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1.
Cell Mol Immunol ; 17(10): 1092-1094, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32917983
4.
J Allergy Clin Immunol ; 146(3): 518-534.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32896310

RESUMO

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 presents with a spectrum of clinical manifestations from asymptomatic or mild, self-limited constitutional symptoms to a hyperinflammatory state ("cytokine storm") followed by acute respiratory distress syndrome and death. The objective of this study was to provide an evidence-based review of the associated pathways and potential treatment of the hyperinflammatory state associated with severe acute respiratory syndrome coronavirus 2 infection. Dysregulated immune responses have been reported to occur in a smaller subset of those infected with severe acute respiratory syndrome coronavirus 2, leading to clinical deterioration 7 to 10 days after initial presentation. A hyperinflammatory state referred to as cytokine storm in its severest form has been marked by elevation of IL-6, IL-10, TNF-α, and other cytokines and severe CD4+ and CD8+ T-cell lymphopenia and coagulopathy. Recognition of at-risk patients could permit early institution of aggressive intensive care and antiviral and immune treatment to reduce the complications related to this proinflammatory state. Several reports and ongoing clinical trials provide hope that available immunomodulatory therapies could have therapeutic potential in these severe cases. This review highlights our current state of knowledge of immune mechanisms and targeted immunomodulatory treatment options for the current coronavirus disease 2019 pandemic.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/virologia , Imunomodulação , Interleucina-6/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Betacoronavirus , Síndrome da Liberação de Citocina/imunologia , Humanos , Pandemias , Sepse/imunologia
5.
Eur Cytokine Netw ; 31(2): 44-49, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933891

RESUMO

BACKGROUND: Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020. RESULTS: Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients' age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42-33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups. CONCLUSIONS: Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Pneumonia Viral/tratamento farmacológico , Idoso , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Feminino , Expressão Gênica , Humanos , Unidades de Terapia Intensiva , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/imunologia , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
6.
J Nanobiotechnology ; 18(1): 130, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912236

RESUMO

Fast point-of-care (POC) diagnostics represent an unmet medical need and include applications such as lateral flow assays (LFAs) for the diagnosis of sepsis and consequences of cytokine storms and for the treatment of COVID-19 and other systemic, inflammatory events not caused by infection. Because of the complex pathophysiology of sepsis, multiple biomarkers must be analyzed to compensate for the low sensitivity and specificity of single biomarker targets. Conventional LFAs, such as gold nanoparticle dyed assays, are limited to approximately five targets-the maximum number of test lines on an assay. To increase the information obtainable from each test line, we combined green and red emitting quantum dots (QDs) as labels for C-reactive protein (CRP) and interleukin-6 (IL-6) antibodies in an optical duplex immunoassay. CdSe-QDs with sharp and tunable emission bands were used to simultaneously quantify CRP and IL-6 in a single test line, by using a single UV-light source and two suitable emission filters for readout through a widely available BioImager device. For image and data processing, a customized software tool, the MultiFlow-Shiny app was used to accelerate and simplify the readout process. The app software provides advanced tools for image processing, including assisted extraction of line intensities, advanced background correction and an easy workflow for creation and handling of experimental data in quantitative LFAs. The results generated with our MultiFlow-Shiny app were superior to those generated with the popular software ImageJ and resulted in lower detection limits. Our assay is applicable for detecting clinically relevant ranges of both target proteins and therefore may serve as a powerful tool for POC diagnosis of inflammation and infectious events.


Assuntos
Biomarcadores/análise , Proteína C-Reativa/análise , Imunoensaio/métodos , Interleucina-6/análise , Pontos Quânticos/química , Sepse/diagnóstico , Anticorpos/imunologia , Betacoronavirus/isolamento & purificação , Proteína C-Reativa/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Humanos , Interleucina-6/imunologia , Limite de Detecção , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Sistemas Automatizados de Assistência Junto ao Leito , Sepse/metabolismo , Software , Raios Ultravioleta
7.
Biosensors (Basel) ; 10(9)2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32847008

RESUMO

Cytokines are a family of proteins which play a major role in the regulation of the immune system and the development of several diseases, from rheumatoid arthritis to cancer and, more recently, COVID-19. Therefore, many efforts are currently being developed to improve therapy and diagnosis, as well as to produce inhibitory drugs and biosensors for a rapid, minimally invasive, and effective detection. In this regard, even more efficient cytokine receptors are under investigation. In this paper we analyze a set of IL-6 cytokine receptors, investigating their topological features by means of a theoretical approach. Our results suggest a topological indicator that may help in the identification of those receptors having the highest complementarity with the protein, a feature expected to ensure a stable binding. Furthermore, we propose and discuss the use of these receptors in an idealized experimental setup.


Assuntos
Técnicas Biossensoriais/métodos , Interleucina-6/análise , Receptores de Interleucina-6/análise , Anticorpos Monoclonais/análise , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/imunologia , Aptâmeros de Nucleotídeos/química , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Humanos , Fragmentos Fab das Imunoglobulinas/análise , Fragmentos Fab das Imunoglobulinas/imunologia , Interleucina-6/imunologia , Limite de Detecção , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Receptores de Interleucina-6/imunologia
9.
Eur Rev Med Pharmacol Sci ; 24(15): 8187-8193, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32767348

RESUMO

The ongoing worldwide pandemic of Coronavirus disease 2019 (COVID-19), raised the urgency to address knowledge gaps and to establish evidence for improving management and control of this viral infection. Throughout a keen analysis of the World Health Organization (WHO) most updated data, a gender-specific difference in the occurrence of infection was determined, which seems to correlate with patient's vitamin D status. Therefore, our purpose is to provide insights into the nutritional importance of vitamin D for its immunomodulatory effect, in order to help counteracting the COVID-19 pandemic. Novel interesting findings suggest that vitamin D, by inducing progesterone-induced blocking factor (PIBF), might regulate the immune response and also modulate cytokine IL-6, which appears to be increased in COVID-19 infections. Therefore, in addition to the standard recommendations to prevent the infection, supplementation of vitamin D might be considered an approach to help counteracting this global epidemic.


Assuntos
Infecções por Coronavirus/imunologia , Interleucina-6/imunologia , Pneumonia Viral/imunologia , Proteínas da Gravidez/imunologia , Fatores Supressores Imunológicos/imunologia , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/imunologia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Geografia , Humanos , Inflamação , Itália/epidemiologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Raios Ultravioleta , Deficiência de Vitamina D/imunologia
11.
Platelets ; 31(8): 1085-1089, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-32857624

RESUMO

Coronavirus disease 2019 (COVID-19) is a global public health emergency with many clinical facets, and new knowledge about its pathogenetic mechanisms is deemed necessary; among these, there are certainly coagulation disorders. In the history of medicine, autopsies and tissue sampling have played a fundamental role in order to understand the pathogenesis of emerging diseases, including infectious ones; compared to the past, histopathology can be now expanded by innovative techniques and modern technologies. For the first time in worldwide literature, we provide a detailed postmortem and biopsy report on the marked increase, up to 1 order of magnitude, of naked megakaryocyte nuclei in the bone marrow and lungs from serious COVID-19 patients. Most likely related to high interleukin-6 serum levels stimulating megakaryocytopoiesis, this phenomenon concurs to explain well the pulmonary abnormal immunothrombosis in these critically ill patients, all without molecular or electron microscopy signs of megakaryocyte infection.


Assuntos
Betacoronavirus/patogenicidade , Medula Óssea/patologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Coagulação Intravascular Disseminada/patologia , Pulmão/patologia , Pneumonia Viral/patologia , Trombose/patologia , Adulto , Idoso , Autopsia , Betacoronavirus/imunologia , Medula Óssea/imunologia , Medula Óssea/virologia , Núcleo Celular/imunologia , Núcleo Celular/patologia , Núcleo Celular/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Estado Terminal , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/imunologia , Coagulação Intravascular Disseminada/virologia , Evolução Fatal , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interleucina-6/biossíntese , Interleucina-6/imunologia , Pulmão/imunologia , Pulmão/virologia , Masculino , Megacariócitos/imunologia , Megacariócitos/patologia , Megacariócitos/virologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Trombopoese/imunologia , Trombose/complicações , Trombose/imunologia , Trombose/virologia
12.
Nat Rev Immunol ; 20(10): 585-586, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788708
13.
mSphere ; 5(4)2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32817460

RESUMO

Many coronavirus disease 2019 (COVID-19) patients demonstrate lethal respiratory complications caused by cytokine release syndrome (CRS). Multiple cytokines have been implicated in CRS, but levels of tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) have not been previously measured in this setting. In this study, we observed significantly elevated serum LIGHT levels in hospitalized COVID-19 patients compared to healthy age- and gender-matched control patients. The assay detected bioavailable LIGHT unbound to the inhibitor Decoy receptor-3 (DcR3). Bioavailable LIGHT levels were elevated in patients both on and off ventilatory support, with a trend toward higher levels in patients requiring mechanical ventilation. In hospitalized patients over the age of 60, who exhibited a mortality rate of 82%, LIGHT levels were significantly higher (P = 0.0209) in those who died than in survivors. As previously reported, interleukin 6 (IL-6) levels were also elevated in these patients, with significantly (P = 0.0076) higher levels observed in patients who died than in survivors, paralleling the LIGHT levels. Although attempts to block IL-6 binding to its receptor have shown limited success in COVID-19 CRS, neutralization of LIGHT may prove to be more effective owing to its more central role in regulating antiviral immune responses. The findings presented here demonstrate that LIGHT is a cytokine which may play an important role in COVID-19 patients presenting with acute respiratory distress syndrome (ARDS) and CRS and suggest that LIGHT neutralization may be beneficial to COVID-19 patients.


Assuntos
Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/virologia , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adulto , Fatores Etários , Idoso , Anticorpos Monoclonais/uso terapêutico , Betacoronavirus , Ensaios Clínicos como Assunto , Infecções por Coronavirus/complicações , Hospitalização/estatística & dados numéricos , Humanos , Interleucina-6/imunologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Respiração Artificial/estatística & dados numéricos
14.
Eur Rev Med Pharmacol Sci ; 24(13): 7475-7484, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32706087

RESUMO

The pandemic caused by the new SARS-CoV2 coronavirus has led to an effort to find treatments that are effective against this disease that the World Health Organization calls COVID-19. In severe cases of COVID-19, there is an increase in cytokines, among which IL-6 seems to play an important role. A search has been performed for studies using IL-6 blocking drugs (tocilizumab, siltuximab, and sarilumab) in PubMed, Web of Science, and Scopus. Also, a search of ongoing trials registered at clinicaltrials.gov was performed. We found very little published clinical experience with these drugs, consisting mainly of case reports or case series with few patients. The results of clinical trials are necessary to clarify the role of these drugs in patients with COVID-19.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Humanos , Interleucina-6/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia
15.
Eur J Endocrinol ; 183(4): 381-387, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698147

RESUMO

Objective: This study assessed thyroid function in patients affected by the coronavirus disease-19 (COVID-19), based on the hypothesis that the cytokine storm associated with COVID-19 may influence thyroid function and/or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly act on thyroid cells, such as previously demonstrated for SARS-CoV-1 infection. Design and methods: This single-center study was retrospective and consisted in evaluating thyroid function tests and serum interleukin-6 (IL-6) values in 287 consecutive patients (193 males, median age: 66 years, range: 27-92) hospitalized for COVID-19 in non-intensive care units. Results: Fifty-eight patients (20.2%) were found with thyrotoxicosis (overt in 31 cases), 15 (5.2%) with hypothyroidism (overt in only 2 cases), and 214 (74.6%) with normal thyroid function. Serum thyrotropin (TSH) values were inversely correlated with age of patients (rho -0.27; P < 0.001) and IL-6 (rho -0.41; P < 0.001). In the multivariate analysis, thyrotoxicosis resulted to be significantly associated with higher IL-6 (odds ratio: 3.25, 95% confidence interval: 1.97-5.36; P < 0.001), whereas the association with age of patients was lost (P = 0.09). Conclusions: This study provides first evidence that COVID-19 may be associated with high risk of thyrotoxicosis in relationship with systemic immune activation induced by the SARS-CoV-2 infection.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Tireotoxicose/virologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Citocinas/sangue , Citocinas/imunologia , Feminino , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/imunologia , Hipotireoidismo/virologia , Interleucina-6/sangue , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Estudos Retrospectivos , Fatores de Risco , Testes de Função Tireóidea , Glândula Tireoide/imunologia , Glândula Tireoide/virologia , Tireotoxicose/epidemiologia , Tireotoxicose/imunologia , Tireotropina/sangue , Tireotropina/imunologia
16.
JCI Insight ; 5(17)2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32687484

RESUMO

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-É£ and monocyte TFN-α production. Circulating T cell subsets were profoundly reduced in COVID-19 patients. Additionally, stimulated blood mononuclear cells produced less than 40%-50% of the IFN-É£ and TNF-α observed in septic and CINS patients, consistent with markedly impaired immune effector cell function. Approximately 25% of COVID-19 patients had increased IL-6 levels that were not associated with elevations in other canonical proinflammatory cytokines. Collectively, these findings support the hypothesis that COVID-19 suppresses host functional adaptive and innate immunity. Importantly, IL-7 administered ex vivo restored T cell IFN-É£ production in COVID-19 patients. Thus, ELISpot may functionally characterize host immunity in COVID-19 and inform prospective therapies.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Tolerância Imunológica/imunologia , Imunidade Inata/imunologia , Pneumonia Viral/imunologia , Sepse/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Estudos de Casos e Controles , Estado Terminal , ELISPOT , Feminino , Voluntários Saudáveis , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Pandemias , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
17.
JCI Insight ; 5(17)2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32706339

RESUMO

BACKGROUNDElevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes.METHODSWe used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1ß, IL-1RA, IL-6, IL-8, IL-18, and TNF-α) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTSFifteen hospitalized COVID-19 patients, 9 of whom were critically ill, were compared with critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1ß, IL-1RA, IL-6, IL-8, IL-18, and TNF-α between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONLevels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDINGFunding was received from NHLBI K23 HL125663 (AJR); The Bill and Melinda Gates Foundation OPP1113682 (AJR and CAB); Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687 NIH/NIAID U19AI057229-16; Stanford Maternal Child Health Research Institute; and Chan Zuckerberg Biohub (CAB).


Assuntos
Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/imunologia , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Sepse/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Síndrome da Liberação de Citocina/sangue , Citocinas/sangue , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Interleucina-18/sangue , Interleucina-18/imunologia , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-8/sangue , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Síndrome do Desconforto Respiratório do Adulto/sangue , Sepse/sangue , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
18.
Ann Rheum Dis ; 79(10): 1277-1285, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32620597

RESUMO

OBJECTIVES: To assess the safety and efficacy of interleukin (IL)-6 blockade with sarilumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation. METHODS: We conducted an open-label study of sarilumab in severe COVID-19 pneumonia (PaO2/FiO2 <300 mm Hg) with hyperinflammation (elevated inflammatory markers and serum IL-6 levels). Sarilumab 400 mg was administered intravenously in addition to standard of care and results were compared with contemporary matched patients treated with standard of care alone. Clinical improvement, mortality, safety and predictors of response were assessed at 28 days. RESULTS: Twenty-eight patients were treated with sarilumab and 28 contemporary patients receiving standard of care alone were used as controls. At day 28 of follow-up, 61% of patients treated with sarilumab experienced clinical improvement and 7% died. These findings were not significantly different from the comparison group (clinical improvement 64%, mortality 18%; p=NS). Baseline PaO2/FiO2 ratio >100 mm Hg and lung consolidation <17% at CT scan predicted clinical improvement in patients treated with sarilumab. Median time to clinical improvement in patients with lung consolidation <17% was shorter after sarilumab (10 days) than after standard treatment (24 days; p=0.01). The rate of infection and pulmonary thrombosis was similar between the two groups. CONCLUSIONS: At day 28, overall clinical improvement and mortality in patients with severe COVID-19 were not significantly different between sarilumab and standard of care. Sarilumab was associated with faster recovery in a subset of patients showing minor lung consolidation at baseline.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Proteína C-Reativa/imunologia , Infecções por Coronavirus/tratamento farmacológico , Inflamação/imunologia , Interleucina-6/imunologia , Pneumonia Viral/tratamento farmacológico , Administração Intravenosa , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Bacteriemia/epidemiologia , Betacoronavirus , Estudos de Coortes , Coinfecção/epidemiologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Itália , Lopinavir/uso terapêutico , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva , Oxigenoterapia , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Modelos de Riscos Proporcionais , Receptores de Interleucina-6/antagonistas & inibidores , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Mediators Inflamm ; 2020: 7527953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724296

RESUMO

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.


Assuntos
Alarminas/imunologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Armadilhas Extracelulares/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Alarminas/antagonistas & inibidores , Autofagia/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Armadilhas Extracelulares/efeitos dos fármacos , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Pulmão/imunologia , Pulmão/patologia , Pandemias , Pneumonia Viral/patologia
20.
Life Sci ; 257: 118097, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679148

RESUMO

Interleukin-6 (IL-6), known as an inflammatory cytokine, can be involved in many innate and adaptive immune responses. The role of IL-6 in the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has recently received much more attention due to the spread of the virus and its pandemic potential. Cytokine storm is among the most critical pathological events in patients affected with coronaviruses (CoVs), i.e., severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and COVID-19, causing inflammation-induced lung injury and also occurring as a result of dysregulation of immune responses to the mentioned viruses. IL-6, along with some other inflammatory cytokines, including IL-1 beta (ß), IL-8, and tumor necrosis factor-alpha (TNF-α), as well as inflammatory chemokines, can significantly contribute to, fever, lymphopenia, coagulation, lung injury, and multi-organ failure (MOF). Therefore, researchers are to explore novel approaches to treat the disease through targeting of IL-6 and its receptors based on prior experience of other disorders. In this review article, the latest findings on the role of IL-6 in the pathogenesis of COVID-19, as well as therapeutic perspectives, were summarized and discussed.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Interleucina-6/imunologia , Pneumonia Viral/imunologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/metabolismo , Citocinas/imunologia , Humanos , Inflamação/imunologia , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pandemias , Pneumonia Viral/metabolismo , Vírus da SARS/imunologia
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