Neutralising antibodies (NAbs) against SARS-CoV-2 in BNT162b2 vaccine recipients with a history of advanced HIV infection: cPass as a simpler alternative to gold-standard tests

Background: Established SARS-CoV-2 NAb tests are labor-intensive. We prospectively measured NAbs vs Wuhan-1 and Omicron BA.2 using the novel GenScript cPass assay and examined correlations with responses measured by gold-standard plaque reduction neutralisation test (PRNT) (Cotugno, Ruggiero et al. Cell Rep 2021) and with anti-Spike IgG quantified by Roche Elecsys. Given the paucity of data, we selected BNT162b2 vaccine recipients with a history of advanced HIV infection (prior AIDS-defining conditions and/or nadir CD4 <200 cells). Method(s): In Mar 2021-Apr 2022, 55 PWH received 2 vaccine doses median 3 weeks apart [IQR 3-3] and a 3rd dose 27 weeks later [23-31]. Plasma samples (n=147) were stored immediately before dose-1 (T0), median 4 weeks [3-5] after dose-2 (T1) and median 13 weeks [9-19] after dose-3 (T2) for batch testing. Result(s): Participants' characteristics: 74% male, 85% white, all on ART, 82% HIV-RNA <50 cps/ml;median age 55 years, ART duration 7 years, nadir CD4 83 cells [36-211], current CD4 440 cells [270-710], CD4:CD8 ratio 0.6 [0.4-1.0];73% had a history of advanced HIV infection;15% received a COVID-19 diagnosis during the study. At T0, T1 and T2, proportions with quantifiable anti-S IgG (>0.8 U/ml) were 11/49 (22%), 50/54 (93%) and 43/43 (100%), respectively;their median anti-S IgG titres were 30 [15-124], 15949 [596-3389] and 8527 [3146-17190] U/ml. Proportions showing Wuhan-1 neutralisation by cPass were 6/50 (12%), 45/53 (85%) and 40/43 (93%), with median neutralisations of 67% [47-70], 97% [91-98] and 98% [98-98] and corresponding NAb titres of 1332 [792-1436], 5354 [3529-6187] and 6242 [5765-6766] U/ml. At T2, 25/28 (89%) showed BA.2 neutralisation by cPass (median 83% [68-93];NAb titre 7836 [3172-12173] U/ml) (Fig 1A). Two participants lacking NAbs at T2 had a history of advanced HIV infection. cPass data were highly correlated with anti-S IgG titres (rho 0.82;p<0.0001) and with PRNT data for both Wuhan-1 (n=27, Fig 1B) and Omicron BA.2 (n=28, Fig 1C). Conclusion(s): cPAss offers a simple methodology for measuring SARS-CoV-2 NAbs. Despite prior advanced HIV infection, neutralising activity improved with successive vaccinations and most participants showed NAbs against both Wuhan-1 and Omicron BA.2 after 3 vaccine doses. (Figure Presented).

Proceedings of the VI National Meeting of the Italian Group of Paleopathology (GIPaleo)

The presence of numerous scientific contributions in the program is certainly demonstrative of the fact that research in the field of paleopathology and anthropology has not stopped since the beginning of Covid-19. Furthermore, the same emergency that we are still partially feeling, has pushed our community scientific research to question itself more intensely in connection to the epidemic relationship and measures that repeatedly led to profound transformations in the societies of the past from different points of view: demographic, economic, social and the history buried under the bioarchaeological strata is today more capable than ever to show this connection. It can do this by bringing to light the paleodemographic data that is obtained from the study of human remains. Today we will listen to many paleopathological stories and among these I am very happy to also present ours. Twenty years ago, the University of Insubria started a collaboration with the Archaeological Superintendence of Lombardy for the study of osteological remains found mostly during emergency archaeology recoveries. These experiences led us to reach those bioarchaeological sites again with the aim of extracting all those cemetery layers that remained there because they were not subjected at that time by building reclamation interventions. Returning to those sites that in the past brought to light fragmentary anthropological data means allowing oneself the possibility of obtaining new palaeodemographic and palaeopathological data which are decisive for reconstructing the demographic and epidemiological history of the populations of the past. These new interventions led us to create an operational model that immediately intended to underline the importance of an evident continuity between the archaeological recovery and the anthropological study of the finds through the setting up of physical anthropology and paleopathology laboratories directly on the sites of the finds. All this in harmony with the final design of the projects or the museumization of bioarchaeological sites in their complexity aimed at enhancing cultural tourist routes in the area. In this regard, I would like to thank the community foundation of Varese and the Cariplo foundation for supporting our current initiatives. These include the project financed by the emblematic provincial tender and which has as its final objective the enhancement of three bioarchaeological sites in Valcuvia: the medieval sites of San Biagio in Cittiglio, Sant’Agostino in Caravate, and the modern crypt of the church of the Convent of Azzio. Today, our Research Centre works in Piedmont in different sites in the province of Vercelli and Alessandria. Aware of the importance of a physical anthropological approach in the field, our young Centre goes beyond the continental borders to reach Eritrea, the ancient city of Adulis, because it is in dissecting the taphonomic events and the funeral actions that will make it possible to identify the funerary ritual adopted by the ancient populations. The operational model of paleopathological research, which gradually enriches itself thanks to the multidisciplinary nature of the interventions and thanks to the individual experiences in the field, is thus continuously transferred and adapted to other anthropological contexts that retain potential both in terms of investigative and enhancement of the bioarchaeological heritage. Through the musealization of the sites it is also possible to acquire an attractive force towards all those potentially bioarchaeological areas but which today are in conditions of neglect because they are marginal with respect to the conventionally understood cultural tourist good. And we all know how important it is to transfer the study data even outside the academic context because making this aspect of archaeology, the truly human one, usable too, cannot fail to arouse a strong awareness of our past. We also know how much more we will have to work, following in the footsteps of the professors who started this path, to ensure that the d sciplines of paleopathology and physical anthropology arrive within all those degree courses still discovered today by these teachings to heal an important lack: knowing the human past from a physical and pathological point of view allows us to understand the evolutionary path of some pathologies, especially those of infectious nature. If my title of the speech “Paleopathology and osteoarchaeology in the province of Varese” does not respond to what is being said today, it is because my feeling about paleopathology and osteoarchaeology in the province of Varese is understood as that of carrying out research, what I could feel everywhere, through the operational model, the enthusiasm for paleopathological research and of course the people I am lucky enough to work with. The Morgagni Museum of Pathological Anatomy of the University of Padua preserves a wide series of pathological specimens, mostly from the second half of the 19th century and the early 20th century. The Museum was recently renewed, as the result of an intervention of enhancement of the museum and cultural heritage of the University of Padua and its Medical School, being also testimony to the history and evolution of human pathology and past population lifestyle. In the collection of the Morgagni Museum there are several specimens affected by atherosclerotic lesions. Atherosclerosis is characterized by a chronic inflammatory disease in which different factors are involved, such as lipoproteins, immune cells and endothelial damage. The main clinical syndromes related to atherosclerosis are angina pectoris, acute myocardial infarction, transient ischemic attack, cerebral stroke, intermittent claudication, aortic aneurysm and nephro-vascular hypertension. Atherosclerosis was believed to be a modern disease, related almost exclusively to age and current lifestyle. The cases from the Morgagni Museum are therefore useful for studying the presence of the atherosclerosis in a recent past population. In the collection there were identified six atherosclerotic cases: an atherosclerotic aneurysm of the ascending aorta: the specimen highlights the left ventricular outflow tract and the aortic root. There is a severe atherosclerosis of the ascending aorta with saccular aneurysm including a large thrombus;a syphilitic aortitis complicated by atherosclerosis: the finding highlights the left ventricular outflow tract and aortic root. It is possible to note the intima of the ascending aorta with ulcer-calcific atherosclerotic plaques and “tree-bark” whitish areas;an atherosclerotic aneurysm of the abdominal aorta: abdominal aorta with saccular atherosclerotic aneurysm, proximal to the iliac bifurcation;a case of aortic atherosclerosis: aorta with severe atherosclerosis complicated by calcification and thrombosis;a case of aortic atherosclerosis: massive dissemination of atheromatous-calcific plaques;a case of aortic atherosclerosis with parietal thrombi: widespread presence of plaques along the aortic wall. Thanks to this collection, it is possible to notice the spread of pathology on an atheromatous basis in the recent past populations. Moreover, current paleopathological investigations on ancient populations mummified remains also showed traces of atherosclerotic lesions in both sexes and different ages. It is therefore possible to support a ubiquitous diffusion in space and time of this complex multifactorial pathology which has so far considered to be almost an exclusive prerogative of old age and current lifestyle. The Morgagni Museum of Pathological Anatomy of the University of Padua, founded by Lodovico Brunetti (1813-1899) in the 1860s, gathers important pathological specimens mainly from the 19th century. Among them, there is a very peculiar preparation: it consists of a dried head representing a case of argyria dating back to 1873. The specimen is preserved in a sealed jar, all the skin has a blue-gray coloration with white-blonde hair and beard. The eyes are not preserved, but since the ocular cavities remain open, it is possible to presume that origin lly there were glass eyes. Two glass sticks are inserted inside the mouth to show that also tongue and gums have the same blue-gray pigmentation as the face. The upper teeth are strongly eroded. Argyria is a rare disease caused by chronic absorption of products with a high silver content, which surpass body’s renal and hepatic excretory capacities, leading to silver granules being deposited in the skin and its appendages, mucosae and internal organs. It is characterized by blue-gray or black staining of the skin and mucous membranes. Our case was first mentioned in 1862 as a syphilitic man who was treating himself with some caustic silver nitrate, the so called “infernal stone”, since 1840s. According to him, this medicament cured the syphilis, but turned him into a “graphite man”. The patient died in 1873 of an intestinal infection, most likely related to the prolonged ingestion of the silver nitrate. This case was described as “spectacular” by Austrian dermatologist Isidor Neumann (1832-1906), who studied a sample of the tongue of the specimen sent by Brunetti. In fact, Brunetti performed the autopsy on the body of the individual and prepared also a plaster cast of the head along with the sample for Neumann. Thus, we can assume Brunetti was also the one who preserved the original head, taxidermizing it (so-called stuffed head preparation) in order to preserve the skin color, because his famous tannisation method would not maintained the original characteristics. Human taxidermy is quite rare, and it is limited to a few cases in the 19th century. Moreover, there are just a few known human stuffed heads in the world, making the Paduan specimen particularly unique both for the pathology and the technique used for the preparation.

HOW HIV MODULATES the SAFETY and IMMUNOGENICITY of the BNT162b2 COVID-19 VACCINE

Background: The pivotal BNT162b2 trials included only ∼60 vaccine recipients, all with well controlled HIV, and there is a need to gather more information on vaccine safety and immunogenicity in diverse populations. This prospective study evaluated solicited and unsolicited adverse events (AEs) and anti-S and anti-NC serological profiles in a diverse cohort of people with HIV undergoing BNT162b2 vaccination (2 doses 3 weeks apart). Methods: Participants completed structured questionnaires modelled on the BNT162b2 trials (FDA submission, Nov 2020) to report solicited and unsolicited AEs in the 7 days after each vaccine dose, indicating severity and duration. Serum samples collected prior to dose-1 (T0) and 3-6 weeks after dose-2 (T1) underwent qualitative anti-NC and quantitative anti-S testing by Elecsys®. Factors associated with T1 anti-S titres were explored in linear regression models including all available parameters. Results: Overall, 259 adults received dose-1 (26% female, 77% white, 44% MSM, 44% history of advanced disease, 31% ≥1 comorbidity, 10% HIV RNA >50 cps/ml [median 122 cps], 7% prior COVID-19 diagnosis, 15% anti-NC positive;median age 48 years, ART duration 7 years, nadir/current CD4 count 225/708 cells/mm3, CD4:CD8 ratio 0.8);257 received dose-2. Local AEs were more common after dose-1 than dose-2 (70% vs. 62%, p=0.015), whereas systemic AEs increased with dose-2 (50% vs 60%;p=0.006) (Fig 1a-c);22% experienced moderate-severe systemic AEs after dose-2. Unsolicited AEs (mainly nausea and light-headedness) were reported by 7% after dose-1 and 9% after dose-2. Among 206 participants with T1 samples, 205 (99%) had measurable anti-S (>0.8 U/ml). Anti-S levels were significantly lower at CD4 counts <200 cells/mm3 (Fig 1d). In adjusted regression analyses, factors associated with anti-S titres comprised anti-NC positivity (fold-change 7.39;95% CI 3.92-13.91;p<0.01), HIV viraemia (FC 0.24;0.11-0.50;p<0.01), reporting moderate-severe systemic AEs after dose-2 (FC 1.77;1.03-3.04;p=0.04) and either the CD4 count (FC 1.01;1.00-1.01;p=0.04) or CD4:CD8 ratio (FC 1.05;1.00-1.10;p=0.05). Conclusion: In this cohort with HIV, AE patterns after vaccination were similar to those seen in the pivotal BNT162b2 trials and most AEs were mild and short-lived. Whilst prior exposure to SARS-CoV-2 predicted higher anti-S responses, CD4 counts <200 cells/mm3 and low-level viraemia predicted reduced anti-S responses, thus identifying a subset potentially vulnerable to reduced vaccine efficacy.

Arts for Inclusive Education: Insights From the Increa+ Project

COVID-19 pandemic has forced schools to accelerate their digitalization process, causing an exacerbation of pre-existing educational disparities and a worldwide increase of students affected by mental health issues. In response to these severe issues, the OECD calls for the adoption of inclusive education strategies addressing both learning and emotional issues. This paper aims to illustrate how specific adoptions of arts education could effectively implement such strategies. Moreover, it will introduce the readers to the goals and future results of InCrea+, a European project aiming to provide an innovative method of inclusive education and promotion of wellbeing through arts education. © 2022, North American Business Press. All rights reserved.

Building Emotionally Stable, Inclusive, and Healthy Communities with ICT: From State of the Art to PSsmile App

There is an increasing interest in Social and Emotional learning (SEL) of youth across the world as testified by many international organizations and institutions. Research clearly shows that higher SEL is linked to successful participation in school life, better health, positive youth development. The COVID-19 pandemic has brought the essential role of SEL into focus and has drawn attention to the need to take a more holistic approach to contrast unexpected and challenging situations. To pursue these goals, it is mandatory that adults acquire and apply knowledge, skills, and attitudes enhancing Social and Emotional competences. To enhance their contribution to social goods, ICTs applications should align with this perspectives’ taking. After providing a picture of main currently available tools, the paper presents the Erasmus+ PSsmile project, aimed at developing Social and Emotional competencies and contribute to building emotionally stable, inclusive, and healthy communities. PSsmile is also the name of the mobile application described in the paper with its five weeks program. It is based on the most relevant outcome within SEL studies, and recent theoretical approaches. It is aimed at raising parents and teachers’ awareness, promoting and strengthening their personal Social-Emotional competences making them more effective agents of positive growth for children and for their communities. © 2021, ICST Institute for Computer Sciences, Social Informatics and Telecommunications Engineering.

Parenting during COVID-19 emergency: Perceived stress and children's emotional difficulties

A growing body of research has documented the negative impact of COVID-19 containment measures on children's psychological well-being. The role of parental stress and the specific impact of different parental stressors on children's difficulties are underinvestigated. The current cross-sectional study was aimed at exploring the link between children's (3-17 years of age) emotional difficulties and some specific sources of parental stress after the first lockdown period and which sources of parental stress contribute to children's difficulties. 506 Italian parents filled in an online questionnaire at the end of June 2020. Results showed that the limitation of social interactions and family life arrangements have a significant impact on children's difficulties, suggesting focused interventions aimed at reducing the negative impact of the pandemic on younger generations. © 2021 Franco Angeli Edizioni. All rights reserved.

COVID-19 risk for patients undergoing anticancer treatment at the outpatient clinic of the National Cancer Institute of Milan: The COVINT study

Background: In the midst of COVID-19 pandemic, cancer patients (pts) are regarded as a highly vulnerable population. Pts requiring hospital admission for treatment (Tx) administration are potentially exposed to a higher risk of infection and worse outcome given the multiple in-hospital exposures and the Tx immunosuppressive effects. Methods: COVINT is an observational study assessing COVID-19 incidence among pts receiving anticancer Tx in the outpatient clinic of the Istituto Nazionale dei Tumori di Milano. All consecutive pts with non-hematologic malignancies treated with intravenous or subcutaneous/intramuscular Tx in the outpatient clinic were enrolled. Pts were admitted to the clinic wearing surgical masks and only if asymptomatic and afebrile. The primary endpoint is the rate of occurrence of COVID-19. Secondary endpoints include the rate of COVID-19 related deaths and Tx interruptions. The association between clinical and biological characteristics and COVID-19 occurrence is also evaluated using nonparametric tests. COVID-19 diagnosis is defined as: a) certain if confirmed by RT-PCR assay of nasopharyngeal swabs (NFS);b) suspected in case of new symptoms and/or CT scan evidence of interstitial pneumonia with negative/not performed NFS;c) negative in case of neither symptoms nor radiological evidence. Results: In the first two months (16th February-10th April 2020) of observation, 1083 pts were included. Of these, 11 (1%) were confirmed and 73 (6.7%) suspected for COVID-19. No significant differences in terms of cancer and Tx type emerged between the three subgroups. Prophylactic use of myeloid growth factors was adopted in 5.3%, 2.7% and 0% of COVID-19-free, -suspected and -confirmed pts (p=0.003). Overall, 96 (8.9%) pts delayed Tx as a precaution for the pandemic. Among the 11 confirmed cases, 6 (55%) died of COVID-19 complications, and anticancer Tx was restarted in only one. Conclusions: During the pandemic peak, accurate protective measures successfully resulted in low rates of COVID-19 diagnosis, though with high lethality. Within the COVINT study, prospective pts surveillance will continue with NFS swabs and IgG/IgM serology performed before each Tx cycle until pandemic resolution. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: F.G.M. De Braud: Advisory/Consultancy: Tiziana Life Sciences;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene;Advisory/Consultancy, Research grant/Funding (institution): Novartis;Advisory/Consultancy: Servier;Advisory/Consultancy: Pharm Research Associated;Advisory/Consultancy: Daiichi Sankyo;Advisory/Consultancy, Speaker Bureau/Expert testimony: Ignyta;Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer;Advisory/Consultancy: Octimet Oncology;Advisory/Consultancy, Research grant/Funding (institution): Incyte;Advisory/Consultancy: Pierre Fabre;Advisory/Consultancy: Eli Lilly;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: Astra Zeneca;Advisory/Consultancy: Gentili;Advisory/Consultancy, Speaker Bureau/Expert testimony: Dephaforum;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD;Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer;Advisory/Consultancy: Fondazione Menarini;Research grant/Funding (self): NMS;Research grant/Funding (institution): Merck KGAA;Research grant/Funding (institution): Kymab;Research grant/Funding (institution): Tesaro;Speaker Bureau/Expert testimony: Biotechespert Ltd;Speaker Bureau/Expert testimony: Prime Oncology. All other authors have declared no conflicts of interest.