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Levels of SARS-CoV-2 Antibodies Among Fully-Vaccinated Individuals With Delta or Omicron Variant Breakthrough Infections: A Prospective Cohort Study

18 Pages Posted: 25 Mar 2022

See all articles by Nina Breinholt Stærke

Nina Breinholt Stærke

Aarhus University - Department of Infectious Diseases

Joanne Reekie

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP

Henrik Nielsen

Aalborg University - Department of Infectious Diseases

Thomas Benfield

University of Copenhagen - Department of Infectious Diseases

Lothar Wiese

Zealand University Hospital - Department of Infectious Diseases

Lene Surland Knudsen

Zealand University Hospital - Department of Medicine

Mette Brouw Iversen

Zealand University Hospital - Department of Medicine

Kasper Karmark Iversen

University of Copenhagen - Department of Cardiology

Kamille Fogh

University of Copenhagen - Department of Cardiology

Jacob Bodilsen

Aalborg University - Department of Infectious Diseases

Maria Ruwald Juhl

Aalborg University - Department of Infectious Diseases

Susan Olaf Lindvig

Odense University Hospital - Department of Infectious Diseases

Anne Øvrehus

Odense University Hospital - Department of Infectious Diseases

Lone Wulff Madsen

Odense University Hospital - Department of Infectious Diseases

Vibeke Klastrup

Aarhus University - Department of Infectious Diseases

Sidsel Dahl Andersen

Aarhus University - Department of Infectious Diseases

Anna Karina Juhl

Aarhus University - Department of Infectious Diseases

Signe Rode Andreasen

Aarhus University - Department of Infectious Diseases

Sisse Rye Ostrowski

University of Copenhagen - Department of Clinical Medicine

Christian Erikstrup

Aarhus University - Department of Clinical Immunology

Thea K. Fischer

University of Copenhagen - Department of Public Health

Martin Tolstrup

Aarhus University - Department of Infectious Diseases

Lars Jørgen Østergaard

Aarhus University - Department of Infectious Diseases

Isik S. Johansen

Odense University Hospital - Department of Infectious Diseases

Jens Lundgren

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP

Ole S. Søgaard

Aarhus University - Department of Infectious Diseases

More...

Abstract

Background: Vaccines based on the Wuhan strain of SARS-CoV-2 are a cornerstone of the global management of the COVID-19 pandemic. However, variants of concern have continuously evolved and may erode previously induced immunity. This study aimed to determine risk of breakthrough infection in a fully vaccinated cohort.

Methods: Participants were enrolled before their first SARS-CoV-2 vaccination and SARS-CoV-2 anti-spike IgG levels were measured after 21–28, 90 and 180 days of follow-up, as well as day -7 and 28 after booster vaccination. Rate of breakthrough infections were ascertained from two weeks after the second vaccine dose, and captured through the Danish National Microbiology database. Poisson regression analysis was used to determine the risk of breakthrough infection at time-updated anti-spike IgG levels after adjustment for age, sex, being health care worker, and time-updated SARS-CoV-2 transmission level.

Findings: Among 6076 participants (median age 64 years, interquartile range 55–75) included in this analysis, breakthrough infections due to the Delta variant were observed in 127 participants and in 363 due to the Omicron variant. The incidence rate ratio (IRR) for breakthrough infection with the Delta variant decreased with higher levels of anti-spike IgG yielding an IRR of 0.28 (95% CI 0·15–0·55) when comparing the highest and lowest quintiles of anti-spike IgG. For the Omicron variant, no significant differences in IRR of breakthrough infection between quintiles of anti-spike IgG was observed. Notably, 1 of 127 (0·8%) SARS-CoV-2 Delta variant and 0 of 336 (0%) Omicron variant breakthrough infections resulted in severe COVID-19.

Interpretation: We observed a strong association between increasing levels of anti-spike antibodies and reduced risk of breakthrough infections with the Delta but not the Omicron variant. However, despite a high proportion of elderly participants, severe COVID-19 was rare in both Delta and Omicron infections.

Trial Registration Details: The study was approved by the Danish Medicines Agency (Eudra CT number:2020-006003-42).

Funding Information: This study was fully funded by the Danish Ministry of Health (act 150, January 28th 2021).

Declaration of Interests: HN declares participation on advisory board meeting with GSK and MSD. TB declares receipt of unrestricted research or travel grants from GSK, Pfizer, Gilead Sciences, MSD; and being principal investigator on trials conducted by Boehringer Ingelheim, Roche, Novartis, Kancera, Pfizer, MSD and Gilead; Board member on Pentabase, and advisory board member for MSD, Gilead, Pfizer, GSK, Janssen and AstraZeneca; consulting fees from GSK and Pfizer; receiving donation of study drug from Eli Lilly; and receiving honorarium for lectures from GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, Abbvie and AstraZeneca. NS declares being principal investigator on studies conducted by Pfizer and Gilead. All other authors declare no conflicts of interest.

Ethics Approval Statement: The study was approved by the Ethics Committee of the Central Denmark Region (#1-10-72-337-20). All participants received written and oral information about the study before providing their consent to participate.

Keywords: SARS-CoV-2, COVID-19, vaccination, antibody, serology, breakthrough infection, Omicron, Delta

Suggested Citation

Stærke, Nina Breinholt and Reekie, Joanne and Nielsen, Henrik and Benfield, Thomas and Wiese, Lothar and Knudsen, Lene Surland and Iversen, Mette Brouw and Iversen, Kasper Karmark and Fogh, Kamille and Bodilsen, Jacob and Juhl, Maria Ruwald and Lindvig, Susan Olaf and Øvrehus, Anne and Madsen, Lone Wulff and Klastrup, Vibeke and Andersen, Sidsel Dahl and Juhl, Anna Karina and Andreasen, Signe Rode and Ostrowski, Sisse Rye and Erikstrup, Christian and Fischer, Thea K. and Tolstrup, Martin and Østergaard, Lars Jørgen and Johansen, Isik S. and Lundgren, Jens and Søgaard, Ole S., Levels of SARS-CoV-2 Antibodies Among Fully-Vaccinated Individuals With Delta or Omicron Variant Breakthrough Infections: A Prospective Cohort Study. Available at SSRN: https://ssrn.com/abstract=4066425 or http://dx.doi.org/10.2139/ssrn.4066425

Nina Breinholt Stærke (Contact Author)

Aarhus University - Department of Infectious Diseases ( email )

Joanne Reekie

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP ( email )

Copenhagen, DK-2100
Denmark

Henrik Nielsen

Aalborg University - Department of Infectious Diseases ( email )

Aalborg
Denmark

Thomas Benfield

University of Copenhagen - Department of Infectious Diseases

Copenhagen
Denmark

Lothar Wiese

Zealand University Hospital - Department of Infectious Diseases ( email )

Roskilde
Denmark

Lene Surland Knudsen

Zealand University Hospital - Department of Medicine ( email )

Roskilde
Denmark

Mette Brouw Iversen

Zealand University Hospital - Department of Medicine ( email )

Roskilde
Denmark

Kasper Karmark Iversen

University of Copenhagen - Department of Cardiology ( email )

Herlev
Denmark

Kamille Fogh

University of Copenhagen - Department of Cardiology ( email )

Herlev
Denmark

Jacob Bodilsen

Aalborg University - Department of Infectious Diseases ( email )

Aalborg
Denmark

Maria Ruwald Juhl

Aalborg University - Department of Infectious Diseases ( email )

Aalborg
Denmark

Susan Olaf Lindvig

Odense University Hospital - Department of Infectious Diseases ( email )

Odense
Denmark

Anne Øvrehus

Odense University Hospital - Department of Infectious Diseases ( email )

Odense
Denmark

Lone Wulff Madsen

Odense University Hospital - Department of Infectious Diseases ( email )

Odense
Denmark

Vibeke Klastrup

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Sidsel Dahl Andersen

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Anna Karina Juhl

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Signe Rode Andreasen

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Sisse Rye Ostrowski

University of Copenhagen - Department of Clinical Medicine ( email )

Nørregade 10
Copenhagen, København DK-1165
Denmark

Christian Erikstrup

Aarhus University - Department of Clinical Immunology ( email )

Aarhus
Denmark

Thea K. Fischer

University of Copenhagen - Department of Public Health ( email )

Denmark

Martin Tolstrup

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Lars Jørgen Østergaard

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Isik S. Johansen

Odense University Hospital - Department of Infectious Diseases ( email )

Odense
Denmark

Jens Lundgren

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP ( email )

Copenhagen, DK-2100
Denmark

Ole S. Søgaard

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark