The effect of previous SARS-CoV-2 infection and COVID-19 vaccination on SARS-CoV-2 Omicron infection and relation with serological response – a prospective cohort study
Authors: de Gier Brechje , Huiberts Anne J. , Hoeve Christina E. , Hartog Gerco den , van Werkhoven Henri , van Binnendijk Rob , Hahné Susan J.M. , de Melker Hester E. , van den Hof Susan , Knol Mirjam J. 
Published: January 2023

Objectives

To estimate the protective effect of previous infections and vaccinations on SARS-CoV-2 Omicron infection.

Design

Prospective cohort study

Setting

Community-based cohort, the Netherlands

Participants

43,257 Community-dwelling adults aged 18-85 years contributed 8,291,966 person-days between 10 January 2022 and 1 September 2022.

Main outcome measures

SARS-CoV-2 infection, defined as either a reported positive (self-administered) antigen or PCR test, or seroconversion or 4-fold increase in Nucleoprotein-antibodies, based on 6-monthly serum samples. Cox proportional hazard models were used with SARS-CoV-2 infection and any COVID-19 vaccination as time-varying exposures, calendar time as underlying time scale and adjustment for age, sex, medical risk and educational level.

Results

In participants with 2, 3 or 4 prior immunizing events (vaccination or previous infection), we found a relative reduction of 71-85% in Omicron infection in weeks 4-10 post-last event with hybrid immunity compared to vaccine-induced immunity. Differences in risk of infection were partly explained by differences in anti-Spike RBD (S) antibody concentration, which showed a similar pattern but with smaller differences between vaccine-induced and hybrid immunity. Compared to the lowest quartile, participants in subsequent quartiles of S-antibody concentrations had 19%, 35% and 71% reduced risk of infection, respectively. Among participants with hybrid immunity, with one previous pre-Omicron infection, there was no relevant difference in risk of Omicron infection by sequence of vaccination(s) and infection. Regardless of the type of previous immunizing events, additional events increased the protection against infection, but not above the level of the first weeks after the previous event.

Conclusions

Our results showed that hybrid immunity is more protective against infection with SARS-CoV-2 Omicron than vaccine-induced immunity, up to at least 30 weeks after the last immunizing event. Among those with hybrid immunity, the sequence and number of immunizing events was not found to be of importance, and its protective effect was partly explained by circulating S-antibodies. In our population with a high level of immunity, additional immunizing events reduced risk of infection with Omicron variants only temporarily.

Trial registration

Dutch Trial Register (NTR), registration number NL9279 (available viaICTRP Search Portal (who.int))

What is already known on this topic

Studies have found that a previous infection combined with vaccination (hybrid immunity) lowers the risk of SARS-CoV-2 Omicron infection compared to vaccination alone. These studies are mainly test-negative case-control studies, and may be influenced by the increasing use of self-administered antigen testing, and by untested infections. The importance of the sequence and number of immunizing events in hybrid immunity against Omicron infection, and its association with circulating antibody concentrations, is largely unknown.

What this study adds

Hybrid immunity confers better protection against Omicron infection compared to vaccine-induced immunity, up to at least 30 weeks post-immunizing event, regardless of the sequence or number of immunizing events.

The patterns in protection of hybrid immunity against Omicron infection are partly explained by patterns in S-antibody concentration, which was associated with risk of infection in a dose-reponse manner.