Risk and symptoms of COVID-19 in health professionals according to baseline immune status and booster vaccination during the Delta and Omicron waves in Switzerland-A multicentre cohort study

Abstract

Background: Knowledge about protection conferred by previous Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and/or vaccination against emerging viral variants allows clinicians, epidemiologists, and health authorities to predict and reduce the future Coronavirus Disease 2019 (COVID-19) burden. We investigated the risk and symptoms of SARS-CoV-2 (re)infection and vaccine breakthrough infection during the Delta and Omicron waves, depending on baseline immune status and subsequent vaccinations.

Methods and findings: In this prospective, multicentre cohort performed between August 2020 and March 2022, we recruited hospital employees from ten acute/nonacute healthcare networks in Eastern/Northern Switzerland. We determined immune status in September 2021 based on serology and previous SARS-CoV-2 infections/vaccinations: Group N (no immunity); Group V (twice vaccinated, uninfected); Group I (infected, unvaccinated); Group H (hybrid: infected and ≥1 vaccination). Date and symptoms of (re)infections and subsequent (booster) vaccinations were recorded until March 2022. We compared the time to positive SARS-CoV-2 swab and number of symptoms according to immune status, viral variant (i.e., Delta-dominant before December 27, 2021; Omicron-dominant on/after this date), and subsequent vaccinations, adjusting for exposure/behavior variables. Among 2,595 participants (median follow-up 171 days), we observed 764 (29%) (re)infections, thereof 591 during the Omicron period. Compared to group N, the hazard ratio (HR) for (re)infection was 0.33 (95% confidence interval [CI] 0.22 to 0.50, p < 0.001) for V, 0.25 (95% CI 0.11 to 0.57, p = 0.001) for I, and 0.04 (95% CI 0.02 to 0.10, p < 0.001) for H in the Delta period. HRs substantially increased during the Omicron period for all groups; in multivariable analyses, only belonging to group H was associated with protection (adjusted HR [aHR] 0.52, 95% CI 0.35 to 0.77, p = 0.001); booster vaccination was associated with reduction of breakthrough infection risk in groups V (aHR 0.68, 95% CI 0.54 to 0.85, p = 0.001) and H (aHR 0.67, 95% CI 0.45 to 1.00, p = 0.048), largely observed in the early Omicron period. Group H (versus N, risk ratio (RR) 0.80, 95% CI 0.66 to 0.97, p = 0.021) and participants with booster vaccination (versus nonboosted, RR 0.79, 95% CI 0.71 to 0.88, p < 0.001) reported less symptoms during infection. Important limitations are that SARS-CoV-2 swab results were self-reported and that results on viral variants were inferred from the predominating strain circulating in the community at that time, rather than sequencing.

Conclusions: Our data suggest that hybrid immunity and booster vaccination are associated with a reduced risk and reduced symptom number of SARS-CoV-2 infection during Delta- and Omicron-dominant periods. For previously noninfected individuals, booster vaccination might reduce the risk of symptomatic Omicron infection, although this benefit seems to wane over time.

Fig 1. Study timeline depicting the longitudinal follow-up of participants in correlation with the virus variants circulating in Eastern Switzerland.

Fig 2

Left: influence of baseline immune status on the time course of (re)infection events, shown separately for the two periods (Delta vs. Omicron) by resetting Kaplan–Meier curves to 0 on December 27, 2021. Note that group differences depicted in the graph include any impact of booster vaccination (in groups V and H). Right: HRs with 95% CIs from Cox regression regarding risk of SARS-CoV-2 (re)infection for each immune status compared with group N (no previous infection or vaccination), both without and with adjustment for booster vaccination. CI, confidence interval; HR, hazard ratio; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2.

Fig 3. Influence of booster on the time course of (re)infection events during Omicron dominance, with HRs and 95% CIs, according to immune status.

Note that participants receiving their booster after December 27, 2021 were initially classified as “no” and subsequently switched to “yes,” so that numbers at risk for “yes” increase initially. CI, confidence interval; HR, hazard ratio.

Fig 4

Number of symptoms reported after (re)infection by baseline immune status, grouped by Delta and Omicron periods (panel A, left) and receipt of booster (panel B, right). N (no immunity): no reported infection and anti-N/-S negative and no previous SARS-CoV-2 vaccination; V (vaccinated): no reported infection and anti-N negative, but twice vaccinated; I (infected): infection reported or anti-N positive (at any time), but no vaccination; H (hybrid immunity): reported infection or anti-N positive (at any time) and vaccination (≥1 dose).