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

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