Humoral immunity induced by mRNA COVID-19 vaccines in Nursing Home Residents previously infected with SARS-CoV-2.

BACKGROUND: Nursing home (NH) residents suffered the greatest impact of the COVID-19 pandemic. Limited data are available on vaccine-induced immunity and on the protection ensured by a prior infection in this population. AIMS: The present study aims to monitor antibody levels and their persistence over a 6-month period in NH residents according to the history of prior SARS-CoV-2 infection. METHODS: We measured anti-trimeric Spike IgG antibody levels in a sample of 395 residents from 25 NHs in 6 Italian Regions at study enrolment (prior to the first dose of vaccine, T0) and then after 2 (T1) and 6 months (T2) following the first vaccine dose. All participants received mRNA vaccines (BNT162b2 or mRNA-1273). Analyses were performed using log-transformed values of antibody concentrations and geometric means (GM) were calculated. RESULTS: Superior humoral immunity was induced in NH residents with previous SARS-CoV-2 infection. (T0: GM 186.6 vs. 6.1 BAU/ml, p < 0.001; T1: GM 5264.1 vs. 944.4 BAU/ml, p < 0.001; T2: GM 1473.6 vs. 128.7 BAU/ml, p < 0.001). Residents with prior SARS-CoV-2 infection receiving two vaccine doses presented significantly higher antibody concentration at T1 and T2. A longer interval between previous infection and vaccination was associated with a better antibody response over time. DISCUSSION: In a frail sample of NH residents, prior SARS-CoV-2 infection was associated with a higher humoral response to vaccination. Number of vaccine doses and the interval between infection and vaccination are relevant parameters in determining humoral immunity. CONCLUSIONS: These findings provide important information to plan future immunization policies and disease prevention strategies in a highly vulnerable population.

Trend in potassium intake and Na/K ratio in the Italian adult population between the 2008 and 2018 CUORE project surveys.

BACKGROUND AND AIMS: Low potassium intake, in addition to high sodium, has been associated with higher risk of hypertension and CVD. The Study assessed habitual potassium intake and sodium/potassium ratio of the Italian adult population from 2008 to 2012 to 2018-2019 based on 24-h urine collection, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU' SALUTE national surveys. METHODS AND RESULTS: Data were from cross-sectional surveys of randomly selected age-and-sex stratified samples of resident persons aged 35-74 years in 10 (out of 20) Italian regions. Urinary electrolyte and creatinine measurements were performed in a central laboratory. Analyses considered 942 men and 916 women, examined in 2008-2012, and 967 men and 1010 women, examined in 2018-2019. In 2008-2012, the age-standardized mean of potassium intake (urinary potassium accounts for 70% of potassium intake) was 3147 mg (95% CI 3086-3208) in men and 2784 mg (2727-2841) in women, whereas in 2018-2019, it was 3043 mg (2968-3118) and 2561 mg (2508-2614) respectively. In 2008-2012, age-adjusted prevalence of persons with an adequate potassium intake (i.e. ≥ 3510 mg/day) was 31% (95% CI 28-34%) for men and 18% (16-21%) for women; in 2018-2019, it was 26% (23-29%) and 12% (10-14%) respectively. The sodium/potassium ratio significantly decreased both in men and women. CONCLUSIONS: The average daily potassium intake of the Italian general adult population remains lower than the WHO and EFSA recommended level. These results suggest the need of a revision to strengthen initiatives for the promotion of an adequate potassium intake at the population level.

Trend of salt intake measured by 24-h urine collection in the Italian adult population between the 2008 and 2018 CUORE project surveys.

BACKGROUND AND AIMS: The WHO Global Action Plan for the Prevention of non-communicable diseases (NCDs) recommends a 30% relative reduction in mean population salt/sodium intake. The study assessed the trend in the habitual salt intake of the Italian adult population from 2008 to 2012 to 2018-2019 based on 24-h urinary sodium excretion, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU' SALUTE national surveys. METHODS AND RESULTS: Data were from cross-sectional surveys of randomly selected age and sex-stratified samples of resident persons aged 35-74 years in 10 (out of 20) Italian Regions distributed in North, Centre and South of the Country. Urinary sodium and creatinine measurements were carried out in a central laboratory. The analyses included 942 men and 916 women examined in 2008-2012, and 967 men and 1010 women examined in 2018-2019. The age-standardized mean daily population salt (sodium chloride) intake was 10.8 g (95% CI 10.5-11.1) in men and 8.3 g (8.1-8.5) in women in 2008-2012 and respectively 9.5 g (9.3-9.8) and 7.2 g (7.0-7.4) in 2018-2019. A statistically significant (p<0.0001) salt intake reduction was thus observed over 10 years for both genders, and all age, body mass index (BMI) and educational classes. CONCLUSIONS: The average daily salt intake of the Italian general adult population remains higher than the WHO recommended level, but a significant reduction of 12% in men and 13% in women has occurred in the past ten years. These results encourage the initiatives undertaken by the Italian Ministry of Health aimed at the reduction of salt intake at the population level.

Nutrition, Physical Activity and Smoking Habit in the Italian General Adult Population: CUORE Project Health Examination Survey 2018-2019.

BACKGROUND: Tobacco consumption, incorrect nutrition and insufficient physical activity/sedentariness represent modifiable NCDs risk factors in Western countries. To evaluate recent lifestyle indicators in Italy, data from the national Health Examination Survey (HES), implemented in 2018-2019 within the CUORE Project, were assessed. METHODS: Age-sex standardized results from random samples of Italian general population (35-74 years) were reported by sex, age-class, educational level and geographical area. From 2106 participants, 2090 were considered for smoking habit, 2016 for physical activity and 1578 for nutrition. Standardized questionnaires were used for smoking habit and physical activity, and the EPIC questionnaire for nutrition. RESULTS: Total cigarette current smokers were 23% in men and 19% in women; sedentariness during leisure time was 34% in men and 45% in women and at work 45% and 47% in men and women, respectively. Prevalence of balanced eating behaviours for vegetables was 28% in men and 39% in women; and for fruits 50% and 52%, respectively; prevalence of correct lifestyle (not smoker, regular physical activity and following at least five correct eating behaviours) was 7% and 12% for men and women, respectively. CONCLUSIONS: In 2018-2019, levels of unhealthy lifestyles were found to be still epidemic and basically stable compared to 10 years earlier (slight smoking habit decrease, slight sedentariness increase and slight nutrition improvements); intersectoral strategies and monitoring need to be continued.

T-Cell Mediated Response after Primary and Booster SARS-CoV-2 Messenger RNA Vaccination in Nursing Home Residents.

OBJECTIVES: Nursing home (NH) residents have been significantly affected by the coronavirus disease 2019 (COVID-19) pandemic. Studies addressing the immune responses induced by COVID-19 vaccines in NH residents have documented a good postvaccination antibody response and the beneficial effect of a third booster vaccine dose. Less is known about vaccine-induced activation of cell-mediated immune response in frail older individuals in the long term. The aim of the present study is to monitor messenger RNA SARS-CoV-2 vaccine-induced T-cell responses in a sample of Italian NH residents who received primary vaccine series and a third booster dose and to assess the interaction between T-cell responses and humoral immunity. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: Thirty-four residents vaccinated with BNT162b2 messenger RNA SARS-CoV-2 vaccine between February and April 2021 and who received a third BNT162b2 booster dose between October and November 2021 were assessed for vaccine-induced immunity 6 (prebooster) and 12 (postbooster) months after the first BNT162b2 vaccine dose. METHODS: Pre- and postbooster cell-mediated immunity was assessed by intracellular cytokine staining of peripheral blood mononuclear cells stimulated in vitro with peptides covering the immunodominant sequence of SARS-CoV-2 spike protein. The simultaneous production of interferon-γ, tumor necrosis factor-α, and interleukin-2 was measured. Humoral immunity was assessed in parallel by measuring serum concentration of antitrimeric spike IgG antibodies. RESULTS: Before the booster vaccination, 31 out of 34 NH residents had a positive cell-mediated immunity response to spike. Postbooster, 28 out of 34 had a positive response. Residents without a previous history of SARS-CoV-2 infection, who had a lower response prior the booster administration, showed a greater increase of T-cell responses after the vaccine booster dose. Humoral and cell-mediated immunity were, in part, correlated but only before booster vaccine administration. CONCLUSIONS AND IMPLICATIONS: The administration of the booster vaccine dose restored spike-specific T-cell responses in SARS-CoV-2 naïve residents who responded poorly to the first immunization, while a previous SARS-CoV-2 infection had an impact on the magnitude of vaccine-induced cell-mediated immunity at earlier time points. Our findings imply the need for a continuous monitoring of the immune status of frail NH residents to adapt future SARS-CoV-2 vaccination strategies.

Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study.

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

Trends of overweight, obesity and anthropometric measurements among the adult population in Italy: The CUORE Project health examination surveys 1998, 2008, and 2018.

BACKGROUND/OBJECTIVES: Obesity is associated with an increased risk of noncommunicable diseases, such as diabetes, coronary heart disease, stroke, cancers, and conditions, including obstructive sleep apnea and osteoarthritis. Obesity is largely preventable, and halting its rise is one of the World Health Organization Global Action Plan for the Prevention of Noncommunicable Diseases targets. This study aimed to assess trends of anthropometric measurements in Italy using the data collected within the CUORE Project health examination surveys (HESs) 1998, 2008, and 2018. SUBJECTS/METHODS: Within the HESs 1998-2002, 2008-2012, and 2018-2019, anthropometric measurements were collected in random samples of the resident population aged 35-74 years, stratified by age and sex, from 10 Italian Regions in Northern, Central, and Southern Italy (2984 men and 2944 women, 2224 men and 2188 women, 1035 men and 1065 women, respectively). Weight, height, and waist and hip circumferences were measured using standardized methodologies. A standardized questionnaire was used to collect data on education. Indicators were age standardized. RESULTS: For both men and women, mean body mass index in 2018 was comparable with those in 1998 and 2008 (in 1998, 2008, and 2018-men: 26.7, 27.5, and 27.0 kg/m2; women: 26.2, 26.6, and 26.3 kg/m2). In 1998, 2008, 2018 prevalence of overweight resulted 49%, 47%, 46% in men and 33%, 32%, 28% in women respectively; prevalence of obesity resulted 17%, 24% 20% in men and 19%, 23%, 23% in women respectively. All indicators of excess weight worsen with increasing age and are more severe in persons with a lower educational level. CONCLUSIONS: Although the overall trend of excess weight over the past two decades appeared to be substantially stable in the Italian adult population, the continuous strengthening of undertaken initiatives should continue since there remains a high proportion of overweight or obesity and a gap between educational levels.

Trends of blood pressure, raised blood pressure, hypertension and its control among Italian adults: CUORE Project cross-sectional health examination surveys 1998/2008/2018.

OBJECTIVES: To assess in the Italian general adult population the trends of blood pressure (BP) and prevalence of raised BP (RBP), hypertension and its control in order to evaluate population health and care, and the achievement of an RBP 25% relative reduction as recommended by the WHO at population level. DESIGN: Results comparison of health examination surveys, cross-sectional observational studies based on health examination of randomly selected age and sex stratified samples including residents aged 35-74 years. Data of the 2018/2019 survey were compared with the previous ones collected in 1998/2002 and 2008/2012. SETTING: Health examination surveys conducted in Italy within the CUORE Project following standardised methodologies. PARTICIPANTS: 2985 men and 2955 women examined in 1998/2002, 2218 men and 2204 women examined in 2008/2012 and 1031 men and 1066 women examined in 2018/2019. PRIMARY AND SECONDARY OUTCOME MEASURES: Age-standardised mean of BP, prevalence of RBP (systolic BP and/or diastolic BP ≥140/90 mm Hg), hypertension (presenting or being treated for RBP) and its awareness and control, according to sex, age class and educational level. RESULTS: In 2018/2019, a significant reduction was observed in systolic BP and diastolic BP in men (1998/2002: 136/86 mm Hg; 2008/2012: 132/84 mm Hg; and 2018/2019: 132/78 mm Hg) and women (132/82 mm Hg, 126/78 mm Hg and 122/73 mm Hg), and in the prevalence of RBP (50%, 40% and 30% in men and 39%, 25% and 16% in women) and of hypertension (54%, 49% and 44% in men and 45%, 35% and 32% in women). Trends were consistent by age and education attainment. In 2018/2019, hypertensive men and women with controlled BP were only 27% and 41%, but a significant favourable trend was observed. CONCLUSIONS: Data from 2018/2019 underlined that RBP is still commonly observed in the Italian population aged 35-74 years, however, the WHO RBP target at that time may be considered met.

Monitoring COVID-19 vaccine use in Italian long term care centers: The GeroCovid VAX study.

The COVID-19 pandemic has changed routine care practice for older persons, especially in those with frailty living in long term care (LTC) facilities. Due to the high mortality rates of Nursing home (NH) residents during the first wave of the COVID-19 pandemic, priority for COVID-19 vaccinations was given to this vulnerable population. However, the safety and efficacy of such vaccines in older frail elders remains questionable due to the fact that initial randomized clinical trials (RCTs) for such vaccines did not include this population. This type of discrimination in patient participation in RCTs continues and has been recognized in the literature. Nevertheless, in the context of a worldwide emergency, COVID-19 vaccination in older persons living in LTC facilities may provide a solid basis to protect against negative outcomes, such as COVID-19 infection and death. In this report, we present the protocol of the GeroCovid Vax study, an Italian study that began in February 2021 which is aimed at investigating the safety and efficacy of the anti-SARS-CoV-2 vaccinations in older persons living in LTCs. This protocol specially aims to continuously and closely monitor events related to- and following- the anti-SARS-CoV-2 vaccination in elderly living in LTC facilities. In this report, we will provide information related to the study protocol and describe baseline characteristics of the sample.

The Perceived Health Status from Young Adults to Elderly: Results of the MEHM Questionnaire within the CUORE Project Survey 2008-2012.

Improving healthy life years requires an effective understanding and management of the process of healthy ageing. Assessing the perceived health status and its determinants is a relevant step in this process. This study explored the potentialities of the Minimum European Health Module (MEHM) to cope with this critical issue. Investigation was conducted on 4798 Italian residents (49.7% women, aged 35-79 years), participating in the CUORE Project Health Examination Survey 2008-2012. The three MEHM questions-perceived health status, chronic morbidity and activity limitations-were examined also in association with living context, seasonality, marital status and level of education. A higher prevalence of health status negative perception was associated with older age (9% and 24% respectively in men and women aged 35-44 years; 46% and 61% respectively in men and women aged 75-79 years). In women, this negative perception was higher than in men in any age group, and reached 50% in the 65-69 age group, 10 years earlier than in men. For both sexes, the level of education had a strong impact on this negative perception (odds ratio 2.32 and 2.72 in men and women respectively), while "living alone" played a greater impact in women than in men. MEHM activity limitations subscale was as much as 30% higher for questionnaires answered during the hottest months. This study identified potential predictors of perceived health status in adults aged 35-79 years, which can be used to target interventions aimed at improving self-perceived health status.

Cardiovascular diseases monitoring: lessons from population-based registries to address future opportunities and challenges in Europe.

BACKGROUND: Population-based registries implement the comprehensive collection of all disease events that occur in a well-characterized population within a certain time period and represent the preferred tools for disease monitoring at a population level. Main characteristics of a Population-based registry are to provide answers to defined research questions, also related to clinical and health policy purposes, assuring completeness of event identification, and implementing a process of case adjudication (validation) according to standardised diagnostic criteria. METHODS: The application of a standard methodology results in the availability of reliable and comparable data and facilitates the transferability of health information for research and evidence-based health policies. Although registries are extremely useful, they require considerable resources to be implemented and maintained, high cost and efforts, to produce stable and reliable indicators. RESULTS: Thanks to available health information and information technology, current administrative databases on hospital admissions and discharges, medication use, in-patient care utilization, surgical operations, drug dispensations, ticket exemption and invasive procedures are increasingly available. They represent basic sources of information for implementing Population-based registries.Main strengths and limitations of Population-based registries are described taking into consideration the example of cardiovascular diseases, as well as future challenges and opportunities for implementing Population-based registries at European level. CONCLUSIONS: The integration of population-based registries and current administrative health databases may help to complete the picture of the disease rebuilding the evolution of the disease as a continuum from the onset to the possible consequent complications.

P4 Medicine versus Hippocrates.

Hippocrates was the first to raise awareness of medicine as a science. He asserted the body being a unified whole and emphasized the importance of preventive and predictive medicine, spurring physicians to foster patient collaboration. Recent achievements today have permitted a new approach "P4 medicine" - Predictive, Preventive, Personalized and Participatory - with the aim of depicting an individual's health history and molecular profile in determining the best medical intervention in maintaining or restoring wellbeing. There is a link, which brings together Hippocrates and P4 Medicine. This review will elaborate further this statement, considering the scientific achievements that paved the way for recent medical approaches. Emphasis will be given to the social impact of new diagnostic and therapeutic protocols, considering their costs and their success probabilities.

Time Trends of High Blood Pressure Prevalence, Awareness and Control in the Italian General Population : Surveys of the National Institute of Health.

INTRODUCTION: High blood pressure (BP) is a major risk factor for cardiovascular disease. The urgency of the problem was underlined by the World Health Organization (WHO) Global Action Plan for the prevention and control of noncommunicable diseases, which recommends a 25% relative reduction in the prevalence of raised BP by 2020. A surveillance system represents a useful tool to monitor BP in the general population. Since 1980s, the National Institute of Health has conducted several surveys of the adult general population, measuring cardiovascular risk factors by standardized procedures and methods. AIM: To describe mean BP levels and high BP prevalence from 1978 to 2012 by sex and quinquennia of age. METHODS: Data were derived from the following three studies: (i) Risk Factors and Life Expectancy (RIFLE), conducted between 1978 and 2002 in 13 Italian regions (>70,000 persons); (ii) Osservatorio Epidemiologico Cardiovascolare (OEC), conducted between 1998-2002 in the general population from all Italian regions (>9000 persons); and (iii) Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey (OEC/HES), conducted between 2008-2012 in the general population from all Italian regions (>9000 persons). RESULTS: A significant decrease in mean systolic and diastolic BP levels and prevalence of high BP from 1978 to 2012 was observed both in men and women. BP and high BP increased by age classes in all considered periods. BP awareness and control also improved. CONCLUSION: Our data suggest that BP control could be achieved by 2020, as recommended by WHO.

[DNA-microarray: new technological approaches on twin studies]. / DNA-microarray: nuovi approcci sperimentali per lo studio dei gemelli.

The completion of the Human Genome Project, and the innovations introduced in biotechnology are changing how to study twins. Here, we summarize some molecular studies performed on populations of discordant monozygotic twins (MZ) applying microarrays. Microarrays are an orderly arrangement of high numbers of probes (DNA, RNA or proteins), immobilized onto a matrix. The microarray approach allows a global analysis of gene expression, and therefore might point out the molecular mechanisms of MZ twins' discordance, such as epigenetic mechanisms. The application of microarray to twin studies will help better define, through bioinformatics, the role of genes and environment in the development of human diseases, thus suggesting new diagnostic and therapeutic approaches.

Cancer: we should not forget the past.

Cancer has been in existence longer than human beings, and man has been facing the illness ever since he made his appearance on Earth. Amazingly, the first human cancer gene was cloned only thirty years ago. This, and other extraordinary scientific goals achieved by molecular cancer research in the last 30 years, seems to suggest that definitive answers and solutions to this severe disease have been finally found. This was not the case, as cancer still remains to be defeated. To do so, cancer must be first understood. This review highlights how cancer onset and progression has been tackled from ancient times to present day. Old theories and achievements have provided the pillars of cancer understanding, in laying the basis of 'modern era' cancer research, are discussed. The review highlights the discovery of oncogenes and suppressor tumor genes, underlining the crucial role of these achievements in cancer diagnosis and therapies. Finally, an overview of how the modern technologies have given impetuous to expedite these goals is also considered.

Rapid methods for identification of poliovirus isolates and determination of polio neutralizing antibody titers in human sera.

A new rapid method for identification and determination of the titer of polioviruses and other enteroviruses in cell monolayers grown in microtiter plates is described. The method is based on immunoperoxidase staining of infected cells with commercial monoclonal antibodies (MAb) and biotin-labeled secondary antibody. The presence of poliovirus or other enteroviruses was established as the appearance of at least one focus of cells with stained cytoplasm 6 h post-infection. Viral titers determined by this method were expressed as focus forming unit (FFU) per ml which was found to correspond approximately to 10 TCID(50)/ml. The suitability of this technique to determine poliovirus antibody titers in human sera was also tested comparing the immunocytochemical neutralization assay with a conventional neutralization in microtiter plates. The test was standardized using reference human sera in order to produce antibody titers expressed in international units (IU). In addition to high reproducibility, the new neutralization test appears to be sensitive, specific and rapid, and might thus represent a useful tool for the diagnosis of polio and other enterovirus infections.