The potential virucidal effects of UV-C irradiation on SARS-CoV-2 were experimentally evaluated for different illumination doses and virus concentrations (1000, 5, 0.05 MOI). At a virus density ...comparable to that observed in SARS-CoV-2 infection, an UV-C dose of just 3.7 mJ/cm
was sufficient to achieve a more than 3-log inactivation without any sign of viral replication. Moreover, a complete inactivation at all viral concentrations was observed with 16.9 mJ/cm
. These results could explain the epidemiological trends of COVID-19 and are important for the development of novel sterilizing methods to contain SARS-CoV-2 infection.
The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord ...plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma. We detect SARS-CoV-2 genome in one umbilical cord blood and in two at-term placentas, in one vaginal mucosa and in one milk specimen. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in one umbilical cord blood and in one milk specimen. Finally, in the three documented cases of vertical transmission, SARS-CoV-2 infection was accompanied by a strong inflammatory response. Together, these data support the hypothesis that in utero SARS-CoV-2 vertical transmission, while low, is possible. These results might help defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.
Abstract
Solar UV-C photons do not reach Earth’s surface, but are known to be endowed with germicidal properties that are also effective on viruses. The effect of softer UV-B and UV-A photons, which ...copiously reach the Earth’s surface, on viruses are instead little studied, particularly on single-stranded RNA viruses. Here we combine our measurements of the action spectrum of Covid-19 in response to UV light, Solar irradiation measurements on Earth during the SARS-CoV-2 pandemics, worldwide recorded Covid-19 mortality data and our “Solar-Pump” diffusive model of epidemics to show that (a) UV-B/A photons have a powerful virucidal effect on the single-stranded RNA virus Covid-19 and that (b) the Solar radiation that reaches temperate regions of the Earth at noon during summers, is sufficient to inactivate 63% of virions in open-space concentrations (1.5 × 10
3
TCID
50
/mL, higher than typical aerosol) in less than 2 min. We conclude that the characteristic seasonality imprint displayed world-wide by the SARS-Cov-2 mortality time-series throughout the diffusion of the outbreak (with temperate regions showing clear seasonal trends and equatorial regions suffering, on average, a systematically lower mortality), might have been efficiently set by the different intensity of UV-B/A Solar radiation hitting different Earth’s locations at different times of the year. Our results suggest that Solar UV-B/A play an important role in planning strategies of confinement of the epidemics, which should be worked out and set up during spring/summer months and fully implemented during low-solar-irradiation periods.
The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. The present study targets the sphingolipid profile of ...twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.
Inflammasome-mediated activation of caspase-1 regulates inflammatory responses and pyroptosis. We analyzed possible associations between inflammasome-related genes and immune reconstitution in ...HIV-infected antiretroviral therapy (ART)-treated patients.
Cross-sectional, case-control study. HIV-infected patients on ART for ≥24 months with HIV-RNA<50 cp/mL for ≥12 months were enrolled and defined as immunological responders (IR) or non-responders (INR) if CD4 count was ≥500 or ≤350 cells/μL, respectively. Expression of inflammasome genes, caspases 1, 3, 4, 5 and γ-interferon-inducible protein 16 (IFI16) was measured in unstimulated and LPS- or aldrithiol-2-treated HIV-1
virions-stimulated peripheral blood mononuclear cells. Microbial translocation markers were evaluated.
Thirty-nine patients (22 IRs; 17 INRs) were enrolled. LPS-stimulated inflammasome genes were significantly upregulated in INRs. Whereas HIV-1
stimulation induced (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) expression in both IRs and INRs, NLRP3 and IL-18 expression was significantly increased in INRs compared to IRs. Significant higher caspase-1 expression was seen as well, whereas caspase 3, 4, and 5 expression was similar in both groups. No differences in microbial translocation markers (LPS and soluble CD14) were detected in the two groups.
Upregulation of NLRP3 and caspase-1 is observed in INR patients. This could play a role in persistent immune activation that characterize INRs. Caspase-1 upregulation could induce CD4 T-cell loss
pyroptosis, contributing to unsatisfactory CD4 T-cells recovery.
To explore the effects of SARS-CoV-2-mRNA vaccines on innate immune responses we enrolled 58 individuals who received 3 doses of the BNT162b2 vaccine in a longitudinal study; 45 of these individuals ...had never been SARS-CoV-2 infected. Results showed that vaccination significantly increased: 1) classical and intermediate inflammatory monocytes, 2) CD56
, CD56
, and CD56
/CD16
NK cells, and 3) IFN-γ+ ;production as well as perforin and granzyme content by NK cells. Vaccination also reduced expression of the NK inhibitory receptor ILT-2, increasing that of the stimulatory molecule 2DS2. These effects were long-lasting and were boosted by every vaccine dose. Notably, ILT-2 expressing NK cells were reduced even more robustly in COVID-19-recovereed vaccines. BNT162b1 mRNA vaccine is known to induce potent adaptive immune responses; results herein show its ability to modulate innate immune responses as well, offering further support to the indication to proceed with worldwide vaccination efforts to end the SARS-CoV-2 pandemic.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic of coronavirus disease (COVID-19). Whereas in most cases COVID-19 is asymptomatic or ...pauci-symptomatic, extremely severe clinical forms are observed. In this case, complex immune dysregulations and an excessive inflammatory response are reported and are the main cause of morbidity and mortality. Natural killer cells are key players in the control of viral infection, and their activity is regulated by a tight balance between activating and inhibitory receptors; an alteration of NK activity was suggested to be associated with the development of severe forms of COVID-19. In this study, we analyzed peripheral NK cell subpopulations and the expression of activating and inhibitory receptors in 30 patients suffering from neurological conditions who recovered from mild, moderate, or severe SARS-CoV-2 infection, comparing the results to those of 10 SARS-CoV-2-uninfected patients. Results showed that an expansion of NK subset with lower cytolytic activity and an augmented expression of the 2DL1 inhibitory receptor, particularly when in association with the C2 ligand (KIR2DL1-C2), characterized the immunological scenario of severe COVID-19 infection. An increase of NK expressing the ILT2 inhibitory receptor was instead seen in patients recovering from mild or moderate infection compared to controls. Results herein suggest that the KIR2DL1-C2 NK inhibitory complex is a risk factor toward the development of severe form of COVID-19. Our results confirm that a complex alteration of NK activity is present in COVID-19 infection and offer a molecular explanation for this observation.
Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a ...need to enhance immunization strategies.
We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation.
Results showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a TH1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of TH1 cytokines.
Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
The immunogenicity of anti-TNF-α drugs may affect their safety and efficacy. Infliximab (IFX), a chimeric monoclonal antibody, induces antibody formation in up to 60 % of cases. Some studies ...have suggested the involvement of a Th1 response to TNFα blockers following immunization, but the triggering of Th17 responses has never been reported. The aim of this study is to investigate whether the immunogenicity of IFX affects the Th1, Th17 and Treg compartments in rheumatoid arthritis (RA) patients failing IFX therapy, and verify whether this may be responsible for treatment failure.
Methods
The study involved 55 patients with RA (15 treatment-naïve patients; 20 IFX responders; 20 IFX non-responders) and 10 healthy controls. PBMCs were cultured in the presence/absence of IFX, and the variations in the percentage of Th1, Th17 and Treg lymphocytes following IFX treatment were analysed.
Results
IFX-specific Th1 and Th17 responses and an increase in IL-21 production were observed in patients failing IFX (
p
< 0.01,
p
< 0.05, and
p
< 0.01 respectively). In contrast, IFX incubation reduced significantly Th1 and Th17 responses and IL-21 production (
p
< 0.05) in successfully-treated subjects, but did not affect these responses in healthy controls or treatment-naïve patients.
Conclusions
RA patients may have impaired peripheral tolerance, which could favour the development of an aberrant immunological response to biological drugs. The loss of therapeutic effectiveness of IFX and the onset of adverse events may be due to a paradoxical activation of Th17 or Th1 lymphocytes following sensitisation, thus worsening the patients’ inflammatory status.
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