COVID-19 Vaccine Hesitancy and Early Adverse Events Reported in a Cohort of 7,881 Italian Physicians.

Background: The COVID-19 vaccination campaign began in Italy at the end of December 2020, with the primary aim of immunizing healthcare professionals, using the EMA approved mRNA vaccines (Comirnaty® by Pfizer/BioNTech; mRNA-1273 by Moderna) and recombinant adenoviral vaccine (Vaxzevria® by AstraZeneca). The study aimed at evaluating the prevalence and motivations underlying Vaccine Hesitancy, as well as the incidence and type of adverse events associated with COVID-19 vaccination. Methods: Cross-sectional study. Data were collected January 1st to 28th 2021 using a purposely created online self-administered questionnaire from a selected cohort of Italian physicians. Results: Overall, 7,881 questionnaires were analyzed: 6,612 physicians had received one dose, and 1,670 two doses of Comirnaty®; 30 had received one dose of mRNA-1273. Vaccine Hesitancy rate was 3.6%; it correlated with prior SARS-CoV-2 infection, diabetes, Adverse Eventss at previous vaccinations and refusal of 2020 flu vaccine, and was mainly motivated by concerns about vaccine Adverse Events. Typical Adverse Events were pain/itching/paresthesia at the inoculation site, followed by headache, fever, fatigue and myalgia/arthralgia occurring more frequently after the second dose (77.8 vs 66.9%; p<0.001), and in subjects with a prior SARS-CoV-2 infection. Conclusion: Adherence to COVID-19 vaccination is high among physicians. Adverse Events are typically mild and more frequent in people with a prior SARS-CoV-2 infection.

Role and potential therapeutic use of antibodies against herpetic infections.

BACKGROUND: The cellular adaptive response directed against herpesviruses is widely described in the scientific literature as a pivotal component of the immune system able to control virus replication. The role of humoral immunity remains unclear and controversial. AIMS: Discussing the role of adaptive immunity in herpesvirus infection control, highlighting the potential role of the humoral branch of immunity through the description of human monoclonal antibodies directed against herpesviruses. SOURCES: PubMed search for relevant publications related to protective immunity against Herpesviridae. CONTENT: This review describes the role of adaptive immunity directed against Herpesviridae, focusing on the human humoral response naturally elicited during their infections. Given the ever-increasing interest in monoclonal antibodies as novel therapeutics, the contribution of humoral immunity in controlling productive infection, during both primary infection and reactivations, is discussed. IMPLICATIONS: Human monoclonal antibodies directed against the different Herpesviridae species may represent novel molecular probes to further characterize the molecular machinery involved in herpesvirus infection; and allow the development of novel therapeutics and effective vaccine strategies.

Early molecular diagnosis of aspergillosis in a patient with acute myeloid leukaemia.

Diagnosis of invasive fungal infection remains challenging. Here we report a case of early diagnosis of invasive aspergillosis in a neutropenic patient affected by acute myeloid leukaemia, achieved through the detection of Aspergillus fumigatus species-specific ribonucleic acid sequences by a sensitive multiplex real-time polymerase chain reaction-based molecular assay. Thanks to the early diagnosis, targeted therapy was promptly established and the severe fungal infection controlled, allowing the patient to subsequently receive allogeneic hematopoietic stem cell transplantation from a haploidentical donor, her only curative option. Also in this instance, targeted secondary antifungal prophylaxis with voriconazole avoided any other fungal infection afterwards. This report suggests how the implementation of molecular assays in combination with routine diagnostic procedures, can improve microbiological diagnosis in sepsis, particularly in case of fungal infection, difficult to detect with standard microbiological culture methods.

Transport and scaling in quenched two- and three-dimensional Lévy quasicrystals.

We consider correlated Lévy walks on a class of two- and three-dimensional deterministic self-similar structures, with correlation between steps induced by the geometrical distribution of regions, featuring different diffusion properties. We introduce a geometric parameter α, playing a role analogous to the exponent characterizing the step-length distribution in random systems. By a single-long-jump approximation, we analytically determine the long-time asymptotic behavior of the moments of the probability distribution as a function of α and of the dynamic exponent z associated with the scaling length of the process. We show that our scaling analysis also applies to experimentally relevant quantities such as escape-time and transmission probabilities. Extensive numerical simulations corroborate our results which, in general, are different from those pertaining to uncorrelated Lévy-walk models.

Effective target arrangement in a deterministic scale-free graph.

We study the random-walk problem on a deterministic scale-free network, in the presence of a set of static, identical targets; due to the strong inhomogeneity of the underlying structure the mean first-passage time (MFPT), meant as a measure of transport efficiency, is expected to depend sensitively on the position of targets. We consider several spatial arrangements for targets and we calculate, mainly rigorously, the related MFPT, where the average is taken over all possible starting points and over all possible paths. For all the cases studied, the MFPT asymptotically scales like ∼Nθ, being N the volume of the substrate and θ ranging from 1-log 2/log 3, for central target(s), to 1, for a single peripheral target.

Random walks on deterministic scale-free networks: exact results.

We study the random walk problem on a class of deterministic scale-free networks displaying a degree sequence for hubs scaling as a power law with an exponent gamma=log 3/log 2. We find exact results concerning different first-passage phenomena and, in particular, we calculate the probability of first return to the main hub. These results allow to derive the exact analytic expression for the mean time to first reach the main hub, whose leading behavior is given by tau approximately V1-1/gamma, where V denotes the size of the structure, and the mean is over a set of starting points distributed uniformly over all the other sites of the graph. Interestingly, the process turns out to be particularly efficient. We also discuss the thermodynamic limit of the structure and some local topological properties.

Complex phase ordering of the one-dimensional Heisenberg model with conserved order parameter.

We study the phase-ordering kinetics of the one-dimensional Heisenberg model with conserved order parameter by means of scaling arguments and numerical simulations. We find a rich dynamical pattern with a regime characterized by two distinct growing lengths. Spins are found to be coplanar over regions of a typical size LV(t), while inside these regions smooth rotations associated to a smaller length LC(t) are observed. Two different and coexisting ordering mechanisms are associated to these lengths, leading to different growth laws LV(t) approximately t1/3 and LC(t) approximately t1/4 violating dynamical scaling.

Phase-ordering kinetics on graphs.

We study numerically the phase-ordering kinetics following a temperature quench of the Ising model with single spin-flip dynamics on a class of graphs, including geometrical fractals and random fractals, such as the percolation cluster. For each structure we discuss the scaling properties and compute the dynamical exponents. We show that the exponent a_{chi} for the integrated response function, at variance with all the other exponents, is independent of temperature and of the presence of pinning. This universal character suggests a strict relation between a_{chi} and the topological properties of the networks, in analogy to what is observed on regular lattices.

Universal features of information spreading efficiency on d-dimensional lattices.

A model for information spreading in a population of N mobile agents is extended to d-dimensional regular lattices. This model, already studied on two-dimensional lattices, also takes into account the degeneration of information as it passes from one agent to the other. Here, we find that the structure of the underlying lattice strongly affects the time tau at which the whole population has been reached by information. By comparing numerical simulations with mean-field calculations, we show that dimension d=2 is marginal for this problem and mean-field calculations become exact for d>2. Nevertheless, the striking nonmonotonic behavior exhibited by the final degree of information with respect to N and the lattice size L appears to be geometry independent.

Topological filters and high-pass/low-pass devices for solitons in inhomogeneous networks.

We show that, by inserting suitable finite networks at a site of a chain, it is possible to realize filters and high-pass/low-pass devices for solitons propagating along the chain. The results are presented in the framework of coupled optical waveguides; possible applications to different contexts, such as photonic lattices and Bose-Einstein condensates in optical networks are also discussed. Our results provide a first step in the control of the soliton dynamics through the network topology.

Aging dynamics and the topology of inhomogenous networks.

We study phase ordering on networks and we establish a relation between the exponent a(x) of the aging part of the integrated auto-response function and the topology of the underlying structures. We show that a(x) > 0 in full generality on networks which are above the lower critical dimension d(L), i.e., where the corresponding statistical model has a phase transition at finite temperature. For discrete symmetry models on finite ramified structures with T(c) = 0, which are at the lower critical dimension d(L), we show that a(x) is expected to vanish. We provide numerical results for the physically interesting case of the 2 - d percolation cluster at or above the percolation threshold, i.e., at or above d(L), and for other networks, showing that the value of a(x) changes according to our hypothesis. For O(N) models we find that the same picture holds in the large-N limit and that a(x) only depends on the spectral dimension of the network.

Efficiency of information spreading in a population of diffusing agents.

We introduce a model for information spreading among a population of N agents diffusing on a square L x L lattice, starting from an informed agent (Source). Information passing from informed to unaware agents occurs whenever the relative distance is < or = 1. Numerical simulations show that the time required for the information to reach all agents scales as N(-alpha)L(beta), where alpha and beta are noninteger. A decay factor z takes into account the degeneration of information as it passes from one agent to another; the final average degree of information of the population tau(av)(z) is thus history dependent. We find that the behavior of tau(av)(z) is nonmonotonic with respect to N and L and displays a set of minima. Part of the results are recovered with analytical approximations.

Propagation of discrete solitons in inhomogeneous networks.

In many physical applications solitons propagate on supports whose topological properties may induce new and interesting effects. In this paper, we investigate the propagation of solitons on chains with a topological inhomogeneity generated by inserting a finite discrete network on a chain. For networks connected by a link to a single site of the chain, we derive a general criterion yielding the momenta for perfect reflection and transmission of traveling solitons and we discuss solitonic motion on chains with topological inhomogeneities.

Localized states on comb lattices.

Complex networks and graphs provide a general description of a great variety of inhomogeneous discrete systems. These range from polymers and biomolecules to complex quantum devices, such as arrays of Josephson junctions, microbridges, and quantum wires. We introduce a technique, based on the analysis of the motion of a random walker, that allows us to determine the density of states of a general local Hamiltonian on a graph, when the potential differs from zero on a finite number of sites. We study in detail the case of the comb lattice and we derive an analytic expression for the elements of the resolvent operator of the Hamiltonian, giving its complete spectrum.

Phage display for the production of human monoclonal antibodies against human pathogens.

In the last decade an increasing number of antibodies have made their way from the research benchtops into the clinics and many more are currently under clinical trial. Among monoclonal antibody-producing techniques, phage-display is undoubtedly the most effective and versatile. Cloning of the entire humoral repertoire derived from an infected patients into a phage display vector allows not only the simple generation of monoclonal antibodies of desired specificity, but also the molecular dissection of the antibody response itself. Generation of large panels of human monoclonal antibodies against human pathogens could open new perspectives in understanding the interplay between the infectious agent and the infected host providing tools for the prevention and the therapy of human communicable diseases. In this paper the basic principles of the phage-display approach as well as its most recent applications are reviewed.

Humoral immune response against hepatitis C virus.

Antibodies are in several instances a reliable marker indicating vigorous immune response against infectious agents and in several viral diseases presence in the blood of specific anti-viral antibodies indicates an effective protection. However, this is not always true. For example, in the case of hepatitis C virus (HCV) an important human pathogen considered the causative agent of the nonA- nonB hepatitis, in spite of an intense antibody response there is no protection against a new infection and in the majority of infected individuals the virus overcomes host defences establishing a persistent infection. Here we describe how the dissection of the humoral immune response against HCV glycoprotein E2 of infected patients was useful for a better comprehension of the virus-host interplay. Cross-reactive antibodies directed against E2 are produced by the HCV-infected patient, but not all of them are protective, and some could even result to be detrimental for the patient. The cross-reactive anti-HCV/E2 humoral antibody response is complex and not necessarily completely beneficial to the host.

Heterogeneity of the humoral anti-HCV/E2 response in persistently infected patients as demonstrated by divergent patterns of inhibition of the binding of anti-HCV/E2 human monoclonal antibodies.

A complete understanding of the molecular features of humoral immune response could be of pivotal importance in the management of persistent viruses as HCV. In this study, 24 HCV-positive samples, characterized by classical virological parameters, are evaluated using a new assay for the quantitation of antibody subpopulations directed against discrete epitopes on surface glycoprotein E2, a key viral protein. The results, besides confirming the usefulness of this new approach, highlight the extreme heterogeneity of anti-HCV/E2 response as far as single epitopes are concerned. The specific epitopes under study are also demonstrated to be widely shared among different genotypes.

Diffusive thermal dynamics for the Ising ferromagnet.

We introduce a thermal dynamics for the Ising ferromagnet where the energy variations occurring within the system exhibit a diffusive character typical of thermalizing agents such as, e.g., localized excitations. Time evolution is provided by a walker hopping across the sites of the underlying lattice according to local probabilities depending on the usual Boltzmann weight at a given temperature. Despite the canonical hopping probabilities the walker drives the system to a stationary state which is not reducible to the canonical equilibrium state in a trivial way. The system still exhibits a magnetic phase transition occurring at a finite value of the temperature larger than the canonical one. The dependence of the model on the density of walkers realizing the dynamics is also discussed. Interestingly the differences between the stationary state and the Boltzmann equilibrium state decrease with increasing number of walkers.

Nonneutralizing human antibody fragments against hepatitis C virus E2 glycoprotein modulate neutralization of binding activity of human recombinant Fabs.

Evidence from clinical and experimental studies indicates that hepatitis C virus E2 (HCV/E2) glycoprotein is the major target of a putatively protective immune response. However, even in the presence of a vigorous production of anti-HCV/E2 antibodies, reinfection can occur. Dissection of the human immune response against HCV/E2 indicated that blocking of binding of HCV/E2 to target cells [neutralization of binding (NOB) activity] varies widely among antibody clones. Moreover, in vivo, simultaneous binding of antibodies to distinct epitopes can induce conformational changes and synergies that may be relevant to understanding the anti-HCV immune response. In this study, human recombinant Fabs were generated by affinity-selecting a phage display repertoire library with antibody-coated HCV/E2. These Fabs, which share the same complementarity-determining region DNA sequences, had higher affinity than other anti-HCV/E2 Fabs but showed no NOB activity even at the highest concentrations. Binding of Fabs to HCV/E2 caused conformational changes modifying Fab-binding patterns and reducing, with a negative synergistic effect, Fab-mediated NOB activity. These data suggest that some antibody clones have the potential to modify HCV/E2 conformation and that, in this state, binding of this glycoprotein to its cellular target is less prone to inhibition by some antibody clones. This can explain why high anti-HCV/E2 antibody titers do not directly correlate with protection from infection. Information on the interactions among different antibody clones can contribute to understanding virus-host interplay and developing more effective vaccines.