Methods and findings
In this prospective, multicenter cohort conducted between August 2020 and March 2022, we recruited hospital staff from ten acute/non-acute 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 time to SARS-CoV-2 smear-positive and number of symptoms according to immune status, viral variant ( ie, Delta dominant before 27 December 2021, Omicron dominant on/after that date) and subsequent vaccinations, adjusting for exposure/behavioral variables. Among 2,595 participants (median follow-up 171 days), we observed 764 (29%) (re)infections, of which 591 occurred during the Omicron period. Compared to the N group, 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 increased significantly during the Omicron period for all groups. in multivariable analyses, only belonging to the H group was associated with protection (adjusted HR [aHR] 0.52, 95% CI 0.35 to 0.77, p = 0.001); booster vaccination was associated with a reduced risk of infection in the 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), observed largely early Omicron period. Group H (vs N, risk ratio (RR) 0.80, 95% CI 0.66 to 0.97, p = 0.021) and boostered participants (vs unboosted, RR 0.79, 95% CI 0.71 to 0.88, p < 0.0) reported fewer symptoms during infection. Important limitations are that the SARS-CoV-2 smear results were self-reported and that the results on virus variants were inferred from the dominant strain circulating in the community at the time, not from sequencing.
conclusions
Our data suggest that hybrid immunity and booster vaccination are associated with reduced risk and reduced number of symptoms of SARS-CoV-2 infection during Delta- and Omicron-dominant periods. For previously uninfected individuals, booster vaccination may reduce the risk of symptomatic Omicron infection, although this benefit appears to wane over time.
Author Summary
Why was this study done?
Preexisting immunity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)—either from previous infection or vaccination—provides protection against severe coronavirus disease 2019 (COVID-19). Few studies have prospectively determined the risk of SARS-CoV-2 infection based on large-scale serological testing to detect previous asymptomatic infections. Actual assessments of infections during periods with distinct SARS-CoV-2 variants are valuable for assessing protection through preexisting immunity and informing health policy guidelines.
What did the researchers do and what did they find?
In September 2021, 2,554 healthcare workers were classified into four different groups based on previous SARS-CoV-2 serology results and infection/vaccination history. Participants were followed until March 2022 to assess the association of immune status and additional vaccinations with self-reported COVID-19 and symptoms. Hybrid immunity (ie, prior infection and at least one vaccination) resulted in a reduced risk of SARS-CoV-2 infection and fewer symptoms during the Delta or Omicron period. Booster vaccination was associated with a reduced risk of infection and fewer symptoms during the first half of the Omicron period analyzed in our study.
What do these findings mean?
People who have been previously infected and vaccinated appear to be better protected and show fewer symptoms of SARS-CoV-2 infection than those with another immune status. Booster vaccination may further reduce both the risk of Omicron infection and the number of reported symptoms, although this benefit wanes over time. These findings may inform healthcare providers and public health authorities to assess the risk of SARS-CoV-2 (re)infection in individuals or communities.
Citation: Babouee Flury B, Güsewell S, Egger T, Leal O, Brucher A, Lemmenmeier E, et al. (2022) Risk and symptoms of COVID-19 in healthcare professionals according to baseline immune status and booster vaccination during the Delta and Omicron waves in Switzerland—A multicenter cohort study. PLoS Med 19(11): e1004125. https://doi.org/10.1371/journal.pmed.1004125 Academic Editor: James G. Beeson, Burnet Institute, AUSTRALIA Received: 31 May 2022. Accepted: 14 October 2022. Published: 7 November 2022 Copyright: © 2022 Babouee Flury et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: Data are available at https://dx.doi.org/10.5281/zenodo.7149075. Funding: This work was supported by the Swiss National Science Foundation (grant number 31CA30_196544 to PK and CRK, grant number PZ00P3_179919 to PK), the Federal Office of Public Health (grant number 20.008218/421-28/1), and the Cantonal Ministry of Health of St. Gallen. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared no competing interests. Abbreviations: aHR, adjusted HR; anti-N, anti-nucleocapsid; anti-S, anti-spike; aRR, adjusted rate ratio; CI, confidence interval. COVID-19, Coronavirus Disease 2019; HCW, health care worker. HR, hazard ratio; NPS, nasopharyngeal swab; PCR, polymerase chain reaction; RAD, rapid antigen diagnosis. RR, hazard ratio; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2
Record
Mitigating coronavirus disease 2019 (COVID-19) relies on building an ideally long-lasting immune barrier against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Studies from the pre-Omicron era show that specific neutralizing antibodies as a marker of humoral immunity reduce the risk of symptomatic (re)infection and thus disease relapse upon re-exposure to a homologous viral strain [1]. Although natural infection with SARS-CoV-2 elicits a broader humoral response than administration of the mRNA vaccine, neutralizing antibody levels are lower after natural infection [2]. However, with regard to (re)infection, previous infection is associated with 85% protection for at least 9 months [3]; Also, infected individuals may be better protected than vaccinated individuals [4]. An even lower risk of reinfection has been reported for individuals with hybrid immunity, e.g. SARS-CoV-2 infection plus at least one vaccination [5–10]. However, the weak or waning humoral response alongside the emergence of new viral variants, potentially able to escape the immune response, lead to a continued risk of reinfection with heterologous SARS-CoV-2 strains [1,11,12]. This is especially true for the Omicron variant [13]which is the dominant viral strain worldwide as of October 2022 [14]causing mostly milder infections compared to previous strains [15–17]. Available evidence from adult and pediatric populations shows good efficacy of prior mRNA vaccination against severe COVID-19 and hospitalization due to Omicron variants, but less so against asymptomatic and symptomatic, mild infections [11,18–21]. Similar to the pre-Omicron era, some studies have shown that prior infection or hybrid immunity (compared to vaccination alone) may provide better protection against the Omicron variant. However, these studies were either small [22] or were based on population-based data [23]ignoring the fact that a significant proportion of SARS-CoV-2 infections remain undetectable at risk of misclassification [24]. Also, behavioral and exposure variables, which are likely to differ between previously vaccinated and unvaccinated individuals, were not considered in these studies. The effect of type and timing of SARS-CoV-2 vaccination on potential risk of infection has been described for previous variants, but not for Omicron [7,25]. In a prospective, multicenter health care worker (HCW) cohort study, we aimed to determine the risk and symptoms of COVID-19 by comparing Delta- and Omicron-dominant periods according to previous immune status based on history infection/vaccination and the serological results. In addition, we examined the role of booster vaccination in these outcomes. For those with two vaccinations, we assessed the role of mRNA vaccine type and timing of vaccine doses on the risk of breakthrough infection.
Methods
Study design and population
This prospective cohort (SURPRISE) started in the summer of 2020, after the first wave of COVID-19 in Switzerland. The study was approved by the ethics committee of Eastern Switzerland (#2020–00502) and participants provided digital written consent. Health…
