Role of vaccines in competitive displacement between SARS-CoV-2 viruses as revealed by the modeling of surveillance data

Infection, vol. 53, pp. 2511–2521

Abstract

PURPOSE: SARS-CoV-2 Omicron onset resulted in the rapid displacement of Delta and subsequent intra-Omicron displacement-events. Evidence of geographical diversity on the dynamics is present between and within countries. Considering Omicron’s immune-evasive potential compared to earlier variants, we investigated whether vaccines have influenced local dominance patterns in Germany. METHODS: We used weekly-binned genomic surveillance-data representing 48 regional outbreaks with as many displacement-events. Displacement occurred when a given variant constituted ≥ 50% of all isolates. We ran mixed-effect models to quantify vaccine-density effects on the time-to-displacement (ttd) and survival analysis to compare displacement-free time-intervals. Finally, we compared antigenic properties between variants, analyzing receptor-binding domain (RBD) epitope mutations and estimating RBD-residues antigenicity in solved S-protein structures. RESULTS: Analyzing 895,000 isolates, we calculated ttd-intervals for the Omicron-Delta, BA.2-BA.1 and BA.5-BA.2 displacements. Mixed-effect models suggested the more vaccines have been administered, the sooner a displacement occurred, observing stronger effects for vaccines administered in temporal proximity to displacement-events (2–7% shorter intervals for one vaccination per 10 immunity-events). Survival analysis suggested stronger effects for Omicron-Delta than intra-Omicron displacements. In silico analysis of ca. 500 epitopes and 27,000 residues suggested antigenic change-driven selection as a likely explanation. CONCLUSION: This is the first indication of vaccines influencing competitive displacement between SARS-CoV-2 species within a single, socio-demographically homogenous healthcare-system. Since Omicron infections resulted in less adverse outcomes than Delta, our results help understanding the success of vaccines in avoiding severe outcomes at population level. This is particularly important for future pandemics with impacts on timeliness and intensity of vaccination campaigns.

Authors 10

1. Hani E. J. Kaba

   Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Department of Infection Control and Infectious Diseases (IH&I), University Medical Center Göttingen (UMG), Göttingen, Germany

2. Felix Hartkopf

   Robert Koch Institute

   Affiliation as printed

   Robert Koch Institute (RKI), Berlin, Germany

3. Maike Hohberg

   Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Department of Medical Statistics, University Medical Center Göttingen (UMG), Göttingen, Germany

4. Josue Bucio-García

   Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Department of Infection Control and Infectious Diseases (IH&I), University Medical Center Göttingen (UMG), Göttingen, Germany

5. Martin Misailovski

   Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Department of Infection Control and Infectious Diseases (IH&I), University Medical Center Göttingen (UMG), Göttingen, Germany

6. Franz‐Christoph Bange

   Medizinische Hochschule Hannover

   Affiliation as printed

   Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH), Hannover, Germany

7. Michael Kleines Aachen Laboratory Diagnostic Center

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Laboratory Diagnostic Center, University Hospital RWTH Aachen, Aachen, Germany

8. Tim Friede

   Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Department of Medical Statistics, University Medical Center Göttingen (UMG), Göttingen, Germany

9. Tim Eckmanns

   Robert Koch Institute

   Affiliation as printed

   Robert Koch Institute (RKI), Berlin, Germany

10. Simone Scheithauer corresponding

    Universitätsmedizin Göttingen · University of Göttingen

    Affiliation as printed

    Department of Infection Control and Infectious Diseases (IH&I), University Medical Center Göttingen (UMG), Göttingen, Germany. krankenhaushygiene.leitung@med.uni-goettingen.de