Search

T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels T cell exhaustion or reshapes T cell functionality. Here, we sampled convalescent donors with a history of mild or severe COVID-19 before and after SARS-CoV-2 vaccination to profile the functional spectrum of hybrid T cell immunity. Using combined single-cell technologies and high-dimensional flow cytometry, we found that the frequencies and functional capabilities of spike-specific CD4+ and CD8+ T cells in previously infected individuals were enhanced by vaccination, despite concomitant increases in the expression of inhibitory receptors such as PD-1 and TIM3. In contrast, CD4+ and CD8+ T cells targeting non-spike proteins remained functionally static and waned over time, and only minimal effects were observed in healthy vaccinated donors experiencing breakthrough infections with SARS-CoV-2. Moreover, hybrid immunity was characterized by elevated expression of IFN-γ, which was linked with clonotype specificity in the CD8+ T cell lineage. Collectively, these findings identify a molecular hallmark of hybrid immunity and suggest that vaccination after infection is associated with cumulative immunological benefits over time, potentially conferring enhanced protection against subsequent episodes of COVID-19.

BACKGROUNDWhile B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODSWe evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.RESULTSIn contrast with control individuals (n = 10), most patients on anti-CD20 therapy (n = 48) did not demonstrate an increase in spike-specific B cells or antibodies after a third dose of vaccine. A third vaccine elicited significantly increased frequencies of spike-specific non-naive T cells. A small subset of B cell-depleted individuals effectively produced spike-specific antibodies, and logistic regression models identified time since last anti-CD20 treatment and lower cumulative exposure to anti-CD20 mAbs as predictors of those having a serologic response. B cell-depleted patients who mounted an antibody response to 3 vaccine doses had persistent humoral immunity 6 months later.CONCLUSIONThese results demonstrate that serial vaccination strategies can be effective for a subset of B cell-depleted patients.FUNDINGThe NIH (R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473, U01CA260507, 75N93019C00065, K24 AG042489), NIH HIPC Consortium (U19 AI089992), the National Multiple Sclerosis Society (CA 1061-A-18, RG-1802-30153), the Nancy Taylor Foundation for Chronic Diseases, Erase MS, and the Claude D. Pepper Older Americans Independence Center at Yale (P30 AG21342).

Aim To determine the prevalence and characteristics of pulmonary embolism (PE) in patients presenting with haemoptysis. Additionally, we assessed the efficiency and failure rates of different clinical diagnostic algorithms for PE in this patient population. Methods We enrolled consecutive adult patients who presented to nine Italian emergency departments with haemoptysis as the primary complaint. PE diagnosis was ruled out in patients with a low pre-test probability in combination with a negative age-adjusted D-dimer (referred to as the “age-adjusted” D-dimer strategy), a negative computed tomography pulmonary angiography or when a clear alternative source of bleeding was identified, along with negative findings for venous thromboembolism during a 30-day follow-up. Results A total of 546 patients were included in the study. The prevalence of PE, including the 30-day follow-up, was 4.2% (95% CI 2.7–6.3%). The majority of these cases (78%) exhibited distal (segmental or subsegmental) emboli and there were no PE-related fatalities. The “age-adjusted” D-dimer strategy initially excluded PE in 24% of patients (95% CI 21–28%), with a failure rate of 0.8% (95% CI 0.0–4.1%). Retrospectively applied, the “clinical probability-adjusted” D-dimer strategies, specifically the YEARS and Pulmonary Embolism Graduated d-Dimer (PEGeD) algorithms, excluded PE in a significantly higher proportion (30% and 32%, respectively) compared with the “age-adjusted” D-dimer strategy (p

The 3D digital reproduction of panel paintings is an efficient practice through which to document their state of conservation thanks to the ability to study artwork both at the microscopic level, visualising the craquelure and the detachments of pictorial layers, and at the macroscopic level, analysing support structures and their deformations. In recent years, research has focused on new methodologies to handle multiple 3D scans acquired over time and to achieve data fusion to obtain multi-resolution products. In this paper, we present the results of the acquisition of the central panel of an earthquake-damaged triptych using two different 3D techniques (close-range photogrammetry and structured light) before and after its restoration to carry out a multi-temporal analysis of the conservation status and document the effects of the restoration. Furthermore, we performed laser scanning micro-profilometry on a small area of the painting to study the artist’s technique and identify previous restorations. Finally, we merged the two 3D datasets (obtained by structured-light projection and micro-profilometry) to produce a multi-resolution 3D model with the aim of increasing the accuracy and readability of the final product.

Background and objectivesParkinson's disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC).MethodsPeripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining.ResultsHere we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets.ConclusionsThese results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.

Despite the widespread use of SARS-CoV-2-specific monoclonal antibody (mAb) therapy for the treatment of acute COVID-19, the impact of this therapy on the development of SARS-CoV-2-specific T cell responses has been unknown, resulting in uncertainty as to whether anti-SARS-CoV-2 mAb administration may result in failure to generate immune memory. Alternatively, it has been suggested that SARS-CoV-2-specific mAb may enhance adaptive immunity to SARS-CoV-2 via a "vaccinal effect." Bamlanivimab (Eli Lilly and Company) is a recombinant human IgG1 that was granted FDA emergency use authorization for the treatment of mild to moderate COVID-19 in those at high risk for progression to severe disease. Here, we compared SARS-CoV-2-specific CD4+ and CD8+ T cell responses of 95 individuals from the ACTIV-2/A5401 clinical trial 28 days after treatment with bamlanivimab versus placebo. SARS-CoV-2-specific T cell responses were evaluated using activation-induced marker assays in conjunction with intracellular cytokine staining. We demonstrate that most individuals with acute COVID-19 developed SARS-CoV-2-specific T cell responses. Overall, our findings suggest that the quantity and quality of SARS-CoV-2-specific T cell memory were not diminished in individuals who received bamlanivimab for acute COVID-19. Receipt of bamlanivimab during acute COVID-19 neither diminished nor enhanced SARS-CoV-2-specific cellular immunity.

The monkeypox virus (MPXV) outbreak confirmed in May 2022 in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is known regarding MPXV immunity in the context of MPXV infection or vaccination with vaccinia-based vaccines (VACV). As with vaccinia, T cells are likely to provide an important contribution to overall immunity to MPXV. Here, we leveraged the epitope information available in the Immune Epitope Database (IEDB) on VACV to predict potential MPXV targets recognized by CD4+ and CD8+ T cell responses. We found a high degree of conservation between VACV epitopes and MPXV and defined T cell immunodominant targets. These analyses enabled the design of peptide pools able to experimentally detect VACV-specific T cell responses and MPXV cross-reactive T cells in a cohort of vaccinated individuals. Our findings will facilitate the monitoring of cellular immunity following MPXV infection and vaccination.

Solitary primary extraosseous plasmacytoma is a rare disease in the gastrointestinal tract, recently classified as an “exceptional” tumor of the colon site. The real incidence (one case/population/year) is unknown but reasonably less than 1/10,000,000 cases/year with very few descriptions in the literature. The rare cases described in the literature are often diagnosed after surgery for perforation and with predominant localization of the left colon. The main endoscopic presentation mimics colon carcinoma with ulcerated mass and obstructing lumen. In this paper, we report a rare case of isolated mass mimicking a submucosal lesion of the ascending colon diagnosed in an older female patient by colonoscopy. The patient was almost asymptomatic; she reported only a history of hematochezia without anemia. This mass was successfully treated by surgery and followed by hematological investigations, including bone marrow biopsy, specific laboratory tests, and CT/PET scan, which confirmed primary isolated plasmacytoma of the colon.

Abstract Background Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine JYNNEOS. Given the potential threat of MPXV resurgence and need for vaccine alternatives, we aimed to assess the capacity COH04S1 and its synthetic MVA (sMVA) backbone to confer MPXV-specific immunity. Methods We evaluated orthopoxvirus-specific and MPXV cross-reactive immune responses in samples collected during a Phase 1 clinical trial of COH04S1 and in non-human primates (NHP) vaccinated with COH04S1 or its sMVA backbone. MPXV cross-reactive immune responses in COH04S1-vaccinated healthy adults were compared to responses measured in healthy subjects vaccinated with JYNNEOS. Additionally, we evaluated the protective efficacy of COH04S1 and sMVA against mpox in mpox-susceptible CAST/EiJ mice. Results COH04S1-vaccinated individuals develop robust orthopoxvirus-specific humoral and cellular responses, including cross-reactive antibodies to MPXV-specific virion proteins as well as MPXV cross-neutralizing antibodies in 45% of the subjects. In addition, NHP vaccinated with COH04S1 or sMVA show similar MPXV cross-reactive antibody responses. Moreover, MPXV cross-reactive humoral responses elicited by COH04S1 are comparable to those measured in JYNNEOS-vaccinated subjects. Finally, we show that mice vaccinated with COH04S1 or sMVA are protected from lung infection following challenge with MPXV clade IIb.1. Conclusions These results demonstrate the capacity of sMVA vaccines to elicit cross-reactive and protective orthopox-specific immunity against MPXV, suggesting that COH04S1 and sMVA could be developed as bivalent or monovalent mpox vaccine alternatives against MPXV.

Essential oils (EOs) are reported to be natural pesticides, but their use to protect crops is very limited due to EOs’ high instability and great volatility. Nanovectors represent a very smart alternative, and in this study, EOs from Artemisia annua (AEO) and Salvia fruticosa (SEO) were formulated into microemulsions and tested against Fusarium verticillioides. The EOs were extracted by steam distillation and analyzed by GC–MS. The main constituents of AEO were camphor, artemisia ketone, and 1,8-cineole; the main constituents of SEO were 1,8-cineole, camphor, α-pinene, and β-pinene. Artemisia ketone and 1,8-cineole were used to calculate the recovery and chemical stability of the microemulsions. The microemulsions were loaded with 10 mg/mL of EOs, and the recoveries were 99.8% and 99.6% for AEO and SEO, respectively. The sizes of the lipid phases were 255.3 ± 0.6 nm and 323.7 ± 2.3 nm for the AEO and SEO microemulsions, respectively. Activity against F. verticillioides was tested using amphotericin B as the positive control. F. verticillioides was very susceptible to both EOs. When loaded in the microemulsions, AEO and SEO remained very active at a dose of 1.4 and 1.2 mg, with a 99.99% reduction of F. verticillioides. The findings suggest AEO and SEO microemulsions are suitable carriers for the protection of crops against F. verticillioides.

Background: This study examines the results of autopsy examinations specifically aimed at documenting complications arising from the implantation phase and treatment with veno–arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with refractory cardiac arrest. ECMO and VA-ECMO in particular are life-saving interventions that, in the case of cardiac arrest, can temporarily replace cardiac pump function. VA-ECMO is, however, a very invasive procedure and is associated with early mechanical, haemorrhagic, and thrombotic events, infections, and late multi-organ dysfunction. Aim: This research aims to evaluate autoptic and histologic findings in patients on VA-ECMO support, providing clinical and forensic evaluation elements with respect to the procedure and clinical settings. Materials and Methods: The study analysed 10 cases, considering variables such as the duration of cardiac arrest, understood as the time between the cardiac arrest event and reperfusion with VA-ECMO, the duration of VA-ECMO support, and any complications detected by clinicians during treatment. Results: The results highlighted the presence of numerous ischemic and haemorrhagic events affecting various organs. Among them, the intestines were particularly vulnerable, even after a short ECMO duration. Conclusions: ECMO was found to accelerate post-mortem decomposition, affecting post-mortem interval estimations, and cardiac damage from reperfusion, underlining the need to meticulously select indications for treatment with VA-ECMO and perform constant clinical evaluations during the treatment itself.

Monitoring atmospheric pollution in urban areas is challenging because pollutant deposition occurs at short distances, requiring a large amount of sampling and analysis to characterize it. Ecological indicators can help overcome this problem, allowing us to select sites with the highest deposition of pollutants from the atmosphere. Nevertheless, a major gap is the temporal characterization of the accumulation rate of magnetic particles in ecological indicators, which is critical to understand if the bioaccumulation process is linear or if saturation occurs. To overcome this problem, Parmotrema perlatum lichens were magnetically and chemically studied in a pollution gradient over space and time. Lichen transplants were exposed over 18 weeks to a high-traffic road. Results show that magnetic properties and element composition reflected both distance from the road (nonlinear decrease of up to 100 m from source) and exposure time (increasingly linearly over the entire study period with eightfold increments), showing that up to 18 weeks, the accumulation rate remained constant over time, with no saturation occurring. Chemical analysis showed a strong linear relationship between the accumulation of zinc (Zn), antimony (Sb), manganese (Mn), copper (Cu) chromium (Cr) and magnetic susceptibility. Magnetization acquisition curves reveal a time-dependent low-coercivity component, interpreted as mainly related to nonexhaust, mostly brake abrasion particle emissions. It is concluded that the magnetic properties of lichen transplants can be used in urban environments to characterize the spatial and temporal patterns of the deposition of pollution metallic particles from the atmosphere.

The phenomenon of child abuse/maltreatment is underestimated and often represents a difficult challenge for healthcare professionals and forensic pathologists who must proceed with the differential diagnosis with accidental or self-induced events, or with lesions due to pathologies that overlap with that of mistreatment, defined as “Mimics”. This study presents a case series with the aim of discussing lesions that may mimic signs of physical abuse in children but are due to a different etiology to raise awareness and train healthcare professionals and forensic pathologists on possible confounding factors in order to avoid diagnostic errors. Six cases of “Mimics” out of 418 cases of suspected mistreatment (1.43% of cases) were identified, presenting skin lesions initially classified as injuries of abuse due to their location and type and, in particular, sexual abuse for three cases. Then, the lesions and the subjects, in particular the anamnestic history, were examined by a multidisciplinary team and the diagnosis of genital lichen sclerosus et atrophicus in three cases, and the results of popular healing techniques (i.e., “cupping”) in the other three cases were ascertained. These situations require specific skills and a forensic background from healthcare professionals to conduct a correct differential diagnosis and the intervention of a multidisciplinary team to investigate every possible pathology or alternative therapeutic practice that could simulate child abuse. In particular, when “mimics” are due to alternative medicine, it should not strictly be considered child abuse, but professionals must be aware of the hypothesis of mistreatment in case of non-medical indication or potential personal injuries from other crimes, such as illegal practice of the medicine. This awareness is also crucial to direct the child toward appropriate medical care, and it is essential to recognize that these conditions can coexist within the same clinical presentation.

BackgroundVaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus.MethodsTwelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay.Results2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p