Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2

Joanne Reekie*, Henrik Stovring, Henrik Nielsen, Isik S Johansen, Thomas Benfield, Lothar Wiese, Nina Breinholt Stærke, Kasper Iversen, Ahmed Basim Mustafa, Kristine Toft Petersen, Maria Ruwald Juhl, Lene Surland Knudsen, Mette Brouw Iversen, Sidsel Dahl Andersen, Fredrikke Dam Larsen, Eva Anna Marianne Baerends, Susan Olaf Lindvig, Line Dahlerup Rasmussen, Lone Wulff Madsen, Wendy BannisterTomas Oestergaard Jensen, Lisa Loksø Dietz, Sisse Rye Ostrowski, Lars Østergaard, Martin Tolstrup, Jens D Lundgren, Ole Schmeltz Søgaard, ENFORCE Study Group

*Corresponding author af dette arbejde

Abstract

OBJECTIVES: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity.

METHODS: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day90, Day180, 28 days after 3rd vaccination (Day251), Day365, and prior to 4th vaccination (Day535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day365, PCR+ after Day365) on anti-spike IgG trajectories.

RESULTS: 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, p=<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity.

CONCLUSION: Hybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.

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