We propose to identify peptides derived from the S protein that can modulate the HLA-E restricted activity of NK cells. Through in-silico analyses, we have already identified in the S protein of SARS-Cov1, SARS-Cov2 and MERS-Cov regions coding for peptides with HLA-E binding motifs. We will perform functional and structural analyses of the binding of these peptides to MHC-E. We will study MHC-E restricted responses of NK cells in blood and tissues during SARS-Cov2 infection in non human primates. From longitudinally collected samples from blood and tissues before and after the SARS-CoV2 infection of the animals, we will analyse the phenotype and transcriptome profile of NK cells and compare to viral loads and disease progression of the animals.

SARS-CoV-2 depends on the activation or inactivation of specific cellular pathways for efficient replication. The project screened small molecule compounds that affected epigenetic regulation of such pathway. The project aims to characterize these specific pathways, so identify specific steps important in the viral replication cycle and with this to describe the mode of action of these compounds.

Vaccines against COVID-19 have been developed for use as homologous two-dose regimens and several of them have demonstrated efficacy. There is limited data on the clinical and the immune response induced by heterologous vaccination regimens (HVR) using alternate vaccine modalities. CORSER-4 is a Viro-Immunology cohort promoted by the Institut Pasteur that will follow-up subjects from the time they receive a prime vaccine dose or a boosting dose. We determined subjects sub-groups of interest defined by the type of vaccine immunization they receive: (i) Heterologous two-dose vaccine regimen, the less frequently used at the moment, (ii) Homologous two-dose vaccine regimen, the more frequently used; (iii) One-dose vaccine regimen and (iv) Infectious-prime vaccine-boost immunization in COVID-19-experienced patients. The subject will be enrolled on the planed last boost injection visit and 5 Follow-up visits will be further conducted (Month1, M3, M6, M12 and M24). We will collect longitudinal clinical data and biological samples. We will explore Viral and Immune Response in sera, nasopharyngeal secretions and in saliva samples. We will assess the immune response obtained by various vaccination regimen against the reference strains and the variants of concern, and the durability of the humoral and cellular response. In addition, we will document any occurring acute infection episode with a supplemental unscheduled visit in order to detect an emerging variant viral strain. Altogether, the CORSER-4 project constitutes an opportunity to evaluate early anti-SARS-CoV-2 immunity in heterologous (and others) vaccine regimens and to estimate their efficacy and their sustainable (M24) protection against circulating virus strains (reference and variants).

Voluntary organizations provide essential support to vulnerable populations and front-line health responders to the COVID-19 pandemic. The French Red Cross (FRC) is prominent among organizations offering health and support services in the current crisis. Comprised primarily of lay volunteers and some trained health workers, FRC volunteers in the Paris (France) region have faced challenges in adapting to pandemic conditions, working with sick and vulnerable populations, managing limited resources, and coping with high demand for their services. Existing studies focus on individual, social and organizational determinants of motivation, but attend less to contextual ones. Public health incertitude about the COVID-19 pandemic is an important feature of this pandemic. Whether and how uncertainty interacts with volunteer understandings and experiences of their work and organizational relations to contribute to Red Cross workonline social listening and surveys.

It is increasingly clear that SARS-CoV-2 infection does not only affect the airways, but also the central nervous system (CNS) by interfering with neurons, glial cells, and the immune response in the brain, sometimes leading to long-lasting neurological signs, including anosmia and anxio-depressive symptoms. These and other persistent symptoms constitute a new entity that is currently called Long-COVID or Post-Acute COVID-19 Syndrome (PACS), however, it still lacks definitive diagnostic criteria and a universally accepted definition, as well a fully comprehensive view of its causative mechanisms. Our working hypothesis is that SARS-CoV-2 and/or the related inflammatory response can trigger a central mechanism in the CNS leading to the persistence of symptoms. The persistence of virus (or viral components, in particular viral RNA) along with the persistence of inflammation in the CNS may be an underlying cause for the occurrence of persistent symptoms in long COVID patients. Consequently, our main objective is to understand the origin and the mechanisms responsible for the persistent neurological symptoms such as long-term anosmia/ageusia or anxio-depressive symptoms post- SARS-CoV-2 infection, and we will focus on how viral neuroinvasion, neuroinflammation and/or signal transmitted by the neural route (lung-brain or visceral-brain axis) account for long-term post COVID-19 CNS alterations. At the end, the LongNeuroCOVID project should lead to several impactful results. From the scientific point of view, this work will improve the understanding of the general mechanisms involved in the spatio-temporal dynamics of SARS-CoV-2 infection, from entry in the CNS to causing long-term inflammation and CNS alterations. Describing these fundamental mechanisms should be of broader interest to the scientific community, as these results may be applicable to other, less understood, neuroinvasive pathogens. For public health, the characterization, in a relevant animal model and in an in vitro model of human neural networks, of the neurotropism of SARS-CoV-2 and its direct or indirect impact on long-term symptoms will be instrumental to the development of future therapies aimed at these clinical presentations. Finally, at the neuropsychiatric level, this study should provide new and interesting findings regarding the occurrence of anxio-depressive signs following the infection by SARS-CoV-2 and their relation with anosmia and neuroinflammation.

Although in the last years the world scientific community has carried out unprecedented research activity to diagnose, treat, and prevent COVID-19, lasting effects after the acute phase of the disease are yet to be discovered. SARS-CoV-2 infection generally causes mild or no symptoms in children. Nevertheless, increasing evidence show that several immune-pathological changes can remain weeks or months after the infection; this persistent condition is known as “Long COVID (LC)”, that in adults is associated to highly activated innate immune cells. In this context, inflammation-related analytes, such as cytokines and chemokines, could have an important role. Hence, we measured the concentration (pg/mL) of several analytes in SARS-CoV2(+) sera of children/adolescent with and without LC symptoms. Blood samples from SARS-CoV2 (+) and (-) children attending Umberto I hospital of Rome, were collected within 3-6 months after SARS-CoV-2 tests. Thirty SARS-CoV2(+) patients (mean age 12 years) with LC symptoms, 30 SARS-CoV2(+) patients (mean age 12 years) without LC symptoms and 20 SARS-CoV-2(-) children (mean age 11 years) were enrolled. Symptoms related to SARS-CoV-2 infection and belonging to the respiratory System, nervous System, gastrointestinal System and musculoskeletal System, have been collected during the acute phase of infection, post COVID (1 month from infection) and/or long COVID stages (3-6 moths from infection). The aim of the study is to characterize the immune-pathological alterations related to SARS-CoV2 several months after infection, investigating the protein-protein interactions (PPIs) with reference to symptomatological and demographic parameters. As already discussed with Dr. Natalia Pietrosemoli, our research group wish to engage a close collaboration in order to enrich our study with your precious bio-informatic analysis/scientific expertise.