COVID-19 Vaccine Effectiveness in Autumn and Winter 2022 to 2023 Among Older Europeans.

Importance: In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns. Objective: To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used. Design, Setting, and Participants: This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription-polymerase chain reaction (RT-PCR) test results. Exposures: The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign. Main Outcomes and Measures: The outcome was RT-PCR-confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex. Results: A total of 9308 primary care patients were included, with 1687 cases (1035 females; median [IQR] age, 71 [65-79] years) and 7621 controls (4619 females [61%]; median [IQR] age, 71 [65-78] years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, -10% to 75%), absolute CVE was 52% (95% CI, -23% to 82%), relative CVE was 47% (95% CI, -8% to 77%), and relative CVE of second boosters was 46% (95% CI, -13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination. Conclusions and Relevance: In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.

Current status and future directions for the development of human papillomavirus vaccines.

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.

IL-10 inhibition during immunization improves vaccine-induced protection against Staphylococcus aureus infection.

Staphylococcus aureus is a major human pathogen. An effective anti-S. aureus vaccine remains elusive as the correlates of protection are ill-defined. Targeting specific T cell populations is an important strategy for improving anti-S. aureus vaccine efficacy. Potential bottlenecks that remain are S. aureus-induced immunosuppression and the impact this might have on vaccine-induced immunity. S. aureus induces IL-10, which impedes effector T cell responses, facilitating persistence during both colonization and infection. Thus, it was hypothesized that transient targeting of IL-10 might represent an innovative way to improve vaccine efficacy. In this study, IL-10 expression was elevated in the nares of persistent carriers of S. aureus, and this was associated with reduced systemic S. aureus-specific Th1 responses. This suggests that systemic responses are remodeled because of commensal exposure to S. aureus, which negatively implicates vaccine function. To provide proof of concept that targeting immunosuppressive responses during immunization may be a useful approach to improve vaccine efficacy, we immunized mice with T cell-activating vaccines in combination with IL-10-neutralizing antibodies. Blocking IL-10 during vaccination enhanced effector T cell responses and improved bacterial clearance during subsequent systemic and subcutaneous infection. Taken together, these results reveal a potentially novel strategy for improving anti-S. aureus vaccine efficacy.

Cold-adapted influenza-vectored RSV vaccine protects BALB/c mice and cotton rats from RSV challenge.

Respiratory syncytial virus (RSV) remains the primary cause of lower respiratory tract infections, particularly in infants and the elderly. In this study, we employed reverse genetics to generate a chimeric influenza virus expressing neuraminidase-3F protein conjugate with three repeats of the RSV F protein protective epitope inserted into the NA gene of A/California/7/2009 ca (CA/AA ca), resulting in rFlu/RSV/NA-3F (hereafter, rFRN3). The expression of NA-3F protein was confirmed by Western blotting. The morphology and temperature-sensitive phenotype of rFRN3 were similar to CA/AA ca. Its immunogenicity and protective efficiency were evaluated in BALB/c mice and cotton rats. Intranasal administration of rFRN3 elicited robust humoral, cellular, and to some extent, mucosal immune responses. Compared to controls, rFRN3 protected animals from RSV infection, attenuated lung injury, and reduced viral titers in the nose and lungs post-RSV challenge. These results demonstrate that rFRN3 can trigger RSV-specific immune responses and thus exhibits potent protective efficacy. The "dual vaccine" approach of a cold-adapted influenza vector RSV vaccine will improve the prophylaxis of influenza and RSV infection. rFRN3 thus warrants further clinical investigations as a candidate RSV vaccine.

Estimating vaccine effectiveness against COVID-19 using cause-specific sick leave as an indicator: a nationwide population-based cohort study, Norway, July 2021 - December 2022.

BACKGROUND: Due to changes in testing policy and increased use of rapid tests, other indicators for SARS-CoV-2 infections are needed to monitor vaccine effectiveness (VE). We aimed to estimate VE against COVID-19 sick leave (> 3 days, certified by a medical professional) among employed individuals (25-64-years-old) in Norway. METHODS: We performed a nationwide cohort study by collating data from the Emergency preparedness register for COVID-19. We used adjusted Cox proportional hazard models with vaccine status as a time-varying covariate and presented results as adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals. Separate models were run against sick leave and against SARS-CoV-2 infections during the Delta period (June-December 2021), and against sick leave during the Omicron period (January-December 2022) when SARS-CoV-2 PCR-testing was replaced by rapid self-tests and infections were underreported. RESULTS: We included 2,236,419 individuals during the Delta period, of whom 73,776 (3.3%) had a reported infection and 54,334 (2.4%) were registered with sick leave. Of the 2,206,952 included individuals in the Omicron period, 300,140 (13.6%) were registered with sick leave. During the Delta period, 55% (26,611) of individuals who had registered sick leave also had a positive test, compared to 32% (96,445) during the Omicron period. The VE against sick leave during the Delta period followed a similar waning pattern to that against SARS-CoV-2 infections. After the second and third dose, the lowest aHRs were estimated for 2-7 days after vaccination for both sick leave (0.25; 95%CI 0.24-0.26 and 0.26; 95% CI 0.24-0.29) and infection ( 0.16; 95% CI 0.15-0.17 and 0.18; 95% CI 0.16-0.19) respectively. During the Omicron period, aHRs for sick leave were higher than during the Delta period, but the lowest aHRs were still found in 2-7 weeks after receiving the second (0.61; 95% CI 0.59-0.64) or third dose (0.63; 95% CI 0.62-0.64). CONCLUSION: Our results showed that sick leave could be a relevant indicator for VE in the surveillance of COVID-19 and a finding that may be important in the surveillance of other respiratory infection.

The impact of the COVID-19 vaccination programme on symptomatic and severe SARS-CoV-2 infection during a period of Omicron variant dominance in Ireland, December 2021 to March 2023.

BackgroundAs Ireland prepared for an autumn 2023 COVID-19 vaccination booster campaign, there was concern that vaccine fatigue would affect uptake, which has been abating.AimThis study aimed to quantify the direct impact of the COVID-19 vaccination programme in Ireland on averted COVID-19-related outcomes including symptomatic presentations to primary care/community testing centres, emergency department (ED) presentations, hospitalisations, intensive care unit (ICU) admissions and deaths, in individuals aged ≥ 50 years, during Omicron dominance.MethodsWe conducted a retrospective observational COVID-19 vaccine impact study in December 2021-March 2023 in Ireland. We used national data on notified outcomes and vaccine coverage, as well as vaccine effectiveness (VE) estimates, sourced from the World Health Organization's live systematic review of VE, to estimate the count and prevented fraction of outcomes in ≥ 50-year-olds averted by the COVID-19 vaccination programme in this age group.ResultsThe COVID-19 vaccination programme averted 48,551 symptomatic COVID-19 presentations to primary care/community testing centres (36% of cases expected in the absence of vaccination), 9,517 ED presentations (53% of expected), 102,160 hospitalisations (81% of expected), 3,303 ICU admissions (89% of expected) and 15,985 deaths (87% of expected).ConclusionsWhen Omicron predominated, the COVID-19 vaccination programme averted symptomatic and severe COVID-19 cases, including deaths due to COVID-19. In line with other international vaccine impact studies, these findings emphasise the benefits of COVID-19 vaccination for population health and the healthcare system and are relevant for informing COVID-19 booster vaccination programmes, pandemic preparedness and communicating the reason for and importance of COVID-19 vaccination in Ireland and internationally.

Predicting Efficacies of Fractional Doses of Vaccines by Using Neutralizing Antibody Levels: Systematic Review and Meta-Analysis.

Background: With the emergence of SARS-CoV-2 variants that have eluded immunity from vaccines and prior infections, vaccine shortages and vaccine effectiveness pose unprecedented challenges for governments in expanding booster vaccination programs. The fractionation of vaccine doses might be an effective strategy for helping society to face these challenges, as fractional doses may have efficacies comparable with those of the standard doses. Objective: This study aims to investigate the relationship between vaccine immunogenicity and protection and to project efficacies of fractional doses of vaccines for COVID-19 by using neutralizing antibody levels. Methods: In this study, we analyzed the relationship between in vitro neutralization levels and the observed efficacies against both asymptomatic infection and symptomatic infection, using data from 13 studies of 10 COVID-19 vaccines and from convalescent cohorts. We further projected efficacies for fractional doses, using neutralization as an intermediate variable, based on immunogenicity data from 51 studies included in our systematic review. Results: In comparisons with the convalescent level, vaccine efficacy against asymptomatic infection and symptomatic infection increased from 8.8% (95% CI 1.4%-16.1%) to 71.8% (95% CI 63%-80.7%) and from 33.6% (95% CI 23.6%-43.6%) to 98.6% (95% CI 97.6%-99.7%), respectively, as the mean neutralization level increased from 0.1 to 10 folds of the convalescent level. Additionally, mRNA vaccines provided the strongest protection, which decreased slowly for fractional dosing with dosages between 50% and 100% of the standard dose. We also observed that although vaccine efficacy increased with the mean neutralization level, the rate of this increase was slower for vaccine efficacy against asymptomatic infection than for vaccine efficacy against symptomatic infection. Conclusions: Our results are consistent with studies on immune protection from SARS-CoV-2 infection. Based on our study, we expect that fractional-dose vaccination could provide partial immunity against SARS-CoV-2 and its variants. Our findings provide a theoretical basis for the efficacy of fractional-dose vaccines, serving as reference evidence for implementing fractional dosing vaccine policies in areas facing vaccine shortages and thereby mitigating disease burden. Fractional-dose vaccination could be a viable vaccination strategy comparable to full-dose vaccination and deserves further exploration.

Effectiveness of influenza vaccine among the population in Chongqing, China, 2018-2022: A test negative design-based evaluation.

Influenza vaccination is the most cost-effective strategy for influenza prevention. Influenza vaccines have been found to be effective against symptomatic and medically attended outpatient influenza illnesses. However, there is currently a lack of data regarding the effectiveness of inactivated influenza vaccines in Chongqing, China. We conducted a prospective observational test-negative design study. Outpatient and emergency cases presenting with influenza-like illnesses (ILI) and available influenza reverse transcription polymerase chain reaction (RT-PCR) were selected and classified as cases (positive influenza RT-PCR) or controls (negative influenza RT-PCR). A total of 7,307 cases of influenza and 7,905 control subjects were included in this study. The overall adjusted influenza vaccine effectiveness (IVE) was 44.4% (95% confidence interval (CI): 32.5-54.2%). In the age groups of less than 6 years old, 6-18 years old, and 19-59 years old, the adjusted IVE were 32.2% (95% CI: 10.0-48.9%), 48.2% (95% CI: 30.6-61.4%), and 72.0% (95% CI: 43.6-86.1%). The adjusted IVE for H1N1, H3N2 and B (Victoria) were 71.1% (95% CI: 55.4-81.3%), 36.1% (95% CI: 14.6-52.2%) and 33.7% (95% CI: 14.6-48.5%). Influenza vaccination was effective in Chongqing from 2018 to 2022. Evaluating IVE in this area is feasible and should be conducted annually in the future.

Hypothesis testing and sample size considerations for the test-negative design.

The test-negative design (TND) is an observational study design to evaluate vaccine effectiveness (VE) that enrolls individuals receiving diagnostic testing for a target disease as part of routine care. VE is estimated as one minus the adjusted odds ratio of testing positive versus negative comparing vaccinated and unvaccinated patients. Although the TND is related to case-control studies, it is distinct in that the ratio of test-positive cases to test-negative controls is not typically pre-specified. For both types of studies, sparse cells are common when vaccines are highly effective. We consider the implications of these features on power for the TND. We use simulation studies to explore three hypothesis-testing procedures and associated sample size calculations for case-control and TND studies. These tests, all based on a simple logistic regression model, are a standard Wald test, a continuity-corrected Wald test, and a score test. The Wald test performs poorly in both case-control and TND when VE is high because the number of vaccinated test-positive cases can be low or zero. Continuity corrections help to stabilize the variance but induce bias. We observe superior performance with the score test as the variance is pooled under the null hypothesis of no group differences. We recommend using a score-based approach to design and analyze both case-control and TND. We propose a modification to the TND score sample size to account for additional variability in the ratio of controls over cases. This work enhances our understanding of the data generating mechanism in a test-negative design (TND) and how it is distinct from that of a case-control study due to its passive recruitment of controls.

Duration of effectiveness of the COVID-19 vaccine in Japan: a retrospective cohort study using large-scale population-based registry data.

BACKGROUND: Most evidence of the waning of vaccine effectiveness is limited to a relatively short period after vaccination. METHODS: Data obtained from a linked database of healthcare administrative claims and vaccination records maintained by the municipality of a city in the Kanto region of Japan were used in this study. The study period extended from April 1, 2020, to December 31, 2022. The duration of the effectiveness of the COVID-19 vaccine was analyzed using a time-dependent piecewise Cox proportional hazard model using the age, sex and history of cancer, diabetes, chronic obstructive pulmonary disease, asthma, chronic kidney disease, and cardiovascular disease as covariates. RESULTS: Among the 174,757 eligible individuals, 14,416 (8.3%) were diagnosed with COVID-19 and 936 (0.54%) were hospitalized for COVID-19. Multivariate analysis based on the time-dependent Cox regression model with reference of non-vaccine group revealed a lower incidence of COVID-19 in the one-dose group (hazard ratio, 0.76 [95% confidence interval, 0.63-0.91]), two-dose (0.89 [0.85-0.93]), three-dose (0.80 [0.76-0.85]), four-dose (0.93 [0.88-1.00]), and five-dose (0.72 [0.62-0.84]) groups. A lower incidence of COVID-19-related hospitalization was observed in the one-dose group (0.42 [0.21-0.81]), two-dose (0.44 [0.35-0.56]), three-dose (0.38 [0.30-0.47]), four-dose (0.20 [0.14-0.28]), and five-dose (0.11 [0.014-0.86]) groups. Multivariable analyses based on the time-dependent piecewise Cox proportional hazard model with reference of non-vaccine group revealed significant preventive effects of the vaccine for 4 months for the incidence of COVID-19 and ≥ 6 months for hospitalization. CONCLUSIONS: Vaccine effectiveness showed gradual attenuation with time after vaccination; however, protective effects against the incidence of COVID-19 and hospitalization were maintained for 4 months and ≥ 6 months, respectively. These results may aid in formulating routine vaccination plans after the COVID-19 pandemic.

Vaccine Effectiveness against SARS-CoV-2 among Household Contacts during Omicron BA.2-Dominant Period, Japan.

We calculated attack rates for household contacts of COVID-19 patients during the SARS-CoV-2 Omicron BA.2-dominant period in Japan. Attack rates among household contacts without recent (<3 months) vaccination was lower for contacts of index patients with complete vaccination than for contacts of index patients without complete vaccination, demonstrating indirect vaccine effectiveness.

Efficacy and effectiveness of COVID-19 vaccines in Africa: A systematic review.

BACKGROUND: Data on COVID-19 vaccine effectiveness to support regional vaccine policy and practice are limited in Africa. Thus, this review aimed to evaluate the efficacy and effectiveness of COVID-19 vaccines administered in Africa. METHODS: We systematically searched peer-reviewed randomized controlled trials (RCTs), prospective and retrospective cohort studies, and case-control studies that reported on VE in Africa. We carried out a risk of bias assessment, and the findings of this review were synthesized and presented in a narrative form, including tables and figures. The synthesis was focused on COVID-19 VE against various levels of the disease condition and outcomes (infection, hospitalization or critical, and death), time points, and variants of concern. RESULTS: A total of 13 studies, with a total sample size of 913,285 participants, were included in this review. The majority (8/13) of studies were from South Africa and 38.5% (5/13) were randomized clinical trials. The studies reported that a full dose of Pfizer-BioNTech vaccine had a VE of 100% against COVID-19 infection by Beta (B.1.351) and Delta variants and 96.7% against hospitalization by Delta variant. The Johnson and Johnson vaccine had VE ranging from 38.1%-62.0% against hospitalization and 51.9%- 86% against critical disease by Beta (B 1.351) variant. The Oxford-AstraZeneca vaccine had a VE of 89.4% against hospitalization by the Omicron variant but was not effective against the B.1.351 variant (10.4%). The Sinopharm vaccine had a VE of 67% against infection and 46% against hospitalization by Delta variant. CONCLUSIONS: COVID-19 vaccines administered in Africa were effective in preventing infections, hospitalization, and death. These review findings underscore the need for concerted efforts of all stakeholders to enhance the access and availability of COVID-19 vaccines and reinforce public awareness to reach the high-risk, unvaccinated group of the African population.

Uptake, safety and effectiveness of inactivated influenza vaccine in inflammatory bowel disease: a UK-wide study.

OBJECTIVE: To investigate (1) the UK-wide inactivated influenza vaccine (IIV) uptake in adults with inflammatory bowel disease (IBD), (2) the association between vaccination against influenza and IBD flare and (3) the effectiveness of IIV in preventing morbidity and mortality. DESIGN: Data for adults with IBD diagnosed before the 1 September 2018 were extracted from the Clinical Practice Research Datalink Gold. We calculated the proportion of people vaccinated against seasonal influenza in the 2018-2019 influenza cycle. To investigate vaccine effectiveness, we calculated the propensity score (PS) for vaccination and conducted Cox proportional hazard regression with inverse-probability treatment weighting on PS. We employed self-controlled case series analysis to investigate the association between vaccination and IBD flare. RESULTS: Data for 13 631 people with IBD (50.4% male, mean age 52.9 years) were included. Fifty percent were vaccinated during the influenza cycle, while 32.1% were vaccinated on time, that is, before the seasonal influenza virus circulated in the community. IIV was associated with reduced all-cause mortality (aHR (95% CI): 0.73 (0.55,0.97) but not hospitalisation for pneumonia (aHR (95% CI) 0.52 (0.20-1.37), including in the influenza active period (aHR (95% CI) 0.48 (0.18-1.27)). Administration of the IIV was not associated with IBD flare. CONCLUSION: The uptake of influenza vaccine was low in people with IBD, and the majority were not vaccinated before influenza virus circulated in the community. Vaccination with the IIV was not associated with IBD flare. These findings add to the evidence to promote vaccination against influenza in people with IBD.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.

BACKGROUND: Bivalent SARS-CoV-2 vaccines were developed to counter increasing susceptibility to emerging SARS-CoV-2 variants. We evaluated the durability of immunity and protection following first bivalent vaccination among nursing home residents. METHODS: We evaluated anti-spike and neutralization titers from blood in 653 community nursing home residents before and after each monovalent booster, and a bivalent vaccine. Concurrent clinical outcomes were evaluated using electronic health record data from a separate cohort of 3783 residents of Veterans Affairs (VA) nursing homes who had received at least the primary series monovalent vaccination. Using target trial emulation, we compared VA residents who did and did not receive the bivalent vaccine to measure vaccine effectiveness against infection, hospitalization, and death. FINDINGS: In the community cohort, Omicron BA.5 neutralization activity rose after each monovalent and bivalent booster vaccination regardless of prior infection history. Titers declined over time but six months post-bivalent vaccination, BA.5 neutralization persisted at detectable levels in 75% of infection-naive and 98% of prior-infected individuals. In the VA nursing home cohort, bivalent vaccine added effectiveness to monovalent booster vaccination by 18.5% for infection (95% confidence interval (CI) -5.6, 34.0%), and 29.2% for hospitalization or death (95% CI -14.2, 56.2%) over five months. INTERPRETATION: The level of protection declined after bivalent vaccination over a 6 month period and may open a window of added vulnerability before the next updated vaccine becomes available, suggesting a subset of nursing home residents may benefit from an additional vaccination booster. FUNDING: CDC, NIH, VHA.

Test-Negative Study Designs for Evaluating Vaccine Effectiveness.

This JAMA Guide to Statistics and Methods article explains the test-negative study design, an observational study design routinely used to estimate vaccine effectiveness, and examines its use in a study that estimated the performance of messenger RNA boosters against the Omicron variant.

Increased efficacy of influenza virus vaccine candidate through display of recombinant neuraminidase on virus like particles.

Vaccination against influenza virus can reduce the risk of influenza by 40% to 60%, they rely on the production of neutralizing antibodies specific to influenza hemagglutinin (HA) ignoring the neuraminidase (NA) as an important surface target. Vaccination with standardized NA concentration may offer broader and longer-lasting protection against influenza infection. In this regard, we aimed to compare the potency of a NA displayed on the surface of a VLP with a soluble NA. The baculovirus expression system (BEVS) and the novel virus-free Tnms42 insect cell line were used to express N2 NA on gag-based VLPs. To produce VLP immunogens with high levels of purity and concentration, a two-step chromatography purification process combined with ultracentrifugation was used. In a prime/boost vaccination scheme, mice vaccinated with 1 µg of the N2-VLPs were protected from mortality, while mice receiving the same dose of unadjuvanted NA in soluble form succumbed to the lethal infection. Moreover, NA inhibition assays and NA-ELISAs of pre-boost and pre-challenge sera confirm that the VLP preparation induced higher levels of NA-specific antibodies outperforming the soluble unadjuvanted NA.

Frequency of SARS-COV-2 infection and COVID-19 vaccine uptake and protection among Syrian refugees : COVID-19 Vaccine among Syrian Refugees.

It is aimed to examine the frequency of COVID-19 disease, the rates of COVID-19 vaccination and the vaccine effectiveness (VE) among Syrian refugees. It is a retrospective cohort study. Syrian refugees aged 18 years and above registered to a family health center in Sultanbeyli district in Istanbul were included. Vaccine effectiveness were calculated for both Pfizer BioN-Tech and CoronaVac (Sinovac) vaccines. The data of 2586 Syrian people was evaluated in the study. The median age of the participants was 34.0 years (min:18.0; max: 90.0). Of the participants 58.4% (n = 1510) were female, 41.6% (n = 1076) were male. In our study of the refugees 15.7% had history of COVID-19 infection. Refugees having full vaccination with Biontech and Sinovac have a significantly lower COVID-19 infection rate than those without vaccination (HR = 8.687; p < 0.001). Adjusted VE for Biontech, Sinovac, and both were 89.2% (95.0% CI:83.3-93.1), 81.2% (95.0% CI:48.72-93.1) and 88.5% (95.0% CI:82.7-92.3), respectively. The results of the study highlight the importance of vaccinations against COVID-19 pandemic, since both vaccines were highly protective in refugees.

Effectiveness of mRNA COVID-19 Vaccines as First Booster Doses in England: An Observational Study in OpenSAFELY-TPP.

BACKGROUND: The UK delivered its first "booster" COVID-19 vaccine doses in September 2021, initially to individuals at high risk of severe disease, then to all adults. The BNT162b2 Pfizer-BioNTech vaccine was used initially, then also Moderna mRNA-1273. METHODS: With the approval of the National Health Service England, we used routine clinical data to estimate the effectiveness of boosting with BNT162b2 or mRNA-1273 compared with no boosting in eligible adults who had received two primary course vaccine doses. We matched each booster recipient with an unboosted control on factors relating to booster priority status and prior COVID-19 immunization. We adjusted for additional factors in Cox models, estimating hazard ratios up to 182 days (6 months) following booster dose. We estimated hazard ratios overall and within the following periods: 1-14, 15-42, 43-69, 70-97, 98-126, 127-152, and 155-182 days. Outcomes included a positive SARS-CoV-2 test, COVID-19 hospitalization, COVID-19 death, non-COVID-19 death, and fracture. RESULTS: We matched 8,198,643 booster recipients with unboosted controls. Adjusted hazard ratios over 6-month follow-up were: positive SARS-CoV-2 test 0.75 (0.74, 0.75); COVID-19 hospitalization 0.30 (0.29, 0.31); COVID-19 death 0.11 (0.10, 0.14); non-COVID-19 death 0.22 (0.21, 0.23); and fracture 0.77 (0.75, 0.78). Estimated effectiveness of booster vaccines against severe COVID-19-related outcomes peaked during the first 3 months following the booster dose. By 6 months, the cumulative incidence of positive SARS-CoV-2 test was higher in boosted than unboosted individuals. CONCLUSIONS: We estimate that COVID-19 booster vaccination, compared with no booster vaccination, provided substantial protection against COVID-19 hospitalization and COVID-19 death but only limited protection against positive SARS-CoV-2 test. Lower rates of fracture in boosted than unboosted individuals may suggest unmeasured confounding. Observational studies should report estimated vaccine effectiveness against nontarget and negative control outcomes.

Mapping and ranking outcomes for the evaluation of seasonal influenza vaccine efficacy and effectiveness: a delphi study.

BACKGROUND: Protection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance. RESEARCH DESIGN AND METHODS: An umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women. RESULTS: The literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9). CONCLUSIONS: Rather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.