells. S-antibody titers were correlated strongly with surrogate neutralization in vitro (R2 = 0.72). N antibodies, however, decayed rapidly with a half-life of 60 days (95% confidence interval, 52–68 days).

Conclusions
The Co-Stars data presented here provide evidence for long-term persistence of neutralizing S antibodies. This has important implications for the duration of functional immunity after SARS-CoV-2 infection. In contrast, the rapid decay of N antibodies must be considered in future seroprevalence studies and public health decision-making. This is the first study to establish a mathematical framework capable of predicting long-term humoral dynamics after SARS-CoV-2 infection.

Clinical Trials Registration
NCT04380896.