Human leukocyte antigen variants associate with BNT162b2 mRNA vaccine response.

BACKGROUND: Since the beginning of the anti-COVID-19 vaccination campaign, it has become evident that vaccinated subjects exhibit considerable inter-individual variability in the response to the vaccine that could be partly explained by host genetic factors. A recent study reported that the immune response elicited by the Oxford-AstraZeneca vaccine in individuals from the United Kingdom was influenced by a specific allele of the human leukocyte antigen gene HLA-DQB1. METHODS: We carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above. RESULTS: Our study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A, HLA-DQA1, and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. Other alleles, from both major histocompatibility complex class I and II are significantly associated with antibody levels. CONCLUSIONS: These results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies in diverse populations and for functional studies aimed to elucidate the relationship between HLA-A*03:01 and CD8+ cell response upon Pfizer-BioNTech vaccination.

It is known that people respond differently to vaccines. It has been proposed that differences in their genes might play a role. We studied the individual genetic makeup of 1351 people from Italy to see if there was a link between their genes and how well they responded to the BNT162b2 mRNA COVID-19 vaccine. We discovered certain genetic differences linked to higher levels of protection in those who got the vaccine. Our findings suggest that individual's genetic characteristics play a role in vaccine response. A larger population involving diverse ethnic backgrounds will need to be studied to confirm the generalizability of these findings. Better understanding of this could facilitate improved vaccine designs against new SARS-CoV-2 variants.

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death.

The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.

A gate-tunable graphene Josephson parametric amplifier.

With a large portfolio of elemental quantum components, superconducting quantum circuits have contributed to advances in microwave quantum optics1. Of these elements, quantum-limited parametric amplifiers2-4 are essential for low noise readout of quantum systems whose energy range is intrinsically low (tens of µeV)5,6. They are also used to generate non-classical states of light that can be a resource for quantum enhanced detection7. Superconducting parametric amplifiers, such as quantum bits, typically use a Josephson junction as a source of magnetically tunable and dissipation-free non-linearity. In recent years, efforts have been made to introduce semiconductor weak links as electrically tunable non-linear elements, with demonstrations of microwave resonators and quantum bits using semiconductor nanowires8,9, a two-dimensional electron gas10, carbon nanotubes11 and graphene12,13. However, given the challenge of balancing non-linearity, dissipation, participation and energy scale, parametric amplifiers have not yet been implemented with a semiconductor weak link. Here, we demonstrate a parametric amplifier leveraging a graphene Josephson junction and show that its working frequency is widely tunable with a gate voltage. We report gain exceeding 20 dB and noise performance close to the standard quantum limit. Our results expand the toolset for electrically tunable superconducting quantum circuits. They also offer opportunities for the development of quantum technologies such as quantum computing, quantum sensing and for fundamental science14.

A haloscope amplification chain based on a traveling wave parametric amplifier.

In this paper, we will describe the characterization of an RF amplification chain based on a traveling wave parametric amplifier. The detection chain is meant to be used for dark matter axion searches, and thus, it is coupled to a high Q microwave resonant cavity. A system noise temperature Tsys = (3.3 ± 0.1) K is measured at a frequency of 10.77 GHz, using a novel calibration scheme, allowing for measurement of Tsys exactly at the cavity output port.

Observation of Two-Mode Squeezing in a Traveling Wave Parametric Amplifier.

Traveling wave parametric amplifiers (TWPAs) have recently emerged as essential tools for broadband near quantum-limited amplification. However, their use to generate microwave quantum states still misses an experimental demonstration. In this Letter, we report operation of a TWPA as a source of two-mode squeezed microwave radiation. We demonstrate broadband entanglement generation between two modes separated by up to 400 MHz by measuring logarithmic negativity between 0.27 and 0.51 and collective quadrature squeezing below the vacuum limit between 1.5 and 2.1 dB. This work opens interesting perspectives for the exploration of novel microwave photonics experiments with possible applications in quantum sensing and continuous variable quantum computing.

Kerr reversal in Josephson meta-material and traveling wave parametric amplification.

Josephson meta-materials have recently emerged as very promising platform for superconducting quantum science and technologies. Their distinguishing potential resides in ability to engineer them at sub-wavelength scales, which allows complete control over wave dispersion and nonlinear interaction. In this article we report a versatile Josephson transmission line with strong third order nonlinearity which can be tuned from positive to negative values, and suppressed second order non linearity. As an initial implementation of this multipurpose meta-material, we operate it to demonstrate reversed Kerr phase-matching mechanism in traveling wave parametric amplification. Compared to previous state of the art phase matching approaches, this reversed Kerr phase matching avoids the presence of gaps in transmission, can reduce gain ripples, and allows in situ tunability of the amplification band over an unprecedented wide range. Besides such notable advancements in the amplification performance with direct applications to superconducting quantum computing and generation of broadband squeezing, the in-situ tunability with sign reversal of the nonlinearity in traveling wave structures, with no counterpart in optics to the best of our knowledge, opens exciting experimental possibilities in the general framework of microwave quantum optics, single-photon detection and quantum limited amplification.

Diagnostic issues faced by a rare disease healthcare network during Covid-19 outbreak: data from the Campania Rare Disease Registry.

BACKGROUND: The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period. METHODS: To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period. RESULTS: Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P < 0.001 and 37 versus 349, P < 0.001, respectively) and 2018 (117 versus 389, P < 0.001 and 37 versus 282, P < 0.001, respectively). Eighty-two among 98 rare disease experts completed the questionnaire. Diagnostic success (95%), access to diagnosis (80%) and follow-up (72%), lack of Personal Protective Equipment (60%), lack of Covid-19 guidelines (50%) and the need for home therapy (78%) were the most important issues raised during Covid-19 outbreak. CONCLUSIONS: This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.

Optimal care for rhino-orbital mucormycosis in child with myeloblastic leukemia. Case report and literature review.

Mucormycosis is an opportunistic and aggressive fungal infection that mainly affects immunocompromised patients who generally suffer from diabetes mellitus, immune impairment, hematological disease. It is a life-threatening infection and the management is not standardized. The literature proposes aggressive and early surgical approach, even at the expense of mutilation. We report a case of rhino-orbital mucormycosis in a child with myeloblastic leukemia and the successful treatment using the instill negative pressure wound therapy combined with reconstructive surgery in order to reduce mortality and to avoid disfigurement. KEY WORDS: Amphotericin B, Apex syndrome, Forehead flap, Instill NPWT, Myeloaplasia Mucormycosis.

Critical slowing down in circuit quantum electrodynamics.

Critical slowing down of the time it takes a system to reach equilibrium is a key signature of bistability in dissipative first-order phase transitions. Understanding and characterizing this process can shed light on the underlying many-body dynamics that occur close to such a transition. Here, we explore the rich quantum activation dynamics and the appearance of critical slowing down in an engineered superconducting quantum circuit. Specifically, we investigate the intermediate bistable regime of the generalized Jaynes-Cummings Hamiltonian (GJC), realized by a circuit quantum electrodynamics (cQED) system consisting of a transmon qubit coupled to a microwave cavity. We find a previously unidentified regime of quantum activation in which the critical slowing down reaches saturation and, by comparing our experimental results with a range of models, we shed light on the fundamental role played by the qubit in this regime.

Probing the Fluctuations of Optical Properties in Time-Resolved Spectroscopy.

We show that, in optical pump-probe experiments on bulk samples, the statistical distribution of the intensity of ultrashort light pulses after interaction with a nonequilibrium complex material can be used to measure the time-dependent noise of the current in the system. We illustrate the general arguments for a photoexcited Peierls material. The transient noise spectroscopy allows us to measure to what extent electronic degrees of freedom dynamically obey the fluctuation-dissipation theorem, and how well they thermalize during the coherent lattice vibrations. The proposed statistical measurement developed here provides a new general framework to retrieve dynamical information on the excited distributions in nonequilibrium experiments, which could be extended to other degrees of freedom of magnetic or vibrational origin.

Photon number statistics uncover the fluctuations in non-equilibrium lattice dynamics.

Fluctuations of the atomic positions are at the core of a large class of unusual material properties ranging from quantum para-electricity to high temperature superconductivity. Their measurement in solids is the subject of an intense scientific debate focused on seeking a methodology capable of establishing a direct link between the variance of the atomic displacements and experimentally measurable observables. Here we address this issue by means of non-equilibrium optical experiments performed in shot-noise-limited regime. The variance of the time-dependent atomic positions and momenta is directly mapped into the quantum fluctuations of the photon number of the scattered probing light. A fully quantum description of the non-linear interaction between photonic and phononic fields is benchmarked by unveiling the squeezing of thermal phonons in α-quartz.

Witnessing the formation and relaxation of dressed quasi-particles in a strongly correlated electron system.

The non-equilibrium approach to correlated electron systems is often based on the paradigm that different degrees of freedom interact on different timescales. In this context, photo-excitation is treated as an impulsive injection of electronic energy that is transferred to other degrees of freedom only at later times. Here, by studying the ultrafast dynamics of quasi-particles in an archetypal strongly correlated charge-transfer insulator (La2CuO(4+δ)), we show that the interaction between electrons and bosons manifests itself directly in the photo-excitation processes of a correlated material. With the aid of a general theoretical framework (Hubbard-Holstein Hamiltonian), we reveal that sub-gap excitation pilots the formation of itinerant quasi-particles, which are suddenly dressed by an ultrafast reaction of the bosonic field.

Cancer cachexia: from molecular mechanisms to patient's care.

Cancer cachexia is a disabling syndrome because of the complex interactions between the tumor, host metabolism, and proinflammatory cytokines that increases patients' morbidity and mortality. Considering the recent new definition and classification of cachexia, we aimed to review cancer cachexia from its underlying mechanisms to the clinical approach. Cancer cachexia is featured by a disruption in energy balance, metabolic changes, a decrease in fat mass, depletion of skeletal muscle mass, and perturbations in proinflammatory cytokines. Diagnostic effort should be focused on the recognition of precachexia to prevent or delay changes in body composition and nutritional complications secondary to cancer. From the point of disease diagnosis, every cancer patient needs continuous monitoring to receive effective, tailored nutritional and metabolic support. To date, practical guidelines to counteract cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. A single therapy may not be effective; only a multimodal approach involving different treatment combinations is more likely to be successful in the prevention and treatment of cancer cachexia.