Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 80
Filtrar
1.
Front Immunol ; 11: 598444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362782

RESUMO

Patients infected with SARS-CoV-2 show a wide spectrum of clinical manifestations ranging from mild febrile illness and cough up to acute respiratory distress syndrome, multiple organ failure, and death. Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-κB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. redundant, triggering, amplifying, and synergistic) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.


Assuntos
/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Inibidores de Proteassoma/farmacologia , /efeitos dos fármacos , Animais , /patologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Modelos Animais de Doenças , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/tratamento farmacológico , /imunologia
3.
Front Immunol ; 11: 583373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149733

RESUMO

Coronaviruses (CoVs) are members of the genus Betacoronavirus and the Coronaviridiae family responsible for infections such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and more recently, coronavirus disease-2019 (COVID-19). CoV infections present mainly as respiratory infections that lead to acute respiratory distress syndrome (ARDS). However, CoVs, such as COVID-19, also present as a hyperactivation of the inflammatory response that results in increased production of inflammatory cytokines such as interleukin (IL)-1ß and its downstream molecule IL-6. The inflammasome is a multiprotein complex involved in the activation of caspase-1 that leads to the activation of IL-1ß in a variety of diseases and infections such as CoV infection and in different tissues such as lungs, brain, intestines and kidneys, all of which have been shown to be affected in COVID-19 patients. Here we review the literature regarding the mechanism of inflammasome activation by CoV infection, the role of the inflammasome in ARDS, ventilator-induced lung injury (VILI), and Disseminated Intravascular Coagulation (DIC) as well as the potential mechanism by which the inflammasome may contribute to the damaging effects of inflammation in the cardiac, renal, digestive, and nervous systems in COVID-19 patients.


Assuntos
Caspase 1/metabolismo , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Inflamassomos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Betacoronavirus/imunologia , Coagulação Intravascular Disseminada/patologia , Humanos , Inflamação/patologia , Interleucina-1beta/metabolismo , Pandemias , Síndrome Respiratória Aguda Grave/patologia , Lesão Pulmonar Induzida por Ventilação Mecânica/patologia
4.
Int J Mol Sci ; 21(21)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138181

RESUMO

The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin-angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.


Assuntos
Lesão Pulmonar Aguda/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Vasoconstrição/fisiologia , Betacoronavirus , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Sistema Calicreína-Cinina/fisiologia , Pandemias , Sistema Renina-Angiotensina/fisiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vasoconstrição/efeitos dos fármacos
5.
J Mol Histol ; 51(6): 613-628, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33011887

RESUMO

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in December 2019 form Wuhan, China leads to coronavirus disease 2019 (COVID-19) pandemic. While the common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure in severe patients. The involvement of different organs in severe patients results in lengthening the hospitalization duration and increasing the mortality rate. In this review, we aimed to investigate the involvement of different organs in COVID-19 patients, particularly in severe cases. Also, we tried to define the potential underlying mechanisms of SARS-CoV2 induced multiorgan failure. The multi-organ dysfunction is characterized by acute lung failure, acute liver failure, acute kidney injury, cardiovascular disease, and as well as a wide spectrum of hematological abnormalities and neurological disorders. The most important mechanisms are related to the direct and indirect pathogenic features of SARS-CoV2. Although the presence of angiotensin-converting enzyme 2, a receptor of SARS-CoV2 in the lung, heart, kidney, testis, liver, lymphocytes, and nervous system was confirmed, there are controversial findings to about the observation of SARS-CoV2 RNA in these organs. Moreover, the organ failure may be induced by the cytokine storm, a result of increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs. Therefore, further investigations are needed to detect the exact mechanisms of pathogenesis. Since the involvement of several organs in COVID-19 patients is important for clinicians, increasing their knowledge may help to improve the outcomes and decrease the rate of mortality and morbidity.


Assuntos
Infecções por Coronavirus/patologia , Cardiopatias/patologia , Nefropatias/patologia , Hepatopatias/patologia , Insuficiência de Múltiplos Órgãos/patologia , Pneumonia Viral/patologia , Betacoronavirus , Síndrome da Liberação de Citocina/patologia , Cardiopatias/virologia , Humanos , Rim/patologia , Nefropatias/virologia , Fígado/patologia , Hepatopatias/virologia , Pulmão/patologia , Insuficiência de Múltiplos Órgãos/virologia , Miocárdio/patologia , Pandemias , Peptidil Dipeptidase A/metabolismo
6.
Front Immunol ; 11: 570919, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101291

RESUMO

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic by the World Health Organization in March 2020. Severe COVID-19 cases develop severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. The higher risk group includes the elderly and subjects with pre-existing chronic illnesses such as obesity, hypertension, and diabetes. To date, no specific treatment or vaccine is available for COVID-19. Among many compounds, naringenin (NAR) a flavonoid present in citrus fruits has been investigated for antiviral and anti-inflammatory properties like reducing viral replication and cytokine production. In this perspective, we summarize NAR potential anti-inflammatory role in COVID-19 associated risk factors and SARS-CoV-2 infection.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Flavanonas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Animais , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Modelos Animais de Doenças , Humanos , Macrófagos/imunologia , Pandemias , Pneumonia Viral/patologia
7.
Front Immunol ; 11: 580641, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101306

RESUMO

The ongoing outbreak of Coronavirus disease 2019 infection achieved pandemic status on March 11, 2020. As of September 8, 2020 it has caused over 890,000 mortalities world-wide. Coronaviral infections are enabled by potent immunoevasory mechanisms that target multiple aspects of innate immunity, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) able to induce a cytokine storm, impair interferon responses, and suppress antigen presentation on both MHC class I and class II. Understanding the immune responses to SARS-CoV-2 and its immunoevasion approaches will improve our understanding of pathogenesis, virus clearance, and contribute toward vaccine and immunotherepeutic design and evaluation. This review discusses the known host innate immune response and immune evasion mechanisms driving SARS-CoV-2 infection and pathophysiology.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Evasão da Resposta Imune/imunologia , Imunidade Inata/imunologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Humanos , Pandemias , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia
8.
Front Immunol ; 11: 570122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117359

RESUMO

The COVID-19 is an acute and contagious disease characterized by pneumonia and ARDS. The disease is caused by SARS-CoV-2, which belongs to the family of Coronaviridae along with MERS-CoV and SARS-CoV-1. The virus has the positive-sense RNA as its genome encoding for ~26 proteins that work together for the virus survival, replication, and spread in the host. The virus gets transmitted through the contact of aerosol droplets from infected persons. The pathogenesis of COVID-19 is highly complex and involves suppression of host antiviral and innate immune response, induction of oxidative stress followed by hyper inflammation described as the "cytokine storm," causing the acute lung injury, tissue fibrosis, and pneumonia. Currently, several vaccines and drugs are being evaluated for their efficacy, safety, and for determination of doses for COVID-19 and this requires considerable time for their validation. Therefore, exploring the repurposing of natural compounds may provide alternatives against COVID-19. Several nutraceuticals have a proven ability of immune-boosting, antiviral, antioxidant, anti-inflammatory effects. These include Zn, vitamin D, vitamin C, curcumin, cinnamaldehyde, probiotics, selenium, lactoferrin, quercetin, etc. Grouping some of these phytonutrients in the right combination in the form of a food supplement may help to boost the immune system, prevent virus spread, preclude the disease progression to severe stage, and further suppress the hyper inflammation providing both prophylactic and therapeutic support against COVID-19.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/dietoterapia , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Compostos Fitoquímicos/uso terapêutico , Pneumonia Viral/dietoterapia , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/dietoterapia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Suplementos Nutricionais , Humanos , Inflamação/tratamento farmacológico , Estresse Oxidativo/fisiologia , Pandemias , Pneumonia Viral/patologia , Probióticos/uso terapêutico
9.
Front Immunol ; 11: 588724, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117402

RESUMO

SARS-CoV-2 infection is a new threat to global public health in the 21st century (2020), which has now rapidly spread around the globe causing severe pneumonia often linked to Acute Respiratory Distress Syndrome (ARDS) and hyperinflammatory syndrome. SARS-CoV-2 is highly contagious through saliva droplets. The structural analysis suggests that the virus enters human cells through the ligation of the spike protein to angiotensin-converting enzyme 2 (ACE2). The progression of Covid-19 has been divided into three main stages: stage I-viral response, stage II-pulmonary phase, and stage III-hyperinflammation phase. Once the patients enter stage III, it will likely need ventilation and it becomes difficult to manage. Thus, it will be of paramount importance to find therapies to prevent or slow down the progression of the disease toward stage III. The key event leading to hyperinflammation seems to be the activation of Th-17 immunity response and Cytokine storm. B2-adrenergic receptors (B2ARs) are expressed on airways and on all the immune cells such as macrophages, dendritic cells, B and T lymphocytes. Blocking (B2AR) has been proven, also in clinical settings, to reduce Th-17 response and negatively modulate inflammatory cytokines including IL-6 while increasing IFNγ. Non-selective beta-blockers are currently used to treat several diseases and have been proven to reduce stress-induced inflammation and reduce anxiety. For these reasons, we speculate that targeting B2AR in the early phase of Covid-19 might be beneficial to prevent hyperinflammation.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Síndrome da Liberação de Citocina/patologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pandemias , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/virologia , Células Th17/imunologia
10.
Front Immunol ; 11: 581338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123167

RESUMO

Objectives: The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods: This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results: All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions: Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Unidades de Terapia Intensiva , Interleucina-10/sangue , Interleucina-6/sangue , Estudos Longitudinais , Linfopenia , Masculino , Pessoa de Meia-Idade , Pandemias , Projetos Piloto , Pneumonia Viral/imunologia , Estudos Retrospectivos , Síndrome Respiratória Aguda Grave/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
11.
Nat Commun ; 11(1): 5243, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067472

RESUMO

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.


Assuntos
Betacoronavirus/imunologia , Linfócitos T CD8-Positivos/imunologia , Neutrófilos/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Biomarcadores/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Citometria de Fluxo , Humanos , Imunofenotipagem/métodos , Interleucina-10/sangue , Interleucina-6/sangue , Contagem de Linfócitos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Índice de Gravidade de Doença
12.
Signal Transduct Target Ther ; 5(1): 235, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037188

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to respiratory illness and multi-organ failure in critically ill patients. Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019 (COVID-19) clinical manifestations, the underlying mechanisms of virus-triggered inflammatory responses are currently unknown. Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells. The processed inflammatory cytokines are released through the virus-induced necroptosis pathway. Virus-induced apoptosis, necroptosis, and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying SARS-CoV-2 pathogenesis. Furthermore, analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration, necrotic cell debris, and pulmonary interstitial fibrosis, typical of immune pathogenesis in the lung. The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients. These discoveries might assist the development of therapeutic strategies to treat COVID-19.


Assuntos
Apoptose/imunologia , Betacoronavirus/patogenicidade , Caspase 8/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Necroptose/imunologia , Pneumonia Viral/imunologia , Fibrose Pulmonar/imunologia , Animais , Caspase 8/genética , Linhagem Celular Tumoral , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Quimiocina CXCL10/genética , Quimiocina CXCL10/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-7/genética , Interleucina-7/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Transgênicos , Pandemias , Pneumonia Viral/genética , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Fibrose Pulmonar/virologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
14.
Open Biol ; 10(9): 200160, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32961074

RESUMO

Coronavirus disease 2019 (COVID-19) has swept the world, unlike any other pandemic in the last 50 years. Our understanding of the disease has evolved rapidly since the outbreak; disease prognosis is influenced mainly by multi-organ involvement. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure are strongly associated with morbidity and mortality. The COVID-19 disease pathology is plausibly linked to the hyperinflammatory response of the body characterized by pathological cytokine levels. The term 'cytokine storm syndrome' is perhaps one of the critical hallmarks of COVID-19 disease severity. In this review, we highlight prominent cytokine families and their potential role in COVID-19, the type I and II interferons, tumour necrosis factor and members of the Interleukin family. We address various changes in cellular components of the immune response corroborating with changes in cytokine levels while discussing cytokine sources and biological functions. Finally, we discuss in brief potential therapies attempting to modulate the cytokine storm.


Assuntos
Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Pneumonia Viral/patologia , Betacoronavirus/imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/tratamento farmacológico , Humanos , Inflamação/patologia , Pandemias
15.
Immunol Res ; 68(6): 398-404, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32989677

RESUMO

This single-center, retrospective study aimed to explore the immune characteristics of COVID-19 and biomarkers to predict the severity of this disease. Patients infected with SARS-CoV-2 (n = 215) treated at the First Affiliated Hospital of Nanchang University from January 24 to March 12, 2020, were included in the study and classified into severe and non-severe groups. Peripheral immunocyte count and cytokine statuses were compared. The correlation between immune status, cytokine levels, and disease severity was analyzed. Leukocyte numbers were normal in both groups; however, they were relatively high (7.19 × 109/L) in patients of the severe group. Leukocyte distributions differed between the two groups; the severe group had a higher percentage of neutrophils and lower percentage of lymphocytes compared with the non-severe group, and absolute lymphocyte numbers were below normal in both groups, and particularly deficient in patients in the severe group. Lymphocyte counts have negative correlation with duration of hospital period whereas neutrophil count has no significant correlation with it. Of tested cytokines, IL-6 levels were significantly higher in the severe group (P = 0.0418). Low level of lymphocyte predicts severity of COVID-19. IL-6 levels were significantly higher in the severe group, especially in some extremely severe patients. But we did not detect the significant correlation between severity of COVID-19 with IL-6 level which may be due to limited case numbers. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Interleucina-6/sangue , Contagem de Linfócitos/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Adulto , Idoso , Betacoronavirus/imunologia , Biomarcadores/análise , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/patologia , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-2/sangue , Interleucina-8/sangue , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
16.
Front Immunol ; 11: 2033, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922406

RESUMO

Immune dysfunction and aberrant cytokine storms often lead to rapid exacerbation of the disease during late infection stages in SARS-CoV and MERS-CoV patients. However, the underlying immunopathology mechanisms are not fully understood, and there has been little progress in research regarding the development of vaccines, anti-viral drugs, and immunotherapy. The newly discovered SARS-CoV-2 (2019-nCoV) is responsible for the third coronavirus pandemic in the human population, and this virus exhibits enhanced pathogenicity and transmissibility. SARS-CoV-2 is highly genetically homologous to SARS-CoV, and infection may result in a similar clinical disease (COVID-19). In this review, we provide detailed knowledge of the pathogenesis and immunological characteristics of SARS and MERS, and we present recent findings regarding the clinical features and potential immunopathogenesis of COVID-19. Host immunological characteristics of these three infections are summarised and compared. We aim to provide insights and scientific evidence regarding the pathogenesis of COVID-19 and therapeutic strategies targeting this disease.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pneumonia Viral/patologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Humanos , Pandemias , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/patologia
18.
Sci Adv ; 6(31)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32937590

RESUMO

The outbreak of the highly contagious and deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), has posed a serious threat to public health across the globe, calling for the development of effective diagnostic markers and therapeutics. Here, we report a highly reliable severity diagnostic biomarker, acetylated 676th lysine transforming growth factor-beta-induced protein (TGFBIp K676Ac). TGFBIp K676Ac was consistently elevated in the blood of patients with SARS-CoV-2 pneumonia (n = 113), especially in patients in the intensive care unit (ICU) compared to non-ICU patients. Patients' blood samples showed increased cytokines and lymphopenia, which are exemplary indicators of SARS-CoV-2 pneumonia. Treatment with TGFBIp neutralizing antibodies suppressed the cytokine storm. The increased level of TGFBIp K676Ac in ICU patients suggests the promise of this protein as a reliable severity diagnostic biomarker for severe SARS-CoV-2 disease.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Síndrome da Liberação de Citocina/diagnóstico , Proteínas da Matriz Extracelular/imunologia , Leucócitos Mononucleares/imunologia , Pneumonia Viral/diagnóstico , Processamento de Proteína Pós-Traducional , Insuficiência Respiratória/diagnóstico , Fator de Crescimento Transformador beta/imunologia , Acetilação , Anticorpos Neutralizantes/farmacologia , Betacoronavirus/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Proteínas da Matriz Extracelular/antagonistas & inibidores , Proteínas da Matriz Extracelular/genética , Expressão Gênica , Humanos , Unidades de Terapia Intensiva , Contagem de Leucócitos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/virologia , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Lisina/metabolismo , NF-kappa B/genética , NF-kappa B/imunologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Cultura Primária de Células , Prognóstico , Insuficiência Respiratória/sangue , Insuficiência Respiratória/imunologia , Insuficiência Respiratória/patologia , Índice de Gravidade de Doença , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/genética
19.
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
20.
Hum Vaccin Immunother ; 16(10): 2363-2365, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-32841579

RESUMO

The cytokine storm following sepsis has been proven to be an important mechanism for triggering acute respiratory distress syndrome, which is a fatal uncontrolled systemic inflammation characterized by high concentrations of pro-inflammatory cytokines and chemokines, secreted by immune effector cells. The cytokine storm also occurs in the recently emerged novel coronavirus disease (COVID-19). Therefore, cytokines which usually help the immune system to fight infections are potentially harmful in the course of COVID-19 infections. Therefore, avoiding or mitigating the cytokine storm may be a key treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/sangue , Imunossupressores/uso terapêutico , Pneumonia Viral/patologia , Betacoronavirus , Receptor gp130 de Citocina/antagonistas & inibidores , Síndrome da Liberação de Citocina/patologia , Citocinas/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Pandemias , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA