ABSTRACT
We estimated vaccine effectiveness (VE) of SARS-CoV-2 Omicron XBB.1.5 vaccination against self-reported infection between 9 October 2023 and 9 January 2024 in 23,895 XBB.1.5 vaccine-eligible adults who had previously received at least one booster. VE was 41% (95%CI:23-55) in 18-59-year-olds and 50% (95%CI:44-56) in 60-85-year-olds. Sequencing data in a subset of infections suggests immune escape of the emerging BA.2.86 (JN.1) variant from recent prior infection (OR:2.6; 95%CI:1.1-6.3) and, although not statistically significant, from XBB.1.5 vaccination (OR:1.6; 95%CI:0.9-2.9).
ABSTRACT
We present early vaccine effectiveness (VE) estimates of the 2023 seasonal COVID-19 vaccination campaign using XBB.1.5 vaccine against COVID-19 hospitalization and ICU admission in previously vaccinated adults [≥]60 years old in the Netherlands. We compared vaccination status of 2050 hospitalizations including 92 ICU admissions with age group-, sex-, region- and date-specific population vaccination coverage between 9 October and 5 December 2023. VE against hospitalization was 70.7% (95% CI: 66.6; 74.3), VE against ICU admission was 73.3% (95% CI: 42.2; 87.6).
Subject(s)
COVID-19ABSTRACT
Background Information on the magnitude and duration of antibody levels after COVID-19 vaccination in different groups may be useful for prioritizing of additional vaccinations. Methods Serum samples were collected every six months in a prospective cohort study among adults in the Netherlands. Geometric mean concentrations (GMCs) of antibodies against the receptor binding domain of the SARS-CoV-2 spike protein were calculated after the primary series, first, and second booster vaccinations. Effects of age (18-59 vs 60-85 years) and medical risk conditions on GMC 2-6 weeks and 21-25 weeks after each vaccination, and on waning during 3-25 weeks after each vaccination, were estimated by linear regression. Results We included 20,816, 16,820 and 5,879 samples collected after primary, first and second booster vaccination, respectively. GMCs at 2-6 and 21-25 weeks after primary series were lower in participants with older age or medical risk conditions. After the first booster, older age was associated with lower GMC at 2-6 weeks, higher GMC at 21-25 weeks, and slower waning. GMCs or waning after the first and second boosters (only 60-85) were not associated with medical risk conditions. Conclusions Since antibody differences by age and medical risk groups have become small with increasing number of doses, other factors such as disease severity rather than antibody levels are useful for prioritization of additional vaccinations.
Subject(s)
COVID-19ABSTRACT
INTRODUCTION: Adverse events (AE) such as pain at injection site or fever are common after COVID-19 vaccination. We aimed to describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations. METHODS: Participants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within two months after COVID-19 vaccination and provided 6-monthly serum samples. Data from May 2021 to November 2022 were included. Logistic regression analyses were performed to investigate determinants of AE after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2 naive participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination. RESULTS: 47,947 AE questionnaires were completed by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention due to AE. AE were reported significantly more frequently by women, younger participants (<60 years), participants with medical risk conditions and Spikevax recipients (versus Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38, 95%CI 1.23-1.54). CONCLUSION: Our study suggests that high pre-vaccination antibody levels induce AE, and that experiencing AE may be a marker for a good antibody response to vaccination.
Subject(s)
COVID-19 , Fever , Pain , Drug-Related Side Effects and Adverse ReactionsABSTRACT
Background: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of non-consenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in the estimation of vaccine effectiveness (VE). Methods: National data were used for the period dominated by the SARS-CoV-2 Delta variant (11 July to 15 November 2021). VE ((1-relative risk)*100%) against COVID-19 hospitalization and ICU admission was estimated for individuals 12-49, 50-69, and [≥]70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iterative data augmentation. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected / corrected relative risk. Results: A total of 8,804 COVID-19 hospitalizations and 1,692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the non-consent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79). Conclusions: VE estimates can be substantially biased with modest non-consent percentages for registration of vaccination. Data on covariate specific non-consent percentages should be available to correct this bias.
Subject(s)
COVID-19ABSTRACT
Background. The Dutch government introduced the CoronaMelder smartphone application for digital contact tracing (DCT) to complement manual contact tracing (MCT) by Public Health Services (PHS) during the 2020-2022 SARS-CoV-2 epidemic. Modelling studies showed great potential but empirical evidence of DCT and MCT impact is scarce. Methods. We determined reasons for testing, and mean exposure-testing intervals by reason for testing, using routine data from PHS Amsterdam (1 December 2020 to 31 May 2021) and data from two SARS-CoV-2 rapid diagnostic test accuracy studies at other PHS sites in the Netherlands (14 December 2020 to 18 June 2021). Throughout the study periods, notification of DCT-identified contacts was via PHS contact-tracers, and self-testing was not yet widely available. Results. The most commonly reported reason for testing was having symptoms. In asymptomatic individuals, it was having been warned by an index case. Only around 2% and 2-5% of all tests took place after DCT or MCT notification, respectively. About 20-36% of those who had received a DCT or MCT notification had symptoms at the time of test request. Test positivity after a DCT notification was significantly lower, and exposure-test intervals after a DCT or MCT notification were longer, than for the above-mentioned other reasons for testing. Conclusions. Our data suggest that the impact of DCT and MCT on the SARS-CoV-2 epidemic in the Netherlands was limited. However, DCT impact might be enlarged if app use coverage is improved, contact-tracers are eliminated from the digital notification process to minimise delays, and DCT is combined with self-testing.
ABSTRACT
We used data of 32,542 prospective cohort study participants who previously received primary and one or two monovalent booster COVID-19 vaccinations. Between 26 September and 19 December 2022, relative effectiveness of bivalent Original/Omicron BA.1 vaccination against self-reported Omicron SARS-CoV-2 infection was 31% in 18-59-year-olds and 14% in 60-85-year-olds. Protection was higher after prior Omicron infection than after bivalent vaccination without prior infection. Although bivalent booster vaccination increases protection against COVID-19 hospitalizations, we found limited added benefit in preventing SARS-CoV-2 infection.
Subject(s)
COVID-19ABSTRACT
Background: Severity of SARS-CoV-2 infection may vary over time. Here, we estimate age-specific risks of hospitalization, ICU admission and death given infection in the Netherlands from February 2020 - June 2021. Methods: A nationwide longitudinal serology study was used to estimate numbers of infections in three epidemic periods (February 2020 - June 2020, July 2020 - February 2021, March 2021 - June 2021). We accounted for reinfections and, as vaccination started in January 2021, breakthrough infections among vaccinated persons. Severity estimates were inferred by combining numbers of infections with aligned numbers of hospitalizations and ICU admissions from a national hospital-based registry, and aligned numbers of deaths based on national excess all-cause mortality estimates. Results: In each period there was a nearly consistent pattern of accelerating, almost exponential, increase in severity of infection with age. The rate of increase with age was highest for death and lowest for hospitalization. In the first period, the overall risk of hospitalization, ICU admission and death were 1.5% (95%-confidence interval [CI] 1.3-1.8%), 0.36% (95%-CI: 0.31-0.42%) and 1.2% (95%-CI: 1.0-1.4), respectively. The risk of hospitalization was higher in the following periods, while the risk of ICU admission remained stable. The risk of death decreased over time, with a substantial drop among [≥]70-years-olds in February 2021 - June 2021. Conclusion: The accelerating increase in severity of SARS-CoV-2 with age remained intact during the first three epidemic periods in the Netherlands. The substantial drop in risk of death among elderly in the third period coincided with the introduction of COVID-19 vaccination.
Subject(s)
COVID-19 , Breakthrough Pain , DeathABSTRACT
Introduction. We aimed to estimate vaccine effectiveness against infection (VE-infection) and infectiousness (VE- infectiousness) in a household setting during Delta and Omicron. Knowing these effects can aid policy makers in deciding which groups to prioritize for vaccination. Methods. Participants with a positive SARS-CoV-2 test were asked about COVID-19 vaccination status and SARS-CoV-2 testing of their household members one month later. VE-infection and VE-infectiousness was estimated using GEE logistic regression adjusting for age and vaccination status, calendar week and household size. Results. 3,409 questionnaires concerning 4,123 household members were included. During the Delta-period, VE-infection of primary series was 47% (95% CI: -27%-78%) and VE-infectiousness of primary series was 70% (95% CI: 28%-87%). During the Omicron-period, VE-infection was -36% (95% CI: -88%-1%) for primary series and -30% (95% CI: -80%-6%) for booster vaccination. The VE-infectiousness was 45% (95% CI: -14%-74%) for primary series and 64% (95% CI: 31%-82%) for booster vaccination. Discussion. Our study shows that COVID-19 vaccination is effective against infection with SARS-CoV-2 Delta and against infectiousness of SARS-CoV-2 Delta and Omicron. Estimation of VE against infection with SARS-CoV-2 Omicron was limited by several factors. Our results support vaccination for those in close contact with vulnerable people to prevent transmission.
Subject(s)
COVID-19 , InfectionsABSTRACT
Introduction - Monitoring of COVID-19 vaccine effectiveness (VE) is needed to inform vaccine policy. We estimated VE of primary vaccination, and first and second booster vaccination, against SARS-CoV-2 infection overall, and in four risk groups defined by age and medical risk condition, in the Delta and Omicron BA.1/BA.2 periods. Methods - VASCO is an ongoing prospective cohort study among vaccinated and unvaccinated Dutch adults. The primary endpoint was a self-reported positive SARS-CoV-2 test during 12 July 2021-6 June 2022. Participants with a prior SARS-CoV-2 infection, based on a positive test or serology, were excluded. We used Cox proportional hazard models with vaccination status as time-varying exposure and adjustment for age, sex, educational level, and medical risk condition. We stratified by Delta and Omicron BA.1/BA.2 periods, risk group, and time since vaccination. Results - 37,170 participants (mean age 57 years) were included. In the Delta period, VE <6 weeks after primary vaccination was 80% (95%CI 69-87) and decreased to 71% (65-77) after 6 months. VE increased to 96% (86-99) shortly after the first booster vaccination. In the Omicron period these estimates were 46% (22-63), 25% (8-39) and 57% (52-62), respectively. VE was 50% (34-62) <6 weeks after a second booster vaccination in participants aged [≥]60 years. For the Omicron period, an interaction term between vaccination status and risk group significantly improved the model (p<0.001), with generally lower VEs for those with a medical risk condition. Conclusions - Our results show the benefit of booster vaccinations against infection, also in risk groups, although the additional protection wanes quite rapidly.
Subject(s)
COVID-19ABSTRACT
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 via ICTRP Search Portal (who.int))
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
We investigate differences in protection from previous infection and/or vaccination against infection with Omicron BA.4/5 or BA.2. We observed a higher percentage of registered previous SARS-CoV-2 infections among 19836 persons infected with Omicron BA.4/5 compared to 7052 persons infected with BA.2 (31.3% vs. 20.0%) between 2 May and 24 July 2022 (adjusted odds ratio (aOR) for testing week, age group and sex: 1.4 (95%CI: 1.3-1.5)). No difference was observed in the distribution of vaccination status between BA.2 and BA.4/5 cases (aOR: 1.1 for primary and booster vaccination). Among reinfections, those newly infected with BA4/5 had a shorter interval between infections and the previous infection was more often caused by BA.1, compared to those newly infected with BA.2 (aOR: 1.9 (1.5-2.6). This suggests immunity induced by BA.1 is less effective against a BA.4/5 infection than against a BA.2 infection.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Background: We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk in non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose. Methods: National registries of causes of death, COVID-19 vaccination and long-term care reimbursements were linked by a unique identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 8 weeks following a first, second or booster dose, adjusting for birth year, sex and country of origin. Results: VE against COVID-19 mortality was >90% for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80% at 7-8 months post-primary series for most groups, and around 60% for elderly receiving a high level of long-term care and for people aged 90+ years. The risk of non-COVID-19 mortality was lower or similar in the 8 weeks following a first booster dose compared to no vaccination, first or second dose, respectively, for all age and long-term care groups. Conclusion: COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was seen at the population level.
Subject(s)
COVID-19 , DeathABSTRACT
Objectives To assess the performances of three commonly used rapid antigen diagnostic tests (Ag-RDTs) used as self-tests in asymptomatic individuals in the Omicron period. Design Cross-sectional diagnostic test accuracy study. Setting Three public health service COVID-19 test sites in the Netherlands. Participants 3,600 asymptomatic individuals aged ≥16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test. Interventions Participants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex (Flowflex), MP Biomedicals (MPBio), or Siemens-Healthineers Clinitest (Clinitest)) to perform unsupervised at home within three hours and blinded to the RT-PCR result. Main Outcome(s) and Measures(s) Diagnostic accuracies (sensitivity, specificity, positive and negative predictive values) of each self-test compared to RT-PCR. Results Overall sensitivities of the three self-tests were 27.5% (95% CI: 21.3-34.3%) for Flowflex, 20.9% (13.9-29.4%) for MPBio, and 25.6% (19.1-33.1%) for Clinitest. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (95% CI: 37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively. No consistent differences were found in sensitivities by COVID-19 vaccination status, having had a prior SARS-CoV-2 infection, gender or age across the three self-tests. Specificities were >99% for all tests in most analyses. Conclusions The sensitivities of three commonly used SARS-CoV-2 Ag-RDTs when used as self-tests in asymptomatic individuals in the Omicron period, were very low. Our findings indicate that Ag-RDT self-testing in asymptomatic individuals may only detect the minority of infections at that point in time and may not be sufficient to prevent the spreading of the virus to other (vulnerable) persons. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield of the self-tests, and individuals should certainly be advised to re-test when symptoms develop. Summary box What is already known on this topic If sufficiently reliable, SARS-CoV-2 self-testing by asymptomatic persons prior to admission in places where groups gather could have a huge public health impact by lowering the reproduction number or keep it below one for longer periods. Current evidence suggests that SARS-CoV-2 rapid antigen diagnostic tests (Ag-RDTs) when used as self-tests by asymptomatic individuals perform suboptimal, but sample sizes of the previous studies were too small to draw robust conclusions, and also empirical data on the accuracy of Ag-RDT self-tests in asymptomatic individuals during the Omicron period are scarce. What this study adds Compared to RT-PCR testing, overall sensitivities of three commercially available SARS-CoV-2 Ag-RDTs when used as self-tests by asymptomatic individuals (primary analysis population of non-confirmatory testers; n= 3600, 87% of full analysis population) in the Omicron period, were very low: 27.5% (95% CI: 21.3-34.3%) for the Acon Flowflex test, 20.9% (13.9-29.4%) for the MP Biomedicals test, and 25.6% (19.1-33.1%) for the Siemens Healthineers Clinitest Ag-RDT, which increased to 48.3% (95% CI: 37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively, when applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL). Our findings indicate that Ag-RDT self-testing in asymptomatic individuals may only detect the minority of infections at that point in time and may not be sufficient to prevent the spreading of the virus to other (vulnerable) persons. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield of the self-tests, and individuals should certainly be advised to re-test when symptoms develop.
Subject(s)
COVID-19ABSTRACT
Purpose - VAccine Study COvid-19 (VASCO) is a cohort study with 5-year follow-up that was initiated when COVID-19 vaccination was introduced in the Netherlands. The primary objective is to estimate real-world vaccine effectiveness (VE) of COVID-19 vaccines against SARS-CoV-2 infection in the Netherlands, overall and in four subpopulations defined by age and medical risk. Participants - The cohort consists of 45,547 community-dwelling participants aged 18-85 years who were included irrespective of their COVID-19 vaccination status or intention to get vaccinated. A medical risk condition is present in 4,289 (19.8%) of 21,679 18-59 year-olds and in 9,135 (38.3%) of 23,821 60-85 year-olds. After one year of follow-up, 5,502 participants had dropped out of the study. At inclusion, and several times after inclusion, participants are asked to take a self-collected fingerprick blood sample in which nucleoprotein and spike protein receptor binding domain-specific antibody titers are assessed. Participants are also asked to complete monthly digital questionnaires in the first year, and 3-monthly in years 2-5, including questions on sociodemographic factors, health status, COVID-19 vaccination, SARS-CoV-2-related symptoms and testing results, and behavioral responses to COVID-19 measures. Findings to date - VASCO data has been used to describe VE against SARS-CoV-2 infection of primary vaccination, first and second booster and bivalent boosters, the impact of hybrid immunity on SARS-CoV-2 infection and VE against infectiousness. Furthermore, data was used to describe antibody response following vaccination and breakthrough infections and to investigate the relation between antibody response and reactogenicity. Future plans - VASCO will be able to contribute to policy decision-making regarding future COVID-19 vaccination. Furthermore, VASCO provides an infrastructure to conduct further studies and to anticipate on changing vaccination campaigns and testing policy, and new virus variants. Registration - VASCO is registered in the online Dutch clinical trials register (trialsearch.who.int) with registration number NL9279.
Subject(s)
COVID-19 , Breakthrough PainABSTRACT
BackgroundPerformances of rapid antigen diagnostic tests (Ag-RDTs) with nasal self-sampling, and oropharyngeal plus nasal (OP-N) self-sampling, in the Omicron period are unknown. MethodsProspective diagnostic accuracy study among 6,497 symptomatic individuals aged >16 years presenting for SARS-CoV-2 testing at three test-sites. Participants were sampled for RT-PCR (reference test) and received one Ag-RDT to perform unsupervised with either nasal self-sampling (during the emergence of Omicron, and after Omicron share was >90%, phase-1) or with OP-N self-sampling (in a subsequent phase-2; Omicron share >99%). The evaluated tests were Acon Flowflex (Flowflex; phase-1 only), MP Biomedicals (MPBio), and Siemens-Healthineers Clinitest (Clinitest). FindingsDuring phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for Flowflex, 69.9% (65.1-74.4%) for MPBio, and 70.2% (65.6-74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points, respectively, when transitioning from 29% to >95% Omicron. During phase-2, 53% of MPBio, and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. Comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively). InterpretatioSensitivities of three Ag-RDTs with nasal self-sampling decreased during Omicron emergence but was only statistically significant for Clinitest. Sensitivities were substantially influenced by the proportion of confirmatory testers. Addition of oropharyngeal to nasal self-sampling improved sensitivities of MPBio and Clinitest. FundingDutch Ministry of Health, Welfare, and Sport. Research into contextO_ST_ABSEvidence before this studyC_ST_ABSSARS-CoV-2 rapid antigen diagnostic tests (Ag-RDTs) require no or minimal equipment, provide a result within 15-30 minutes, and can be used in a range of settings including for self-testing at home. Self-testing may potentially lower the threshold to testing and allows individuals to obtain a test result quickly and at their own convenience, which could support the early detection of infectious cases and reduce community transmission. Real world evidence on the performance of unsupervised nasal and oropharyngeal plus nasal (OP-N) self-sampling in the Omicron variant period is needed to accurately inform end-users and policymakers. Therefore, we conducted a large prospective diagnostic accuracy study of three commercially available Ag-RDTs with self-sampling (the Acon Flowflex test, the MP Biomedicals test, and the Siemens-Healthineers Clinitest) during and after the emergence of Omicron using RT-PCR as the reference standard. Our aims were to evaluate whether the accuracies of Ag-RDTs with nasal self-sampling changed over time with the emergence of Omicron; and to determine whether addition of oropharyngeal to nasal self-sampling with the same swab yielded higher diagnostic accuracies. What this study addsThe large comprehensive study was conducted in almost 6,500 participants with symptoms when presenting for routine SARS-CoV-2 testing at three public health service COVID-19 test-sites in the Netherlands. During the study, conducted between 21 December 2021 and 10 February 2022, the percentage of the Omicron variant in samples from the national SARS-CoV-2 pathogen surveillance increased from 29% in the first week to 99% in the last week of the study. The period during which the Omicron variant was dominant was divided into a nasal sampling phase (phase-1; Omicron present in >90% of surveillance samples) and an OP-N sampling phase (phase-2; Omicron share was >99%). In phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants visited the test-site because of a positive self-test (confirmatory testers). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for the Flowflex, 69.9% (65.1-74.4%) for the MPBio, and 70.2% (65.6-74.5%) for the Clinitest Ag-RDT. Sensitivities were 94%, 84%, and 86%, respectively, for confirmatory testers, and 52%, 52%, and 50%, respectively, for those who had other reasons for getting tested. Sensitivities were 87.0% (79.7-92.4%), 83.1% (72.9-90.7%), and 80.0% (51.9-95.7%), respectively, in the first week, and decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points in the final week of the study. In Phase-2, 53% of MPBio and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. When comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%). Implications of all the available evidenceThe sensitivities of three commercially available Ag-RDTs performed with nasal self-sampling decreased during the emergence of Omicron, but this trend was only statistically significant for Clinitest. Addition of oropharyngeal to nasal self-sampling improved the sensitivity of the MPBio and Clinitest, most notably in individuals who visited the test-site for other reasons than to confirm a positive self-test. Based on these findings, the manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal sampling, and other manufacturers may consider evaluating this as well.
Subject(s)
COVID-19ABSTRACT
Given the emergence of the SARS-CoV-2 Omicron BA.1 variant and the roll-out of booster COVID-19 vaccination, evidence is needed on protection conferred by primary vaccination, booster vaccination and previous SARS-CoV-2 infection against Omicron BA.1 compared with Delta infection. We employed a test-negative design and used multinomial logistic regression on data from community PCR testing in the Netherlands, from 22 November 2021 to 19 January 2022. S-gene target failure (SGTF) was used as proxy for Omicron BA.1 infection versus Delta. A total of 528,488 tests were included, of which 38,975 SGTF and 41,245 non-SGTF infections. Protection from primary vaccination was 25% (95% confidence interval (CI): 21-29) and from previous infection 33% (95% CI: 31-35) against Omicron BA.1 infection. Protection against Delta infection was higher with 76% (95% CI: 75-76) for primary vaccination and 78% (95% CI: 76-80) for previous infection. Higher protection was observed in individuals with both primary vaccination and earlier infection compared with either one. Waning of vaccine- or infection-induced protection over time was observed against both variants. Booster vaccination considerably increased vaccine effectiveness against Omicron BA.1 to 76% (95% CI: 72-79) and 68% (95% CI: 67-69) with and without previous infection, respectively. Primary vaccination with current COVID-19 vaccines and pre-Omicron SARS-CoV-2 infections offer low protection against Omicron BA.1 infection. Booster vaccination considerably increases protection against Omicron BA.1, although protection remains lower than against Delta.
Subject(s)
COVID-19 , Severe Acute Respiratory Syndrome , Hepatitis DABSTRACT
The SARS-CoV-2 Omicron variant has a growth advantage over the Delta variant, due to higher transmissibility, immune evasion, or a shorter serial interval. Using S-gene target failure (SGTF) as indication for Omicron, we identify 220 SGTF and 869 non-SGTF serial intervals in the same week. Within households, we find a mean serial interval of 3.4 days for SGTF and 3.9 days for non-SGTF cases. This suggests that the growth advantage of Omicron is partly due to a shorter serial interval.
ABSTRACT
Infections by the Omicron SARS-CoV-2 variant are rapidly increasing worldwide. Among 70,983 infected individuals (age [≥] 12 years), we observed an increased risk of S-gene target failure, predictive of the Omicron variant, in fully vaccinated (odds ratio: 5.0; 95% confidence interval: 4.0-6.1) and previously infected individuals (OR: 4.9: 95% CI: 3.1-7.7) compared with infected naive individuals. This suggests a substantial decrease in protection from vaccine- or infection-induced immunity against SARS-CoV-2 infections caused by the Omicron variant compared with the Delta variant.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
BackgroundSARS-CoV-2 self-tests may lower the threshold of testing and produce a result quickly. This could support the early detection of infectious cases and reduce further community transmission. However, the diagnostic accuracy of (unsupervised) self-testing with rapid antigen diagnostic tests (Ag-RDTs) is mostly unknown. We therefore conducted a large-scale head-to-head comparison of the diagnostic accuracy of a self-performed SARS-CoV-2 saliva and nasal Ag-RDT, each compared to a molecular reference test, in the general population in the Netherlands. MethodsIn this cross-sectional study we consecutively included individuals aged 16 years and older presenting for SARS-CoV-2 testing at three Dutch public health service test sites irrespective of their indication for testing, vaccination status, and symptomatology. Participants were sampled for molecular testing at the test site and received two self-tests (the Hangzhou AllTest saliva self-test and the SD Biosensor nasal self-test by Roche Diagnostics) to perform at home within a few hours without knowledge of their molecular test result. Information on presence and type of symptoms, user experiences, and results of both self-tests were collected via an online questionnaire. For each self-test, sensitivity, specificity, positive and negative predictive values were determined with molecular testing as reference standard. FindingsThe SARS-CoV-2 molecular reference test positivity rate was 6.5% in the 2,819 participants. Overall sensitivities with 95% confidence intervals were 46.7% (85/182; 39.3%-54.2%) for the saliva Ag-RDT, and 68.9% (124/180; 61.6%-75.6%) for the nasal Ag-RDT. With a viral load cut-off ([≥]5.2 log10 SARS-CoV-2 E-gene copies/mL) as a proxy of infectiousness, sensitivities increased to 54.9% (78/142; 46.4%-63.3%) for the saliva Ag-RDT and 83.9% (120/143; 76.9%-89.5%) for the nasal Ag-RDT. For the nasal Ag-RDT, sensitivities were 78.5% [71.1%-84.8%] and 22.6% [9.6%-41.1%] in those with and without symptoms at the time of sampling, which increased to 90.4% (113/125; 83.8%-94.9%) and 38.9% (7/18; 17.3%-64.3%) after applying the viral load cut-off. In those with and without prior confirmed SARS-CoV-2, sensitivities were 36.8% [19/372; 16.3%-61.6%] and 72.7% [161/2437; 65.1%-79.4%] for the nasal Ag-RDT, which increased to 100% (7/7; 59.0%-100%) and 83.1% (113/126; 75.7%-89.0%) after applying the viral load cut-off. The diagnostic accuracy of the nasal Ag-RDT did not differ by COVID-19 vaccination status, sex, and age. Specificities were >99%, positive predictive values >70% and negative predictive values >95%, for the saliva Ag-RDT, and >99%, >90%, and >95% for the nasal Ag-RDT, respectively, in most analyses. Interpreting the results was considered (very) easy for both self-tests. InterpretationThe Hangzhou AllTest self-performed saliva Ag-RDT is not reliable for SARS-CoV-2 infection detection overall nor in the studied subgroups. The SD Biosensor self-performed nasal Ag-RDT had high sensitivity in individuals with symptoms and in those without a prior SARS-CoV-2 infection. The overall accuracy in individuals with symptoms was comparable to that found in previous studies with professional sampling for this Ag-RDT. The extremely low sensitivity of the nasal Ag-RDT in asymptomatic individuals and in individuals who had had a prior SARS-CoV-2 infection is an important finding and warrants further investigation. FundingDutch Ministry of Health, Welfare, and Sport.