mRNA VACCINES INDUCES A HIGHER ANTIBODIES RESPONSE IN CHILDREN WITH PREVIOUS COVID-19

Background: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is lacking. This study aimed to evaluate the early and long-term immunological response after the BNT162b2 vaccine in children with or without a previous SARS-CoV-2 infection. Method(s): In a multicenter, prospective, observational study we profiled the immune response to the BNT162b2 vaccine in children aged 5-11 years attending the Pediatric Departments at the University of Padua and Bambino Gesu Children's Hospital in Rome (Italy). Forty-four healthy children (HC), 20 immune compromised (IC), and 18 children who previously developed MIS-C (MIS-C) were included in the study. Blood samples were collected pre-, 1, and 6 months after a 2-doses vaccination schedule. Neutralizing antibodies (NAbs) and anti-S-RBD IgG titers were analyzed through Plaque Reduction Neutralization Test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. B and T cell phenotypes were analyzed by flow cytometry. Geometric mean titers (GMTs) and 95% confidence intervals and median and interquartile range (IQR) of variables were evaluated according to pre-existing confirmed COVID-19. Result(s): Eighty-two children were studied;60 with a molecular-documented previous COVID-19 (Group A) and 22 without previous infection defined as the absence of antigen-specific antibodies before the vaccination (Group B). Overall, in Group A we observed higher NAbs GMTs, anti-S-RBD titers, and T- and B-reg cells than in Group A, at both 1 and 6 mo after vaccination (table);Nabs against the parental virus resulted to be greater in Group A than in Group B by a factor of 18 and 11, at 1 and 6 mo after vaccination, respectively. Both Groups recorded a decrease in antibody titers of approximately 50-70% between 1 and 6 months. A significant difference for Omicron NAbs (p=0.02) and anti-S-RBD (p=0.07) titers decay was observed between Group A and B;in contrast, Parental NAbs titers appeared to have similar trends in the 2 groups (p=0.47). Comparable antibody titers at 1 and 6 mo. (p=0.37) were detected across the three categories of HC, IC, and MIS-C (table). Conclusion(s): mRNA vaccination triggers a higher humoral response in children with a previous history of COVID-19, regardless of the immune deficiency or previous MIS-C, at least up to 6 mo, providing insight into boosting preexisting immunity with mRNA vaccines.

PERSISTENCE of SARS-CoV-2 ANTIBODES in CHILDREN and ADULTS 1 YEAR after INFECTION

Background: Understanding the long-term kinetics of the immune response against SARS-CoV-2 infection is crucial in guiding public health policies and optimizing of vaccination strategies. While it is known that SARS-CoV-2 specific antibodies may persist in adults 12 months after infection, data are lacking in the pediatric population. We herein describe the long-term immune response in children following SARS-CoV-2 infection. Methods: Single-centre, prospective observational study analyzing family clusters of COVID-19 attending the Pediatric Department, University of Padua (Italy). Confirmed COVID-19 infection was defined by positive SARS-CoV-2 PCR and/or IgG serology. All patients with confirmed infection at enrolment underwent serological follow-up at 1-4, 5-10, and >10 months after infection. Plasma was analyzed to quantify anti-SARS-CoV-2 S-RBD IgG, by chemiluminescent immunoassay, performed on MAGLUMI™2000 Plus (Snibe Diagnostics). IgG title >4.3 kBAU/L was considered positive. Results: Among 902 subjects (252 COVID-19 family clusters), 698 had confirmed COVID-19, including 352 children/older siblings aged 8.6 ±5.1 years, and 346 parents aged 42.5 ±7.1 years;of those, 96.5% cases had asymptomatic/mild COVID-19. Children showed significantly higher S-RBD IgG titers than older subjects across all follow-up time points, with an overall mean S-RBD IgG titer <3 years of age five-fold higher than adults (282.3 [139-516.6] kBAU/L vs 56.7 [24.6-136.9] kBAU/L, p<0.001) (Table). The longitudinal analysis of 60 subjects sampled at least twice during follow-up demonstrated the persistence of antibodies up to 10 months from infection in all age classes. Subjects >6 years of age showed a significant progressive decline of the S-RBD IgG titer from the first serological follow-up. While, in younger children antibodies remained stable at 5-10 months of follow-up (p=0.0625), with a subsequent significant decline afterwards (p<0.001). Conclusion: In our unique family cluster cohort, we confirmed the different kinetics of the COVID-19 humoral response across several age groups of asymptomatic/mild COVID-19 cases in our family-cluster cohort. Children presented with higher S-RBD IgG titer at every time point up to 10 months of follow-up. Children less than 3 years demonstrated a more intense long-term resilience of their immune response, which started to decline significantly only after ten months from infection.

Should the endoscopic restrictions during COVID-19 pandemic remain unchanged?

(Background) Endoscopic procedures are interventions that have been defined as carrying a high-risk of infection with COVID-19. Most endoscopy units restrict their activity based on pre-endoscopic diagnosis. (Objective) To determine the consequences of endoscopic restrictions as a result of the COVID-19 pandemic and their impact on digestive cancer diagnosis. (Design) A comparison of upper digestive endoscopies and colonoscopies with gastrointestinal cancers diagnosed between three endoscopic centers, two of which restricted their procedures and one that did not but performed the procedures under a strict protocol. (Setting) A retrospective analysis was performed collecting data between 15 March 2019 and 15 August 2020. Two-factor ANOVA and a Tukey's a posteriori test were used as statistical tests. (Main outcome measures) There was variation in gastrointestinal cancer diagnosis between 2019 and 2020, considering the endoscopic procedures performed each year. (Result) There was a significant decrease in the total endoscopic procedures performed between 2019 and 2020 (p < 0.001), the result of reduced testing at the two centers (p < 0.001) with pre-endoscopic restrictions, which was not compensated for by a slight increase in procedures at the center without restrictions (p = 0.139). Regarding the total cancers diagnosed, while a significant decrease was observed for the two centers with pre-endoscopic restrictions (p = 0.007), a significant increase was registered in the center that maintained its endoscopic productivity (p < 0.001). After 851 procedures (537 upper digestive endoscopies and 314 colonoscopies) there was no evidence of COVID-19 infection in the endoscopic staff. (Conclusion) Endoscopic restrictions based on preendoscopic diagnosis should be reassessed in consideration of local pandemic situations, and a balance should be sought between COVID-19 infection risk and the detrimental delay of potential cancer diagnosis.

Toward Efficient Academia-Industry Collaboration: A Case Study of Joint VR System Development

Collaborative academia-industry development and evaluation of virtual reality (VR) systems is a mutually beneficial opportunity to investigate VR technology in a real context and conduct user studies with target users. However, such collaboration is rarely performed due to variations in project pace and work methods. In this article, we introduce the process of action research on joint design, development, and evaluation of a collaborative VR system to address industrial needs. The paper further presents employees' subjective opinions and perceived value of industrial VR applications and reflects on their involvement throughout the process. The article concludes with a process-oriented framework for remote academia-industry collaboration, supported with practical suggestions on how to support this collaboration. Our experiences reveal the methods and advantages of remote collaboration in all phases of the process and signify the efficiency of the remote framework for academia-industry collaboration, especially relevant in the light of the COVID-19 pandemia. © 2021 ACM.

Characterisation of SARS-CoV-2-infected children developing neutralising antibodies

Background: Further knowledge on adaptive immunity to SARS-CoV-2 (CoV-2) in children is needed in order to define possible immunization strategies and reconsider pandemic control measures. We analyzed anti-CoV-2 antibodies (Ab) and their neutralizing activity (PRNT), alongside antigen (Ag) specific cellular response, in relation to virus load in nasopharyngeal swabs. Methods: We analysed 42 CoV-2 patients at 7 days after symptoms onset. CoV-2 viral load (VL) was measured by RT-PCR and digital droplet PCR on longitudinal samples of nasopharyngeal swabs (NP). Virus infectivity (FFU) was tested by virus focus forming assay. CoV-2 antibodies were investigated by Diasorin (CoV-2 Ab) and neutralization assay (PRNT). CoV-2-specific CD4-CD40L+ T-cells and Spike specific B-cells were analysed by flow cytometry. Plasma proteomic profiling was measured by 2 Olink panels. We calculated the area under the curve (AUC) of the viral load from NP collected every 48 hours up to undetectable VL. Mann-Whitney was used to compare means in individuals with neutralizing activity (PRNT+) or not (PRNT-);linear regression was used to evaluate the associations between virus load and infectivity over time. Principal component analysis (PCA) was used to analyse proteomic data. Results: Higher VL was found in seronegative patients expressed in terms of both CoV-2 Ab (p=0.003) and PRNT (p=0.0007). Similarly, lower FFU was associated with higher CoV-2 Ab (p=0.003;rho=-0.67) and PRNT (p=0.023;rho=-0.46). Further, the AUC of the viral load in NP showed an inverse correlation with CoV-2 Ab (p=0.031;rho=-0.54). Development of humoral response was associated with the presence of CoV-2 specific IgD-CD27+ B cells, with a higher frequency of CoV-2 specific B cells found in seropositive compared to seronegative (p=0.001). Besides, individuals developing neutralizing Ab had higher frequency CD4-CD40L+ T-cells compared to PRNT- (p=0.03). The plasma proteome confirmed the association between cellular and humoral CoV-2 immunity, with PRNT+ showing higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). Conclusion: This work provides a virological and immunological characterization of SARS-CoV-2 infected children presenting a differential Abmediated neutralizing activity. It demonstrates that children with neutralizing antibodies present reduced viral load, faster virus clearance and lower in vitro infectivity. These data provide information that can drive vaccination endpoints and quarantine measures policies.

Asymptomatic sars-cov-2 children have lower infectivity and intact memory responses

Background: SARS-CoV-2 (CoV-2) infected children often range from being paucysymptomatic to fully asymptomatic. The impact of this population on the epidemics due to their ability to transmit the virus and achieve protective immunity has been poorly defined. We explored CoV-2 infectivity potential and anti-CoV-2 cellular (CD8, NK and B) and humoral response in symptomatic (SY) and asymptomatic (AS) CoV-2 infected children, screened for a family member resulted infected. Methods: CoV-2 viral load was measured by RT-PCR and digital droplet PCR (ddPCR) on longitudinal samples of nasopharyngeal swabs in 9 AS and 33 SY (samples were paired according to symptoms'onset for SY and first family contact for AS). Virus infectivity was tested by Virus focus forming assay (FFA). CoV-2 antibodies were investigated by Diasorin (CoV-2 Ab) and Ab-mediated neutralization activity (PRNT) at diagnosis, (samples collected >5 days from symptoms onset in SY, or from first family contact in AS were excluded from this timepoint), and in the convalescent phase (CP) (10-14 days after infection). Cellular response was analyzed by flow cytometry: 1) Ag-specific B cells, by a S1+S2 CoV2-R-PE probe;2) Ag-specific CD8+T cells by ICAM+;3) natural-killer (NK) phenotype. Mann-Whitney was used for comparison;linear regression was used to evaluate the associations between virus load and infectivity. Results: AS showed lower viral load (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Virus infectivity was associated with ddPCR (rho=0.66;p=0.002). ASY and SY showed similar levels of CoV-2 Ab and PRNT, at both diagnosis and at follow up. During the CP, the proportion of CoV-2 Ab negative was 33,3% for both groups and PRNT was negative in 16,6% and 15,7% of AS and SY respectively. Anti-CoV-2 cellular immunity was comparable between ASY and SY. Indeed Ag-specific B cells and CD8 T cells were detectable despite symptomatology and no major differences were found between the groups. Total NK frequency was similar between the groups, while a regulatory NK subset (CD56bright NK cells) was higher in AS compared to SY (p=0.01). Conclusion: These data show that AS have a lower infectivity potential compared to SY suggesting that mitigated restrictive measures or alternative screening may be considered for this population. In addition, these patients showed an intact ability to produce humoral and cellular CoV-2 specific responses hence contributing to achieve herd immunity as much as SY.

Simulink Modelling for Simulating Intensive Care Mechanical Ventilators

This paper proposes a modelling approach for simulating mechanical ventilators for intensive care units (ICUs). The shortage of ventilators during the coronavirus disease 2019 (COVID-19) pandemic has focused attention on their design and performance. The proposed modelling approach consists in using the Mathworks® Simulink software tool and the SimScape Fluids (gas) library, so as to use well-established subroutines to simulate all the pneumatic components of typical ventilators for ICUs, such as the pressure reducing valves, pressure relief valves, check valves, tanks, ON\OFF and proportional directional valves, etc. The patient is simulated by setting the values of lung compliance and pressure losses occurring in the trachea. The proposed modelling approach is used in this paper to simulate a pneumatic scheme employed in some commercial ventilators. The model allows a very accurate prediction of fundamental parameters, such as the inspiratory flow rate, the inspiratory pressure, the end-expiratory pressure. Since the software interface is user-friendly, it can easily be used by manufacturers to correctly choose the geometrical and operating parameters of the components during the design stage or to assess different scenarios. © 2020 The Authors, published by EDP Sciences.

Epidemics on the margins: the bubonic plague (1903-1905) and COVID-19 epidemics in the Peruvian South Andean region. (Special Issue: Especial de pandemias.) [Spanish]

Introduction: The COVID-19 epidemic has revealed a series of inequality problems in the access to public health services in Peru, especially in provinces far from the capital where precariousness in both infrastructure and sanitary personnel is observed. In this study, we analyzed how the population and authorities in southern Peru faced epidemics, using COVID-19 epidemic and bubonic plague in 1903 and 1905 as case studies to understand continuities in the management of epidemic crises and social response to them. Development: We studied the bubonic plague epidemic in the cities of Arequipa and Mollendo in 1903 and 1905 as well as the COVID-19 epidemic, focusing on the functioning of local and national health systems, health infrastructure available to face epidemics, and finally, the social response of the population, paying particular attention to the skepticism of the population toward measures imposed by the authorities and increase in self-medication. Conclusions: The COVID-19 epidemic in southern Peru presents important similarities with the bubonic plague epidemic that affected the region at the beginning of the 20th century, including a disorder of responsibilities, lack of foresight to face epidemic diseases, insufficient infrastructure, and a population with a high degree of distrust in the recommendations given by the civil and health authorities.

Epidemics on the Margins: The Bubonic Plague (1903–1905) and covid-19 Epidemics in the Peruvian South Andean Region

Introduction: The covid-19 epidemic has revealed a series of inequality problems in the access to public health services in Peru, especially in provinces far from the capital where precariousness in both infrastructure and sanitary personnel is observed. In this study, we analyzed how the population and authorities in southern Peru faced epidemics, using covid-19 epidemic and bubonic plague in 1903 and 1905 as case studies to understand continuities in the management of epidemic crises and social response to them. Development: We studied the bubonic plague epidemic in the cities of Arequipa and Mollendo in 1903 and 1905 as well as the covid-19 epidemic, focusing on the functioning of local and national health systems, health infrastructure available to face epidemics, and finally, the social response of the population, paying particular attention to the skepticism of the population toward measures imposed by the authorities and increase in self-medication. Conclusions: The covid-19 epidemic in southern Peru presents important similarities with the bubonic plague epidemic that affected the region at the beginning of the 20th century, including a disorder of responsibilities, lack of foresight to face epidemic diseases, insufficient infrastructure, and a population with a high degree of distrust in the recommendations given by the civil and health authorities. © The Authors.