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1.
Clinical Microbiology and Infection ; 2022.
Article in English | ScienceDirect | ID: covidwho-1800136

ABSTRACT

Objective People with Down syndrome (DS) are particularly vulnerable to Covid-19 and show altered immune response to vaccination. We aimed to evaluate the immune response of a group of adults with DS treated with standard regimens of SARS-CoV-2 vaccine as compared with an aged- and sex-matched group of persons without DS. Methods We compared antibody responses between 42 subjects with DS (41.6 ±10.8 years, 57% male), and an age- and sex-matched comparison group of healthy health care workers (HCW) (41.4±8.8 years, 54.8% male) after SARS-CoV2 vaccination with the standard regimen of BNT162b2 mRNA COVID-19. Receptor binding domain (RBD) IgG antibodies were assessed at 4 time points (baseline, 21 days after the first dose, 21 days after the second dose and 6 months after the first dose) with Siemens SARS-CoV-2 IgG (COV2G) antibody test. Results We observed significantly different antibody responses at all time points after vaccination (HCW vs. DS: 7.9±3.9 vs. 1.4±3.6 IU/ml at 21 days after first dose;358.5±3.8 vs. 38.1±3.0 IU/ml at 21 days after second dose;34.6±2.4 vs. 7.9±3.1 IU/ml at 6 months after vaccination) and a significantly different time course of decline in antibody titers between the two groups. Conclusions Subjects with DS have a valid antibody response to SARS-CoV2 vaccination. However, this response is lower than that of subjects in the HCW group. This finding could indicate a more rapid decline in the protective effects of the vaccination in subjects with DS and could suggest that people with DS may benefit from a booster dose of vaccine.

2.
Carbon N Y ; 194: 34-41, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1739589

ABSTRACT

Additive manufacturing has played a crucial role in the COVID-19 global emergency allowing for rapid production of medical devices, indispensable tools for hospitals, or personal protection equipment. However, medical devices, especially in nosocomial environments, represent high touch surfaces prone to viral infection and currently used filaments for 3D printing can't inhibit transmission of virus [1]. Graphene-family materials are capable of reinforcing mechanical, optical and thermal properties of 3D printed constructs. In particular, graphene can adsorb near-infrared light with high efficiency. Here we demonstrate that the addition of graphene nanoplatelets to PLA filaments (PLA-G) allows the creation of 3D-printed devices that can be sterilized by near-infrared light exposure at power density analog to sunlight. This method has been used to kill SARS-CoV-2 viral particles on the surface of 3D printed PLA-G by 3 min of exposure. 3D-printed PLA-G is highly biocompatible and can represent the ideal material for the production of sterilizable personal protective equipment and daily life objects intended for multiple users.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316218

ABSTRACT

Background: The Envelope (E) protein of SARS-CoV-2 is the most enigmatic protein among the four structural ones on the viral genome. Most of the current knowledge on the E protein is based on the direct comparison to the SARS E protein, initially mistakenly undervalued and subsequently proved to be a key factor in the ER-Golgi localization and in tight junction disruption. Methods: : We compared the genomic sequences of E protein of SARS-CoV-2, SARS-CoV and the closely related genomes of bats and pangolins obtained from the GISAID and GenBank databases. Multiple sequence alignments were done with the Geneious software using the MAFFT algorithm. In silico modelling analyses of E proteins conformation and docking with PALS1 were performed with the Schrodinger Suite. Results: : When compared to the known SARS E protein, we observed a different amino acidic sequence in the C-terminal of SARS-CoV-2 E protein which might have a key role in the current COVID-19 pathogenesis. In silico docking results provide evidence of a strengthened binding of SARS-CoV-2 E protein with the tight junction-associated PALS1 protein. Conclusions: : We suggest that SARS-CoV-2 E protein may interfere with the tight junction stability and formation leading to an enhanced epithelial barrier disruption, amplifying the inflammatory processes, and promoting tissue remodelling. These findings raise a warning on the underestimated role of the E protein in the pathogenic mechanism and could open the route to detailed experimental investigations.

6.
Eur J Pediatr ; 181(4): 1507-1520, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1616131

ABSTRACT

The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48-72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48-72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth (P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%). CONCLUSIONS: Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of children exposed to SARS-CoV-2 in utero and in the early postnatal life. WHAT IS KNOWN: • In utero mother-to-child transmission of SARS-CoV-2 has been documented by several independent studies. • Neonatal COVID-19 is a systemic disease that can be severe, although rarely. WHAT IS NEW: • Newborns exposed in utero to SARS-CoV-2 have mostly a normal auxological, audiological, and neurological development during the first months of life. • Fundus fluorescein angiography revealed that up to 5% of newborns exposed in utero to SARS-CoV2 can show retinal and choroidal abnormalities, including peripheral hypofluorescence of the choroid and increased vascular tortuosity.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/diagnosis , RNA, Viral , SARS-CoV-2
7.
EClinicalMedicine ; 27: 100553, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1385448

ABSTRACT

BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

8.
JCI Insight ; 6(13)2021 06 18.
Article in English | MEDLINE | ID: covidwho-1346128

ABSTRACT

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.


Subject(s)
Arthritis, Rheumatoid/immunology , COVID-19/immunology , Monocytes/immunology , Neutrophils/immunology , Osteopontin/immunology , Arthritis, Rheumatoid/metabolism , B7-H1 Antigen/immunology , Bronchoalveolar Lavage Fluid/immunology , CD48 Antigen/immunology , COVID-19/chemically induced , COVID-19/metabolism , Fatty Acid-Binding Proteins/immunology , Humans , Lectins/immunology , Lipopolysaccharide Receptors/immunology , Lipopolysaccharide Receptors/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Lung/pathology , Macrophages/immunology , Macrophages/metabolism , Membrane Glycoproteins/immunology , Monocytes/metabolism , Neutrophils/metabolism , Osteopontin/blood , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Immunologic/immunology , S100A12 Protein/immunology , S100A12 Protein/metabolism , Synovial Membrane/immunology , Tomography, X-Ray Computed
10.
iScience ; 24(7): 102788, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1284161

ABSTRACT

Recent advancements in bidimensional nanoparticles production such as graphene (G) and graphene oxide (GO) have the potential to meet the need for highly functional personal protective equipment (PPE) against SARS-CoV-2 infection. The ability of G and GO to interact with microorganisms provides an opportunity to develop engineered textiles for use in PPE and limit the spread of COVID-19. PPE in current use in high-risk settings for COVID transmission provides only a physical barrier that decreases infection likelihood and does not inactivate the virus. Here, we show that virus pre-incubation with soluble GO inhibits SARS-CoV-2 infection of VERO cells. Furthermore, when G/GO-functionalized polyurethane or cotton was in contact SARS-CoV-2, the infectivity of the fabric was nearly completely inhibited. The findings presented here constitute an important innovative nanomaterial-based strategy to significantly increase PPE efficacy in protection against the SARS-CoV-2 virus that may implement water filtration, air purification, and diagnostics methods.

11.
Pediatr Pulmonol ; 56(6): 1374-1377, 2021 06.
Article in English | MEDLINE | ID: covidwho-1064418

ABSTRACT

Weather and the susceptibility of children to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still a debated question and currently a hot topic, particularly in view of important decisions regarding opening schools. Therefore, we performed this prospective analysis of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies in children with known household exposure to SARS-CoV-2 and compared their IgG status with the other adults exposed to the index case in the same household. A total of 30 families with a documented COVID-19 index case were included. A total of 44 out of 80 household contacts (55%) of index patients had anti SARS-CoV-2 IgG antibodies. In particular, 16/27 (59,3%) adult partners had IgG antibodies compared with 28/53 (52,3%) of pediatric contacts (p > .05). Among the pediatric population, children ≥5 years of age had a similar probability of having SARS-CoV-2 IgG antibodies (21/39, 53.8%) compared to those less than 5 years old (7/14, 50%) (p > .05). Adult partners and children also had a similar probability of having SARS-CoV-2 IgG antibodies. Interestingly, 10/28 (35.7%) of children and 5/27 (18.5%) of adults with SARS-CoV-2 IgG antibodies were previously diagnosed as COVID-19 cases. Our study shows evidence of a high rate of IgG antibodies in children exposed to SARS-CoV-2. This report has public health implications, highlighting the need to establish appropriate guidelines for school openings and other social activities related to childhood.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , Immunoglobulin G/blood , SARS-CoV-2 , Adolescent , Adult , COVID-19/immunology , COVID-19/virology , Child , Child, Preschool , Environmental Exposure , Humans , Infant , Infant, Newborn , Middle Aged , Seroepidemiologic Studies
12.
Pediatr Infect Dis J ; 40(1): e1-e6, 2021 01.
Article in English | MEDLINE | ID: covidwho-965334

ABSTRACT

BACKGROUND: To date, there are no comprehensive data on pediatric COVID-19 from Latin America. This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) in Latin American children, to appropriately plan and allocate resources to face the pandemic on a local and international level. METHODS: Ambispective multicenter cohort study from 5 Latin American countries. Children 18 years of age or younger with microbiologically confirmed SARS-CoV-2 infection or fulfilling MIS-C definition were included. FINDINGS: Four hundred nine children were included, with a median age of 3.0 years (interquartile range 0.6-9.0). Of these, 95 (23.2%) were diagnosed with MIS-C. One hundred ninety-one (46.7%) children were admitted to hospital and 52 (12.7%) required admission to a pediatric intensive care unit. Ninety-two (22.5%) patients required oxygen support: 8 (2%) were started on continuous positive airway pressure and 29 (7%) on mechanical ventilation. Thirty-five (8.5%) patients required inotropic support. The following factors were associated with pediatric intensive care unit admission: preexisting medical condition (P < 0.0001), immunodeficiency (P = 0.01), lower respiratory tract infection (P < 0.0001), gastrointestinal symptoms (P = 0.006), radiologic changes suggestive of pneumonia and acute respiratory distress syndrome (P < 0.0001) and low socioeconomic conditions (P = 0.009). CONCLUSIONS: This study shows a generally more severe form of COVID-19 and a high number of MIS-C in Latin American children, compared with studies from China, Europe and North America, and support current evidence of a more severe disease in Latin/Hispanic children or in people of lower socioeconomic level. The findings highlight an urgent need for more data on COVID-19 in Latin America.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/pathology , Adolescent , COVID-19/diagnosis , COVID-19/therapy , Child , Child, Preschool , Cohort Studies , Critical Care , Female , Hospitalization , Humans , Infant , Infant, Newborn , Latin America/epidemiology , Male , Risk Factors , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy
13.
Microbes Infect ; 22(10): 592-597, 2020.
Article in English | MEDLINE | ID: covidwho-744191

ABSTRACT

The Envelope (E) protein of SARS-CoV-2 is the most enigmatic protein among the four structural ones. Most of its current knowledge is based on the direct comparison to the SARS E protein, initially mistakenly undervalued and subsequently proved to be a key factor in the ER-Golgi localization and in tight junction disruption. We compared the genomic sequences of E protein of SARS-CoV-2, SARS-CoV and the closely related genomes of bats and pangolins obtained from the GISAID and GenBank databases. When compared to the known SARS E protein, we observed a significant difference in amino acid sequence in the C-terminal end of SARS-CoV-2 E protein. Subsequently, in silico modelling analyses of E proteins conformation and docking provide evidences of a strengthened binding of SARS-CoV-2 E protein with the tight junction-associated PALS1 protein. Based on our computational evidences and on data related to SARS-CoV, we believe that SARS-CoV-2 E protein interferes more stably with PALS1 leading to an enhanced epithelial barrier disruption, amplifying the inflammatory processes, and promoting tissue remodelling. These findings raise a warning on the underestimated role of the E protein in the pathogenic mechanism and open the route to detailed experimental investigations.


Subject(s)
COVID-19/metabolism , Membrane Proteins/chemistry , Nucleoside-Phosphate Kinase/chemistry , SARS-CoV-2/chemistry , Tight Junctions/chemistry , Viral Envelope Proteins/chemistry , Amino Acid Sequence , Animals , COVID-19/genetics , Chiroptera/virology , Databases, Genetic , Humans , Membrane Proteins/genetics , Membrane Proteins/metabolism , Molecular Dynamics Simulation , Nucleoside-Phosphate Kinase/genetics , Nucleoside-Phosphate Kinase/metabolism , Pangolins/virology , SARS Virus/chemistry , SARS Virus/genetics , SARS Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Tight Junctions/metabolism , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism
14.
Pediatr Pulmonol ; 55(10): 2547-2555, 2020 10.
Article in English | MEDLINE | ID: covidwho-669965

ABSTRACT

Since its first description in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide being declared a pandemic by the World Health Organization. More than 10.3 million people have been infected and more than 506 000 people died. However, SARS-CoV-2 had a lower impact on the pediatric population. Only about 1% to 2% of infected people are children and few deaths under the age of 14 are described so far. In this article, we discuss microbiological and immunological characteristics of SARS-CoV-2 infection in children highlighting the main differences from adult SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , COVID-19/microbiology , SARS-CoV-2 , Animals , Carrier State , Child , Host-Pathogen Interactions , Humans , Microbiota , SARS-CoV-2/physiology
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