Test-negative Design Research Articles

Re: Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness

Re: Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness

Response to Letter to the Editor, “Re: Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness”

Response to Letter to the Editor, “Re: Comparison of the test-negative design and cohort design with explicit target trial emulation for evaluating COVID-19 vaccine effectiveness”

Prospective clinical surveillance for severe acute respiratory illness and COVID-19 vaccine effectiveness in Kenyan hospitals during the COVID-19 pandemic.

There are limited data from sub-Saharan Africa describing the demographic characteristics, clinical features and outcome of patients admitted to public hospitals with severe acute respiratory infections during the COVID-19 pandemic. We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. We collected data on demographic and clinical characteristics, SARS-CoV-2 infection and COVID-19 vaccination status and, admission episode outcomes. We determined COVID-19 vaccine effectiveness (VE) against admission with SARS-CoV-2 positive severe acute respiratory illness (SARI) (i.e., COVID-19) andprogression to inpatient mortality among patients admitted with SARI, using a test-negative case control design. Of the 52,636 patients included in the study, 17,950 (34.1%) were admitted with SARI. The median age was 50 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, Human Immunodeficiency Virus (HIV) infection and Diabetes Mellitus were the most common chronic comorbidities. SARS-CoV-2 test results were positive in 2,364 (27.9%) of the 8,471 patients that underwent testing. After adjusting for age, sex and presence of a chronic comorbidity, SARI patients were more likely to progress to inpatient mortality compared to non-SARI patients regardless of their SARS-CoV-2 infection status (adjusted odds ratio (aOR) for SARI and SARS-CoV-2 negative patients 1.22, 95% CI 1.10-1.37; and aOR for SARI and SARS-CoV-2 positive patients 1.32, 95% CI 1.24-1.40). After adjusting for age, sex and presence of a chronic comorbidity, COVID-19 VE against progression to inpatient mortality following admission with SARI for those with a confirmed vaccination status was 0.59 (95% CI 0.27-0.77). We have provided a comprehensive description of the demographic and clinical pattern of admissions with SARI in Kenyan hospitals during the COVID-19 pandemic period as well as the COVID-19 VE for these patients. These data were useful in providing situational awareness during the first three years of the pandemic in Kenya and informing national response measures.

Effectiveness of Original Monovalent and Bivalent COVID-19 Vaccines Against COVID-19-Associated Hospitalization and Severe In-Hospital Outcomes Among Adults in the United States, September 2022-August 2023.

Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes. During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region. Among 7028 patients, 2924 (41.6%) were COVID-19 case patients, and 4104 (58.4%) were control patients. Compared to unvaccinated patients, absolute VE against COVID-19-associated hospitalization was 6% (-7%-17%) for original monovalent doses only (median time since last dose [IQR] = 421 days [304-571]), 52% (39%-61%) for a bivalent dose received 7-89 days earlier, and 13% (-10%-31%) for a bivalent dose received 90-179 days earlier. Absolute VE against COVID-19-associated invasive mechanical ventilation or death was 51% (34%-63%) for original monovalent doses only, 61% (35%-77%) for a bivalent dose received 7-89 days earlier, and 50% (11%-71%) for a bivalent dose received 90-179 days earlier. Bivalent vaccination provided protection against COVID-19-associated hospitalization and severe in-hospital outcomes within 3 months of receipt, followed by a decline in protection to a level similar to that remaining from previous original monovalent vaccination by 3-6 months. These results underscore the benefit of remaining up to date with recommended COVID-19 vaccines.

Designs for Vaccine Studies

Due to dependent happenings, vaccines can have different effects in populations. In addition to direct protective effects in the vaccinated, vaccination in a population can have indirect effects in the unvaccinated individuals. Vaccination can also reduce person-to-person transmission to vaccinated individuals or from vaccinated individuals compared with unvaccinated individuals. Design of vaccine studies has a history extending back over a century. Emerging infectious diseases, such as the SARS-CoV-2 pandemic and the Ebola outbreak in West Africa, have stimulated new interest in vaccine studies. We focus on some recent developments, such as target trial emulation, test-negative design, and regression discontinuity design. Methods for evaluating durability of vaccine effects were developed in the context of both blinded and unblinded placebo crossover studies. The case-ascertained design is used to assess the transmission effects of vaccines. The novel ring vaccination trial design was first used in the Ebola outbreak in West Africa.

Influenza vaccine effectiveness in Ireland during two influenza seasons, 2022/23 and 2023/24

Abstract Background Live Attenuated Influenza Vaccine (LAIV) is recommended in Ireland for all children aged 2-17 years. Quadrivalent influenza vaccine is recommended for all others eligible for vaccination, including those aged ≥18 years with underlying medical conditions and all aged ≥65 years. We aimed to estimate influenza vaccine effectiveness (IVE) against Acute Respiratory Infection (ARI) presentations to primary care due to influenza over two influenza seasons in Ireland, to inform vaccination recommendations and communication campaigns. Methods We undertook a test-negative design case control study within the national sentinel surveillance General Practice network, as part of the European Vaccine Effectiveness Burden and Impact Studies (VEBIS) network. We compared influenza vaccination status among influenza Polymerase Chain Reaction (PCR) positive cases with influenza PCR negative controls, amongst patients consulting with ARI. We verified vaccination status using the national influenza vaccination database. We estimated end of season IVE for 2022/23, and mid-season IVE (up to 7th April 2024) for 2023/24, using multivariable logistic regression and adjusting for age, onset time, medical condition, and sex. Results In 2022/23, there were 288 cases and 765 controls. In 2023/24 there were 515 cases and 1,482 controls. Overall vaccination coverage was 23% in both seasons. Coverage in 2-17 year-olds was 10% in 2022/23 and 12% in 2023/24. In 2022/23, overall IVE was 42% (95%CI 9-54) and 50% (95%CI -30-83) in 2-17 year-olds. Overall IVE in 2023/24 was 37% (95%CI 16-54) and was 67% (95%CI 28-87) in 2-17 year-olds. Conclusions Influenza vaccination reduced medical attendance to primary care with ARI due to influenza, demonstrating benefits of vaccination, particularly among children. Influenza vaccination should continue to be offered and promoted to recommended groups, including children. Key messages • This study suggests that influenza vaccination protected population health and the health service from medical attendance to primary care with acute respiratory infection due to influenza. • Higher influenza vaccine effectiveness was observed in children aged 2-17 years. These findings can inform influenza vaccination programmes with LAIV for children in Ireland and internationally.

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.

Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis

Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. The Centers for Disease Control and Prevention.

Improved Methods for Vaccine Effectiveness Studies.

Evaluating the impact of public health investments in vaccination programs is crucial for ensuring their efficiency and effectiveness. Vaccine effectiveness (VE) studies, such as those using the test-negative design (TND), are commonly used to confirm the impact of vaccines and to guide future improvements. The TND, favored for its simplicity and cost efficiency, mitigates biases common in other epidemiological study designs. However, its validity can be compromised by inconsistent symptom definitions and retrospective data application. Here we summarize recent findings that highlight the need to address correlated vaccination behaviors when estimating VE, that suggest using negative control variables to reduce confounding, and that recommend accounting for prior infection history in VE studies to improve accuracy and reliability. These insights are important for refining VE estimation methods.

Effectiveness of the original monovalent mRNA COVID-19 vaccination series against hospitalization for COVID-19-associated venous thromboembolism.

COVID-19 is a strong risk factor for venous thromboembolism (VTE). Few studies have evaluated the effectiveness of COVID-19 vaccination in preventing hospitalization for COVID-19 with VTE. Adults hospitalized at 21 sites between March 2021 and October 2022 with symptoms of acute respiratory illness were assessed for COVID-19, completion of the original monovalent mRNA COVID-19 vaccination series, and VTE. Prevalence of VTE was compared between unvaccinated and vaccinated patients with COVID-19. Vaccine effectiveness in preventing COVID-19 hospitalization with VTE was calculated using a test negative design. Vaccine effectiveness was also stratified by predominant circulating SARS-CoV-2 variant. Among 18,811 patients (median age 63 [IQR:50-73], 49% women, 59% non-Hispanic White, 20% non-Hispanic Black, 14% Hispanic, and median of 2 comorbid conditions [IQR:1-3]), 9,792 were admitted with COVID-19 (44% vaccinated) and 9,019 were test-negative controls (73% vaccinated). Among patients with COVID-19, 601 were diagnosed with VTE by hospital day 28, of whom 170 were vaccinated. VTE was more common among unvaccinated than vaccinated COVID-19 patients (7.8% versus 4.0%; p=0.001). Vaccine effectiveness against COVID-19 hospitalization with VTE was 84% (95% CI: 80-87%) overall. Vaccine effectiveness stratified by predominant circulating variant was 88% (73-95%) for alpha, 93% (90-95%) for delta, and 68% (58-76%) for omicron variants. Vaccination with the original monovalent mRNA series was associated with a decrease in COVID-19 hospitalization with VTE, though data detailing prior history of VTE and use of anticoagulation were not available. These findings will inform risk-benefit considerations for those considering vaccination.

5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children (TyVOID): a cluster randomised trial

WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination. We conducted a cluster randomised controlled trial (TyVAC; ISRCTN11643110) in Dhaka, Bangladesh, between 2018 and 2021. Children aged 9 months to 15 years were invited to receive a single dose of TCV or Japanese encephalitis vaccine between April 15, 2018, and November 16, 2019, based on the randomisation of their clusters of residence. Children who received the Japanese encephalitis vaccine were invited to receive TCV at the final visit between Jan 6, and Aug 31, 2021, according to the protocol. This follow-on study extended the follow-up of the original trial until Aug 14, 2023. The primary endpoint of this study was to compare the incidence of blood culture-confirmed typhoid between children who received TCV in 2018-19 (the previous-TCV group) and those who received the vaccine in 2021 (the recent-TCV group), to evaluate the relative decline in vaccine protection. We also did a nested study using the test-negative design comparing the recent-TCV and previous-TCV groups with unvaccinated individuals, as well as an immunogenicity study in a subset of 1500 children. Compared with the recent-TCV group, the previous-TCV group had an increased risk of typhoid fever between 2021-23, with an adjusted incidence rate ratio of 3·10 (95% CI 1·53 to 6·29; p<0·0001), indicating a decline in the protection of a single-dose of TCV 3-5 years after vaccination. The extrapolated vaccine effectiveness in years 3-5 was 50% (95% CI -13 to 78), and was validated using the test-negative design analysis, with a vaccine effectiveness of 84% (74 to 90) in the recent-TCV group and 55% (36 to 68) in the previous-TCV group, compared with unvaccinated individuals. Anti-Vi-IgG responses declined over the study period. The highest rate of decay was seen in children vaccinated at younger than 2 years in the original trial. The inverse correlation between age and the decay of antibodies was also seen in the subgroup analysis of vaccine effectiveness, where the youngest age group (<7 years at fever visits) exhibited the fastest waning, with vaccine effectiveness dropping to 24% (95% CI -29 to 55) at 3-5 years after vaccination. A decline in the protection conferred by a single-dose TCV was observed 3-5 years after vaccination, with the greatest decline in protection and immune responses observed in children vaccinated at younger ages. A booster dose of TCV around school entry age might be needed for children vaccinated while younger than 2 years to sustain protection against typhoid fever during the school years when the risk is the highest. The Bill & Melinda Gates Foundation.

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.

Nirsevimab Effectiveness Against Severe RSV Infection in the Primary Care Setting.

This study assesses the effectiveness of nirsevimab, a monoclonal antibody, in preventing medically attended respiratory syncytial virus-lower respiratory tract infections (RSV-LRTI) in a large primary care network in Spain, in both overall and catch-up infants under ten months of age. The 2023-24 immunization campaign with nirsevimab in Spain targeted all infants born after April 1st, 2023. Those born after October 1st received it at birth in hospitals, while others received it through a catch-up program. The MEDIPRIM network of primary care centers recruited all infants with LRTI for RSV PCR testing and employed a test-negative design (TND) approach to estimate the effectiveness of nirsevimab. The study included 160 infants, 141 (88%) of them received nirsevimab and 128 belonged to the catch-up group (88% received nirsevimab). Overall, RSV was detected in 44 infants (27.5%). Within the catch-up group, 37 (28.9%) were positive for RSV. The overall effectiveness was 75.8% (95% CI: 40.4-92.7), and 80.2% (95% CI: 44.3-95.4) in infants belonging to the catch-up group. This study underscores the effectiveness of nirsevimab in preventing medically attended LRTI in infants in outpatient settings and emphasizes the importance of a catch-up immunization program to reduce the disease burden in primary care.

Interim Effectiveness Estimates of 2024 Southern Hemisphere Influenza Vaccines in Preventing Influenza-Associated Hospitalization - REVELAC-i Network, Five South American Countries, March-July 2024.

To reduce influenza-associated morbidity and mortality, countries in South America recommend annual influenza vaccination for persons at high risk for severe influenza illness, including young children, persons with preexisting health conditions, and older adults. Interim estimates of influenza vaccine effectiveness (VE) from Southern Hemisphere countries can provide early information about the protective effects of vaccination and help guide Northern Hemisphere countries in advance of their season. Using data from a multicountry network, investigators estimated interim VE against influenza-associated severe acute respiratory illness (SARI) hospitalization using a test-negative case-control design. During March 13-July 19, 2024, Argentina, Brazil, Chile, Paraguay, and Uruguay identified 11,751 influenza-associated SARI cases; on average, 21.3% of patients were vaccinated against influenza, and the adjusted VE against hospitalization was 34.5%. The adjusted VE against the predominating subtype A(H3N2) was 36.5% and against A(H1N1)pdm09 was 37.1%. These interim VE estimates suggest that although the proportion of hospitalized patients who were vaccinated was modest, vaccination with the Southern Hemisphere influenza vaccine significantly lowered the risk for hospitalization. Northern Hemisphere countries should, therefore, anticipate the need for robust influenza vaccination campaigns and early antiviral treatment to achieve optimal protection against influenza-associated complications.

Effectiveness of influenza vaccines in children aged 6 to 59 months: a test-negative case-control study at primary care and hospital level, Spain 2023/24.

During 2023/24, all children aged 6 to 59 months were targeted for seasonal influenza vaccination in Spain nationally. Using a test-negative case-control design with sentinel surveillance data, we estimated adjusted influenza vaccine effectiveness (IVE) against any influenza type to be 70% (95% confidence interval (CI): 51 to 81%) for primary care patients with acute respiratory illness (ARI) and 77% (95% CI: 21 to 93%) for hospitalised patients with severe ARI. In primary care, where most subtyped viruses (61%; 145/237) were A(H1N1), adjusted IVE was 77% (95% CI: 56 to 88%) against A(H1N1)pdm09.

Influenza Vaccine Effectiveness against Influenza A-Associated Outpatient and Emergency-Department-Attended Influenza-like Illness during the Delayed 2022-2023 Season in Beijing, China.

During the 2022-2023 influenza season, the influenza activities in most regions of China were postponed, including Beijing. The unusually delayed influenza epidemic posed a challenge to the effectiveness of the influenza vaccine. Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 influenza season against influenza A-associated outpatient and emergency-department-attended influenza-like illness (ILI) in Beijing, China, from 9 January to 30 April 2023. The analysis included 8301 medically attended ILI patients, of which 1342 (46.2%) had influenza A(H1N1)pdm09, 1554 (53.4%) had influenza A(H3N2), and 11 (0.4%) had co-infection of the two viruses. VE against influenza A-associated ILI patients was 23.2% (95% CI: -6.5% to 44.6%) overall, and 23.1%, 9.9%, and 33.8% among children aged 6 months to 17 years, adults aged 18-59 years, and adults aged ≥60 years, respectively. VE against influenza A(H1N1)pdm09 and against influenza A(H3N2) were 36.2% (95% CI: -1.9% to 60.1%) and 9.5% (95% CI: -34.1% to 39.0%), respectively. VE of the group with vaccination intervals of 14-90 days (70.1%, 95% CI: -145.4 to 96.4) was higher than that of the groups with a vaccination interval of 90-149 days (18.7%, 95% CI: -42.4% to 53.6%) and ≥150 days (21.2%, 95% CI: -18.8% to 47.7%). A moderate VE against influenza A(H1N1)pdm09 and a low VE against influenza A(H3N2) were observed in Beijing during the 2022-2023 influenza season, a season characterized with a delayed and high-intensity influenza epidemic. VE appears to be better within three months after vaccination. Our findings indicate a potential need for the optimization of vaccination policies and underscore the importance of continuous monitoring of influenza to enhance vaccines and optimizing vaccination timing.

Estimates of vaccine effectiveness of the updated monovalent XBB.1.5 COVID-19 vaccine against symptomatic SARS-CoV-2 infection, hospitalization, and receipt of oxygen therapy in South Korea - October 26 to December 31, 2023

ObjectivesWe evaluated the vaccine effectiveness of monovalent XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and the need for oxygen therapy in South Korea. DesignThis study employed a test-negative case-control design. COVID-19 test results in symptomatic subjects from six university hospitals across South Korea were collected (October 26–December 31, 2023). The adjusted absolute and relative vaccine effectiveness were assessed. ResultsIn total, 5516 subjects were enrolled: 4,824 were unvaccinated with XBB.1.5, and 692 were vaccinated with XBB.1.5 COVID-19 mRNA vaccines. The absolute vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 65.2% (95% CI, 36.1-81.0), 77.3% (95% CI, 51.1-89.5), and 85.3% (95% CI, 57.8-94.9), respectively. The relative vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no XBB.1.5 vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 57.7% (95% CI, 34.7-72.6), 64.3% (95% CI, 35.9-80.2), and 65.5% (95% CI, 27.0-83.7), respectively. ConclusionThe short-term effectiveness of the XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and receipt of oxygen therapy in South Korea was significant. Long-term vaccine effectiveness warrants evaluation, and these assessments should be conducted regularly.

Indirect effectiveness of COVID-19 vaccines in the pre-omicron and omicron periods: A nation-wide test-negative case-control study in Brazil

ObjectivesMass COVID-19 immunization campaigns altered the pandemic's progress by protecting the vaccine recipient and reducing transmission. However, evidence for indirect vaccine effectiveness (IVE) is limited due to the difficulties of ascertaining this type of protection. MethodsUsing linked national Brazilian databases, we adapted the test-negative design to evaluate the IVE against symptomatic infection. We analyzed data from January 1 to December 1, 2021 (pre-omicron) and January 1 to April 30, 2022 (omicron BA.1 and BA.2). We compared the probability of testing positive across various levels of second ancestral-strain monovalent COVID-19 vaccine dose coverage, including only unvaccinated individuals in the main analysis and both vaccinated and unvaccinated individuals in additional analyses. Sensitivity analysis focused on children younger than 12 years who did not have access to COVID-19 vaccines during the pre-omicron period. ResultsWe included 11,039,315 unvaccinated individuals tested during the pre-omicron study period. IVE was minimal until 30% vaccination coverage (<10%), then it followed a dose-dependent pattern, peaking at 37.7 (95% confidence interval 32-42.8) at 70% coverage. For children younger than 12 years, IVE peaked at 59.8% (95% confidence interval 52.7-65.9) at 70% coverage. During the omicron period, IVE remained constant at about 5% across all comparisons. ConclusionsOur findings confirm that high vaccination coverage using vaccines that prevent infection indirectly protects the community. However, IVE was substantially higher during the pre-omicron period.

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022.

Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children.

Effectiveness of EV-A71 Vaccine and Its Impact on the Incidence of Hand, Foot and Mouth Disease: A Systematic Review.

Vaccination is a highly effective strategy for the prevention of enterovirus A71 (EV-A71)-hand, foot, and mouth disease (HFMD). Three inactivated EV-A71 vaccines in China have demonstrated remarkable efficacy against EV-A71-HFMD during clinical trials, exhibiting vaccine effectiveness (VE) exceeding 90% and few adverse events (AEs). However, the effectiveness of vaccines in the real world and its impact on the epidemiological characteristics of HFMD after the use of EV-A71 inactivated vaccine are uncertain. The odd ratio (OR) and 95% confidence (CI) were used as the effect estimates of the meta-analysis in the test-negative design (TND), and the OR was used to calculate VE: VE = (1 - OR) × 100%. According to the literature search strategy, a comprehensive search was conducted in PubMed, Web of Science (including Chinese Science Citation Database and MEDLINE), and Embase, and 18 records were ultimately included in this study. Subsequently, the overall VE and 95% CI of different vaccine doses were analyzed, with the one-dose vaccine at 66.9% (95% CI: 45.2-80.0%) and the two-dose vaccine at 84.2% (95% CI: 79.4-87.9%). Additionally, the most reported AEs were mild general reactions without any rare occurrences. Simultaneously, the widespread use of the EV-A71 vaccine would lead to a reduction in both the incidence of EV-A71-associated HFMD and severe cases caused by EV-A71. The administration of the two-dose EV-A71 vaccine is highly effective in preventing HFMD in the real world, and the widespread use of the EV-A71 vaccine leads to a reduction in the incidence of EV-A71-associated HFMD and that of severe cases caused by EV-A71. The findings suggest that administering the two-dose EV-A71 inactivated vaccine to children aged 6 months to 71 months can be effective in preventing EV-A71-associated HFMD, highlighting the need for developing a multivalent HFMD vaccine for preventing cases not caused by EV-A71.