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2.
Nat Med ; 27(3): 401-410, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33723456

RESUMO

The twenty-first century has already recorded more than ten major epidemic or pandemic virus emergence events, including the ongoing and devastating coronavirus disease 2019 (COVID-19) pandemic. As viral disease emergence is expected to accelerate, these data dictate a need for proactive approaches to develop broadly active family-specific and cross-family therapeutics for use in future disease outbreaks. Emphasis should focus not only on the development of broad-spectrum small-molecule and antibody direct-acting antivirals, but also on host-factor therapeutics, including repurposing previously approved or in-pipeline drugs. Another new class of therapeutics with great antiviral therapeutic potential is RNA-based therapeutics. Rather than only focusing on known risks, dedicated efforts must be made toward pre-emptive research focused on outbreak-prone virus families, ultimately offering a strategy to shorten the gap between outbreak and response. Emphasis should also focus on orally available drugs for outpatient use, if possible, and on identifying combination therapies that combat viral and immune-mediated pathologies, extend the effectiveness of therapeutic windows and reduce drug resistance. While such an undertaking will require new vision, dedicated funding and private, federal and academic partnerships, this approach offers hope that global populations need never experience future pandemics such as COVID-19.


Assuntos
Doenças Transmissíveis Emergentes/terapia , Terapias em Estudo , Viroses/terapia , Antivirais/uso terapêutico , /epidemiologia , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/tendências , Reposicionamento de Medicamentos , História do Século XXI , Humanos , Invenções/tendências , Pandemias , Terapias em Estudo/métodos , Terapias em Estudo/tendências
3.
Bioessays ; 43(4): e2000315, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33569817

RESUMO

The versatile clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has emerged as a promising technology for therapy and molecular diagnosis. It is especially suited for overcoming viral infections outbreaks, since their effective control relies on an efficient treatment, but also on a fast diagnosis to prevent disease dissemination. The CRISPR toolbox offers DNA- and RNA-targeting nucleases that constitute dual weapons against viruses. They allow both the manipulation of viral and host genomes for therapeutic purposes and the detection of viral nucleic acids in "Point of Care" sensor devices. Here, we thoroughly review recent advances in the use of the CRISPR/Cas system for the treatment and diagnosis of viral deleterious infections such as HIV or SARS-CoV-2, examining their strengths and limitations. We describe the main points to consider when designing CRISPR antiviral strategies and the scientific efforts to develop more sensitive CRISPR-based viral detectors. Finally, we discuss future prospects to improve both applications. Also see the video abstract here: https://www.youtube.com/watch?v=C0z1dLpJWl4.


Assuntos
Técnicas Biossensoriais/métodos , Sistemas CRISPR-Cas , Viroses/diagnóstico , Viroses/terapia , Vírus/genética , /diagnóstico , /terapia , Técnicas de Introdução de Genes , Genoma Viral , Humanos , RNA Guia/genética
4.
Obstet Gynecol Clin North Am ; 48(1): 53-74, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33573790

RESUMO

Viral infections are common complications of pregnancy. Although some infections have maternal sequelae, many viral infections can be perinatally transmitted to cause congenital or chronic infection in fetuses or infants. Treatments of such infections are geared toward reducing maternal symptoms and complications and toward preventing maternal-to-child transmission of viruses. The authors review updates in the treatment of herpes simplex virus, cytomegalovirus, hepatitis B and C viruses, human immunodeficiency virus, and COVID-19 during pregnancy.


Assuntos
Transmissão Vertical de Doença Infecciosa , Complicações Infecciosas na Gravidez/terapia , Viroses/terapia , Viroses/transmissão , Adulto , Antivirais/uso terapêutico , /transmissão , Infecções por Citomegalovirus/terapia , Infecções por Citomegalovirus/transmissão , Feminino , Infecções por HIV/terapia , Infecções por HIV/transmissão , Hepatite B/terapia , Hepatite B/transmissão , Hepatite C/terapia , Hepatite C/transmissão , Herpes Simples/terapia , Herpes Simples/transmissão , Humanos , Lactente , Gravidez , Complicações Infecciosas na Gravidez/virologia
5.
Stem Cell Rev Rep ; 17(1): 214-230, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33403490

RESUMO

The COVID-19 pandemic has profoundly influenced public health and contributed to global economic divergences of unprecedented dimensions. Due to the high prevalence and mortality rates, it is then expected that the consequence and public health challenges will last for long periods. The rapid global spread of COVID-19 and lack of enough data regarding the virus pathogenicity multiplies the complexity and forced governments to react quickly against this pandemic. Stem cells represent a small fraction of cells located in different tissues. These cells play a critical role in the regeneration and restoration of injured sites. Because of their specific niche and a limited number of stem cells, the key question is whether there are different anti-viral mechanisms against viral infection notably COVID-19. Here, we aimed to highlight the intrinsic antiviral resistance in different stem cells against viral infection. These data could help us to understand the possible viral infections in different stem cells and the activation of specific molecular mechanisms upon viral entrance.


Assuntos
/terapia , Pandemias , Transplante de Células-Tronco , Viroses/terapia , /virologia , Surtos de Doenças/prevenção & controle , Humanos , Células-Tronco/patologia , Viroses/virologia
8.
Nutrients ; 12(9)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967126

RESUMO

Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections.


Assuntos
Fatores Imunológicos/uso terapêutico , Viroses/terapia , Deficiência de Vitamina D/terapia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Suplementos Nutricionais , Humanos , Sistema Imunitário , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Viroses/imunologia , Viroses/virologia , Vitamina D/sangue , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/virologia
9.
Viruses ; 12(9)2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967229

RESUMO

As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.


Assuntos
Fatores Imunológicos/imunologia , Viroses/imunologia , Vírus/imunologia , Animais , Antivirais/uso terapêutico , Doença Crônica , Humanos , Fatores Imunológicos/antagonistas & inibidores , Imunoterapia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Viroses/terapia , Vírus/classificação
10.
Appl Microbiol Biotechnol ; 104(19): 8089-8104, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32813065

RESUMO

Interspecies transmissions of viruses between animals and humans may result in unpredictable pathogenic potential and new transmissible diseases. This mechanism has recently been exemplified by the discovery of new pathogenic viruses, such as the novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic, Middle-East respiratory syndrome-coronavirus epidemic in Saudi Arabia, and the deadly outbreak of Ebola in West Africa. The. SARS-CoV-2 causes coronavirus disease-19 (COVID-19), which is having a massive global impact in terms of economic disruption, and, above all, human health. The disease is characterized by dry cough, fever, fatigue, myalgia, and dyspnea. Other symptoms include headache, sore throat, rhinorrhea, and gastrointestinal disorders. Pneumonia appears to be the most common and severe manifestation of the infection. Currently, there is no vaccine or specific drug for COVID-19. Further, the development of new antiviral requires a considerable length of time and effort for drug design and validation. Therefore, repurposing the use of natural compounds can provide alternatives and can support therapy against COVID-19. In this review, we comprehensively discuss the prophylactic and supportive therapeutic role of probiotics for the management of COVID-19. In addition, the unique role of probiotics to modulate the gut microbe and assert gut homeostasis and production of interferon as an antiviral mechanism is described. Further, the regulatory role of probiotics on gut-lung axis and mucosal immune system for the potential antiviral mechanisms is reviewed and discussed.Key points• Gut microbiota role in antiviral diseases• Factors influencing the antiviral mechanism• Probiotics and Covid-19.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Probióticos/uso terapêutico , Animais , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Trato Gastrointestinal/microbiologia , Humanos , Imunidade nas Mucosas , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/virologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Probióticos/metabolismo , Infecções Respiratórias/microbiologia , Viroses/prevenção & controle , Viroses/terapia , Viroses/transmissão , Vitamina D/fisiologia , Zinco/metabolismo
11.
Eur J Health Econ ; 21(9): 1329-1350, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32789780

RESUMO

Pandemics and major outbreaks have the potential to cause large health losses and major economic costs. To prioritize between preventive and responsive interventions, it is important to understand the costs and health losses interventions may prevent. We review the literature, investigating the type of studies performed, the costs and benefits included, and the methods employed against perceived major outbreak threats. We searched PubMed and SCOPUS for studies concerning the outbreaks of SARS in 2003, H5N1 in 2003, H1N1 in 2009, Cholera in Haiti in 2010, MERS-CoV in 2013, H7N9 in 2013, and Ebola in West-Africa in 2014. We screened titles and abstracts of papers, and subsequently examined remaining full-text papers. Data were extracted according to a pre-constructed protocol. We included 34 studies of which the majority evaluated interventions related to the H1N1 outbreak in a high-income setting. Most interventions concerned pharmaceuticals. Included costs and benefits, as well as the methods applied, varied substantially between studies. Most studies used a short time horizon and did not include future costs and benefits. We found substantial variation in the included elements and methods used. Policymakers need to be aware of this and the bias toward high-income countries and pharmaceutical interventions, which hampers generalizability. More standardization of included elements, methodology, and reporting would improve economic evaluations and their usefulness for policy.


Assuntos
Cólera/epidemiologia , Controle de Doenças Transmissíveis/organização & administração , Epidemias/economia , Viroses/epidemiologia , Cólera/economia , Cólera/terapia , Controle de Doenças Transmissíveis/economia , Análise Custo-Benefício , Humanos , Pandemias , Viroses/economia , Viroses/terapia
12.
Cochrane Database Syst Rev ; 8: CD004370, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32835416

RESUMO

BACKGROUND: This is an update of a previous review. Case reports and case series have described dramatic responses to intravenous immunoglobulin (IVIG) in people with presumed viral myocarditis, and its administration has become commonplace. OBJECTIVES: The primary objective of this review was to compare event-free (death, requirement for a cardiac transplant, or placement of a left ventricular assist device) or overall (death) survival of adults and children with presumed viral myocarditis treated with IVIG versus those who did not receive IVIG. A secondary objective was to determine if a group of patients with presumed viral myocarditis could be identified (on the basis of age, duration of symptoms, acuity of onset of symptoms, cardiac function at presentation, virological results, or the presence or absence of histological evidence of acute myocarditis on cardiac biopsy in patients in whom a biopsy was performed) who would be the most likely to benefit from IVIG. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, DARE, CINAHL, Web of Science Core Collection, and LILACS in July 2019, and two trial registries in November 2019. We contacted authors of trials and checked reference lists of relevant papers. We applied no language restrictions. SELECTION CRITERIA: We included studies if (1) participants had a clinical diagnosis of acute myocarditis with a left ventricular ejection fraction (LVEF) ≤ 0.45, left ventricular end-diastolic diameter (LVEDD) > 2 standard deviations (SDs) above the norm, or a left ventricular shortening fraction (LVSF) > 2 SDs below the mean, with duration of cardiac symptoms < 6 months; (2) participants had no evidence of non-infectious or bacterial cardiac disease; and (3) participants were randomly assigned to receive at least 1 g/kg of IVIG versus no IVIG or placebo. We excluded studies if (1) participants had received immunosuppression before outcome assessment; or (2) onset of myocarditis was reported to have occurred < 6 months postpartum. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and extracted data. We assessed risk of bias with the Cochrane 'Risk of bias' tool. We conducted meta-analysis for two outcomes (overall survival and improvement in LVEF) with two adult trials. Other meta-analyses were not possible because only three relevant trials were included, and researchers analysed markedly different populations and used different outcome measures. MAIN RESULTS: In this update we added two trials to the two previously included trials. A quasi-randomised trial was previously included due to a paucity of evidence from randomised trials; however, with the addition of two new randomised trials, it was removed from this update. For two adult trials, the overall risk of bias was unclear with very low-certainty evidence for all outcomes. The first trial studied 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The effect on event-free survival between groups was uncertain (risk ratio (RR) of any event 1.76, 95% confidence interval (CI) 0.48 to 6.40). The second trial studied 41 adults with acute myocarditis randomised to either high-dose IVIG (1 to 2 g/kg over two days) or no treatment. The IVIG group reported greater survival time after 60 days (no raw data, P < 0.01), but the evidence is uncertain. We pooled the reported number of deaths in both trials, with no evidence of a difference between groups (RR 0.91, 95% CI 0.23 to 3.62, I2 = 31%, very low-certainty evidence). The evidence on the effect of IVIG treatment on LVEF (pooled mean difference (MD) -0.01, 95% CI -0.06 to 0.05) after 12 months and an unknown time frame is uncertain. The results for functional capacity, assessed by peak oxygen consumption at 12 months, were uncertain (MD -0.80, 95% CI -4.57 to 2.97). The results for infusion-related side effects were also uncertain due to a very large CI (RR 20.29, 95% CI 1.25 to 329.93). Lastly, there was uncertain evidence addressing failure to attain complete recovery (RR 0.46, 95% CI 0.19 to 1.14).  Evidence for improvement in LVEDD, left ventricular shortening fraction, and hospitalisation status in adults was not reported.  In the single included paediatric trial, the overall risk of bias was low with very low-certainty evidence for all outcomes. The trial included 86 children in Egypt presenting with acute myocarditis. Children were randomly assigned to 1 g/kg IVIG daily for two consecutive days or placebo followed by echocardiography one and six months post randomisation for recording of LVEDD and LVSF. The evidence for overall survival after six months was uncertain (risk of death RR 0.48, 95% CI 0.20 to 1.15). The evidence was also uncertain for improvement in LVEDD and LVSF after six months (LVEDD MD -4.00, 95% CI -9.52 to 1.52; LVSF no raw data).  Evidence for improvement in LVEF, functional capacity, side effects, complete recovery, and hospitalisation status in children was not reported.  AUTHORS' CONCLUSIONS: Evidence from two trials of very low certainty and with unclear risk of bias provides contradictory evidence on the use of IVIG in the treatment of adults with presumed viral myocarditis. One trial reported that use of IVIG results in longer survival time after 60 days, whilst the other trial found that IVIG does not provide an appreciable benefit. The evidence of a difference in event-free or overall survival, LVEDD, or LVSF is of very low certainty in a single paediatric trial with a low risk of bias. Until higher-quality studies with low risk of bias and larger sample sizes have demonstrated benefit in a particular group of patients, the evidence for treatment with IVIG for presumed viral myocarditis is uncertain. Further studies of the pathophysiology of myocarditis would lead to improved diagnostic criteria, which would facilitate future research.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Miocardite/terapia , Viroses/terapia , Doença Aguda , Adulto , Viés , Criança , Humanos , Miocardite/mortalidade , Miocardite/virologia , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico/efeitos dos fármacos , Viroses/mortalidade
13.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32611687

RESUMO

The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections.


Assuntos
Imunossupressores/uso terapêutico , Neoplasias/complicações , Viroses/terapia , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/terapia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/imunologia , Hepatite C/terapia , Humanos , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Influenza Humana/terapia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Viroses/complicações , Viroses/tratamento farmacológico , Viroses/imunologia
14.
Curr Res Transl Med ; 68(3): 105-110, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32616467

RESUMO

The relative ease of isolation of mesenchymal stem cells (MSCs) from different tissues coupled with their culture expansion in vitro and their differentiation capacity to mesodermal, endodermal and ectodermal lineages have made these cells attractive for a large number of therapeutic applications. In recent years, there has been remarkable progress in the utilization of MSCs in diverse clinical indications both in animal models and human clinical trials. However, the potential of MSCs to control or treat viral diseases is still in its infancy. In this study, we report quantitative data on the MSC-based clinical trials over the last ten years as they appear on the online database of clinical research studies from US National Institutes of Health. In particular, we provide comprehensive review of either completed or ongoing clinical trials using MSCs for virus-associated diseases focusing on HIV, hepatitis B virus and COVID-19 virus.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Viroses/terapia , Fenômenos Fisiológicos Virais , Animais , Betacoronavirus/fisiologia , Técnicas de Cultura de Células , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , HIV/fisiologia , Vírus da Hepatite B/fisiologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/tendências , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Viroses/epidemiologia , Viroses/imunologia , Vírus/patogenicidade
15.
PLoS One ; 15(7): e0236199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673355

RESUMO

Antimicrobial-resistant and novel pathogens continue to emerge, outpacing efforts to contain and treat them. Therefore, there is a crucial need for safe and effective therapies. Ultraviolet-A (UVA) phototherapy is FDA-approved for several dermatological diseases but not for internal applications. We investigated UVA effects on human cells in vitro, mouse colonic tissue in vivo, and UVA efficacy against bacteria, yeast, coxsackievirus group B and coronavirus-229E. Several pathogens and virally transfected human cells were exposed to a series of specific UVA exposure regimens. HeLa, alveolar and primary human tracheal epithelial cell viability was assessed after UVA exposure, and 8-Oxo-2'-deoxyguanosine was measured as an oxidative DNA damage marker. Furthermore, wild-type mice were exposed to intracolonic UVA as an in vivo model to assess safety of internal UVA exposure. Controlled UVA exposure yielded significant reductions in Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Clostridioides difficile, Streptococcus pyogenes, Staphylococcus epidermidis, Proteus mirabilis and Candida albicans. UVA-treated coxsackievirus-transfected HeLa cells exhibited significantly increased cell survival compared to controls. UVA-treated coronavirus-229E-transfected tracheal cells exhibited significant coronavirus spike protein reduction, increased mitochondrial antiviral-signaling protein and decreased coronavirus-229E-induced cell death. Specific controlled UVA exposure had no significant effect on growth or 8-Oxo-2'-deoxyguanosine levels in three types of human cells. Single or repeated in vivo intraluminal UVA exposure produced no discernible endoscopic, histologic or dysplastic changes in mice. These findings suggest that, under specific conditions, UVA reduces various pathogens including coronavirus-229E, and may provide a safe and effective treatment for infectious diseases of internal viscera. Clinical studies are warranted to further elucidate the safety and efficacy of UVA in humans.


Assuntos
Infecções Bacterianas/terapia , Micoses/terapia , Infecções Oportunistas/terapia , Terapia Ultravioleta/métodos , Viroses/terapia , Animais , Apoptose/efeitos da radiação , Bactérias/efeitos da radiação , Infecções Bacterianas/microbiologia , Sobrevivência Celular/efeitos da radiação , Colo/microbiologia , Colo/efeitos da radiação , Coronavirus Humano 229E/efeitos da radiação , Dano ao DNA/efeitos da radiação , Modelos Animais de Doenças , Enterovirus Humano B/efeitos da radiação , Feminino , Células HeLa , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos da radiação , Masculino , Camundongos , Micoses/microbiologia , Infecções Oportunistas/microbiologia , Cultura Primária de Células , Terapia Ultravioleta/efeitos adversos , Viroses/virologia , Leveduras/efeitos da radiação
16.
Pediatr Pulmonol ; 55(8): 2150-2155, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32492284

RESUMO

BACKGROUND: Children who require chronic positive pressure ventilation (CPPV) are frequently hospitalized with acute respiratory infections. Although respiratory viral testing is often performed, it is unclear how positive results impact antibiotic use. We sought to assess the impact of respiratory viral testing on antibiotic use in hospitalized children on CPPV. METHODS: This retrospective cohort study included hospitalized children on CPPV who had respiratory viral polymerase chain reaction (RVP) testing on admission. Primary exposure was a positive RVP result; primary outcome was antibiotic de-escalation, defined as discontinuation of antibiotics or narrowing of antimicrobial spectra. To determine the independent association of positive RVP and antibiotic de-escalation, a generalized linear mixed effect model was used to account for within patient clustering and confounders defined a priori (blood and respiratory cultures, leukocytosis, bandemia, chest radiograph findings, aspiration risk, and recent admission). RESULTS: A total of 200 admissions representing 118 patients were included. A viral pathogen was identified in 46.5% (93/200) of admissions; rhinovirus was most frequently identified (61.5% of positive RVPs). Antibiotic de-escalation occurred in 33% of admissions (35.5% of RVP-positive admissions vs 30.8% of RVP-negative admissions; P = .49). In adjusted analysis, there was no association between positive RVP and antibiotics de-escalation (adjusted OR: 0.86; 95% confidence interval: 0.32-2.26). CONCLUSION: This single center cohort study suggests that respiratory viral testing may not impact antibiotic prescribing for hospitalized children on CPPV. There is need for improved stewardship of both diagnostic testing and antimicrobial use in this population.


Assuntos
Antibacterianos/uso terapêutico , Reação em Cadeia da Polimerase , Respiração com Pressão Positiva , Infecções Respiratórias/diagnóstico , Viroses/diagnóstico , Criança , Pré-Escolar , Feminino , Hospitalização , Humanos , Masculino , Padrões de Prática Médica , Infecções Respiratórias/terapia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Viroses/terapia , Viroses/virologia , Vírus/genética
17.
Hum Genomics ; 14(1): 25, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591003

RESUMO

Human-induced pluripotent stem cells (hiPSCs) and CRISPR/Cas9 gene editing system represent two instruments of basic and translational research, which both allow to acquire deep insight about the molecular bases of many diseases but also to develop pharmacological research.This review is focused to draw up the latest technique of gene editing applied on hiPSCs, exploiting some of the genetic manipulation directed to the discovery of innovative therapeutic strategies. There are many expediencies provided by the use of hiPSCs, which can represent a disease model clinically relevant and predictive, with a great potential if associated to CRISPR/Cas9 technology, a gene editing tool powered by ease and precision never seen before.Here, we describe the possible applications of CRISPR/Cas9 to hiPSCs: from drug development to drug screening and from gene therapy to the induction of the immunological response to specific virus infection, such as HIV and SARS-Cov-2.


Assuntos
Sistemas CRISPR-Cas , Descoberta de Drogas , Edição de Genes , Terapia Genética , Células-Tronco Pluripotentes Induzidas/citologia , Viroses/terapia , Animais , Reprogramação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/transplante , Viroses/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-32450013

RESUMO

Because viruses still represent a significant threat to human and animal health worldwide, the development of effective weapons against viral infections remains a top priority for the biopharmaceutical industry. This article reviews the dietary and pharmaceutical applications of polysaccharides (PS), first of all chitosan, in the prevention and treatment of viral diseases, focusing more particularly on solid or gel micro/nanoparticulate systems. The intrinsic antiviral activity of PS and their immunostimulatory effects, implemented in animal and human diets, are first surveyed. Then the review discusses the potential of PS-based particles as carriers of antiviral drugs and vaccines, with emphasis on the adjuvant potency of PS in solid vaccine formulations. The gap between the abundance of academic studies in this area and the lack of actual antiviral formulations dispensed to human patients is underlined, notwithstanding a number of branded products on the market.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Polissacarídeos/administração & dosagem , Polissacarídeos/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Viroses/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Animais , Antivirais/administração & dosagem , Humanos , Polissacarídeos/farmacologia , Viroses/imunologia , Viroses/terapia
19.
Cleve Clin J Med ; 87(11): 659-663, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32393593

RESUMO

In COVID-19, respiratory infection with SARS-CoV-2 plus another virus (viral co-infection) or with SARS-CoV-2 plus a bacterial pathogen (combined viral and bacterial pneumonia) has been described. Secondary bacterial pneumonia can follow the initial phase of viral respiratory infection or occur during the recovery phase. No obvious pattern or guidelines exist for viral co-infection, combined viral and bacterial pneumonia, or secondary bacterial pneumonia in COVID-19. Based on existing clinical data and experience with similar viruses such as influenza and SARS-CoV, the management approach in COVID-19 should, ideally, take into consideration the overall presentation and the trajectory of illness.


Assuntos
Antibacterianos/administração & dosagem , Coinfecção , Infecções por Coronavirus , Pandemias , Administração dos Cuidados ao Paciente/métodos , Pneumonia Bacteriana , Pneumonia Viral , Viroses , Bactérias/classificação , Bactérias/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Coinfecção/diagnóstico , Coinfecção/etiologia , Coinfecção/terapia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/terapia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/terapia , Diagnóstico Diferencial , Humanos , Pneumonia Bacteriana/epidemiologia , Pneumonia Bacteriana/etiologia , Pneumonia Bacteriana/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Viroses/epidemiologia , Viroses/terapia
20.
BMC Public Health ; 20(1): 568, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345248

RESUMO

BACKGROUND: This study aimed to make a quantitative assessment of the management of influenza-like illnesses (ILI) in Japanese healthcare settings. METHODS: We analysed participants' healthcare-seeking behaviour and physicians' practice in January 2019 using an online survey of 200 households in Japan. Quality of life score, quality-adjusted life years lost, the duration of symptoms, and the duration of absence from work were compared between the influenza ILI group and the non-influenza ILI group with one-to-one propensity score matching. Missing data were imputed using multiple imputation. RESULTS: In total, 261 of the 600 (43.5%) participants had at least one episode of influenza-like illness during January 2019. Of these, 194 (75.5%) visited healthcare facilities, 167 (86.1%) within 2 days of onset of symptoms. A total of 169 out of 191 (88.5%) received a rapid influenza diagnostic test and 101 were diagnosed with influenza, of whom 95.0% were treated with antivirals. The median quality-adjusted life-years (QALYs) lost was 0.0055 (interquartile range, IQR 0.0040-0.0072) and median absence from work for a single episode of influenza-like illness was 2 days (IQR 1-5 days). Albeit QALYs lost per episode was not different between two groups, the influenza ILI group showed longer duration of absence from work (5 days, IQR 4-6 days) than the non-influenza ILI group (2 days, IQR 1-3 days). CONCLUSIONS: In Japan, most people with influenza-like illnesses visit healthcare facilities soon after symptoms first occur and receive a diagnostic test. Those with influenza are usually treated with antivirals. Absence from work was longer for influenza than other similar illnesses.


Assuntos
Influenza Humana/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Infecções Respiratórias/terapia , Viroses/terapia , Adulto , Antivirais/uso terapêutico , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Infecções Respiratórias/virologia , Fatores de Tempo
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