The COVID-19 pandemic exposed the vulnerability of immunocompromised hosts and the scarcity of evidence guiding their management. Within the European Horizon 2020 ORCHESTRA project, a multinational consortium connected existing and new cohorts to harmonize data, laboratory methods, and clinical expertise across fragile populations. The fragile patients' cohort became a model for how collaborative infrastructure can generate actionable evidence during a crisis. Through prospective follow-up and centralized immunologic assessment, ORCHESTRA defined the clinical spectrum of COVID-19 in transplant recipients, identified vaccine-modified disease phenotypes, and clarified the kinetics and correlates of immune protection. The project also demonstrated the feasibility of real-time immunologic monitoring, the value of data interoperability, and the need for adaptive harmonization across health systems. Integrating these results through Delphi consensus, ORCHESTRA translated research into practice, providing pragmatic guidance for clinicians across Europe. This experience underscores that harmonized, multidisciplinary research-rooted in collaboration and flexibility-can transform variability into knowledge and ultimately improve care for the most immunologically fragile patients.

BACKGROUND:Variant-adapted vaccines are recommended in vulnerable populations to address the waning immunity and the emergence of immune-escaping SARS-CoV-2 variants, yet data about immune responses to such vaccines in people living with HIV (PLWH) are limited. We therefore aimed to assess long-term immune responses to an original-BA.4/5 mRNA booster in this population. METHODS:In this prospective longitudinal study, PLWH receiving either an original-BA.4/5 bivalent booster or an original monovalent booster and HIV-negative healthcare workers (HCWs) receiving a bivalent booster were enrolled and sampled before (T0), 1 month (T1), and 4-9 months (T2) after the vaccine administration. SARS-CoV-2-specific T and B cells, RBD-binding antibodies, and RBD-blocking antibodies against both wild type (WT) and omicron BA.4/5 virus were determined. RESULTS:The bivalent booster is able to transiently increase both humoral and polyfunctional T cell responses in PLWH, with humoral responses comparable to those observed in HCWs. While T cell responses are cross-reactive against viral variants and stable over time, humoral immunity is imprinted to the ancestral virus and wanes quickly. Furthermore, whilst previous SARS-CoV-2 infection does not affect the trajectory of vaccine-elicited immune responses, markers of HIV-related T cell dysfunction are associated with lower antibody peak responses and higher antibody waning. Lastly, the bivalent booster was superior to the monovalent one in inducing BA.4/5-reactive RBD-blocking antibodies. CONCLUSIONS:The original-BA.4/5 bivalent booster is highly immunogenic in PLWH and superior to the monovalent one in inducing humoral responses against the BA.4/5 virus, although HIV-related T cell dysfunction markers are associated with blunted and less durable antibody immunity.

OBJECTIVES:COVID-19 poses a significant risk to individuals with haematological malignancies (HM), as they are particularly vulnerable to severe disease progression and hospitalization due to their compromised immune systems. Many clinical decisions regarding the management of COVID-19 in these patients are yet to be fully addressed by existing guidelines, leading to variability in care. METHODS:A 28-item Delphi survey was developed to gather expert opinions on key areas of COVID-19 management in patients with HM, including risk stratification for severe COVID-19, diagnostic processes, and treatment decisions. RESULTS:Twenty-one experts with backgrounds in haematology and infectious diseases were enrolled. Of the 28 questions posed to the experts, consensus was reached on 15 statements. DISCUSSION:These Delphi consensus statements offer valuable suggestions with direct implications for clinical practice, addressing critical areas such as risk identification, appropriate diagnostic approaches, and tailored treatment strategies for patients with HM with COVID-19. The findings provide actionable insights that may help fill gaps in current scientific literature, enhancing patient care and decision-making in this high-risk population.

Importance:Antimicrobial stewardship (AMS) programs optimize antibiotic use and mitigate antimicrobial resistance. The literature on the efficacy of AMS programs in pancreatic surgery is limited. Objective:To investigate the association of a multifaceted AMS intervention targeting surgical antibiotic prophylaxis (SAP) with the rate of surgical site infections (SSIs) following pancreatic surgery. Design, Setting, and Participants:This cross-sectional study was a multicenter, before-and-after analysis conducted at 3 Italian centers. The intervention cohort included adult patients aged 18 years or older who underwent pancreatectomy between January 1, 2020, and December 31, 2022, while the historical cohort included patients from January 1, 2015, to December 31, 2019. Exposure:A multiprofessional, multidimensional ASM program that included a bundle of interventions and pivoted on preoperative rectal screening for multidrug-resistant bacteria and targeted SAP. Main Outcomes and Measures:The primary outcomes were SSI incidence and SAP appropriateness, assessed through the coverage rate of rectal and biliary isolates. Data were analyzed using propensity score weighting. Secondary outcomes evaluated were other postoperative outcomes (eg, pancreatic fistula rate, length of stay), antibiotic use, and costs. Results:A total of 3387 patients (median [IQR] age, 66 [66-73] years; 1788 male [52.8%]) were included, with 1219 in the intervention cohort and 2168 in the historical cohort. After implementing the AMS program, a statistically significant reduction was found in rates of overall (30.1% vs 20.6%), superficial (5.8% vs 2.5%), deep (0.9% vs 0.3%), and organ-space (26.3% vs 19.3%) SSIs. After propensity score weighting, the odds ratios for the estimated mean treatment effect were 0.92 (95% CI, 0.89-0.96) for overall, 0.85 (95% CI, 0.78-0.93) for superficial, and 0.95 (95% CI, 0.92-0.99) for organ-space SSIs. Surgical antibiotic prophylaxis coverage increased significantly for rectal screening (87.2% vs 100%) and biliary bacterial colonization (59.7% vs 68.7%). Complications, infections, length of stay, and antibiotic consumption also decreased, with an overall cost savings of 247 460 euros. Conclusions and Relevance:These findings suggest that a multifaceted, pancreatic surgery-specific AMS program is associated with decreased rates of SSIs, increased coverage of isolated bacteria, improved clinical outcomes, more judicious antibiotic use, and lower costs.

OBJECTIVES:The interaction between HIV and COVID-19 resulted in a syndemic that showed an excess burden of disease for people with HIV (PWH). Four years of the COVID-19 pandemic have raised many unsolved questions about the optimal care of COVID-19 in PWH. METHODS:We performed a study using a three-round Delphi methodology involving a panel of physicians with expertise in HIV and COVID-19 infections. The main aim of the study was to provide recommendations on critical clinical issues of COVID-19 among PWH and to inform physicians and policy-makers for improving care and prevention of COVID-19 in PWH. A total of 27 questions were conceived, focusing on four main areas of interest in the management of COVID-19 in PWH; a panel of 34 experts in HIV and COVID-19 care expressed their level of agreement on each item. Questions that received agreement/disagreement ≥79.4% of panellists were identified and statements were generated accordingly. RESULTS:Consensus was reached on 19/27 items, resulting in 18 final statements. These statements addressed: (a) risk of COVID-19 progression to severe disease among PWH; (b) COVID-19 diagnostics and laboratory procedures; (c) early treatments with antivirals and/or monoclonal antibodies; (d) use of corticosteroids; (e) COVID-19 preventive strategies. DISCUSSION:This consensus's study guides infectious diseases physicians in making decisions regarding the care of PWH for COVID-19, where results from the scientific literature are limited or conflicting.

OBJECTIVES:Post-COVID-19 condition (PCC) remains poorly understood, especially in clinically vulnerable groups. We applied the Delphi approach to drive recommendations for the diagnosis, management, and prevention of PCC in people living with HIV (PWH) and patients affected by rheumatological diseases (RD) and haematological malignancies. METHODS:On the basis of literature review, three areas of interest in PCC in PWH, haematological malignancies, and RD were identified: (a) features and risk factors; (b) diagnosis and management; and (c) prevention. A three-round Delphi anonymous survey consisting of 15 questions was conducted including 69 experts. Consensus was measured by the six-point Likert scale categorized into four tiers: strong disagreement, moderate disagreement, moderate agreement, and strong agreement. Statements were generated on questions achieving consensus. RESULTS:Eleven statements were generated: six on features and risk factors of PCC in clinically vulnerable populations, two on diagnosis and management, and three on prevention. Chronic fatigue was identified as the most frequent presentation of PCC in PWH and RD populations. A different case definition of PCC is required for RD population, as symptoms of PCC and autoimmune disorders may overlap. Risk factors for PCC include age >65, severity of COVID-19, and female sex; the latter is also associated with increased smell/taste impairment. A clinical assessment or a routine laboratory test performed 3 months after acute infection is not suggested to diagnose PCC in PWH. PWH and RD should be screened to exclude additional autoimmune disorders in case of chronic fatigue/arthralgia of new onset. Full-course vaccination and early treatment for COVID-19 should be promoted to prevent PCC, whereas corticosteroids during acute infection are not recommended. DISCUSSION:Diagnosis, management, and prevention of PCC are still under discussion. This Delphi offers valuable insights on PCC in selected clinically vulnerable populations and suggests a tailored approach in vulnerable populations.

BackgroundThe VACCELERATE Pan-European Scientific network aims to strengthen the foundation of vaccine trial research across Europe by following the principles of equity, inclusion, and diversity. The VACCELERATE Volunteer Registry network provides access to vaccine trial sites across the European region and supports a sustainable volunteer platform for identifying potential participants for forthcoming vaccine clinical research. ObjectiveThe aim of this study was to approach members of patient advocacy groups (PAGs) across Europe to assess their willingness to register for the VACCELERATE Volunteer Registry and their perspectives related to participating in vaccine trials. MethodsIn an effort to understand how to increase recruitment for the VACCELERATE Volunteer Registry, a standardized survey was developed in English and translated into 8 different languages (Dutch, English, French, German, Greek, Italian, Spanish, and Swedish) by the respective National Coordinator team. The online, anonymous survey was circulated, from March 2022 to May 2022, to PAGs across 10 European countries (Belgium, Cyprus, Denmark, France, Germany, Greece, Ireland, Italy, Spain, and Sweden) to share with their members. The questionnaire constituted of multiple choice and open-ended questions evaluating information regarding participants’ perceptions on participating in vaccine trials and their willingness to become involved in the VACCELERATE Volunteer Registry. ResultsIn total, 520 responses were collected and analyzed. The PAG members reported that the principal criteria influencing their decision to participate in clinical trials overall are (1) the risks involved, (2) the benefits that will be gained from their potential participation, and (3) the quality and quantity of information provided regarding the trial. The survey revealed that, out of the 520 respondents, 133 individuals across all age groups were “positive” toward registering in the VACCELERATE Volunteer Registry, with an additional 47 individuals reporting being “very positive.” Respondents from Northern European countries were 1.725 (95% CI 1.206-2.468) times more likely to be willing to participate in the VACCELERATE Volunteer Registry than respondents from Southern European countries. ConclusionsFactors discouraging participants from joining vaccine trial registries or clinical trials primarily include concerns of the safety of novel vaccines and a lack of trust in those involved in vaccine development. These outcomes aid in identifying issues and setbacks in present registries, providing the VACCELERATE network with feedback on how to potentially increase participation and enrollment in trials across Europe. Development of European health communication strategies among diverse public communities, especially via PAGs, is the key for increasing patients’ willingness to participate in clinical studies.

People living with HIV (PLWH) despite having an appreciable depletion of CD4+ T-cells show a good severe acute respiratory syndrome coronavirus 2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T-cell responses in PLWH receiving anti-retroviral therapy stratified on CD4+ counts as PLWH-high (CD4 ≥ 500 cells/mm3) and PLWH-low (<500 cells/mm3). Responses were assessed longitudinally before the first vaccination (T0), 1-month after the first dose (T1), 3-months (T2), and 6-months (T3) after the second dose. Expectedly, both PLWH-high and -low groups developed similar serological responses after T2, which were also non-significantly different from age and vaccination-matched HIV-negative controls at T3. The immunoglobulin G titers were also protective showing a good correlation with angiotensin-converting enzyme 2-neutralizations (R = 0.628, p = 0.005). While surface and intracellular activation analysis showed no significant difference at T3 between PLWH and controls in activated CD4+CD154+ and CD4+ memory T-cells, spike-specific CD4+ polyfunctional cytokine expression analysis showed that PLWH preferentially express interleukin (IL)-2 (p < 0.001) and controls, interferon-γ (p = 0.017). CD4+ T-cell counts negatively correlated with IL-2-expressing CD4+ T-cells including CD4+ memory T-cells (Spearman ρ: -0.85 and -0.80, respectively; p < 0.001). Our results suggest that the durable serological and CD4+ T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4+ T-cell activation that likely compensates for CD4+ T-cell depletion in PLWH.

ObjectivesTo investigate if SARS-CoV-2 mRNA vaccination has an impact on HIV-related viro-immunological parameters.MethodsPWH of the VAXICONA-ORCHESTRA cohort who received ≥1 dose of SARS-CoV-2 mRNA vaccine and for whom paired measures of immuno-virological markers [Viral Load (VL), CD4, CD8 count 1 month before and after a vaccine dose (VD)] were available, were included. Paired t-test and generalized estimating equation linear regression analyses were used to study changes over ± 1 month around the VD. Subgroup analyses were performed.Results510 PWH enrolled: median age 55 y (IQR 46-60), CD4 and CD8 count 489(287-719) and 790 (59-1104) cells/mm3. 81% received 3 VDs. After a median of 28 days (3-53) from VD, CD4 count increased by +15 cells/mm3 (SD ±129.7; p=0.001), CD8 by +12 (±250.5; p=0.199), VL decreased by -0.11 log10 (±0.88; p=0.001). Similar results were observed after restricting the analysis to viro-suppressed PWH, with CD4 ≤200/mm3, more than 6 months of ART before VD and after excluding previous COVID-19.ConclusionsA small significant increase in CD4 count and a negligible drop in HIV-RNA were observed. Our findings are consistent with the hypothesis that SARS-CoV-2 mRNA vaccine can prime CD4 T spike specific cells even in the more immuno-compromised PWH.

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within—and across—countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

BACKGROUND:Our aim was to estimate the rates of not achieving a robust/above-average humoral response to the COVID-19 mRNA vaccine in people living with HIV (PLWH) who received ≥2 doses and to investigate the role of the CD4 and CD4/CD8 ratio in predicting the humoral response. METHODS:We evaluated the humoral anti-SARS-CoV-2 response 1-month after the second and third doses of COVID-19 mRNA vaccine as a proportion of not achieving a robust/above-average response using two criteria: (i) a humoral threshold identified as a correlate of protection against SARS-CoV-2 (<90% vaccine efficacy): anti-RBD < 775 BAU/mL or anti-S < 298 BAU/mL, (ii) threshold of binding antibodies equivalent to average neutralization activity from the levels of binding (nAb titer < 1:40): anti-RBD < 870 BAU/mL or anti-S < 1591 BAU/mL. PLWH were stratified according to the CD4 count and CD4/CD8 ratio at first dose. Logistic regression was used to compare the probability of not achieving robust/above-average responses. A mixed linear model was used to estimate the mean anti-RBD titer at various time points across the exposure groups. RESULTS:a total of 1176 PLWH were included. The proportions of participants failing to achieve a robust/above-average response were significantly higher in participants with a lower CD4 and CD4/CD8 ratio, specifically, a clearer gradient was observed for the CD4 count. The CD4 count was a better predictor of the humoral response of the primary cycle than ratio. The third dose was pivotal in achieving a robust/above-average humoral response, at least for PLWH with CD4 > 200 cells/mm3 and a ratio > 0.6. CONCLUSIONS:A robust humoral response after a booster dose has not been reached by 50% of PLWH with CD4 < 200 cells mm3. In the absence of a validated correlate of protections in the Omicron era, the CD4 count remains the most solid marker to guide vaccination campaigns in PLWH.

Background and purpose Bacterial infections represent a major cause of morbidity and mortality in cirrhotic patients. Our aim was to assess the incidence of bacterial infections, in particular due to multidrug-resistant organisms (MDROs) before and after the introduction of the antimicrobial stewardship program, "Stewardship Antimicrobial in VErona" (SAVE). In addition, we also analysed the liver complications and the crude mortality during the whole follow up. Methods We analysed 229 cirrhotic subjects without previous hospitalization for infections enrolled at the University Verona Hospital from 2017 to 2019 and followed up until December 2021 (mean follow-up 42.7 months). Results 101 infections were recorded and 31.7% were recurrent. The most frequent were sepsis (24.7%), pneumonia (19.8%), spontaneous bacterial peritonitis (17.8%). 14.9% of infections were sustained by MDROs. Liver complications occurred more frequently in infected patients, and in case of MDROs infections with a significantly higher MELD and Child-Pugh score. In Cox regression analysis, mortality was associated with age, diabetes and bacterial infections episodes (OR 3.30, CI 95%: (1.63-6.70). Despite an increase in total infections over the past three years, a decrease in the incidence rate in MDROs infections was documented concurrently with the introduction of SAVE (IRD 28.6; 95% CI: 4.6-52.5, p = 0.02). Conclusions Our study confirms the burden of bacterial infections in cirrhotic patients, especially MDROs, and the strong interconnection with liver complications. The introduction of SAVE decreased MDROs infections. Cirrhotic patients require a closer clinical surveillance to identify colonized patients and avoid the horizontal spread of MDROs in this setting.

IntroductionResidency in LTCFs increases the likelihood of colonization with multidrug resistant Gram-negative bacteria (MDR-GNB). We assessed the prevalence and risk factors for enteric colonization by III-generation cephalosporins-resistant and carbapenem-resistant (CR) GNB in a large group of LTCFs in a high endemic setting. We also assessed the prevalence and risk factors for C. difficile colonization.MethodsA point prevalence survey with rectal screening (RS) was conducted in 27 LTCFs in north Italy. Epidemiological and clinical variables on the survey day, history of hospitalization and surgery within one year, and antibiotics within three months, were collected. The presence of III-generation cephalosporin resistant and CR GNB was assessed using a selective culture on chromogenic medium and PCR for carbapenemase detection. The presence of C. difficile was assessed using ELISA for GDH and RT-PCR to identify toxigenic strains. Multi-variable analyses were performed using two-level logistic regression models.ResultsIn the study period 1947 RSs were performed. The prevalence of colonization by at least one GNB resistant to III-generation cephalosporin was 51% (E. coli 65%, K. pneumoniae 14% of isolates). The prevalence of colonization by CR GNB was 6%. 6% of all isolates (1150 strains) resulted in a carbapenem-resistant K. pneumoniae, and 3% in a carbapenem-resistant E. coli. KPC was the most frequent carbapenemase (73%) identified by PCR, followed by VIM (23%). The prevalence of colonization by C. difficile was 11.7%. The presence of a medical device (OR 2.67) and previous antibiotic use (OR 1.48) were significantly associated with III-generation cephalosporin resistant GNB colonization. The presence of a medical device (OR 2.67) and previous hospitalization (OR 1.80) were significantly associated with CR GNB. The presence of a medical device (OR 2.30) was significantly associated with C. difficile colonization. Main previously used antibiotic classes were fluoroquinolones (32% of previously treated subjects), III-generation cephalosporins (21%), and penicillins (19%).ConclusionAntimicrobial stewardship in LTCFs is a critical issue, being previous antibiotic treatment a risk factor for colonization by MDR-GNB. The prevalence of colonization by III-generation cephalosporin and CR GNB among LTCF residents also underlines the importance to adhere to hand hygiene indications, infection prevention and control measures, and environmental hygiene protocols, more achievable than rigorous contact precautions in this type of social setting.

BACKGROUND:The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. METHODS:Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. RESULTS:As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. CONCLUSIONS:The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.

Main aim of this systematic review is to quantify the risk and identify predictors of clinical evolution of SARS-CoV-2 in hematological patients compared to different control populations. Two independent reviewers screened the literature assessing clinical outcomes of SARS-CoV-2 infection in adult patients with active hematological malignancies published up to June 2021. Primary outcome was COVID-19 related mortality, secondary outcomes were hospital and intensive-care admission, mechanical ventilation (MV), and thromboembolic events. Variables related to study setting, baseline patients' demographic, comorbidities, underlying hematological disease, ongoing chemotherapy, COVID-19 presentation, and treatments were extracted. A total of 67 studies including 10,061 hematological patients and 111,143 controls were included. Most of the studies were retrospective cohorts (51 studies, 76%) and only 19 (13%) provided data for a control group. A significant increased risk of clinical progression in the hematological population compared to the controls was found in terms of COVID-19 related mortality (OR, 2.12; 95% CI, 1.77-2.54), hospitalization (OR, 1.98; 95% CI, 1.15-3.43), intensive-care admission (OR, 1.77; 95% CI, 1.38-2.26), and MV (OR, 2.17; 95% CI, 1.71-2.75). The risk remained significantly higher in the subgroup analysis comparing hematological patients versus solid cancer. Meta-regression analysis of uncontrolled studies showed that older age, male sex, and hypertension were significantly related to worse clinical outcomes of COVID-19 in hematological population. Older age and hypertension were found to be associated also to thromboembolic events. In conclusion, hematological patients have a higher risk of COVID-19 clinical progression compared to both the general population and to patients with solid cancer.

Background The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial–related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. Objective This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. Methods Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients’ Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. Results This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. Conclusions The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents’ concerns for potential participation of children in vaccine trials.

ORCHESTRA ("Connecting European Cohorts to Increase Common and Effective Response To SARS-CoV-2 Pandemic") is an EU-funded project which aims to help rapidly advance the knowledge related to the prevention of the SARS-CoV-2 infection and the management of COVID-19 and its long-term sequelae. Here, we describe the early results of this project, focusing on the strengths of multiple, international, historical and prospective cohort studies and highlighting those results which are of potential relevance for vaccination strategies, such as the necessity of a vaccine booster dose after a primary vaccination course in hematologic cancer patients and in solid organ transplant recipients to elicit a higher antibody titer, and the protective effect of vaccination on severe COVID-19 clinical manifestation and on the emergence of post-COVID-19 conditions. Valuable data regarding epidemiological variations, risk factors of SARS-CoV-2 infection and its sequelae, and vaccination efficacy in different subpopulations can support further defining public health vaccination policies.

Long-term care facilities (LTCFs) are important reservoirs of antimicrobial-resistant (AMR) bacteria which colonize patients transferred from the hospital, or they may emerge in the facility as a result of mutation or gene transfer. In the present study, we characterized, from a molecular point of view, 43 E. coli strains collected from residents of LTCFs in Northern Italy. The most common lineage found was ST131, followed by sporadic presence of ST12, ST69, ST48, ST95, ST410 and ST1193. All strains were incubators of several virulence factors, with iss, sat, iha and senB being found in 84%, 72%, 63% and 51% of E. coli, respectively. Thirty of the ST131 analyzed were of the O25b:H4 serotype and H30 subclone. The ST131 isolates were found to be mainly associated with IncF plasmids, CTX-M-1, CTX-M-3, CTX-M-15, CTX-M-27 and gyrA/parC/parE mutations. Metallo-β-lactamases were not found in ST131, whereas KPC-3 carbapenemase was found only in two ST131 and one ST1193. In conclusion, we confirmed the spread of extended-spectrum β-lactamase genes in E. coli ST131 isolated from colonized residents living inside LTCFs. The ST131 represents an incubator of fluoroquinolones, aminoglycosides and other antibiotic resistance genes in addition to different virulence factors.