Correlates of protection and determinants of SARS-CoV-2 breakthrough infections 1 year after third dose vaccination.

BACKGROUND: The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. METHODS: We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. RESULTS: Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26-0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. CONCLUSIONS: Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections.

SARS-CoV-2 Seroprevalence and Antibody Kinetics Among Health Care Workers in a Spanish Hospital After 3 Months of Follow-up.

BACKGROUND: At the COVID-19 spring 2020 pandemic peak in Spain, prevalence of SARS-CoV-2 infection in a cohort of 578 randomly selected health care workers (HCWs) from Hospital Clínic de Barcelona was 11.2%. METHODS: A follow-up survey 1 month later (April-May 2020) measured infection by rRT-PCR and IgM, IgA, and IgG to the receptor-binding domain of the spike protein by Luminex. Antibody kinetics, including IgG subclasses, was assessed until month 3. RESULTS: At month 1, the prevalence of infection measured by rRT-PCR and serology was 14.9% (84/565) and seroprevalence 14.5% (82/565). We found 25 (5%) new infections in 501 participants without previous evidence of infection. IgM, IgG, and IgA levels declined in 3 months (antibody decay rates 0.15 [95% CI, .11-.19], 0.66 [95% CI, .54-.82], and 0.12 [95% CI, .09-.16], respectively), and 68.33% of HCWs had seroreverted for IgM, 3.08% for IgG, and 24.29% for IgA. The most frequent subclass responses were IgG1 (highest levels) and IgG2, followed by IgG3, and only IgA1 but no IgA2 was detected. CONCLUSIONS: Continuous and improved surveillance of SARS-CoV-2 infections in HCWs remains critical, particularly in high-risk groups. The observed fast decay of IgA and IgM levels has implications for seroprevalence studies using these isotypes.

Cellular and humoral response after MRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients.

According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-naïve. After vaccination, naïve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with antithymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.

Jumping rope and whole-body vibration program effects on bone values in Olympic artistic swimmers.

INTRODUCTION: Artistic swimming seems not to benefit bone development like other out-of-water physical activities. To increase bone acquisition, artistic swimming should combine water training with weight-bearing impact or strength activities. Artistic swimmers can be a population at risk of developing osteopenia and osteoporosis in later life. The aim of the present study was to evaluate the effects of a training program on bone mineral density (BMD), bone mineral content (BMC) and body composition in an Olympic artistic swimming team. METHODS: Sixteen women aged 17-21 years, who train 30 h/week, at the Olympic Training Centre (Barcelona, Spain), were followed up over two seasons. The 1st season involved regular artistic swimming training without specific training to reduce the risk of osteopenia. The exercise intervention, jumping rope and whole-body vibration, was added in the 2nd season. The protocol included 20 min of training 2 days per week, over a 22-week period. Dual energy x-ray absorptiometry measured the bone variables and body composition. The daily diet, medical history and bone turnover markers were evaluated. RESULTS: The intervention program increased BMD on lumbar spine (2.10%, p = 0.002), total hip (2.07%, p = 0.001), and femoral neck (2.39%, p = 0.02). Lower limb's fat mass decreased (10.17%, p = 0.038). No significant differences were found for any of the measured anthropometric characteristics between both time points in the 1st season. In conclusions, combined jump rope and vibration should be considered to reduce the risk of bone damage in artistic swimmers.

The COVID-19 Pandemic-an Epidemiological Perspective.

PURPOSE OF REVIEW: The ongoing COVID-19 pandemic is a matter of great concern worldwide. After the first wave, several countries, notably in the European Union, are suffering a very rapid increase in the number of cases in the pandemic second wave. Health systems are under stress; hospital beds and ICU beds are increasingly occupied by COVID-19 patients, and hospitals are struggling to keep their normal operations. We review some basic epidemiological data of this new disease, regarding its appearance, reproductive rate, ways of transmission, number of cases, death rate, usefulness of diagnostic tests, basic treatment options, and prevention and control strategies, including vaccines. RECENT FINDINGS: The basic control strategy falls into two well established categories: active attack (control) or organized defense (mitigation). The control strategy relies on classic testing, tracing, and tracking possible cases of COVID-19. Those actions draw from classical epidemiology: to actively find and detect cases, isolate if positive for 10 days and treat when needed. At the same time, the search for close contacts, test them when needed and quarantine and monitor for 10 to 14 days in order to break chains of transmission. The mitigation strategy include basic measures to protect people at increased risk of severe illness, like social distancing, wearing a mask when social distancing is not possible, avoiding crowds, avoiding indoor crowded spaces, increase ventilation indoors and washing or sanitizing hands often. They include also targeted restrictions in people's mobility, and lock-downs, widely used during the first wave in order to spare the health system, become overwhelmed and increasingly used in Europe once more in the current strong second wave. Waiting for effective and safe vaccines and treatments, stopping the ongoing COVID-19 transmission is our only defense wall. We do not know yet which strategy or strategies worked best. We all must work as a team to give an adequate response to this pandemic. We have just one world and one health. Nobody will be safe until everybody is safe.

Multi-professional simulation and risk perception of health care workers caring for Ebola-infected patients.

INTRODUCTION: Treatment of infections that require high-level isolation can cause anxiety and fear among health care workers. Adequate and complete multi-professional simulation-based training could reduce those feelings and improve patient care. OBJECTIVE: The purpose of this study was to assess the impact of multi-professional simulation-based training on the risk perception and preparedness of health care workers (registered nurses, doctors and ancillary staff) who care for patients assessed to be at risk or confirmed to have Ebola, level 3-4 biohazard. METHODS: A prospective before-after study was designed. Health care workers who participated in a multi-professional simulation training course to improve the care of patients potentially infected with Level 3 and 4 biohazards were evaluated about their risk perception. The training was based on clinical scenarios. The evaluation was conducted using questionnaire based on Likert scale. After the training, a satisfaction survey about the most important aspects of the course was also conducted. RESULTS: Fifty-eight health care workers participated in the training course, 22 of whom were registered nurses. Participants presented positive changes after the training, increasing their sense of security, predisposition and confidence (p < 0.000001 for all). CONCLUSION: Multi-professional simulation-based training significantly improves the perception of safety and preparedness of health care workers regarding the care of patients potentially infected with Ebola virus and other Level 3-4 biohazards. RELEVANCE TO CLINICAL PRACTICE: The implementation of educational training strategies - such as simulations - is beneficial in improving the capacity of response and coping, as well as in reducing feelings of fear and insecurity.

Prediction of higher cost of antiretroviral therapy (ART) according to clinical complexity. A validated clinical index.

BACKGROUND: The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. OBJECTIVE: To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. METHODS: Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. RESULTS: In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). CONCLUSIONS: The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity.

[Immigrant perceptions of the Spanish National Healthcare System and its services]. / Percepciones de un grupo de inmigrantes sobre el Sistema Nacional de Salud y sus servicios.

OBJECTIVE: To analyse the perception, use and satisfaction of a group of immigrants living in Barcelona taking into account their gender, origin and social class. DESIGN: Cross sectional study. LOCATION: City of Barcelona, Spain. PARTICIPANTS: A group of 225 immigrant residents and users of social services in the city of Barcelona, from June to July 2012. MAIN MEASURES: the level of access and relationship with the public health system of immigrants living in Barcelona was analysed, based on a questionnaire. The responses were analysed in relation to: gender, age, social class, self-perceived health, national origin, time since arrival, and marital status. RESULTS: The large majority (89%) of the population surveyed declared that the most important aspect was «to have been treated with respect¼ in health services. However, 59.4% reported a perception of «discrimination against immigrants¼, and 68.4% said that cultural differences affect «totally or partially¼ the quality of care received. For 66.7% of the participants, health care received in Barcelona is better than in their home country, mainly for its scientific, technical quality, and universal access. CONCLUSIONS: Despite the good assessment of universal public health care system this study showed deficiencies of the system in terms of the psychosocial component of health care to immigrants in Barcelona. It is necessary to deepen the study of knowledge and perceptions of minority groups in the current context.

Educating on professional habits: attitudes of medical students towards diverse strategies for promoting influenza vaccination and factors associated with the intention to get vaccinated.

BACKGROUND: Influenza vaccination coverage in medical students is usually low. Unlike health care workers, there is little information on the attitudes to and predictors of vaccination among medical students, and their attitudes towards institutional strategies for improving rates are unknown. METHODS: This cross-sectional study evaluated the effect of three influenza vaccination promotional strategies (Web page, video and tri-fold brochure) on medical students' intention to get vaccinated and associated factors. A total of 538 medical students were asked to answer an anonymous questionnaire assessing the intention to get vaccinated after exposure to any of the promotional strategies. Sociodemographic data collected included: sex, age, university year, influenza risk group and cohabiting with member of a risk group. RESULTS: Four hundred twenty-one students answered the questionnaire, of whom 312 (74.1%) were female, 113 (26.8%) had done clinical rotations, and 111 (26.6%) reported intention to get the flu shot. Logistic regression showed the web group had a greater intention to get vaccinated than the reference group (OR: 2.42 95% CI: 1.16-5.03). Having done clinical rotations (OR: 2.55 95% CI: 1.36-4.38) and having received the shot in previous flu seasons (OR: 13.69 95% CI: 7.86-23.96) were independently associated with the intention to get vaccinated. CONCLUSION: Given that previous vaccination is a factor associated with the intention to get vaccinated, education on vaccination of health care workers should begin while they are students, thereby potentiating the habit. In addition, the intention to get vaccinated was greater during the clinical phase of the university career, suggesting this is a good time to introduce promotion strategies. Online promotional campaigns, such as a thematic Web to promote vaccination of health workers, could improve the intention to get vaccinated.

Development and Promotion of an mHealth App for Adolescents Based on the European Code Against Cancer: Retrospective Cohort Study.

BACKGROUND: Mobile health technologies, underpinned by scientific evidence and ethical standards, exhibit considerable promise and potential in actively engaging consumers and patients while also assisting health care providers in delivering cancer prevention and care services. The WASABY mobile app was conceived as an innovative, evidence-based mobile health tool aimed at disseminating age-appropriate messages from the European Code Against Cancer (ECAC) to adolescents across Europe. OBJECTIVE: This study aims to assess the outcomes of the design, development, and promotion of the WASABY app through a 3-pronged evaluation framework that encompasses data on social media promotion, app store traffic, and user engagement. METHODS: The WASABY app's content, cocreated with cancer-focused civil society organizations across 6 European countries, drew upon scientific evidence from the ECAC. The app's 10 modules were designed using the health belief model and a gamification conceptual framework characterized by spaced repetition learning techniques, refined through 2 rounds of testing. To evaluate the effectiveness of the app, we conducted a retrospective cohort study using the WASABY app's user database registered from February 4 to June 30, 2021, using a 3-pronged assessment framework: social media promotion, app store traffic, and user engagement. Descriptive statistics and association analyses explored the relationship between sociodemographic variables and user performance analytics. RESULTS: After extensive promotion on various social media platforms and subsequent traffic to the Apple App and Google Play stores, a sample of 748 users aged between 14 and 19 years was included in the study cohort. The selected sample exhibited a mean age of 16.08 (SD 1.28) years and was characterized by a predominant representation of female users (499/748, 66.7%). Most app users identified themselves as nonsmokers (689/748, 92.1%), reported either no or infrequent alcohol consumption (432/748, 57.8% and 250/748, 33.4%, respectively), and indicated being physically active for 1 to 5 hours per week (505/748, 67.5%). In aggregate, the app's content garnered substantial interest, as evidenced by 40.8% (305/748) of users visiting each of the 10 individual modules. Notably, sex and smoking habits emerged as predictors of app completion rates; specifically, male and smoking users demonstrated a decreased likelihood of successfully completing the app's content (odds ratio 0.878, 95% CI 0.809-0.954 and odds ratio 0.835, 95% CI 0.735-0.949, respectively). CONCLUSIONS: The development and promotion of the WASABY app presents a valuable case study, illustrating the effective dissemination of evidence-based recommendations on cancer prevention within the ECAC through an innovative mobile app aimed at European adolescents. The data derived from this study provide insightful findings for the implementation of Europe's Beating Cancer Plan, particularly the creation of the EU Mobile App for Cancer Prevention.

Implementation of a quality management system in a liver transplant programme.

BACKGROUND: The management of liver transplantation has become a complex process involving different healthcare professionals. Teamwork, standardisation and definition of the best practices are essential for success, patient satisfaction and society's favourable perception of transplantation programmes.ISO 9001:2015 certification provides the necessary elements to help implement a quality management system (QMS) to ensure that patient care is performed with the highest guarantees of clinical quality and safety. The aim of this study is to describe the steps, strengths and limitations in the implementation of a QMS in a liver transplant programme (LTP). PROJECT MANAGEMENT METHOD: This included analysing the starting point, setting up a working group, training, defining the scope of certification, preparing documentation, and conducting an internal and external audit, which culminated in the ISO 9001 quality certification award. The scope of QMS includes all the processes of LTP, from referral of candidates to long-term follow-up after transplantation. RESULTS: The project was structured in seven phases that took place between 2008 and 2011. The implementation of QMS led to the generation of all the necessary documentation to meet the requirements of the standard, including internal and legal requirements related to the transplant activity. The establishment of indicators to measure the effectiveness of processes, risk management and the identification of incidents allows us to implement measures devoted to avoiding the deficiencies and to meet the established objectives. CONCLUSION: ISO 9001:2015 certification has contributed to the adaptation of a new quality and safety culture focused on the patient. All activities are protocolised, everything is recorded, measured, and verified, and all steps are taken as planned. Work is carried out in terms of continuous improvement. This has led to less variability in daily clinical practice and a better understanding of work dynamics.

Effectiveness of COVID-19 Vaccination Mandates and Incentives in Europe.

During 2021-2022 many countries in the European region of the World Health Organization (WHO) adopted mandatory and incentive-based vaccination measures to stimulate immunization against COVID-19. The measures ranged from positive incentive-based programs (i.e., cash incentives, meal discounts, and lotteries) to introducing COVID-19 certificates and enforcing the universal mandatory vaccination with fines. We assessed the effect of such interventions on COVID-19 vaccine uptake in the population of eight countries within the region. An interrupted time series (ITS) analysis was performed using an autoregressive integrated moving average (ARIMA) approach to account for autocorrelation and seasonality. The results showed the immediate positive impact of vaccination incentives on vaccine uptake in most cases, with the highest impact being cash incentives for the population (1197 per million population per day). Discount incentives did not show any significant impact. The introduction of COVID-19 certificates was associated with a significant immediate or gradual increase in daily administered vaccine doses in all the countries included in the study, up to 117,617 doses gained per million per month. The effect of mandatory vaccination for all or some groups of the population varied from a continuous decrease in daily administered doses (332 per million capita per day), no significant effect, or a delayed or temporary increase (1489 per million capita per day).

Knowledge, attitudes, beliefs and barriers of healthcare professionals and adults ≥ 65 years about vaccine-preventable diseases in Spain: the ADult Vaccination drIverS and barriErs (ADVISE) study.

Since 2018, Spanish National Immunization Guidelines include vaccination recommendations for adults ≥65 years. To determine whether health-care professionals and the ≥65 years target group value the need for these recommendations, a cross-sectional study was conducted to capture and describe their knowledge, attitudes, beliefs and behaviors about vaccination. Online surveys were administered to representative groups of general practitioners (GPs), primary care nurses and adults ≥65 years from six major cities (and surrounding rural areas) in Spain. Main topics were attitudes and awareness of vaccines, perceptions about vaccination in adults ≥65 years, and impact of the COVID-19 pandemic on vaccination uptake. A total of 286 health-care professionals (185 GPs, 101 nurses) and 400 adults aged ≥65 years participated in the survey. GP and nurse groups agreed strongly about the importance of influenza and pneumococcal vaccination in the target population. Longer patient visit times were identified as a key factor toward promoting vaccination. The ≥65 years sample group, especially those ≥75+ years and/or with chronic diseases, was reasonably positive about the effectiveness and benefits of vaccines. Lower vaccination rates for the pneumococcal than influenza vaccine (29% vs. 80%) in the ≥65 years sample group suggest that efforts are needed to improve pneumococcal vaccine uptake. Aligning with other published works, GPs have a key role in promoting vaccination in the target population. The COVID-19 pandemic appears to have heightened awareness about the importance of vaccination among health-care professionals and adults ≥65 years.

Tolerability and Reactogenicity Profile of mRNA SARS-Cov-2 Vaccines from a Mass Vaccination Campaign in a Tertiary Hospital: Between-Vaccine and Between-Population Prospective Observational Study (VigilVacCOVID Study).

BACKGROUND: The comparative safety profile of SARS-Cov2 vaccines requires further characterization in real-world settings. OBJECTIVES: The aim of the VigilVacCOVID study was to assess the short-term safety of BNT162b2 and mRNA-1273 during the vaccination campaign of healthcare professionals (HCPs) and solid-organ transplant recipients (SOTRs) at a hospital clinic. METHODS: We conducted an observational, prospective, single-center, post-authorization study to characterize short-term adverse reactions (ARs) after vaccination. The primary endpoint was to assess between-vaccine differences (HCPs receiving BNT162b2 or mRNA-1273) and between-population differences (HCPs and SOTRs, both receiving mRNA-1273) in the risk of any ARs. Propensity score and covariate-adjusted multivariate models were used. The key secondary endpoint was to provide a descriptive assessment of the frequencies and intensity distribution of ARs. RESULTS: We included 5088 HCPs and 1289 patients. mRNA-1273 showed greater reactogenicity than BNT162b2, with an odds ratio (OR) for any AR of 3.04 (95% confidence interval (CI) 2.48-3.73; p value: < 0.001) and a higher frequency and intensity of reported ARs. Compared with HCPs vaccinated with mRNA-1273, SOTRs showed a lower risk of ARs (OR = 0.36; 95% CI 0.25-0.50), with fewer and less severe ARs. Age, sex, and previous SARS-CoV-2 infection were statistically significant covariates for the risk of any AR. A history of drug allergy was significant in the comparison between vaccines (BNT162b2 vs. mRNA-1273), but not in that between SOTRs and HCPs. CONCLUSIONS: Our study shows that mRNA-1273 had greater reactogenicity than BNT162b2. Overall, both vaccines had an adequate tolerability profile. mRNA-1273 vaccination caused fewer ARs with milder severity in SOTRs.

SARS-CoV2 hospital surveillance and control system with contact tracing for patients and health care workers at a large reference hospital in Spain during the first wave: An observational descriptive study.

BACKGROUND AND AIMS: During the first peak of the COVID-19 pandemic, the Preventive Medicine Department and the Occupational Health Department at Hospital Clinic de Barcelona (HCB), a large Spanish referral hospital, developed an innovative comprehensive SARS-CoV2 Surveillance and Control System (CoSy-19) in order to preserve patients' and health care workers' (HCWs) safety. We aim to describe the CoSy-19 and to assess the impact in the number of contacts that new cases generated along this time. METHODS: Observational descriptive study of the findings of the activity of contact tracing of all cases received at the HCB during the first peak of COVID-19 in Spain (February 25th-May 3rd, 2020). RESULTS: A team of 204 professionals and volunteers performed 384 in-hospital contact-tracing studies which generated contacts, detecting 298 transmission chains which suggested preventive measures, generated around 22 000 follow-ups and more than 30 000 days of work leave. The number of contacts that new cases generated decreased during the study period. CONCLUSION: Coordination between Preventive Medicine and Occupational Health departments and agile information systems were necessary to preserve non-COVID activity and workers safety.

Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers.

BACKGROUND: Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. METHODS: We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. FINDINGS: Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. INTERPRETATION: Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. FUNDING: This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.

Humoral and Cellular Immune Responses After a 3-dose Course of mRNA-1273 COVID-19 Vaccine in Kidney Transplant Recipients: A Prospective Cohort Study.

In kidney transplant recipients, there is discordance between the development of cellular and humoral response after vaccination against SARS-CoV-2. We sought to determine the interplay between the 2 arms of adaptive immunity in a 3-dose course of mRNA-1273 100 µg vaccine. Methods: Humoral (IgG/IgM) and cellular (N- and S-ELISpot) responses were studied in 117 kidney and 12 kidney-pancreas transplant recipients at the following time points: before the first dose, 14 d after the second dose' and before and after the third dose, with a median of 203 and 232 d after the start of the vaccination cycle, respectively. Results: After the second dose, 26.7% of naive cases experienced seroconversion. Before the third dose and in the absence of COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion occurred in 80.0% of patients. Naive patients who had at any time point a detectable positivity for S-ELISpot were 75.2% of the population, whereas patients who maintained S-ELISpot positivity throughout the study were 34.3%. S-ELISpot positivity at 42 d was associated with final seroconversion (odds ratio' 3.14; 95% confidence interval' 1.10-8.96; P = 0.032). Final IgG titer was significantly higher in patients with constant S-ELISpot positivity (P < 0.001). Conclusions: A substantial proportion of kidney transplant recipients developed late seroconversion after 2 doses. Cellular immunity was associated with the development of a stronger humoral response.

A statistical model for hospital admissions caused by seasonal diseases.

We present a model based on two-order integer-valued autoregressive time series to analyze the number of hospital emergency service arrivals caused by diseases that present seasonal behavior. We also introduce a method to describe this seasonality, on the basis of Poisson innovations with monthly means. We show parameter estimation by maximum likelihood and model validation and show several methods for forecasting, on the basis of long-time means and short-time and long-time prediction regions. We analyze an application to model the number of hospital admissions per week caused by influenza.

Effectiveness of Mandatory and Incentive-Based Routine Childhood Immunization Programs in Europe: A Systematic Review of the Literature.

There is a lack of comprehensive and systematic data and evidence regarding the effectiveness of mandatory and incentive-based vaccination schemes. The results of such programs in some countries have not been adequately studied. A number of countries have recently introduced tightening vaccination measures, and it is important to analyze and assess the results of these programs. The unprecedented situation due to the COVID-19 pandemic and mass vaccination made the topic of the effectiveness of vaccination policies and mandates even more relevant. The aim of the study is to assess childhood vaccination programs implemented in selected countries. The study focuses on initiatives implemented in the European Region of the World Health Organization (WHO). A total of 466 full-text articles were assessed for eligibility, and 26 articles on seven countries were included in the synthesis. Additionally, we obtained and performed an analysis of data on the impact of COVID-19 on vaccine coverage and incidence of vaccine-preventable diseases, and the implementation of vaccine mandates in the selected countries. The evidence collected and analyzed in this review allowed us to conclude that the introduction of children routine vaccination mandates increases vaccine coverage and reduces the incidence of vaccine-preventable diseases when compared to the situation before the introduction of the mandates.

Low birth weight as a potential risk factor for severe COVID-19 in adults.

The identification of factors predisposing to severe COVID-19 in young adults remains partially characterized. Low birth weight (LBW) alters cardiovascular and lung development and predisposes to adult disease. We hypothesized that LBW is a risk factor for severe COVID-19 in non-elderly subjects. We analyzed a prospective cohort of 397 patients (18-70 years) with laboratory-confirmed SARS-CoV-2 infection attended in a tertiary hospital, where 15% required admission to Intensive Care Unit (ICU). Perinatal and current potentially predictive variables were obtained from all patients and LBW was defined as birth weight ≤ 2.500 g. Age (adjusted OR (aOR) 1.04 [1-1.07], P = 0.012), male sex (aOR 3.39 [1.72-6.67], P < 0.001), hypertension (aOR 3.37 [1.69-6.72], P = 0.001), and LBW (aOR 3.61 [1.55-8.43], P = 0.003) independently predicted admission to ICU. The area under the receiver-operating characteristics curve (AUC) of this model was 0.79 [95% CI, 0.74-0.85], with positive and negative predictive values of 29.1% and 97.6% respectively. Results were reproduced in an independent cohort, from a web-based survey in 1822 subjects who self-reported laboratory-positive SARS-CoV-2 infection, where 46 patients (2.5%) needed ICU admission (AUC 0.74 [95% CI 0.68-0.81]). LBW seems to be an independent risk factor for severe COVID-19 in non-elderly adults and might improve the performance of risk stratification algorithms.