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1.
Urol Clin North Am ; 47(4): 443-456, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008495

RESUMO

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.


Assuntos
Vacinas Anticâncer/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/mortalidade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
2.
Discov Med ; 29(158): 145-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007190

RESUMO

Coronavirus disease 2019 (COVID-19), a newly identified acute respiratory disease caused by a strain of novel coronavirus (SARS-CoV-2), has become a worldwide pandemic. From December 2019 to present, millions of cases have been reported, bringing unprecedented pressure on both health and epidemic prevention services in every country. As frontline healthcare workers, ophthalmologists face an increased threat of viral infection, not only because of close contact with patients during examinations or operations, but also due to evidence showing that ocular fluids such as tears or conjunctival secretions may carry the virus. The risk that healthcare workers face is emphasized by the loss of our colleagues who have sacrificed themselves in combating the virus. As a result, it is necessary to have a comprehensive understanding of the threats that we face. In the first part of this review, we start by explaining the structure of SARS-CoV-2 and examining its transmission and means of infection. Next, we summarize the latest scientific advancements of epidemiology, clinical presentations, and current treatments of COVID-19. In the second half of the review, we emphasize the ocular transmission, symptomatic manifestations, and the essential knowledge in an ophthalmology clinic setting. As the pandemic of COVID-19 continues to pose a threat to global health, we hope that this review makes a contribution to combating COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Oftalmopatias/virologia , Pneumonia Viral/complicações , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Reposicionamento de Medicamentos , Oftalmopatias/diagnóstico , Oftalmopatias/imunologia , Oftalmopatias/terapia , Humanos , Imunização Passiva/métodos , Fatores Imunológicos/uso terapêutico , Medicina Tradicional Chinesa/métodos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
3.
Front Immunol ; 11: 558898, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072097

RESUMO

The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This "cytokine storm" produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities. In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1, and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases and conditions often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Infecções por Coronavirus/mortalidade , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/mortalidade , Pandemias , Pneumonia Viral/mortalidade , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/virologia
4.
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
5.
BMJ Case Rep ; 13(9)2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32895254

RESUMO

A 40-year-old man presented with altered mental status after a recenthospitalisation for COVID-19 pneumonia. Cerebrospinal fluid (CSF) analysis showed lymphocytosis concerning for viral infection. The CSF PCR for SARS-CoV-2 was negative, yet this could not exclude COVID-19 meningoencephalitis. During hospitalisation, the patient's mentation deteriorated further requiring admission to the intensive care unit (ICU). Brain imaging and electroencephalogram (EEG) were unremarkable. He was, thus, treated with intravenous immunoglobulin (IVIg) for 5 days with clinical improvement back to baseline. This case illustrates the importance of considering COVID-19's impact on the central nervous system (CNS). Haematogenous, retrograde axonal transport, and the effects of cytokine storm are the main implicated mechanisms of CNS entry of SARS-CoV-2. While guidelines remain unclear, IVIg may be of potential benefit in the treatment of COVID-19-associated meningoencephalitis.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/etiologia , Pneumonia Viral/complicações , Adulto , Humanos , Masculino , Pandemias , Resultado do Tratamento
6.
Curr Rheumatol Rep ; 22(10): 75, 2020 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-32924089

RESUMO

PURPOSE OF REVIEW: Provide the most recent updates on the epidemiology, pathogenesis, and treatment advances in Kawasaki disease. RECENT FINDINGS: Treatment advances in complex, IVIG-refractory cases of Kawasaki disease. Multisystem inflammatory syndrome, a newly reported inflammatory condition with Kawasaki-like features and an association with the 2019 Coronavirus (COVID-19). Kawasaki disease (KD) is a rare systemic inflammatory disease that predominately affects children less than 5 years of age. Pathogenesis of KD remains unknown; the leading theory is that an unknown stimulus triggers an immune-mediated inflammatory cascade in a genetically susceptible child. Classic KD is a clinical diagnosis based on set criteria and excluding other similar clinical entities. Patients who do not fulfill complete diagnostic criteria for KD are often referred to as atypical (or incomplete) KD. The most feared complication of KD is coronary artery abnormality development, and patients with atypical KD are also at risk. Administration of intravenous immunoglobulin (IVIG) and aspirin has greatly reduced the incidence of coronary lesions in affected children. Several other immune-modulating therapies have recently been utilized in complex or refractory cases.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Diagnóstico por Imagem/métodos , Fatores Imunológicos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Pandemias , Pneumonia Viral/complicações , Infecções por Coronavirus/epidemiologia , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/terapia , Pneumonia Viral/epidemiologia
7.
Mult Scler ; 26(10): 1137-1146, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32924838

RESUMO

Concerns regarding infection with the novel coronavirus SARS-CoV-2 leading to COVID-19 are particularly marked for pregnant women with autoimmune diseases such as multiple sclerosis (MS). There is currently a relative paucity of information to guide advice given to and the clinical management of these individuals. Much of the limited available data around COVID-19 and pregnancy derives from the obstetric literature, and as such, neurologists may not be familiar with the general principles underlying current advice. In this article, we discuss the impact of potential infection on the pregnant woman, the impact on her baby, the impact of the current pandemic on antenatal care, and the interaction between COVID-19, MS and pregnancy. This review provides a framework for neurologists to use to guide the individualised advice given to both pregnant women with MS, and those women with MS who are considering pregnancy. This includes evidence derived from previous novel coronavirus infections, and emerging evidence from the current pandemic.


Assuntos
Infecções por Coronavirus/imunologia , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Pneumonia Viral/imunologia , Complicações Infecciosas na Gravidez/imunologia , Complicações na Gravidez/tratamento farmacológico , Betacoronavirus , Aleitamento Materno , Assistência à Saúde , Parto Obstétrico , Suscetibilidade a Doenças , Feminino , Retardo do Crescimento Fetal , Humanos , Esclerose Múltipla/imunologia , Pandemias , Cuidado Pré-Concepcional , Gravidez , Complicações na Gravidez/imunologia , Nascimento Prematuro , Cuidado Pré-Natal , Recidiva
8.
Medicine (Baltimore) ; 99(37): e21788, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925716

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common neoplasms encountered, and its incidence is increasing worldwide. In this study, we explored the characteristics of gut microbiota in patients with primary hepatocellular carcinoma in advanced stage who received immune checkpoint inhibitors (ICIs) based on a large population with hepatitis B virus infection. An initial cohort of 65 patients with metastatic melanoma were included in this study. All patients were treated with ICIs at Fujian provincial geriatric hospital between August 2016 and June 2018. The 16S rDNA V4 region was amplified by Polymerase chain reaction and sequenced on the MiSeq platform. We found that the diversities of the gut microbiota in HCC who received ICIs were obviously increased. Negative feedback, which is controlled by interplay between microbial metabolic activities and host pathways, is thought to promote high bacterial diversity. We focused on the Faecalibacterium genus in response group, and Bacteroidales order in non-response group, and stratified patients into high versus low categories based on the median relative abundance of these taxa in the gut microbiome. Patients with high Faecalibacterium abundance had a significantly prolonged PFS versus those with a low abundance. Conversely, patients with a high abundance of Bacteroidales had a shortened progressive free survival compared to those with a low abundance. In summary, the present study examined the oral and gut microbiome of HCC patients undergoing immune checkpoint inhibitors immunotherapy. Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus non-responders.


Assuntos
Carcinoma Hepatocelular/microbiologia , Microbioma Gastrointestinal , Fatores Imunológicos/uso terapêutico , Imunoterapia/mortalidade , Neoplasias Hepáticas/microbiologia , Idoso , Bacteroides/crescimento & desenvolvimento , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , China , Faecalibacterium/crescimento & desenvolvimento , Feminino , Humanos , Imunoterapia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , RNA Ribossômico 16S/análise , Resultado do Tratamento
9.
BMJ ; 370: m3176, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958461

RESUMO

Despite considerable advances in treatment approaches in the past two decades, multiple myeloma remains an incurable disease. Treatments for myeloma continue to evolve with many emerging immunotherapies. The first immunotherapy used to treat hematologic cancers, including multiple myeloma, was an allogeneic stem cell transplant. In the mid-2000s, immunomodulatory drugs thalidomide, lenalidomide, and subsequently pomalidomide were proven to be effective in multiple myeloma and substantially improved survival. The next wave of immunotherapies for multiple myeloma included the monoclonal antibodies daratumumab and elotuzumab, which were approved by the Food and Drug Administration in 2015. Subsequently, a variety of immunotherapies have been developed for multiple myeloma, including chimeric antigen receptor T cells, bispecific antibodies, antibody drug conjugates, and checkpoint inhibitors. Many of these emerging treatments target the B cell maturation antigen, which is expressed on plasma cells, although several other novel receptors are also being studied. This review summarizes the evidence of these various immunotherapies, their mechanism of action, and data from clinical trials regarding the treatments' safety and efficacy.


Assuntos
Imunoterapia , Mieloma Múltiplo/terapia , Drogas em Investigação/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Transplante de Células-Tronco
10.
Acta Biomed ; 91(3): e2020038, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32921732

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that mainly affects the upper and lower respiratory tract and is responsible for extremely different degrees of disease, ranging from flu-like symptoms to atypical pneumonia that may evolve to acute respiratory distress syndrome and, ultimately, death. No specific therapy for SARS-CoV-2 has yet been identified, but since the beginning of the outbreak, several pre-existing therapeutics have been reconsidered for the treatment of infected patients. The aim of this article is to discuss current therapeutics against SARS-CoV-2. A literature review was performed using PubMed, collecting data from English-language articles published until June 20th, 2020. Literature analysis showed that with the acquisition of more in-depth knowledge on the characteristics of SARS-CoV-2 and the pathogenesis of the different clinical manifestations, a more rationale use of available drugs has become possible. However, the road to defining which drugs are effective and which schedules of administration must be used to maximize efficacy and minimize adverse events is still very long. To date, it is only clear that no drug can alone cope with all the problems posed by SARS-CoV-2 infection and effective antivirals and inflammatory drugs must be given together to reduce COVID-19 clinical manifestations. Moreover, choice of therapy must always be tailored on clinical manifestations and, when they occur, drugs able to fight coagulopathy and venous thromboembolism that may contribute to respiratory deterioration must be prescribed.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Humanos
11.
Int J Med Sci ; 17(14): 2133-2146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922174

RESUMO

The SARS-CoV-2 spread quickly across the globe. The World Health Organization (WHO) on March 11 declared COVID-19 a pandemic. The mortality rate, hospital disorders and incalculable economic and social damages, besides the unproven efficacy of the treatments evaluated against COVID-19, raised the need for immediate control of this disease. Therefore, the current study employed in silico tools to rationally identify new possible SARS-CoV-2 main protease (Mpro) inhibitors. That is an enzyme conserved among the coronavirus species; hence, the identification of an Mpro inhibitor is to make it a broad-spectrum drug. Molecular docking studies described the binding sites and the interaction energies of 74 Mpro-ligand complexes deposited in the Protein Data Bank (PDB). A structural similarity screening was carried out in order to identify possible Mpro ligands that show additional pharmacological properties against COVID-19. We identified 59 hit compounds and among them, melatonin stood out due to its prominent immunomodulatory and anti-inflammatory activities; it can reduce oxidative stress, defence cell mobility and efficiently combat the cytokine storm and sepsis. In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. Interestingly, one of the most promising hits in our docking study was melatonin. It revealed better interaction energy with Mpro compared to ligands in complexes from PDB. Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation. These results definitely do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Descoberta de Drogas , Melatonina/farmacologia , Pneumonia Viral/tratamento farmacológico , Proteínas não Estruturais Virais/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Cisteína Endopeptidases , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Melatonina/uso terapêutico , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/virologia , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico
12.
Trials ; 21(1): 766, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891160

RESUMO

OBJECTIVES: To investigate the potential efficacy of Acacia Senegal extract Gum Arabic (GA) supplementation as immunomodulatory and anti-inflammatory dietary intervention among newly diagnosed COVID 19 Sudanese patients. To study the effect of GA on the level of cytokines, TNFα, IL8, IL6 IL10, CRP and the viral load. Secondary outcomes will be the effect of GA oral intake on mortality rate and days of hospital admission. TRIAL DESIGN: Quadruple blind, randomized placebo-controlled clinical trial Phase II & III. Prospective, two-arm, parallel-group, randomised (1:1 allocation ratio) superiority trial of oral GA among seropositive COVID-19 patients. PARTICIPANTS: Inclusion criteria: COVID-19 infected (newly diagnosed) as proved by real-time PCR within 72 hours of PCR. Age 8-90 years Both genders Exclusion criteria: Intubated patients on parenteral treatment Allergy to Gum Arabic The study will be conducted in COVID Isolation Centres and Soba University Hospital Khartoum State Sudan. INTERVENTION AND COMPARATOR: Experimental: Intervention Group This arm will receive 100% natural Gum Arabic provided in a powder form in 30-grams-dose once daily for four weeks Placebo Comparator: Control group: This group will be provided with pectin powder provided as one-gram-dose once daily for four weeks Both GA and placebo will be in addition to standard care treatment based on local clinical guidelines. MAIN OUTCOMES: Mean change from baseline score of Immune Response to end of the trial. Changes of the level of Tumor Necrosis Factor (TNFα), interleukin IL8, IL6, and IL10 from the baseline values (Four weeks from the start of randomization). Mortality rate: The percentage of deaths among COVID 19 patients received Gum Arabic compared to placebo (Four weeks from the start of randomization]). RANDOMISATION: Randomization (1:1 allocation ratio) and will be conducted using a sequence of computer-generated random numbers by an independent individual. Each participating centre will be assigned a special code generated by the computer. The randomization will be kept by the PI and a research assistant. BLINDING (MASKING): Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 110 eligible patients will be randomly assigned to either GA (n=55) or placebo (n=55) groups. TRIAL STATUS: Protocol Version no 2, 30th June 2020. Recruitment will start on 15th September 2020. The intended completion date is 15th January 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04381871 . Date of trial registration: 11 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Goma Arábica/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Criança , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Goma Arábica/efeitos adversos , Interações entre Hospedeiro e Microrganismos , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Drug Discov Ther ; 14(4): 171-176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908072

RESUMO

The healthcare sector has been overwhelmed by the global rise in the number of COVID-19 cases. The primary care physicians at the forefront of this pandemic are being provided with multiple guidelines (state, national, international). The aim of this review was to examine the existing guidelines for congruence and critically analyze them in light of current evidence. A discordance was noted between the national and state guidelines with respect to indication, duration and dosage of antivirals, steroids/immunomodulators, anticoagulation and convalescent plasma. The lack of concordance between various guidelines mandates the need for a unified national guideline that is regularly updated.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Anticoagulantes/uso terapêutico , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Imunização Passiva , Fatores Imunológicos/uso terapêutico , Índia/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Esteroides/uso terapêutico
15.
Front Immunol ; 11: 2056, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973814

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19), a disease which causes severe lung injury and multiple organ damage, presents an urgent need for new drugs. The case severity and fatality of COVID-19 are associated with excessive inflammation, namely, a cytokine storm. Metformin, a widely used drug to treat type 2 diabetes (T2D) mellitus and metabolic syndrome, has immunomodulatory activity that reduces the production of proinflammatory cytokines using macrophages and causes the formation of neutrophil extracellular traps (NETs). Metformin also inhibits the cytokine production of pathogenic Th1 and Th17 cells. Importantly, treatment with metformin alleviates various lung injuries in preclinical animal models. In addition, a recent proteomic study revealed that metformin has the potential to directly inhibit SARS-CoV-2 infection. Furthermore, retrospective clinical studies have revealed that metformin treatment reduces the mortality of T2D with COVID-19. Therefore, metformin has the potential to be repurposed to treat patients with COVID-19 at risk of developing severe illness. This review summarizes the immune pathogenesis of SARS-CoV-2 and addresses the effects of metformin on inhibiting cytokine storms and preventing SARS-CoV-2 infection, as well as its side effects.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Metformina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/efeitos adversos , Antivirais/farmacologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/antagonistas & inibidores , Reposicionamento de Medicamentos/métodos , Armadilhas Extracelulares/efeitos dos fármacos , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Metformina/efeitos adversos , Metformina/farmacologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia
16.
Front Immunol ; 11: 2159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983179

RESUMO

The rapid spread, severity, and lack of specific treatment for COVID-19 resulted in hasty drug repurposing. Conceptually, trials of antivirals were well-accepted, but twentieth century antimalarials sparked an impassioned global debate. Notwithstanding, antiviral and immunomodulatory effects of aminoquinolines have been investigated in vitro, in vivo and in clinical trials for more than 30 years. We review the mechanisms of action of (hydroxy)chloroquine on immune cells and networks and discuss promises and pitfalls in the fight against SARS-CoV-2, the agent of the COVID-19 outbreak.


Assuntos
Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunomodulação , Pneumonia Viral/tratamento farmacológico , Antimaláricos/efeitos adversos , Antimaláricos/farmacologia , Antivirais/efeitos adversos , Antivirais/farmacologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reposicionamento de Medicamentos/métodos , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia
18.
Int J Mol Sci ; 21(18)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957696

RESUMO

At present, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has quickly become a health emergency because no specifics vaccines or drugs, at this moment, are available. Recent studies have shown that the transplantation of mesenchymal stem cells (MSCs) into Coronavirus Disease 2019 (COVID-19) patients could represent a promising strategy for the development of new therapeutic methods. We speculate and suggest that the secretome of human Oral Tissue Stem Cells (hOTSCs), for their immunomodulatory and anti-inflammatory specific properties, could exert beneficial effects on the COVID-19 patients through an innovative aerosolisation technique. This non-invasive technique can offer multiple advantages in prophylaxis, as well as the prevention and treatment of severe epidemic respiratory syndrome with minimum risk and optimal therapeutic effects. This has the potential to create a novel pathway towards immunomodulatory therapy for the treatment of COVID-19 positive patients.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Células-Tronco Mesenquimais/metabolismo , Mucosa Bucal/citologia , Pneumonia Viral/tratamento farmacológico , Proteoma/uso terapêutico , Humanos , Fatores Imunológicos/metabolismo , Pandemias , Proteoma/metabolismo , Via Secretória
20.
Food Chem Toxicol ; 145: 111767, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32971210

RESUMO

Currently, coronavirus disease 2019 (COVID-19), has posed an imminent threat to global public health. Although some current therapeutic agents have showed potential prevention or treatment, a growing number of associated adverse events have occurred on patients with COVID-19 in the course of medical treatment. Therefore, a comprehensive assessment of the safety profile of therapeutic agents against COVID-19 is urgently needed. In this study, we proposed a network-based framework to identify the potential side effects of current COVID-19 drugs in clinical trials. We established the associations between 116 COVID-19 drugs and 30 kinds of human tissues based on network proximity and gene-set enrichment analysis (GSEA) approaches. Additionally, we focused on four types of drug-induced toxicities targeting four tissues, including hepatotoxicity, renal toxicity, lung toxicity, and neurotoxicity, and validated our network-based predictions by preclinical and clinical evidence available. Finally, we further performed pharmacovigilance analysis to validate several drug-tissue toxicities via data mining adverse event reporting data, and we identified several new drug-induced side effects without labeling in Food and Drug Administration (FDA) drug instructions. Overall, this study provides forceful approaches to assess potential side effects on COVID-19 drugs, which will be helpful for their safe use in clinical practice and promoting the discovery of antiviral therapeutics against SARS-CoV-2.


Assuntos
Antineoplásicos/efeitos adversos , Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Farmacovigilância , Pneumonia Viral/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ensaios Clínicos como Assunto , Humanos , Fatores Imunológicos/uso terapêutico , Pandemias
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