Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study

Heterologous vaccination; Neutralisation; SARS-CoV-2Vacunación heteróloga; Neutralización; SARS-CoV-2Vacunació heteròloga; Neutralització; SARS-CoV-2Background The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49–5956·71) in the IG and 7298·22 BAU/mL (6739·41–7903·37) in the CG (p 1:100 at day 180 (19% and 22%, respectively). Interpretation Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180.Funded by Instituto de Salud Carlos III (ISCIII)

What do we know about Immunity to SARS-CoV-2? Implications for Public Health Policies

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóAs the COVID-19 pandemic progresses, so does our knowledge of the magnitude, type and durability of the immune response to SARS-CoV-2 as a result of natural infection or vaccination. This information is crucial since it will largely define the strategies we need to implement in order to protect individuals and populations. With this in mind, the GCMSC presents its second report, where they review the current knowledge on immunity to SARS-CoV-2 and the implications in terms of public health policies

Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in highrisk populations, Spain, 2016

Introduction: Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide. Aim: To find and summarise the best available evidence of HPV vaccination in high-risk patients aiding clinicians and public health workers in the day-to-day vaccine decisions relating to HPV in Spain. Methods: We conducted a systematic review of the immunogenicity, safety and efficacy/effectiveness of HPV vaccination in high-risk populations between January 2006 and June 2016. HPV vaccination recommendations were established with levels of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A strong recommendation about HPV vaccination was made in the following groups: HIV infected patients aged 9-26 years; men who have sex with men aged 9-26 years; women with precancerous cervical lesions; patients with congenital bone marrow failure syndrome; women who have received a solid organ transplant or hematopoietic stem cell transplantation aged 9-26 years; and patients diagnosed with recurrent respiratory papillomatosis. Conclusions: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence- based guidelines on HPV vaccination in highrisk populations in Spain, based on best available scientific evidence

Post-Acute COVID Syndrome (PACS): Definition, Impact and Management

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóA variety of studies suggest that up to 10-15% of all patients with COVID-19 may present persistent symptomatology weeks or even months after the original infection. Given the accumulated burden of COVID-19 in Catalonia, Spain, we speculate that over 90,000 patients could have been or are currently affected by persistent symptoms or sequelae. The Multidisciplinary Collaborative Group for the Scientific Monitoring of COVID-19 (GCMSC) presents its third report where they propose a clear set of case definitions of Post-Acute COVID syndrome (PACS) and its sub-categories and recommend a comprehensive medical examination to characterise the clinical features and complications when assessing PACS

Reactogenicity to the mRNA-1273 Booster According to Previous mRNA COVID-19 Vaccination

COVID-19-vaccination; Adverse reactions; Booster doseVacunación de COVID-19; Reacciones adversas; Dosis de refuerzoVacunació de COVID-19; Reaccions adverses; Dosi de reforçThe objective of this study was to assess the local and systemic adverse reactions after the administration of a COVID-19 mRNA-1273 booster between December 2021 and February 2022 by comparing the type of mRNA vaccine used as primary series (mRNA-1273 or BNT162b2) and homologous versus heterologous booster in health care workers (HCW). A cross-sectional study was performed in HCW at a tertiary hospital in Barcelona, Spain. A total of 17% of booster recipients responded to the questionnaire. The frequency of reactogenicity after the mRNA-1273 booster (88.5%) was similar to the mRNA-1273 primary doses (85.8%), and higher than the BNT162b2 primary doses (71.1%). The reactogenicity was similar after receiving a heterologous booster compared to a homologous booster (88.0% vs. 90.2%, p = 0.3), and no statistically significant differences were identified in any local or systemic reactions. A higher frequency of medical leave was identified in the homologous booster dose group vs. the heterologous booster dose group (AOR 1.45; 95% CI: 1.00–2.07; p = 0.045). Our findings could be helpful in improving vaccine confidence toward heterologous combinations in the general population and in health care workers

Coordinated response to imported vaccine-derived poliovirus infection, Barcelona, Spain, 2019-2020

In 2019, the Public Health Agency of Barcelona, Spain, was notifi ed of a vaccine-derived poliovirus infection. The patient had an underlying common variable immunodefi ciency and no signs of acute fl accid paralysis. We describe the ongoing coordinated response to contain the infection, which included compassionate-use treatment with pocapavir

Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018

Bordetella pertussis not expressing pertactin has increased in countries using acellular pertussis vaccines (ACV). The deficiency is mostly caused by pertactin gene disruption by IS481. To assess the effect of the transition from whole-cell vaccine to ACV on the emergence of B. pertussis not expressing pertactin in Spain, we studied 342 isolates collected during 1986-2018. We identified 93 pertactin-deficient isolates. All were detected after introduction of ACV and represented 38% of isolates collected during the ACV period; 58.1% belonged to a genetic cluster of isolates carrying the unusual prn::del(-292, 1340) mutation. Pertactin inactivation by IS481 insertion was identified in 23.7% of pertactin-deficient isolates, arising independently multiple times and in different phylogenetic branches. Our findings support the emergence and dissemination of a cluster of B. pertussis with an infrequent mechanism of pertactin disruption in Spain, probably resulting from introduction of ACV.This work was supported by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, and cofinanced by the European Regional Development Fund “A Way to Achieve Europe” (Spanish Network for Research in Infectious Diseases, grant no. FIS PI18/00703) and by the Centro de Investigación Biomédica en Red (CIBER de Enfermedades Infecciosas), the Red Española de Investigación en Patología Infecciosa (grant no. CB21/13/00054). A.M.C. is supported by the Agència de Gestió d’Ajuts Universitaris i de Recerca de la Generalitat de Catalunya at Vall d’Hebron Institut de Recerca (Ajuts per a la Contractació de Personal Investigador FI, grant no. 2020FI_B2_00145) and by the Spanish Network for Research in Infectious Diseases (grant no. RD16/ 0016/0003). A.M.M. is supported by a grant from the Fondo de Investigación Sanitaria at Vall d’Hebron Institut de Recerca (Contratos Predoctorales de Formación en Investigación, grant no. FI19/00315).S

BA.5 Omicron subvariant in Catalonia: Current impact and recommendations for booster vaccination strategies

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóCirculation of the Omicron BA.5 subvariant has led to a considerable increase in cases and also in hospitalisations (but not severe cases or deaths) in recent weeks in Catalonia, the rest of Spain and many other countries. Based on scientific evidence and the current epidemiological situation, the Multidisciplinary Collaborative Group for the Scientific Monitoring of COVID-19 (GCMSC) has conducted an analysis of the impact of the BA-5 subvariant in Catalonia and, with the support of the COVID-19 Scientific Advisory Committee (CCAC) attached to the Department of Health of the Government of Catalonia, has issued a series of recommendations for booster vaccination strategies

COVID-19 Immunisation Strategy: Priority Populations

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóWith a limited initial supply of COVID-19 vaccines doses and an expected delay for the universal vaccination of those eligible to receive it, it is relevant to analyse how best to prioritise the first available doses to achieve the greatest impact, both in terms of protecting individuals and minimising community transmission. Ethical issues are key in guiding a fair distribution. Different scenarios on vaccine implementation are summarised in this report. After a critical review of the documents and considering that these criteria are applied to Spanish citizens, the members of theGCMSC establish a priority vaccination list based on ethical principles and adapted to our count

Attributes influencing parental decision-making to receive the Tdap vaccine to reduce the risk of pertussis transmission to their newborn – outcome of a crosssectional conjoint experiment in Spain and Italy

Pertussis vaccination of parents and household contacts (‘cocooning’) to protect newborn infants is an established strategy in many countries, although uptake may be low. Many aspects may influence such decision-making. We conducted a cross-sectional survey (NCT01890447) of households and other close contacts of newborns aged ≤6 months (or of expectant mothers in their last trimester) in Spain and Italy, using an adaptive discrete-choice experiment questionnaire. Aims were to assess the relative importance of attributes influencing vaccine adoption, and to estimate variation in vaccine adoption rates and the impact of cost on vaccination rates. Six hundred and fifteen participants (Spain, n = 313; Italy, n = 302) completed the survey. Of 144 available questionnaire scenarios, the most frequently selected (14% of respondents in both countries) were infant protection by household vaccination at vaccination center, recommendation by family physician and health authorities, with information available on leaflets and websites. The attribute with highest median relative importance was ‘reduction in source of infection’ in Spain (23.1%) and ‘vaccination location’ in Italy (18.8%). Differences between other attributes were low in both countries, with media attributes showing low importance. Over 80% of respondents indicated a definite or probable response to vaccine adoption (at no-cost) with estimated probability of adoption of 89–98%; applying vaccine costs (25€ per person) would reduce the probability of uptake by 7–20% in definite/probable respondents. Awareness of these determinants is helpful in informing Health Authorities and healthcare practitioners implementing a cocooning strategy for those populations where maternal immunization is not a preferred option