Test-negative Study Research Articles

COVID-19 vaccine effectiveness and hybrid immunity in the respiratory season of 2022-23 in Hungary

Abstract Background There has been an increase in COVID-19 vaccine hesitancy among the general population, accompanied by a decline in confidence that vaccines provide adequate protection. We estimated the effectiveness of the COVID-19 vaccines (CVE) and hybrid immunity against medically attended COVID-19 during the 2022-2023 respiratory season in Hungary. Methods We conducted a test-negative design study involving 68 GPs. Patients aged ≥18 years presenting with acute respiratory infection were swabbed. Cases and controls were patients testing positive and negative for SARS-CoV-2 by RT-PCR, respectively. Exposure was defined as having received at least one COVID-19 booster dose, taking into account the time since the last vaccination. CVE was estimated using logistic regression, adjusted for symptom onset date, age, chronic condition and sex. Results We included 247 cases and 1073 controls in the analysis. 196 samples were sequenced, and Omicron BA.5, BQ.1 and XBB.1 were the most frequent sub-variants. The CVE was 52.9% (95% CI: 15.2-73.9%), and 72.3% (95% CI: 32.0-88.7%) in the 18-59, and 60+-year-old population who received the final dose within the past year, respectively. Self-reported COVID-19 in the previous 60-365 days did not confer protection against reinfection, however, when combined with booster vaccination, it reduced the risk of COVID-19 by 63.0% (95% CI: −28.0-89.3%) and 87.6% (95% CI: 26.4-97.9%) among the 18-59 and 60+ age groups, respectively. Conclusions Booster vaccination within one year after the last dose confers significant protection against symptomatic infection, particularly among the elderly. Those who have previously been infected with SARS-CoV-2 may also benefit from booster vaccinations. Key messages • COVID-19 booster campaigns must be intensified, focusing mainly on the elderly. • Providing clear guidance on the timing and target groups of vaccination and emphasising the benefits of vaccination can help to achieve higher coverage.

Update to: Study Pre-protocol for "BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study".

In 2021 we launched the BronchStart study, which collected information on 17,899 presentations in children with serious respiratory tract infections following the release of lockdown restrictions. Our study informed the Joint Committee on Vaccination and Immunisation's decision to recommend the introduction maternal respiratory syncytial virus (RSV) vaccination, which was introduced in the United Kingdom in August/September 2024. We modified our original protocol to conduct a United Kingdom-wide assessment of maternal vaccination against RSV. We will conduct a multi-centre study, utilising the PERUKI network used in the original BronchStart study, to assess the effectiveness of maternal vaccination using a test-negative study design. We will gather detailed clinical information on children admitted with bronchiolitis in the post-RSV vaccination era, and understand possible reasons for incomplete vaccine uptake.

A tentative exploration for the association between influenza virus infection and SARS-CoV-2 infection in Shihezi, China: A test-negative study

The outbreak of respiratory diseases, such as COVID-19 and influenza, has drawn global attention. However, it remains unclear whether the risk of influenza A infection may be affected by the history of SARS-CoV-2 infection. In this study, we conducted a test-negative case-control study, and utilized a logistic regression model to analyze the relationship between SARS-CoV-2 and influenza A infections. Among 258 eligible patient samples with influenza-like illness (ILI), we did not detect a statistically significant association between the history of SARS-CoV-2 infection and the risk of influenza A infection. These findings might indicate that antibodies against COVID-19 acquired through vaccination or natural immunity have not protected against influenza.

Elevated body mass index is not significantly associated with reduced influenza vaccine effectiveness

Elevated body mass index (BMI) has been linked to severe influenza illness and impaired vaccine immunogenicity, but the relationship between BMI and clinical vaccine effectiveness (VE) is less well described. This secondary analysis of data from a test-negative study of outpatients with acute respiratory illness assessed BMI and VE against medically attended, PCR-confirmed influenza over seven seasons (2011–12 through 2017–18). Vaccination status was determined from electronic medical records (EMR) and self-report; BMI was estimated from EMR-documented height and weight categorized for adults as obesity (≥ 30 kg/m2), overweight (25–29 kg/m2), or normal and for children based on standardized z-scales. Current season VE by virus type/subtype was estimated separately for adults and children. Pooled VE for all seasons was calculated as 1—adjusted odds ratios from logistic regression with an interaction term for BMI and vaccination. Among 28,089 adults and 12,380 children, BMI category was not significantly associated with VE against outpatient influenza for any type/subtype. Adjusted VE against A/H3N2, A/H1N1pdm09, and B in adults ranged from 16–31, 46–54, and 44–57%, and in children from 29–34, 57–65, and 50–55%, respectively, across the BMI categories. Elevated BMI was not associated with reduced VE against laboratory confirmed, outpatient influenza illness.

Population-Based Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza Infection in Southern China, 2023-2024 Season.

In China, the 2022-2023 influenza season began earlier and was characterized by higher levels of influenza activity and co-circulation of various respiratory pathogens compared with seasons before the coronavirus disease 2019 (COVID-19) pandemic. Timely and precise estimates of influenza vaccine effectiveness (IVE) against infections can be used to guide public health measures. A test-negative study was conducted to estimate IVE against laboratory-confirmed influenza using data from the CHinese Electronic health Records Research in Yinzhou (CHERRY) study that prospectively integrated laboratory, vaccination, and health administrative data in Yinzhou, southern China. We included patients who presented influenza-like illness and received nucleic acid tests and/or antigen tests between October 2023 and March 2024. Estimates of IVE were adjusted for age, gender, month of specimen submitted, chronic comorbidities, and hospitalization status. A total of 205 028 participants, including 96 298 influenza cases (7.6% vaccinated) and 108 730 influenza-negative controls (13.4% vaccinated), were eligible for this analysis. The estimates of IVE were 49.4% (95% CI, 47.8%-50.9%), 41.9% (95% CI, 39.8%-44.0%), and 59.9% (95% CI, 57.9%-61.9%) against overall influenza, influenza A, and influenza B, respectively. A lower IVE was observed for individuals aged 7-17 years (38.6%), vs 45.8% for 6 months-6 years, 46.7% for 18-64 years, and 46.1% for ≥65 years. Vaccination reduced the risk of infection by 44.4% among patients with chronic comorbidities. IVEs varied by epidemic weeks with the changes in influenza activity levels and the switch of dominant influenza strains. Influenza vaccination in the 2023-2024 season was protective against infection for the entire population.

Potential Biases in Test-Negative Design Studies of COVID-19 Vaccine Effectiveness Arising from the Inclusion of Asymptomatic Individuals.

The test-negative design (TND) is a popular method for evaluating vaccine effectiveness (VE). A "classical" TND study includes symptomatic individuals tested for the disease targeted by the vaccine to estimate VE against symptomatic infection. However, recent applications of the TND have attempted to estimate VE against infection by including all tested individuals, regardless of their symptoms. In this article, we use directed acyclic graphs and simulations to investigate potential biases in TND studies of COVID-19 VE arising from the use of this "alternative" approach, particularly when applied during periods of widespread testing. We show that the inclusion of asymptomatic individuals can potentially lead to collider stratification bias, uncontrolled confounding by health and healthcare-seeking behaviors (HSBs), and differential outcome misclassification. While our focus is on the COVID-19 setting, the issues discussed here may also be relevant in the context of other infectious diseases. This may be particularly true in scenarios where there is either a high baseline prevalence of infection, a strong correlation between HSBs and vaccination, different testing practices for vaccinated and unvaccinated individuals, or settings where both the vaccine under study attenuates symptoms of infection and diagnostic accuracy is modified by the presence of symptoms.

Effectiveness of rVSV-ZEBOV vaccination during the 2018-20 Ebola virus disease epidemic in the Democratic Republic of the Congo: a retrospective test-negative study.

The recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only WHO prequalified vaccine recommended for use to respond to outbreaks of Ebola virus (species Zaire ebolavirus) by WHO's Strategic Advisory Group of Experts on Immunization. Despite the vaccine's widespread use during several outbreaks, no real-world effectiveness estimates are currently available in the literature. We conducted a retrospective test-negative analysis to estimate effectiveness of rVSV-ZEBOV vaccination against Ebola virus disease during the 2018-20 epidemic in the Democratic Republic of the Congo, using data on suspected Ebola virus disease cases collected from Ebola treatment centres. Those eligible for inclusion had an available Ebola virus RT-PCR result, available key data, were eligible for vaccination during the outbreak, and had symptom onset aligning with the period in which a ring-vaccination protocol was in use. After imputing missing data, each individual confirmed by RT-PCR to be Ebola virus disease-positive (defined as a case) was matched to one individual negative for Ebola virus disease (control) by sex, age, health zone, and month of symptom onset. Effectiveness was estimated from the odds ratio of being vaccinated (≥10 days before symptom onset) versus being unvaccinated among cases and controls, after adjusting for the matching factors. The imputation, matching and effectiveness estimation, was repeated 500 times. 1273 (4·8%) of 26 438 eligible individuals were positive for Ebola virus disease (cases) and 25 165 (95·2%) were negative (controls). 40 (3·1%) cases and 1271 (5·1%) controls were reported as being vaccinated at least 10 days before symptom onset. After selecting individuals who reported exposure to an individual with Ebola virus disease within the 21 days before symptom onset and matching, the analysis datasets comprised a median of 309 cases and 309 controls. 10 days or more after vaccination, the effectiveness of rVSV-ZEBOV against Ebola virus disease was estimated to be 84% (95% credible interval 70-92). This analysis is the first to provide estimates of the real-world effectiveness of the rVSV-ZEBOV vaccine against Ebola virus disease, amid the widespread use of the vaccine during a large Ebola virus disease outbreak. Our findings confirm that rVSV-ZEBOV is highly protective against Ebola virus disease and support its use during outbreaks, even in challenging contexts such as in the eastern Democratic Republic of the Congo. Médecins Sans Frontières. For the French translation of the abstract see Supplementary Materials section.

Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5–11 years of age in Brazil: A prospective test-negative design study

ObjectiveTo estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5–11 years of age. MethodsThis prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5–11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. ResultsA total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). ConclusionIn this study with children 5–11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. Trial registration numberClinicalTrials.gov number, NCT05403307 (https://classic.clinicaltrials.gov/ct2/show/NCT05403307)

Relative vaccine effectiveness of MF59-adjuvanted vs high-dose trivalent inactivated influenza vaccines for prevention of test-confirmed influenza hospitalizations during the 2017–2020 influenza seasons

ObjectivesThis study evaluated relative vaccine effectiveness (rVE) of MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) vs high-dose trivalent inactivated influenza vaccine (HD-TIV) for prevention of test-confirmed influenza emergency department visits and/or inpatient admissions (“ED/IP”) and for IP admissions alone pooled across the 2017–2020 influenza seasons. Exploratory individual season analyses were also performed. MethodsThis retrospective test-negative design study included United States (US) adults age ≥65 years vaccinated with aTIV or HD-TIV who presented to an ED or IP setting with acute respiratory or febrile illness during the 2017–2020 influenza seasons. Test-positive cases and test-negative controls were grouped by vaccine received. The rVE of aTIV vs HD-TIV was evaluated using a combination of inverse probability of treatment weighting and logistic regression to adjust for potential confounders. ResultsPooled analyses over the three seasons found no significant differences in the rVE of aTIV vs HD-TIV for prevention of test-confirmed influenza ED/IP (−2.5% [−19.6, 12.2]) visits and admissions or IP admissions alone (−1.6% [−22.5, 15.7]). The exploratory individual season analyses also showed no significant differences. ConclusionsEvidence from the 2017–2020 influenza seasons indicates aTIV and HD-TIV are comparable for prevention of test-confirmed influenza ED/IP visits in US adults age ≥65 years.

Prior infections and effectiveness of SARS-CoV-2 vaccine in test-negative studies: A systematic review and meta-analysis.

Prior infection with SARS-CoV-2 can provide protection against infection and severe COVID-19. We aimed to determine the impact of pre-existing immunity on the vaccine effectiveness (VE) estimates. We systematically reviewed and meta-analysed 66 test-negative design (TND) studies that examined VE against infection or severe disease (hospitalization, ICU admission, or death) for primary vaccination series. Pooled VE among studies that included people with prior COVID-19 infection was lower against infection (pooled VE: 77%; 95% confidence interval (CI): 72%, 81%) and severe disease (pooled VE: 86%; 95% CI: 83%, 89%), compared with studies that excluded people with prior COVID-19 infection (pooled VE against infection: 87%; 95% CI: 85%, 89%; pooled VE against severe disease: 93%; 95% CI: 91%, 95%). There was a negative correlation between VE estimates against infection and severe disease, and the cumulative incidence of cases before the start of the study or incidence rates during the study period. We found clear empirical evidence that higher levels of pre-existing immunity were associated with lower VE estimates. Prior infections should be treated as both a confounder and effect modificatory when the policies target the whole population or stratified by infection history, respectively.

Effectiveness of COVID-19 vaccines administered in the 2023 autumnal campaigns in Europe: Results from the VEBIS primary care test-negative design study, September 2023–January 2024

In autumn 2023, European vaccination campaigns predominantly administered XBB.1.5 vaccine. In a European multicentre study, we estimated 2023 COVID-19 vaccine effectiveness (VE) against laboratory-confirmed symptomatic infection at primary care level between September 2023 and January 2024. Using a test-negative case–control design, we estimated VE in the target group for COVID-19 vaccination overall and by time since vaccination. We included 1057 cases and 4397 controls. Vaccine effectiveness was 40 % (95 % CI: 26–53 %) overall, 48 % (95 % CI: 31–61 %) among those vaccinated < 6 weeks of onset and 29 % (95 % CI: 3–49 %) at 6–14 weeks. Our results suggest that COVID-19 vaccines administered to target groups during the autumn 2023 campaigns showed clinically significant effectiveness against laboratory-confirmed, medically attended symptomatic SARS-CoV-2 infection in the 3 months following vaccination. A longer study period will allow for further variant-specific COVID-19 VE estimates, better understanding decline in VE and informing booster administration policies.

Pneumococcal vaccination effectiveness (PCV13 and PPSV23) in individuals with and without reduced kidney function: a test-negative design study.

Streptococcus pneumoniae vaccination effectiveness (VE) in individuals with reduced kidney function is unknown. We estimated pneumococcal conjugate vaccine (PCV13), pneumococcal polysaccharide vaccine (PPSV23), and combined PCV13 and PPSV23 effectiveness against pneumococcal disease in individuals with and without reduced estimated glomerular filtration rate (eGFR). All eligible individuals (case and controls) were adults (aged ≥18 years) hospitalized within the Geisinger Health System and required to have S. pneumoniae urinary antigen testing (i.e. test-negative design). Vaccination records were obtained from the electronic health record and statewide vaccination registry. After controlling for the probability of receiving a pneumococcal vaccine, we used multivariable logistic regression models to estimate the odds ratios (ORs) of vaccination between those who did and did not meet the S. pneumoniae case definition. VE was calculated as (1-OR)×100%. There were 180 cases and 3889 controls (mean age 69 years, female 48%, white 97%, mean eGFR 71mL/min/1.73m2). The adjusted population PCV13 VE was 39% (95% CI 13%-58%), and combination PCV13 and PPSV23 was 39% (95% CI 12%-58%). PPSV23 VE was -3.7% (95% CI -57% to 32%). Stratified by eGFR, adjusted PCV13 VE was consistent in eGFR ≥60 [VE 38% (95% CI 2.9%-61%)] and 30-59 [VE 61% (95% CI 24%-80%)] without significant interaction. VE was not calculable for eGFR <30 due to small sample size. PCV13 vaccination was associated with reduced risk of S. pneumoniae hospitalization in individuals with a reduced eGFR (30-59mL/min/1.73m2).

Vaccine Effectiveness against GP-Attended Symptomatic COVID-19 and Hybrid Immunity among Adults in Hungary during the 2022-2023 Respiratory Season Dominated by Different SARS-CoV-2 Omicron Subvariants.

A test-negative study was conducted during the 2022-2023 respiratory season at the primary care level to determine the effectiveness of at least one COVID-19 booster dose in preventing medically attended symptomatic RT-PCR-confirmed SARS-CoV-2 infection in adults. Unvaccinated patients were used as a reference group. A total of 247 cases and 1073 controls were included in the analysis. CVE was 56.8% (95% CI: 11.9-78.8%) in the population aged 60 years and older and 2.3% (95% CI: -50.0-36.3%) in the younger adults against COVID-19 caused by Omicron subvariants, mainly BA.5, BQ.1, and XBB.1. Self-reported COVID-19 in the 60-365 days prior to the current illness did not confer protection against reinfection without vaccination, but together with booster vaccination, it reduced the risk of COVID-19 by 63.0% (95% CI: -28.0-89.3%) and 87.6% (95% CI: 26.4-97.9%) among the 18-59 and 60+ age groups, respectively. CVE against COVID-19 was moderately high in the 60+ age groups. Because of the benefit of hybrid immunity, persons with previous SARS-CoV-2 infection should still be considered for vaccination campaigns.

Assessing the Burden of Respiratory Syncytial Virus-related Bronchiolitis in Primary Care and at 15-Day and 6-Month Follow-up Before Prophylaxis in France: A Test-negative Study.

To assess the burden of respiratory syncytial virus (RSV)-related bronchiolitis in primary care and at 15 days and 6 months after a primary care visit. In this test-negative study, children <2 years old with a first episode of bronchiolitis were prospectively enrolled by 45 ambulatory pediatricians in France from February 2021 to April 2023. RSV was assessed with a rapid antigen detection test. The burden of the disease was assessed with a questionnaire, including quality of life (PedsQL 1.0 Infant Scales), at 15-day and 6-month follow-up. Children with a positive RSV test result (RSV+) were compared to those with a negative test result (RSV-). Among the 1591 children enrolled, 750 (47.1%) were RSV+. At 15 days follow-up (data availability: 69%), as compared with RSV- children, RSV+ children more frequently had fever (20.5% vs. 13.7%, P = 0.004) and decreased food intake (27.0% vs. 17.4%, P < 0.001) during the last 3 days. They had higher rates of hospitalization (11.8% vs. 5.8%, P < 0.001), childcare absenteeism (83.5% vs. 66.1%, P < 0.001) and parents who had to stop working to care for them (59.1% vs. 41.0%, P < 0.001) as well as lower quality of life (median PedsQL score 76.2 vs. 78.4, P = 0.03). At 6 months (data availability: 48.5%), the 2 groups did not differ in proportion of medical attendance, hospitalization, antibiotic treatment or quality of life. RSV+ children experienced much more severe disease and follow-up family and societal burden than RSV- children. These data may be used as baseline data as RSV prophylaxis is about to be implemented.

Effectiveness and durability of mRNA-1273 BA.4/BA.5 bivalent vaccine (mRNA-1273.222) against SARS-CoV-2 BA.4/BA.5 and XBB sublineages

ABSTRACT Emerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received any COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases (September 1, 2022 to June 30, 2023), were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to ≥2 or 0 doses of original monovalent vaccine, respectively. The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14–60 days and 121–180 days was 52.7% (46.9–57.8%) and 35.5% (−2.8–59.5%) for infection, and 59.3% (49.7–67.0%) and 33.2% (−28.2–68.0%) for Emergency Department/Urgent Care (ED/UC) encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9–85.1%) and 52.0% (−1.2–77.3%) at 14–60 days and 61–120 days, respectively. rVE against XBB at 14–60 days and 121–180 days was 48.8% (33.4–60.7%) and −3.9% (−18.1–11.3%) for infection, 70.7% (52.4–82.0%) and 15.7% (−6.0–33.2%) for ED/UC encounters, and 87.9% (43.8–97.4%) and 57.1% (17.0–77.8%) for hospitalization. VE and subgroup analyses (age, immunocompromised status, previous SARS-CoV-2 infection) results were similar to rVE analyses. rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic revaccination with vaccines targeting emerging variants may be important in reducing COVID-19 morbidity and mortality.

Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis

ObjectiveTo assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes.DesignSystematic review and meta-analysis.Data sourcesMajor databases between December 2019 and...

Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021-June 2022.

We assessed associations between binding antibody (bAb) concentration <5 days of symptom onset and testing positive for COVID-19 among patients in a test-negative study. From October 2021─June 2022, study sites in seven states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent change in odds of COVID-19 by increasing anti-RBD bAb was estimated using logistic regression as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. Out of 2,018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb were lower among COVID-19 cases than SARS-CoV-2 test-negative patients during both the Delta-predominant (112 vs. 498 BAU/mL) and Omicron-predominant (823 vs. 1,189 BAU/mL) periods. Acute phase ancestral spike RBD bAb associated with 50% lower odds of COVID-19 were 1,968 BAU/mL against Delta and 3,375 BAU/mL against Omicron; thresholds may differ in other laboratories. During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19.

Influenza vaccine effectiveness against hospitalizations associated with influenza A(H3N2) in Hong Kong children aged 9 months to 17 years, June-November 2023

A test negative study was carried out from 13 June through to 15 November 2023 enrolling 3183 children hospitalized with acute respiratory illness in Hong Kong. Influenza A and B viruses were detected in 528 (16.6%) children, among which 419 (79.4%) were influenza A(H3N2). The overall vaccine effectiveness against hospitalization associated with any influenza virus infection was estimated as 22.4% (95% CI: −11.7%, 46.1%), and against influenza A(H3N2) specifically was 14.3% (95% CI: −29.2%, 43.2%). Despite the moderate to low VE estimated here, which could be a result of waning immunity and antigenic drift, influenza vaccination remains an important approach to reduce the impact of influenza in children.

Bivalent mRNA vaccine effectiveness against COVID-19 among older adults in Japan: a test-negative study from the VENUS study

BackgroundBivalent COVID-19 vaccines have been implemented worldwide since the booster vaccination campaigns of autumn of 2022, but little is known about their effectiveness. Thus, this study holistically evaluated the effectiveness of bivalent vaccines against infection in older adults in Japan.MethodsWe adopted the test-negative design using COVID-19 test data of individuals, aged ≥ 65 years, residing in three municipalities in Japan, who underwent tests in medical institutions between October 1 and December 30, 2022. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. Vaccine effectiveness was defined as (1 − odds ratio) × 100%.ResultsA total of 3,908 positive and 16,090 negative results were included in the analyses. Receiving a bivalent dose in addition to ≥ 2 monovalent doses was 33.6% (95% confidence interval [CI]: 20.8, 44.3%) more effective than receiving no vaccination, and 18.2% (95% CI: 9.4, 26.0%) more effective than receiving ≥ 2 monovalent doses but not receiving a bivalent vaccination. In addition, the effectiveness peaked at 14–20 days after administration and then gradually declined over time. Furthermore, a bivalent booster dose provided 18.6% (95% CI: 9.9, 26.5%) additional protection among those vaccinated with ≥ 2 monovalent doses, in the absence of a previous infection history. However, we did not find sufficient evidence of effectiveness of bivalent vaccines among previously infected older adults.ConclusionsBivalent vaccines are effective against COVID-19 infections among older adults without a history of infection.

Effectiveness of Covid-19 Vaccines Administered in the 2023 Autumnal Campaigns in Europe: Results from the Vebis Primary Care Test-Negative Design Study, September 2023–January 2024

Effectiveness of Covid-19 Vaccines Administered in the 2023 Autumnal Campaigns in Europe: Results from the Vebis Primary Care Test-Negative Design Study, September 2023–January 2024