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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
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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.
Author summary
Why was this study done?
- Preexisting immunity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)—either from previous infection or vaccination—confers protection against severe Coronavirus Disease 2019 (COVID-19).
- Few studies have prospectively determined the SARS-CoV-2 infection risk based on large-scale serologic testing to detect previous asymptomatic infections.
- Real-world evaluations of infections during periods with distinct SARS-CoV-2 variants are valuable to assess protection by preexisting immunity and inform health policy guidelines.
What did the researchers do and 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 (i.e., previous infection and at least one vaccination) resulted in a reduced SARS-CoV-2 infection risk and less symptoms during the Delta or Omicron period.
- Booster vaccination was associated with reduced infection risk and less symptoms during the first half of the Omicron period analysed in our study.
What do these findings mean?
- Individuals who were previously infected and vaccinated seem to be best protected and exhibit less symptoms of SARS-CoV-2 infection than those with other immune status.
- Booster vaccination might further reduce both the risk of Omicron breakthrough infection and the number of reported symptoms, although this benefit fades over time.
- These findings might inform healthcare providers and public health authorities in estimating 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 health professionals according to baseline immune status and booster vaccination during the Delta and Omicron waves in Switzerland—A multicentre cohort study. PLoS Med 19(11):
e1004125.
https://doi.org/10.1371/journal.pmed.1004125
Academic Editor: James G. Beeson, Burnet Institute, AUSTRALIA
Received: May 31, 2022; Accepted: October 14, 2022; Published: November 7, 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 Sciences 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 Health Department of the Canton of St. Gallen. Funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
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,
healthcare worker; HR,
hazard ratio; NPS,
nasopharyngeal swab; PCR,
polymerase chain reaction; RAD,
rapid antigen diagnostic; RR,
risk ratio; SARS-CoV-2,
Severe Acute Respiratory Syndrome Coronavirus 2
Background
Mitigation of Coronavirus Disease 2019 (COVID-19) relies on establishing 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 marker for humoral immunity reduce the risk of symptomatic (re)infection and thus disease recurrence upon reexposure to a homologous viral strain [1]. Although natural infection with SARS-CoV-2 elicits a broader humoral response than mRNA vaccine administration, levels of neutralizing antibodies are lower after natural infection [2]. Concerning (re)infection however, previous infection is associated with 85% protection over at least 9 months [3]; also, infected individuals might be even better protected than only vaccinated individuals [4]. A still lower reinfection risk has been reported for individuals with hybrid immunity, i.e., SARS-CoV-2 infection plus at least one vaccination [5–10].
Yet, weak or waning humoral response in tandem with the emergence of new viral variants, capable of potentially escaping immune response, lead to a continued risk of reinfection with heterologous SARS-CoV-2 strains [1,11,12]. This is particularly true for the Omicron variant [13], which is the predominant viral strain globally as of October 2022 [14], causing mostly milder infections compared to preceding strains [15–17]. Available evidence from adult and pediatric populations points towards good effectiveness of prior mRNA vaccination against severe COVID-19 and hospitalisation due to Omicron variants, but less so against asymptomatic and symptomatic, mild breakthrough infections [11,18–21]. Similar to the pre-Omicron era, some studies have shown that previous infection or hybrid immunity (compared to vaccination alone) might provide better protection against the Omicron variant. However, these studies were either small [22] or relied on population-based data [23], ignoring the fact that a substantial proportion of SARS-CoV-2 infections remain undetected with the risk of misclassification [24]. Also, behavior and exposure variables, which are likely to be different between previously vaccinated and unvaccinated individuals, were not considered in these studies. The influence of type and timing of SARS-CoV-2 vaccination on eventual risk of breakthrough infection has been described for previous variants, but not for Omicron [7,25].
Within a prospective, multicentre healthcare worker (HCW) cohort study, we aimed to determine the risk for and symptoms of COVID-19 by comparing Delta- and Omicron-dominant periods, depending on previous immune status based on infection/vaccination history and serology results. Furthermore, we examined the role of booster vaccination on these outcomes. For those with two vaccinations, we assessed the role of mRNA vaccine type and timing of vaccine doses on breakthrough infection risk.
Methods
Study design and population
This prospective cohort (SURPRISE) was initiated in summer 2020, after the first COVID-19 wave in Switzerland. The study was approved by the ethics committee of Eastern Switzerland (#2020–00502), and participants provided digital written informed consent. Health professionals (with and without patient contact) aged 16 years or older from ten healthcare networks located in Northern and Eastern Switzerland were included between June 2020 and March 2021. From their inclusion until September 2021, participants were prospectively followed through weekly questionnaires on SARS-CoV-2 infections/vaccinations, and periodic SARS-CoV-2 serology measurements in August 2020, January 2021, and August/September 2021 [26]. Participants without available serology from August/September 2021 were excluded. For the present work, no prespecified analysis plan was designed.
Baseline immune status was assessed as of September 20, 2021 (Fig 1), based on previous infection/vaccination history and all available serology results. During the local emergence of the Delta (October to December 2021) and Omicron B.1.1.529.1 (Nextstrain 21K; BA.1) variant (January to March 2022), the follow-up survey through questionnaires was continued at monthly intervals. Information collected included SARS-CoV-2 exposures, reports of nasopharyngeal swab (NPS) tests (positive and negative), symptoms associated with positive NPS, and receipt of subsequent (booster or first) vaccinations.
SARS-CoV-2 diagnostics
Participants were asked to get tested for SARS-CoV-2 in case of compatible symptoms, according to national recommendations. SARS-CoV-2 was detected by polymerase chain reaction (PCR) or rapid antigen diagnostic (RAD) test, depending on the participating institutions. Some facilities also switched from PCR to RAD in the course. No sequencing for determination of the viral variants was performed; the viral variant was inferred from the predominating strain circulating in the community at that time (see below). To verify the completeness and accuracy of self-reported NPS results (PCR or RAD), all positives and a random sample of negatives were validated for a subgroup of HCWs from the largest participating institution as described previously [27]. Anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies were measured using the Roche Elecsys (Roche Diagnostics, Rotkreuz, Switzerland) electro-chemiluminescence immunoassay [28].
Definition of predictor variables
We defined four distinct immune status groups (i.e., main predictor) as of September 20, 2021, according to previous questionnaires and serology results: (i) Group N (reference): no reported infection and anti-N/anti-S negative and no previous SARS-CoV-2 vaccination; (ii) Group V (vaccinated): no reported infection and anti-N negative, but twice vaccinated (with any time interval between doses) with the second dose being at least 7 days ago; (iii) Group I (infected): infection reported or anti-N positive (at any time), but no vaccination; (iv) Group H (hybrid immunity): reported infection or anti-N positive (at any time) and vaccination (≥1 dose) at least 7 days ago. In addition, we collected information on vaccination after September 20, 2021, either booster vaccination (available from November 2021 on) for groups V and H or first vaccinations for groups N and I. Again, participants were considered as boosted 7 days after receipt of the vaccine. Immune status was treated as time-dependent variable, so that participants switched from group I to H after the first vaccination, and from group N to V after the second vaccination. Participants in group N with only one vaccination were not considered and were only included 7 days after receipt of their second dose. The different groups and outcomes are illustrated in S1 Fig. For other predictor variables, S1 Table shows definitions and time points of the corresponding questionnaire.
Outcomes
The main outcome was time to the first SARS-CoV-2-positive NPS reported after September 20, 2021. Outcomes occurring between September 20, 2021 and March 6, 2022 were included. The period before December 27, 2021 was defined as Delta-dominant (i.e., Delta period), the period on and after this date as Omicron-dominant (i.e., Omicron period), based on sequencing data from North-Eastern Switzerland [29]. We treated our outcome as a survival event, i.e., participants were no longer at risk after their first positive NPS. We also calculated the number of symptoms reported during SARS-CoV-2 infection.
Statistical analysis regarding infection risk
We computed Kaplan–Meier curves to compare the occurrence of SARS-CoV-2 (re)infection (first positive NPS) through time according to immune status; noninfected participants were censored at the time of the last available follow-up questionnaire. The risk of (re)infection was compared among groups (treated as time-dependent variable) using Cox regression; hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated. This analysis was performed separately for the Delta and Omicron periods, with and without adjusting for receipt of booster vaccination. In addition, Kaplan–Meier curves were computed to visualize the association of booster vaccination on infection risk during the Omicron period, when most of these vaccinations had already been received.
Multivariable Cox-regression analysis was performed to correct for additional confounding variables, which were a priori selected based on previous analyses and expected importance [30]. Multiple imputation was used to substitute missing values (S1 Methods). Time-dependent variables were, besides immune status, receipt of booster vaccination, SARS-CoV-2 infection of a household contact within the same month, and documentation of ≥1 negative test in the previous month (to adjust for differences in testing behaviour). Time-independent variables included baseline anthropometric data and further variables reflecting SARS-CoV-2 risk exposures and behaviours (S1 Table). We performed a sensitivity analysis excluding infections occurring during the period of variant overlap between December 6, 2021 and January 3, 2022 to minimize contamination of infections occurring in the Delta and Omicron periods with the respective other viral variant.
Supplementary analyses
Because model diagnostics showed that the influence of booster vaccination was time dependent in the Omicron period, we further split this period into an early (before February 15, 2022) and late Omicron phase (after this date).
To estimate the influence of time since last immunization event, we included time from previous infection or vaccination (i.e., time of preimmunization) until September 20, 2021 for those individuals where this information was available. The exact day of initial infection could not be assessed in those with only positive anti-N but no report of positive NPS; also, group N, which per definition did not have an immunization event, was excluded and group V was chosen as reference category instead.
Finally, to assess the impact of type and timing of vaccination within group V, we included the type of vaccine (i.e., mRNA-1273 or BNT162b2), the time of preimmunization, and time between first and second vaccination dose.
Frequency of SARS-CoV-2 symptoms
We used univariable and multivariable Poisson regression to assess the impact of baseline immune status on symptom number for infections that occurred before any booster or first vaccination. Covariables included the virus variants (Delta versus Omicron period), the month of (re)infection (to adjust for the fact that immune protection wanes over time), and a priori selected variables based on their importance in previous analyses [31].
To assess the impact of booster vaccination on number of symptoms, we performed a second analysis restricted to groups V and H, and to infections occurring during the Omicron period (because of the small number of infections preceded by booster in the Delta period). The study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 STROBE Checklist) [32]. R version 4.1.2 was used for statistical analyses.
Results
Study population
Of the 5,792 initial cohort participants, 2,595 (45%) underwent serology testing in August/September 2021 and completed at least one follow-up questionnaire. Thereof, 2,554 were classified into one of the immune status groups at baseline: 581 (22.7%) in group H, 162 (6.3%) in I, 1,643 (64.3%) in V, and 168 (6.6%) in N; additionally, 41 individuals were assigned to group V during follow-up (after their second vaccination) (S2 Fig). Median follow-up was 171 days (interquartile range 131 to 171). Baseline characteristics are summarized in Table 1.
SARS-CoV-2 (re)infections by immune status and time period
A total of 764 (29.4%) infections were reported in 2,595 participants, whereof 173 (22.6%) occurred during the Delta and 591 (77.4%) during the Omicron period. During Delta, the risk for COVID-19 was significantly reduced for groups V (HR 0.33, 95% CI 0.22 to 0.50, p < 0.001), I (HR 0.25, 95% CI 0.11 to 0.57, p = 0.001), and H (HR 0.04, 95% CI 0.02 to 0.10, p < 0.001) compared to group N. These associations were less pronounced during the Omicron period for all groups (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.
Booster vaccination and risk of infection
By March 2022, 80% of participants in groups V and H had received a booster (median time of booster was December 14, 2021) (S3 Fig). Adjusting the univariable model for booster vaccination, the adjusted HR (aHR) remained similar for the Delta period as in the unadjusted model. In the Omicron period, only group H showed a reduced risk (aHR 0.45, 0.30 to 0.67, p < 0.001) compared to group N, whereas no significant risk reduction was observed for groups V and I (Fig 2). Restricting the analysis to the Omicron period, receipt of booster vaccination was associated with reduced 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) (Fig 3).
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.
Multivariable analysis and sensitivity analyses
When models included exposure and behaviour variables, results were similar, with group H being the only group with reduced infection risk (aHR 0.52, 95% CI 0.35 to 0.77, p = 0.001) in the Omicron period (Table 2). The main risk correlate for SARS-CoV-2 positivity was having a SARS-CoV-2-positive household (as reported by the participant), both in the Delta (aHR 9.66, 95% CI 7.15 to 13.05, p < 0.001) and the Omicron period (aHR 6.17, 95% CI 5.24 to 7.27, p < 0.001).
Excluding infections during the Delta-Omicron overlap period and performing further missing value imputations as well as a complete case analysis yielded similar HRs as the main analysis (S3 Table).
Supplementary analyses
Splitting the Omicron period into an early and late phase suggested a benefit of the booster vaccination for the early Omicron phase (aHR 0.60, 95% CI 0.47 to 0.76, p < 0.001), but not for the late Omicron phase (aHR 1.02, 95% CI 0.75 to 1.38, p = 0.90) (S4 Table).
Time since preimmunization was associated with infection risk during the Delta period (aHR 1.16 per additional months, 95% CI 1.06 to 1.28, p = 0.003), but not the Omicron period (aHR 1.00, 95% CI 0.96 to 1.04, p = 0.82). Hybrid immunity remained the immune status, which best protected against infection in both periods. Of note, group I (compared to group V) was better protected against infection in the Delta period (aHR 0.27, 95% CI 0.09 to 0.82, p = 0.023), but not in the Omicron period (aHR 0.84, 95% CI 0.49 to 1.44, p = 0.527) (S5 Table).
Within group V, neither the time interval between dose 1 and dose 2 (HR 0.96 per month, 95% CI 0.73 to 1.27 p = 0.788) nor receipt of the mRNA-1273 (versus BNT162b2) vaccine (HR 0.79, 95% CI 0.62 to 1.01, p = 0.060) were significantly associated with reduced infection risk (S6 Table).
SARS-CoV-2 symptoms according to immune status and time period
Participants reported a median of four symptoms during SARS-CoV-2 episodes in the Delta period, and three in the Omicron period (Fig 4). Group H reported fewer symptoms (median of three) than group N (median of four, adjusted rate ratio [aRR] 0.81, 95% CI 0.67 to 0.97, p = 0.026), even after adjusting for multiple covariables. Groups V and I did not report less symptoms compared to group N (S7 Table). Restricting the analysis to vaccinated participants, hybrid immunity (group H versus V, aRR 0.80, 95% CI 0.71 to 0.91, p < 0.001) and receipt of booster vaccination (aRR 0.79, 95% CI 0.71 to 0.88, p < 0.001), were associated with fewer symptoms, whereas having a comorbidity at baseline (aRR 1.17, 95% CI 1.06 to 1.28, p = 0.001) and being infected later during the Omicron period (aRR 1.22 per additional months, 95% CI 1.13 to 1.31, p < 0.001) were associated with more symptoms (S8 Table).
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).
Discussion
In this prospective multicentre study, we observed that participants with hybrid immunity and those receiving booster vaccination reported the lowest risk for COVID-19 during the Delta and Omicron periods, and, when infected during the Omicron period, were less symptomatic than those only vaccinated or previously infected. However, this association with booster vaccination waned over time. Type and timing of baseline mRNA vaccines were not associated with the outcomes.
Hybrid immunity, defined as immunity acquired from previous infection plus at least one vaccination, was shown to be associated with reduced risk of SARS-CoV-2 reinfection compared to previous infection only, for up to 9 months [33]. We confirm findings of this Swedish study, which ended in October 2021 (i.e., before Delta was the predominant variant in Europe including Sweden) [34]. Also, our data are in line with a study from Israel performed mainly during the Delta period showing that persons with hybrid immunity were better protected against breakthrough infection compared to only vaccinated persons [10]. In addition, our findings suggest that hybrid immunity acquired from infections with previous variants not only provides protection against infections by the Delta, but also the Omicron variant, as described in a previous study from Qatar [23]. In contrast to this latter study, which relied on population-level data, we used baseline serology results allowing us to additionally capture previous asymptomatic infections and to adequately assign participants to the respective immune status groups. Furthermore, our study revealed that hybrid immunity was the only immune status associated with less symptoms compared to the group without any preexisting immunity, for both time periods. These findings are in line with results of a laboratory-based study, which showed that antibodies from sera of people with hybrid immunity were able to better neutralize the Omicron variant, compared to antibodies from only vaccinated or infected individuals [35].
When ignoring the booster, we did no longer observe any additional protection of two-dose vaccination in noninfected participants during the Omicron period. This finding adds to data from Qatar, where the effectiveness of two-dose BNT162b2 vaccination against symptomatic Omicron infection was found to be negligible [23]. For the Delta period, we observed a higher risk of (re)infection in twice vaccinated compared to previously infected, nonvaccinated participants. Similarly, in a large retrospective observational study in 124,500 participants, naturally acquired immunity to SARS-CoV-2 conferred stronger protection against infection and symptomatic disease caused by the Delta variant, compared to the BNT162b2 two-dose vaccine-induced immunity [36]. The benefit of previous infection could be explained by the broader immune response elicited by natural infection, with humoral and cellular immune responses not only targeting the spike protein but also other viral antigens. However, in our study, this association was no longer apparent during the Omicron period, where the infection risk of participants with only infection-induced immunity compared to those with vaccine-induced immunity was similar.
The effectiveness of previous infection in preventing reinfection with the Alpha, Beta, and Delta variants of SARS-CoV-2 was around 90% and 60% for Omicron in another study from Qatar [37]. These estimates are higher than in our study, where previous infection was associated with a 75% risk reduction during the Delta, and 25% during the Omicron dominating period. In contrast to Altarawneh and colleagues, we included individuals with previous asymptomatic infection. As the humoral immune response elicited by asymptomatic is weaker compared to symptomatic infection [38], the benefit against reinfections might be lower, which could explain the observed discrepancy.
Previous data have shown that the effectiveness of mRNA-1273 might be superior to BNT162b2, likely because of the slower rise and faster decay of neutralizing antibody titers elicited by BNT162b2 [39,40]. Our study was not designed to assess true vaccine effectiveness. However, when adjusting for receipt of booster vaccine, the risk for breakthrough infection in participants receiving either vaccine was similar, as has also been reported from Qatar [23]; the time interval between first and second vaccine did not impact these results, as has shown previously for the ChAdOx1 vaccine [25].
Our data point towards a benefit of booster vaccination against infection in the Omicron period of approximately 30%, which is below the 47% booster effectiveness reported previously [6]. Also, in a study among US adults with COVID-like illness, the odds ratio for boosted versus nonboosted individuals was 0.16 for Delta and 0.34 for Omicron infections [19], which is in the range of a prospective cohort of frontline workers, where booster mRNA vaccine provided around 90% protection against Delta and 60% against Omicron infection [18]. In the latter study, participants were routinely tested for SARS-CoV-2, resulting in a relevant proportion of asymptomatic infections, which could have overestimated the benefit of the booster vaccination. Another explanation for the lower figures observed in our study is that we collected data over a longer period of Omicron activity (over 2 months), during which the booster effect might have waned [41]. Indeed, most participants in our cohort received their booster vaccination before onset of the Omicron period; at the same time, in a supplementary analysis of our data, the benefit associated with booster vaccination vanished in the late Omicron period.
Nevertheless, both with the Delta and the Omicron variants, mRNA booster lead to strong protection against COVID-19–related hospitalization and death [20,42]. Although these outcomes were not relevant in our context, we observed a reduction of symptoms among boosted versus nonboosted individuals during the Omicron period. However, we did not assess whether this reduction of symptoms led to less work absenteeism or visits to healthcare providers.
The most important strengths of this study are the availability of baseline serology data along with behavioural and exposure variables, the prospective nature, and the coverage of symptoms associated with COVID-19 are. Limitations of our study include that SARS-CoV-2 testing was not mandatory and that results were self-reported. However, we previously showed that self-reported NPS results were highly consistent with documented (for positive NPS) and nondocumented (negative NPS) infections [27]. In addition, we adjusted our analysis for the participants’ testing behaviour. Viral variants were categorized based on the community epidemiology only (predominating viral strain) and not on sequencing results. This potential imprecision could have led to underestimation of the differential impact of viral variant; yet, excluding infections occurring during the overlap period as sensitivity analysis did not significantly change the results. SARS-CoV-2-specific T-cell immunity is also likely relevant, for assessing the risk for (re)infection, particularly of severe infection. However, as we did not sample cells from the blood, we were not able to assess this part of the specific immune response. Our results are insofar not generalizable, as the cohort consisted of a well-defined group of young and healthy HCW with an increased exposure to SARS-CoV-2.
Conclusions
In this real-life study using large-scale serology data, we evaluated SARS-CoV-2 infections during the Delta and Omicron waves in Switzerland and observed that hybrid immunity in HCW—compared to other immune status—was associated with the lowest risk of (re)infection and less symptoms in case of infection. Booster vaccination was associated with a risk reduction and with fewer symptoms of SARS-CoV-2 breakthrough infection, although this benefit seemed to fade during the Omicron period. Thus, our findings might inform healthcare providers and public health authorities in prioritizing SARS-CoV-2 vaccinations.
Supporting information
S3 Table. Sensitivity analyses: Comparison of hazard ratios obtained in Cox models with three independent missing value imputations, without missing value imputation (i.e., complete case analysis), and with exclusion of events occurring during the period of variant overlap between December 6, 2021 and January 3, 2022.
https://doi.org/10.1371/journal.pmed.1004125.s005
(PDF)
S5 Table. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) from multivariable Cox regression regarding risk of SARS-CoV-2 (re)infection; group N (no immunity) excluded and group V (vaccinated) defined as reference group.
Model additionally includes time from preimmunization to serology (i.e., months since last infection or vaccination) compared to the main analysis.
https://doi.org/10.1371/journal.pmed.1004125.s007
(PDF)
S6 Table. Hazard ratios (HR) with 95% confidence intervals (CI) from multivariable Cox regression regarding risk of SARS-CoV-2 infection in the subgroup of those vaccinated but not infected (group V).
Model includes type of vaccine and timing of vaccinations between dose 1 and dose 2.
https://doi.org/10.1371/journal.pmed.1004125.s008
(PDF)
S7 Table. Rate ratio (RR) and 95% confidence intervals (CI) from multivariable Poisson regression regarding number of symptoms reported from SARS-CoV-2 infections during the Delta and Omicron period.
Model includes only infections not preceded by booster or first vaccination.
https://doi.org/10.1371/journal.pmed.1004125.s009
(PDF)
S8 Table. Rate ratio (RR) and 95% confidence intervals (CI) from multivariable Poisson regression regarding number of symptoms reported from SARS-CoV-2 infections during the Omicron period.
Model includes booster vaccine and is therefore restricted to groups V and H.
https://doi.org/10.1371/journal.pmed.1004125.s010
(PDF)
S2 Fig. Flow sheet of participants in the SURPRISE study showing reasons (and respective number of participants) for exclusion from current analysis as well as participants within each immune status including number of subsequently vaccinated individuals, respectively.
https://doi.org/10.1371/journal.pmed.1004125.s012
(PDF)
S3 Fig. Time course of subsequent vaccinations (booster and new vaccinations).
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).
https://doi.org/10.1371/journal.pmed.1004125.s013
(TIFF)
Acknowledgments
The members of the SURPRISE study team are (in alphabetical order): Ulrike Besold, Angela Brucher, Thomas Egger, Andrée Friedl, Fabian Grässli, Sabine Güsewell, Eva Lemmenmeier, Christian R. Kahlert, Joelle Keller, Dorette Meier Kleeb, Philipp Kohler, Stefan P. Kuster, Onicio Leal, Dorette Meier Kleeb, Allison McGeer, J. Carsten Möller, Maja F. Müller, Vaxhid Musa, Manuela Ortner, Philip Rieder, Lorenz Risch, Markus Ruetti, Matthias Schlegel, Hans-Ruedi Schmid, Reto Stocker, Pietro Vernazza, Matthias von Kietzell, Danielle Vuichard-Gysin, and Benedikt Wiggli.
We would like to thank the employees of the participating healthcare institutions who either took part in this study themselves or supported it. Furthermore, we thank the laboratory staff for shipment, handling, and analysis of the blood samples.
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Health
B.C. initiative aims to expand genetic screening for Ashkenazi Jewish people at risk of hereditary cancers
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The final gift Catriona Remocker’s father gave her was discovered by a lab in a vial of his blood.
Dr. Geoffrey Remocker died of Stage IV prostate cancer in 2016, just two weeks after testing confirmed he was a carrier for genetic mutations that increase the likelihood of developing ovarian, breast, prostate and pancreatic cancers.
These hereditary BRCA1 and BRCA2 mutations are ten times more common among both men and women of Ashkenazi Jewish descent, like Remocker and her father, than non-Jewish people.
About one in 40 individuals with Ashkenazi heritage carry the mutations, according to the U.S. Centre for Disease Control, which increase the likelihood of women developing ovarian cancer, for example, from one per cent to 30 per cent before age 70.
Both men and women are at risk, though most people know only of their links to breast and ovarian cancer.
“It’s not guaranteed that you will develop cancer, but there may be a mutation in a gene that is associated with cancer that puts you at the higher risk,” said Dr. Sophie Sun, co-director of B.C. Cancer’s Hereditary Cancer program.
The increased risk is likely because founding members of the Ashkenazi Jewish community, in Central and Eastern Europe, had such mutations and then reproduced in relative isolation.
Catriona Remocker and her mother, Jane Remocker, are working to expand awareness and genetic screening for Ashkenazi Jewish people at higher risks of certain cancers in B.C.
But without a family history of cancer, Remocker says she was “shocked and surprised” to find out her father was a carrier, and later, that she carries the mutation as well.
“We didn’t know that as people with Jewish heritage we were at increased risk,” said Remocker, who co-founded non-profit BRCA in BC with her mother, Jane Remocker.
The Remockers are now teaming up with B.C. Cancer’s Hereditary Cancer program to expand genetic testing for Jewish people in B.C. to save them the same shock and pain.
Ashkenazi Jewish people in B.C. qualify for free genetic testing if they have a history of cancer in their families, Sun said.
But due to genocide during the Holocaust and displacement, many people don’t know they have such heritage or that their risk of certain cancers, among both men and women, are heightened.
An imminent pilot project, largely funded by Vancouver’s Diamond Foundation, will study the prevalence of the BRCA mutations among Ashkenazi Jewish peoples in B.C. and aims to offer free, voluntary genetic testing to everyone with that heritage, regardless of family cancer history.
Early detection of the mutations when one is young and healthy can help avoid invasive treatments if cancer does develop and thereby save lives, said Sun.
“Some of these cancers are potentially preventable,” she said.
Empowerment through early detection
Knowing she carried the gene allowed Remocker, now 39, to qualify for regular scans and take measures to reduce her risk of developing cancer, including a mastectomy to remove her breast tissue before the recommended age of 40.
“I’m a lot more empowered and I have a lot more tools to deal with it and to do something about my risk,” said Remocker. “It was really hard watching my dad go through what he went through and that’s certainly not something I want for myself.”
Sun says people should get as familiar with their family histories as possible, and speak to a doctor or visit the Hereditary Cancer program website to see if they are eligible for free testing.
But raising awareness among the Jewish community in B.C. is difficult, said Remocker. There are only around 35,000 Jewish people in B.C, according to a 2019 estimate from the Jewish Federations of North America, and Remocker says they are more “fragmented” than in other cities with more established Jewish communities and dedicated hospitals.
Remocker hopes spreading the word will ensure others can make the decision to get tested for the mutations without having to lose a loved one.
She said that it was “really important that we start to develop more of a voice for Jewish people in the province around these health issues.”
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Please note that this information is based on personal experience with baby’s food allergies and should not take the place of the advice of a medical professional. If you suspect your child is having an allergic reaction please seek immediate medical attention.
Our First Experience with Baby’s Food Allergies
I wasn’t exactly sure why, but when my daughter Elise hit six months-old and it was time for her to start eating solids, I was extremely nervous to introduce allergens. I put it off month after month until my doctor reminded me that introducing allergens before your child’s first birthday reduces their chances of developing lifelong allergies. I discussed my concerns and she told me that we wouldn’t know unless we tried. Our families didn’t have a history of food allergies, so there was no reason to continue putting it off.
The next day I decided to take our doctor’s advice to start introducing allergens to Elise’s diet. I knew that peanut butter when served on its own was a choking hazard, so I mixed a teaspoon of peanut butter with two teaspoons of her favourite fruit and veggie puree to thin it out. I plopped her in her highchair and decided to go for it. I placed a spoonful of the mixture into her mouth. She made a happy sound and opened her mouth for more. I gave her another spoonful and waited a few minutes. She seemed fine. I was starting to feel like we were out of the woods. She asked for more and as I was filling another spoon with food something in her eyes changed. I examined her face and saw that her cheeks and underneath her chin were more red than usual. Seconds later, hives began forming and spread across her face.
We had just moved into a new home a few months prior, and proximity to a hospital hadn’t been at the top of my “must haves” list. Whether the home was move in ready, had the correct number of bedrooms and more than one bathroom had been my main concerns. At the time, being twenty minutes away from the closest hospital did not seem unreasonable. Sitting there watching the hives and redness spread like a wave over her face I fell deep into mom guilt. Why the hell hadn’t being around the corner from a hospital been at the top of my list? I have children and emergencies can happen at any time. Shouldn’t a hospital have been more important than an extra bathroom?
And why did I decide to give her a top allergen at home? If I had been smarter I would have driven to a hospital and given her the peanut butter there, that way if she reacted I could’ve just run inside and she would have received immediate attention. Stupid! You stupid, horrible mother!
I grabbed my phone with shaking hands and called 911. I had never had to dial for an ambulance or the police before, I had never been in an emergency. The small red hives were now down her neck and continuing underneath her clothes. Elise was screeching and clawing at the itchy bumps all over her body. Her ears were red and swollen now. What was happening? Were the hives in her throat? Was her throat going to close? Was my baby going to die? I could feel the tears running down my face, but I had to keep it together. She was the one dealing with a medical emergency. I needed to do everything I could to get her through it. She was still screaming, but screaming was good. Screaming meant she could still breathe.
The emergency operator picked up the phone, “Hello 911. What’s your emergency?”
“Hi, I gave my daughter peanuts for the first time and she is having a major allergic reaction. I need paramedics.”
The operator told me the fire department and ambulance was on its way. She asked me to describe what was happening and provide our personal information. I held my baby and began packing up in case we were going to the hospital. She told me to remain calm and asked for updates. She stayed on the line until they arrived. The fire department arrived first, with the ambulance five minutes behind them. The paramedics looked my daughter over and hooked her up to a machine to check her oxygen levels. While they were helping her the allergic reaction began to go down. After an hour had passed since her initial reaction they thought that she was stable and went to head out to their next emergency. Before they left they gave Elise a moose stuffed animal that was wearing a paramedics t-shirt and told me that I did the right thing by calling.
I took Elise upstairs, nursed her, and held her close. I closed my eyes and took some deep breaths. I would call the doctor in the morning and find out if she needed an EpiPen and also ask for a referral to an allergist. While I was just beginning to relax, Elise started squirming aggressively in my arms and making unhappy sounds. I looked down and a fresh batch of hives were making their way around the back of her neck. They were moving fast and soon were on her cheeks and even on one of her eyelids. The angry hives stopped looking like small bumps and started to look more like water blisters. The blister-like hives were getting bigger and bigger and began to merge into super-hives.
My daughter didn’t even look like herself anymore. A blister expanded and took over her eye, it was now swollen shut. She unlatched her swollen lips and began screeching again. NO, NO, NO! Please, not again! I was so confused. Could there have been left over peanut residue in her mouth that was rinsed down while she was nursing? Why was a new reaction happening?
I called 911 again. The paramedics were on their way back. When the same paramedics walked through the door they looked surprised at how much bigger Elise’s second reaction was. They examined her again and told me to grab our bags and put her in her car seat, we were going to the hospital. They strapped the car seat to the stretcher and off we went. Elise was
mesmerized by all of the lights and beeping equipment in the ambulance. She pointed at different items and looked over to make sure I was paying close attention to everything that she was showing me. I nodded and gave her the words for as many items as I could. I told her that she was brave and that I loved her. I told her the hospital was going to make her all better and we’d be able to go back home soon. She seemed very uncomfortable, still itching and unable to see out of one eye.
We got to the hospital and checked in. We were given a room in the ER and then it was a revolving door of nurses and the doctor coming in and out to look at Elise and monitor her. They administered an EpiPen and it worked like magic. Immediately the hives began to disappear, the swelling went down and Elise looked at me in wonder.
I could tell she was starting to feel better too because she started to babble more and was no longer scratching at her skin. They gave her oral steroids and other medication. They told us we would have to stay until it had been six hours from her initial reaction because multiple waves of allergic reactions were possible.
I learned that because Eli had eczema, she was more likely to have food allergies. Apparently food allergies, eczema, and asthma often go hand-in-hand. The first allergic reaction tends to be the most mild, and Elise would require an EpiPen to be with her at all times moving forward. The doctor prescribed one EpiPen for daycare and two for home. The doctor sent the referral to an allergist and advised me to keep her away from products containing peanuts.
We would now have to be diligent about checking food labels moving forward. My head swam with all of this information and all I kept thinking was, “food could kill my baby.” I felt helpless. I may be able to protect her at home, but what about all of the places she could be exposed to peanuts outside of the house: restaurants, school, camp, planes, friend’s and family’s homes. I opened my phone and sent a quick email to the daycare letting them know of her diagnosis.
It’s now been six months since Elise’s first allergic reaction. Our allergist works with us to navigate Elise’s allergy and I’ve had time to come to terms with her diagnosis. We’ve had to feed her other allergens to rule them out. She’s also had allergy appointments, blood tests, skin prick tests, as well as her first oral food challenge. We are currently considering oral immunotherapy, a treatment where the patient is given increasing amounts of the food they are allergic to in order to build up tolerance to it. We are hopeful that this treatment could help keep her safer in life moving forward.
I still feel that her allergy is out of our control, but we are careful to avoid peanuts and I am thankful that modern day medicine and treatments exist. Elise and her peanut allergy are a package deal. We love her the way she is and so we will manage her food allergy and continue to protect her.
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The freshness of spring is giving way to the languor of summer. It’s also that time of year when I step up my health and fitness habits, with the help of a wellness weekend getaway. Check out these ten wholesome ways to experience Whistler.
1. Eat well, be well at a new event series
Making its debut the Nourish Spring Series by Cornucopia celebrates the season every weekend in June with farm-to-table fare, farm tours, lavish wellness dinners, healthy brunches and activities to refresh both mind and body. Sit down to a four-course spring harvest tasting menu (Brome Lake duck breast with Pemberton beets, anyone?), brush up on grilling skills with an expert chef, pick up painting pointers on an art picnic or jump into an outdoor Zumba class. Order tickets online at whistler.com/events/spring-cornucopia.
2. Chill at a spa
With more than 12 spa facilities in town, it could be said that Whistler has everyone’s back. Pop into the Whistler Day Spa for a 75-minute stress relief massage using Swedish relaxation techniques or the Taman Sari Royal Heritage Spa for an 80-minute herbal steam massage using pouches filled with Javanese turmeric, ginger and other spices. Have more time? Dip into the hot-cold-and-relaxing thermal journey at the silent Scandinave Spa Whistler, home to open-air pools, cold-plunge baths, a Finnish sauna, Nordic showers and solariums in a tranquil forest setting.
3. Lace up for new guided hikes
Trek past alpine meadows flush with wildflowers on the way to glacier-fed Garibaldi Lake or meander through a fragrant rainforest before taking a dip in Crater Rim’s warm Loggers Lake. These are just a couple of guided hike options from Mountain Skills Academy & Adventures. Prefer to stay close to town? Sign up for the Whistler Alpine Hike and explore the gondola-accessed terrain of Whistler Blackcomb.
4. Embark on an ebike adventure
Sneak in some good clean fun with an ebike rental or guided tour. Explore Whistler’s car-free Valley Trail, a 46-km network of paved paths and boardwalks linking the resort town’s neighbourhoods and lakes, beaches, parks and viewpoints along the way. Go it alone or hop on a full-suspension electric-assist mountain bike with Whistler Eco Tours for a two-hour guided ride. Prefer an old-school ride or want to hit the alpine trails? Comfort cruisers, cross-country and downhill bikes are also on hand.
5. Expand the mind at an Indigenous exhibit
You have until October to view, the Squamish Lil’wat Cultural Centre’s Unceded: A Photographic Journey into Belonging. Shot at striking locales throughout the Sea to Sky Corridor, the exhibit brings together aspects of ancient traditions, modern Indigenous life, and colonization and development. Behold the bear dancer on Blackcomb Mountain, the cultural chief in the Fairmont Chateau Whistler lobby and the Squamish Nation chair standing in the middle of downtown Vancouver’s West Cordova St.
6. Get down, be healthy at a new café
Boogie back in time to the ’70s and ’80s at the new Rockit Coffee in Whistler Creekside. From the speaker-lined wall and vintage phones, radios and ghetto blasters to menu items like Espresso Greatest Hits and Drinks Just Wanna Have Fun, the colourful café exudes a decidedly retro vibe. Pull up a chair and order a nutritious Aero-Smoothie – choose from the Green Day, Bananarama or Strawberry Fields Forever – and pair it with a Veggie Eilish breakfast wrap or Prosciutto Rhapsody sandwich.
7. Check into wellness
Go for the Fairmont Chateau Whistler’s healthful options like daily yoga classes, guided excursions and access to pools, steam rooms, the fitness centre, tennis court and (soon) new pickle ball courts. But stay for the regionally sourced seasonal menus – complemented by the rooftop garden’s bounty from May to October – and no-proof cocktail selection in the Mallard Lounge.
8. Float down a winding river
Canoe, kayak or stand-up paddleboard along the meandering five-km-long River of Golden Dreams. After putting in at Alta Lake, paddle past riverbanks lined with wildflowers, foliage and forest, all the while keeping an eye out for beavers, otters, eagles and bears. Newbie paddlers are advised to go with a guide, as changing water levels can make for tricky steering and mandatory portages.
9. Connect with nature on a new birding trail
Watch for whiskey jacks, Clark’s nutcrackers and, come summer, lots and lots of swallows along the Sea to Sky Bird Trail. The fifth and most recent route to be added to the BC Bird Trail network along the Pacific Flyway, the new trail takes birders to alpine heights (lift ticket required) where they can spot olive-sided flycatchers and various raptors. Then it’s off to Rainbow Park on Alta Lake to spy common yellow throats and merlins.
10. Wake up beside a lake
Perched along the southern tip of Nita Lake in Whistler Creekside, Nita Lake Lodge checks off all the boxes for a dreamy wellness escape. Start with stunning water and valley views from luxe suites, currently undergoing a modern refresh slated to wrap in time for summer. Then there’s the new onsite restaurant, The Den, where plant-based alternatives share space with meat and seafood items on the seasonal menus. Topping off a salubrious stay at Whistler’s only lakeside hotel is an award-winning spa with rooftop hot tubs.
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