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1.
Front Immunol ; 13: 827889, 2022.
Article in English | MEDLINE | ID: covidwho-1731779

ABSTRACT

It is well established that pregnancy induces deep changes in the immune system. This is part of the physiological adaptation of the female organism to the pregnancy and the immunological tolerance toward the fetus. Indeed, over the three trimesters, the suppressive T regulatory lymphocytes are progressively more represented, while the expression of co-stimulatory molecules decreases overtime. Such adaptations relate to an increased risk of infections and progression to severe disease in pregnant women, potentially resulting in an altered generation of long-lived specific immunological memory of infection contracted during pregnancy. How potent is the immune response against SARS-CoV-2 in infected pregnant women and how long the specific SARS-CoV-2 immunity might last need to be urgently addressed, especially considering the current vaccinal campaign. To address these questions, we analyzed the long-term immunological response upon SARS-CoV-2 infection in pregnant women from delivery to a six-months follow-up. In particular, we investigated the specific antibody production, T cell memory subsets, and inflammation profile. Results show that 80% developed an anti-SARS-CoV-2-specific IgG response, comparable with the general population. While IgG were present only in 50% of the asymptomatic subjects, the antibody production was elicited by infection in all the mild-to-critical patients. The specific T-cell memory subsets rebalanced over-time, and the pro-inflammatory profile triggered by specific SARS-CoV-2 stimulation faded away. These results shed light on SARS-CoV-2-specific immunity in pregnant women; understanding the immunological dynamics of the immune system in response to SARS-CoV-2 is essential for defining proper obstetric management of pregnant women and fine tune gender-specific vaccinal plans.


Subject(s)
COVID-19/immunology , Immunologic Memory/immunology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , Adult , Animals , Antibodies, Viral/immunology , Antibody Formation/immunology , B-Lymphocytes/immunology , Cell Line , Chlorocebus aethiops , Female , Humans , Pregnancy , Pregnant Women , Prospective Studies , Spike Glycoprotein, Coronavirus/immunology , Vero Cells , Young Adult
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320772

ABSTRACT

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 observed 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 in-patients suffering from chronic 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.

3.
J Photochem Photobiol ; 10: 100107, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1611878

ABSTRACT

We performed an in-depth analysis of the virucidal effect of discrete wavelengths: UV-C (278 nm), UV-B (308 nm), UV-A (366 nm) and violet (405 nm) on SARS-CoV-2. By using a highly infectious titer of SARS-CoV-2 we observed that the violet light-dose resulting in a 2-log viral inactivation is only 104 times less efficient than UV-C light. Moreover, by qPCR (quantitative Polymerase chain reaction) and fluorescence in situ hybridization (FISH) approach we verified that the viral titer typically found in the sputum of COVID-19 patients can be completely inactivated by the long UV-wavelengths corresponding to UV-A and UV-B solar irradiation. The comparison of the UV action spectrum on SARS-CoV-2 to previous results obtained on other pathogens suggests that RNA viruses might be particularly sensitive to long UV wavelengths. Our data extend previous results showing that SARS-CoV-2 is highly susceptible to UV light and offer an explanation to the reduced incidence of SARS-CoV-2 infection seen in the summer season.

4.
J Clin Med ; 10(24)2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-1572519

ABSTRACT

BACKGROUND: The effects of immunomodulators in patients with Coronavirus Disease 2019 (COVID-19) pneumonia are still unknown. We investigated the cellular inflammatory and molecular changes in response to standard-of-care + pidotimod (PDT) and explored the possible association with blood biomarkers of disease severity. METHODS: Clinical characteristics and outcomes, neutrophil-to-lymphocyte ratio (NLR), plasma and cell supernatant chemokines, and gene expression patterns after SARS-CoV-2 and influenza (FLU) virus in vitro stimulation were assessed in 16 patients with mild-moderate COVID-19 pneumonia, treated with standard of care and PDT 800 mg twice daily (PDT group), and measured at admission, 7 (T1), and 12 (T2) days after therapy initiation. Clinical outcomes and NLR were compared with age-matched historical controls not exposed to PDT. RESULTS: Hospital stay, in-hospital mortality, and intubation rate did not differ between groups. At T1, NLR was 2.9 (1.7-4.6) in the PDT group and 5.5 (3.4-7.1) in controls (p = 0.037). In the PDT group, eotaxin and IL-4 plasma concentrations progressively increased (p < 0.05). Upon SARS-CoV-2 and FLU-specific stimulation, IFN-γ was upregulated (p < 0.05), while at genetic transcription level, Pathogen Recognition Receptors (TRLs) were upregulated, especially in FLU-stimulated conditions. CONCLUSIONS: Immunomodulation exerted by PDT and systemic corticosteroids may foster a restoration in the innate response to the viral infection. These results should be confirmed in larger RCTs.

6.
Cells ; 10(11)2021 11 16.
Article in English | MEDLINE | ID: covidwho-1523883

ABSTRACT

While the risk of SARS-CoV-2 infection and/or COVID-19 disease progression in the general population has been largely assessed, its impact on HIV-positive individuals remains unclear. We present clinical and immunological data collected in a cohort of HIV-infected young individuals during the first wave of COVID-19 pandemic. SARS-CoV-2 RNA, virus-specific antibodies, as well as the expression of factors involved in the anti-viral immune response were analyzed. Moreover, we set up an in vitro coinfection assay to study the mechanisms correlated to the coinfection process. Our results did not show any increased risk of severe COVID-19 in HIV-positive young individuals. In those subjects who contracted SARS-CoV-2 infection, an increase in IL-10 expression and production was observed. Furthermore, in the in vitro coinfection assay, we revealed a reduction in SARS-CoV-2 replication associated to an upregulation of IL-10. We speculate that IL-10 could play a crucial role in the course of SARS-CoV-2 infection in HIV-positive individuals. These results might help defining clinical management of HIV/SARS-CoV-2 co-infected young individuals, or putative indications for vaccination schedules in this population.


Subject(s)
COVID-19/immunology , Coinfection/immunology , HIV Infections/immunology , Adolescent , Adult , COVID-19/virology , Child , Child, Preschool , Coinfection/virology , HIV Infections/virology , Humans , Infant , Inflammation , Interleukin-10/blood , Interleukin-10/genetics , Male , RNA, Messenger/blood , SARS-CoV-2/immunology , Young Adult
7.
Int J Mol Sci ; 22(19)2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1438628

ABSTRACT

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.


Subject(s)
COVID-19/blood , Sphingolipids/blood , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , Female , Humans , Lipidomics , Male , Middle Aged , Prognosis , SARS-CoV-2/isolation & purification , Severity of Illness Index , Sphingolipids/analysis , Sphingomyelins/analysis , Sphingomyelins/blood , Young Adult
8.
Front Immunol ; 11: 603428, 2020.
Article in English | MEDLINE | ID: covidwho-1389167

ABSTRACT

In this work we present the case of SARS-CoV-2 infection in a 1.5-year-old boy affected by severe Wiskott-Aldrich Syndrome with previous history of autoinflammatory disease, occurring 5 months after treatment with gene therapy. Before SARS-CoV-2 infection, the patient had obtained engraftment of gene corrected cells, resulting in WASP expression restoration and early immune reconstitution. The patient produced specific immunoglobulins to SARS-CoV-2 at high titer with neutralizing capacity and experienced a mild course of infection, with limited inflammatory complications, despite pre-gene therapy clinical phenotype.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Genetic Therapy , SARS-CoV-2 , Wiskott-Aldrich Syndrome , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , COVID-19/therapy , Humans , Infant , Male , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Wiskott-Aldrich Syndrome/blood , Wiskott-Aldrich Syndrome/immunology , Wiskott-Aldrich Syndrome/therapy , Wiskott-Aldrich Syndrome Protein/biosynthesis , Wiskott-Aldrich Syndrome Protein/immunology
9.
Mol Neurobiol ; 58(12): 6111-6120, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1375838

ABSTRACT

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.


Subject(s)
COVID-19/immunology , Killer Cells, Natural/immunology , Receptors, KIR/metabolism , B-Lymphocytes/immunology , COVID-19/physiopathology , Histocompatibility Antigens/immunology , Humans , Ligands , Lymphocyte Subsets/immunology , T-Lymphocytes/immunology
10.
Reprod Sci ; 28(10): 2939-2941, 2021 10.
Article in English | MEDLINE | ID: covidwho-1321928

ABSTRACT

Pregnant women display a higher risk of progression to disease and higher viral loads during infections due to their more permissive, tolerogenic immune system. However, only few studies have focused on SARS-CoV-2 intrapartum vertical transmission via vaginal secretions or faeces. The aim of this study was to investigate the presence of the virus in vaginal, rectal and blood specimens from pregnant women characterized by different COVID-19 disease severity. We enrolled 56 SARS-CoV-2-positive pregnant women, of which 46 (82%) were in the third trimester of pregnancy, 6 (10%) in the second and 4 (7%) in the first. QPCR was performed to detect the virus in vaginal and rectal swabs and in plasma samples. SARS-CoV-2 was detected in 27% of rectal swabs of pregnant women in the third trimester, while no virus particles were detected in vaginal swabs of the same patients. Furthermore, only 4% plasma samples tested positive to SARS-CoV-2. No virus was detected in newborn's nasopharyngeal swabs. Despite the low number of subjects enrolled, our data suggest that, while theoretically possible, intrapartum vaginal or orofecal SARS-CoV-2 transmission seems to be unlikely.


Subject(s)
COVID-19/transmission , COVID-19/virology , Infectious Disease Transmission, Vertical , Nasopharynx/virology , Parturition , Pregnancy Complications, Infectious/virology , Rectum/virology , SARS-CoV-2/isolation & purification , Vagina/virology , Adult , COVID-19/blood , COVID-19/diagnosis , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/diagnosis , Prospective Studies , Risk Assessment , Risk Factors , Young Adult
11.
Sci Rep ; 11(1): 14805, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1319047

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 × 103 TCID50/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.


Subject(s)
COVID-19/epidemiology , SARS-CoV-2/radiation effects , Sunlight , Humans , Seasons
12.
Sci Rep ; 11(1): 6260, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1142456

ABSTRACT

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/cm2 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/cm2. 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.


Subject(s)
SARS-CoV-2/radiation effects , Ultraviolet Rays , Virus Inactivation , Virus Replication/radiation effects
13.
Cells ; 10(3)2021 03 10.
Article in English | MEDLINE | ID: covidwho-1125934

ABSTRACT

We herein characterize the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation (bLTx). Removed lungs underwent histopathological evaluation. Gene expression profiling (GEP) for immune-related signatures was performed on lung specimens and SARS-CoV-2-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine levels were measured on lungs, bronchoalveolar lavage fluids and in culture supernatants. Pathological assessment showed extensive lung damage with the pattern of proliferative to fibrotic phases, with diffuse alveolar damage mimicking usual interstitial pneumonia (UIP). Lungs' GEP revealed overexpression of pathogen recognition receptors, effector cytokines and chemokines, immune activation receptors and of the inflammasome components. Multiplex cytokine analysis confirmed a proinflammatory state, with high levels of monocyte/macrophage chemotactic and activating factors and of IL-6 and TNF-α. A similar profile was observed in SARS-CoV-2-stimulated PBMCs collected 7 days after transplant. The pattern of tissue damage observed in the lungs suggests that this may represent the output of protracted disease, resembling a diffuse UIP-like picture. The molecular immune profiling supports the paradigm of a persistent proinflammatory state and sustained humoral immunity, conditions that are maintained despite the iatrogenic immunosuppression.


Subject(s)
COVID-19/surgery , Chemokines/metabolism , Cytokines/metabolism , Leukocytes, Mononuclear/metabolism , Lung Transplantation , Lung/pathology , Respiratory Distress Syndrome/surgery , Adolescent , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/virology , COVID-19/blood , Gene Expression Profiling , Gene Expression Regulation/immunology , Genotype , Humans , Inflammasomes/metabolism , Interleukin-6/metabolism , Lung/immunology , Lung/metabolism , Lung/virology , Lymph Nodes/pathology , Lymph Nodes/virology , Male , Middle Aged , Plasma/virology , Polymorphism, Single Nucleotide , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , Tumor Necrosis Factor-alpha/metabolism
14.
Nat Commun ; 11(1): 5128, 2020 10 12.
Article in English | MEDLINE | ID: covidwho-851277

ABSTRACT

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.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/transmission , Coronavirus Infections/virology , Infectious Disease Transmission, Vertical , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Pregnancy Complications, Infectious/virology , Adolescent , Adult , Antibodies, Viral/analysis , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Female , Genome, Viral , Humans , Infant, Newborn , Inflammation , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/pathology , SARS-CoV-2 , Young Adult
15.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1354

ABSTRACT

It is well known that 200-290 nm ultraviolet photons (hereinafter UV-C radiation) photo-chemically interacts with DNA and RNA and are endowed with germicidal pr

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