Nieves Derqui

Vaccination timeliness is often not considered among standard performance indicators of routine vaccination programmes, such as vaccination coverage, yet quantifying vaccination delay could inform policies to promote in-time vaccination and help design vaccination schedules. Here, we analysed vaccination timeliness for 24 routine childhood immunisations for 54 countries. We extracted individual vaccination status and timing from Demographic and Health Surveys data from 54 countries with surveys from 2010 onwards. Individual data was used to estimate age at vaccination for <5 year-old children. Recommended age of vaccination for each country and vaccine was compared to the age at vaccination to determine vaccination delay. The evolution of vaccination delay over time was described using estimates from different birth cohorts. To identify socio-demographic indicators associated with delayed vaccination, we used multivariable Cox regression models with country as random effect and estimated the Hazard Ratio for vaccination with each vaccine-dose for each week post recommended vaccination age. Vaccine coverage at the recommended age was highest for birth and first doses (e.g. 50.5% BCG, 18.5% DTP-D1) and lowest for later doses (e.g. 5.5% DTP-D3, 16.3% MCV-D1, 8.2% MCV-D2). Median delay was lowest for birth doses, e.g. BCG (1 week (IQR: 0 to 4)), and it increased with later doses in vaccination courses: 1 (0, 4) week for DTP-D1 versus 4 (2, 9) weeks for DTP-D3. Although the median delay for each vaccine-dose remained largely constant over time, the range of delay estimates moderately decreased. Children living in rural areas, their countries’ poorer wealth quintiles and whose mothers had no formal education were more likely to received delayed vaccinations. Although we report most children are vaccinated within the recommended age window, we found little reduction on routine immunisation delays over the last decade and that children from deprived socioeconomic backgrounds are more likely to receive delayed vaccinations.

While the efficacy of SARS-CoV-2 vaccination against severe disease and mortality is well-established, its impact on population-level transmission remains a critical yet poorly quantified frontier in public health. Previous evidence has largely relied on small-scale cohort or household studies. However, these settings often lack the scale to capture the broader ecological impact of vaccination on epidemic growth, and therefore its implications for epidemic control. Here, we quantify the effectiveness of SARS-CoV-2 vaccination against transmission in England by fitting a Bayesian hierarchical model to estimates of the time-varying effective reproduction number ( R _t ) during 2021. Vaccine effectiveness for one, two and three doses was defined as the proportional reduction in R _t . The model integrates high-resolution data on vaccination uptake by age group, the shifting landscape of circulating variants, and regional transmission trends across 221 Lower Tier Local Authorities. We find that a first vaccine dose provided moderate-to-large effectiveness against transmission (45.4% (95% CrI: 38.5–51.9%)), whereas the second dose offered negligible additional transmission-blocking effects. A third dose significantly restored effectiveness (66.3% (40.3–90.1%)), albeit with higher uncertainty. Surprisingly, although a link between socio-economic deprivation and transmission is highly plausible, we find that deprivation was not a significant driver of transmission heterogeneity during the vaccination rollout. The model accurately reproduces observed spatial and temporal variation in R _t across England. To our knowledge, these findings provide the first population-level evidence that vaccination substantially reduces the SARS-CoV-2 reproduction number, supporting the UK’s “first-doses-first” prioritization as effective tools for epidemic control. More broadly, our modelling framework offers an approach for assessing transmission-blocking effects of vaccines against respiratory pathogens using routinely collected surveillance data, and has implications beyond SARS-CoV-2 for emerging threats such as avian influenza (H5N1).

Purpose: Influenza hospitalizations contribute substantially to healthcare disruption. We explored the impact of ageing, comorbidities and other risk factors to better understand associations with severe clinical outcomes in adults hospitalized with influenza.Methods: We analysed multi‐season data from adults ≥18 years, hospitalized with laboratory‐confirmed influenza in Valencia, Spain. Severity was defined as intensive care unit (ICU) admission, assisted ventilation and/or death. Generalized estimating equations were used to estimate associations between risk factors and severity. Rate of hospital discharge was analysed with a cumulative incidence function.Results: Only 26% of influenza patients had their primary discharge diagnosis coded as influenza. Comorbidities were associated with severity among adults aged 50–79 years, with the highest odds ratio (OR) in patients with ≥3 comorbidities aged 50–64 years (OR = 6.7; 95% CI: 1.0–44.6). Morbid obesity and functional dependencies were also identified risk factors (ORs varying from 3 to 5 depending on age). The presence of increasing numbers of comorbidities was associated with prolonged hospital stay.Conclusions: Influenza clinical outcomes are aggravated by the presence of comorbidities and ageing. Increased awareness of influenza among hospitalized patients could prompt clinical and public health interventions to reduce associated burden.

Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.

Background: The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS),i.e.fever, cough and loss or change in smell or taste, could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.Methods: Two prospective longitudinal London (UK)-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and area under the receiver operating characteristic curve. Improvements in sensitivity and time to detection were compared with penalties in terms of specificity and number needed to test.Results: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion “≥1 of the CS, or ≥2 of the EP” identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than “≥1 of the CS”, with only modest reduction in specificity (5.7%).Conclusions: Broadening symptom criteria to include individuals with at least two of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time to detection, providing greater opportunities to prevent SARS-CoV-2 transmission.

Background: The SARS-CoV-2 Delta variant is highly transmissible and spreading globally but a detailed understanding of community transmission risks in highly vaccinated populations is lacking. Methods: Between September 2020 and August 2021, we recruited 510 community contacts of 422 UK COVID-19 cases to a cohort study. A total of 7194 upper respiratory tract (URT) samples were tested from sequential daily sampling of participants for up to 20 days. We analysed transmission risk by vaccination status for 139 contacts exposed to the Delta variant. We compared viral load (VL) trajectories from fully-vaccinated cases of Delta infection (n=19) with unvaccinated Delta (n=10), Alpha (n=39) and pre-Alpha (n=49) infections. Findings: The household secondary attack rate for fully-vaccinated contacts exposed to Delta was 19.7% (95%CI:11.6-31.3%), compared with 35.7% (95%CI:16.4-61.2%) in the unvaccinated. One third of infections in Delta-exposed contacts arose from fully-vaccinated index cases and one half of infected contacts were also fully-vaccinated. Seven transmission events between fully vaccinated index-contact pairs occurred. Genomic analysis confirmed transmission pathways between fully-vaccinated individuals within three households. Peak VL was similar in vaccinated and unvaccinated individuals with Delta variant infection but vaccinated Delta cases saw significantly faster VL decline than unvaccinated Alpha or Delta cases. Within infected individuals, faster VL growth was correlated with higher peak VL and slower decline. Interpretation: Although vaccination reduces the risk of Delta infection and causes some changes to viral kinetics, fully-vaccinated individuals with breakthrough infections have peak URT VL similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Funding: National Institute for Health Research (Award:NIHR200927) Declaration of Interest: The authors declare no relevant conflicts. Ethical Approval: The study was approved by the Health Research Authority (Research Ethics Committee reference: 20/NW/0231).