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1.
Mediterr J Hematol Infect Dis ; 14(1): e2022021, 2022.
Article in English | MEDLINE | ID: covidwho-1744830

ABSTRACT

Since the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) at the end of 2019, a number of medications have been used to treat the infection and the related Coronavirus disease - 19 (COVID-19). Some of the administered drugs were tested or used in practice only on the basis of biological plausibility; a promising strategy was to target the host immune response, with host directed therapies (HDTs), to reduce systemic hyperinflammation and hypercytokinemia responsible for additional tissue damage. We summarize the treatments against SARS-CoV-2 and underline their possible effects on Mycobacterium tuberculosis (Mtb) infection. Both SARS-CoV-2 and Mtb respiratory infections impair the host's immune response. Furthermore, little research has been conducted on the impact of medicaments used to counteract COVID-19 disease in patients with Latent Tuberculosis Infection (LTBI). A number of these drugs may modulate host immune response by modifying LTBI dynamic equilibrium, favoring either the host or the bacteria.

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.
Cells ; 11(1)2021 12 24.
Article in English | MEDLINE | ID: covidwho-1580994

ABSTRACT

The ongoing pandemic of coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), needs better treatment options both at antiviral and anti-inflammatory levels. It has been demonstrated that the aminothiol cysteamine, an already human applied drug, and its disulfide product of oxidation, cystamine, have anti-infective properties targeting viruses, bacteria, and parasites. To determine whether these compounds exert antiviral effects against SARS-CoV-2, we used different in vitro viral infected cell-based assays. Moreover, since cysteamine has also immune-modulatory activity, we investigated its ability to modulate SARS-CoV-2-specific immune response in vitro in blood samples from COVID-19 patients. We found that cysteamine and cystamine decreased SARS-CoV-2-induced cytopathic effects (CPE) in Vero E6 cells. Interestingly, the antiviral action was independent of the treatment time respect to SARS-CoV-2 infection. Moreover, cysteamine and cystamine significantly decreased viral production in Vero E6 and Calu-3 cells. Finally, cysteamine and cystamine have an anti-inflammatory effect, as they significantly decrease the SARS-CoV-2 specific IFN-γ production in vitro in blood samples from COVID-19 patients. Overall, our findings suggest that cysteamine and cystamine exert direct antiviral actions against SARS-CoV-2 and have in vitro immunomodulatory effects, thus providing a rational to test these compounds as a novel therapy for COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Cysteamine/pharmacology , Drug Repositioning/methods , SARS-CoV-2/drug effects , Aged , Animals , COVID-19/virology , Cell Line, Tumor , Chlorocebus aethiops , Cystamine/pharmacology , Cystine Depleting Agents/pharmacology , Female , Humans , Male , Middle Aged , RNA, Viral/genetics , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Vero Cells , Virus Replication/drug effects , Virus Replication/genetics
4.
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.

5.
J Immunol ; 206(10): 2420-2429, 2021 05 15.
Article in English | MEDLINE | ID: covidwho-1215526

ABSTRACT

We have recently shown that type 2 transglutaminase (TG2) plays a key role in the host's inflammatory response during bacterial infections. In this study, we investigated whether the enzyme is involved in the regulation of the STING pathway, which is the main signaling activated in the presence of both self- and pathogen DNA in the cytoplasm, leading to type I IFN (IFN I) production. In this study, we demonstrated that TG2 negatively regulates STING signaling by impairing IRF3 phosphorylation in bone marrow-derived macrophages, isolated from wild-type and TG2 knockout mice. In the absence of TG2, we found an increase in the IFN-ß production and in the downstream JAK/STAT pathway activation. Interestingly, proteomic analysis revealed that TG2 interacts with TBK1, affecting its interactome composition. Indeed, TG2 ablation facilitates the TBK1-IRF3 interaction, thus indicating that the enzyme plays a negative regulatory effect on IRF3 recruitment in the STING/TBK1 complex. In keeping with these findings, we observed an increase in the IFNß production in bronchoalveolar lavage fluids from COVID-19-positive dead patients paralleled by a dramatic decrease of the TG2 expression in the lung pneumocytes. Taken together, these results suggest that TG2 plays a negative regulation on the IFN-ß production associated with the innate immunity response to the cytosolic presence of both self- and pathogen DNA.


Subject(s)
COVID-19/immunology , GTP-Binding Proteins/immunology , Immunity, Innate , Interferon Regulatory Factor-3/immunology , Membrane Proteins/immunology , SARS-CoV-2/immunology , Signal Transduction/immunology , Transglutaminases/immunology , Animals , COVID-19/genetics , COVID-19/pathology , GTP-Binding Proteins/genetics , Humans , Interferon Regulatory Factor-3/genetics , Interferon-beta/genetics , Interferon-beta/immunology , Membrane Proteins/genetics , Mice , Mice, Knockout , Signal Transduction/genetics , Transglutaminases/genetics
6.
Eur Respir J ; 56(4)2020 10.
Article in English | MEDLINE | ID: covidwho-890060

ABSTRACT

Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.


Subject(s)
Respiratory Tract Infections/epidemiology , Tuberculosis/epidemiology , Virus Diseases/epidemiology , BCG Vaccine/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Epidemics , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/immunology , Humans , Influenza A Virus, H1N1 Subtype , Influenza, Human/diagnosis , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Influenza, Human/immunology , Lung/immunology , Middle East Respiratory Syndrome Coronavirus , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Public Health , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/immunology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/immunology , Tuberculosis/diagnosis , Tuberculosis/immunology , Tuberculosis/prevention & control , Virus Diseases/diagnosis , Virus Diseases/drug therapy , Virus Diseases/immunology
7.
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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