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1.
Sci Rep ; 11(1): 11462, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075090

RESUMO

An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.


Assuntos
Abatacepte/farmacologia , COVID-19/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Imunossupressores/farmacologia , SARS-CoV-2/imunologia , Transdução de Sinais/efeitos dos fármacos , Abatacepte/uso terapêutico , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , COVID-19/sangue , COVID-19/complicações , COVID-19/imunologia , China , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , RNA-Seq , Índice de Gravidade de Doença , Transdução de Sinais/imunologia , Análise de Célula Única , Espanha , Estados Unidos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia
2.
Front Immunol ; 12: 659419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079547

RESUMO

Highly pathogenic virus infections usually trigger cytokine storms, which may have adverse effects on vital organs and result in high mortalities. The two cytokines interleukin (IL)-4 and interferon (IFN)-γ play key roles in the generation and regulation of cytokine storms. However, it is still unclear whether the cytokine with the largest induction amplitude is the same under different virus infections. It is unknown which is the most critical and whether there are any mathematical formulas that can fit the changing rules of cytokines. Three coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2), three influenza viruses (2009H1N1, H5N1 and H7N9), Ebola virus, human immunodeficiency virus, dengue virus, Zika virus, West Nile virus, hepatitis B virus, hepatitis C virus, and enterovirus 71 were included in this analysis. We retrieved the cytokine fold change (FC), viral load, and clearance rate data from these highly pathogenic virus infections in humans and analyzed the correlations among them. Our analysis showed that interferon-inducible protein (IP)-10, IL-6, IL-8 and IL-17 are the most common cytokines with the largest induction amplitudes. Equations were obtained: the maximum induced cytokine (max) FC = IFN-γ FC × (IFN-γ FC/IL-4 FC) (if IFN-γ FC/IL-4 FC > 1); max FC = IL-4 FC (if IFN-γ FC/IL-4 FC < 1). For IFN-γ-inducible infections, 1.30 × log2 (IFN-γ FC) = log10 (viral load) - 2.48 - 2.83 × (clearance rate). The clinical relevance of cytokines and their antagonists is also discussed.


Assuntos
Síndrome da Liberação de Citocina/imunologia , Citocinas/sangue , Modelos Imunológicos , Viroses/complicações , Biomarcadores/sangue , Biomarcadores/metabolismo , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/virologia , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Carga Viral/imunologia , Viroses/sangue , Viroses/imunologia , Viroses/virologia
3.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065210

RESUMO

Previous studies have shown that COVID-19 leads to thrombotic complications, which have been associated with high morbidity and mortality rates. Neutrophils are the largest population of white blood cells and play a pivotal role in innate immunity. During an infection, neutrophils migrate from circulation to the infection site, contributing to killing pathogens. This mechanism is regulated by chemokines such as IL-8. Moreover, it was shown that neutrophils play an important role in thromboinflammation. Through a diverse repertoire of mechanisms, neutrophils, apart from directly killing pathogens, are able to activate the formation of thrombi. In COVID-19 patients, neutrophil activation promotes neutrophil extracellular trap (NET) formation, platelet aggregation, and cell damage. Furthermore, neutrophils participate in the pathogenesis of endothelitis. Overall, this review summarizes recent progress in research on the pathogenesis of COVID-19, highlighting the role of the prothrombotic action of neutrophils in NET formation.


Assuntos
COVID-19/imunologia , Armadilhas Extracelulares/imunologia , Imunidade Inata , Pulmão/imunologia , Neutrófilos/imunologia , Trombose/imunologia , COVID-19/complicações , COVID-19/patologia , COVID-19/terapia , Síndrome da Liberação de Citocina/metabolismo , Síndrome da Liberação de Citocina/virologia , Armadilhas Extracelulares/virologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Rim/citologia , Rim/imunologia , Rim/patologia , Rim/virologia , Pulmão/citologia , Pulmão/patologia , Pulmão/virologia , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/virologia , SARS-CoV-2 , Trombose/complicações , Trombose/patologia , Trombose/virologia
4.
Ann Med ; 53(1): 777-785, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34042528

RESUMO

The coronavirus SARS-CoV-2, the aetiological agent of COVID-19 disease, is representing a worldwide threat for the medical community and the society at large so that it is being defined as "the twenty-first-century disease". Often associated with a severe cytokine storm, leading to more severe cases, it is mandatory to block such occurrence early in the disease course, to prevent the patients from having more severe, sometimes fatal, outcomes. In this framework, early detection of "danger signals", possibly represented by alarmins, can represent one of the most promising strategies to effectively tailor the disease and to better understand the underlying mechanisms eventually leading to death or severe consequences. In light of such considerations, the present article aims at evaluating the role of alarmins in patients affected by COVID-19 disease and the relationship of such compounds with the most commonly reported comorbidities. The conducted researches demonstrated yet poor literature on this specific topic, however preliminarily confirming a role for danger signals in the amplification of the inflammatory reaction associated with SARS-CoV-2 infection. As such, a number of chronic conditions, including metabolic syndrome, gastrointestinal and respiratory diseases, in turn, associated with higher levels of alarmins, both foster the infection and predispose to a worse prognosis. According to these preliminary data, prompt detection of high levels of alarmins in patients with COVID-19 and co-morbidities could suggest an immediate intense anti-inflammatory treatment.Key messageAlarmins have a role in the amplification of the inflammatory reaction associated with SARS-CoV-2 infectiona prompt detection of high levels of alarmins in patients with COVID-19 could suggest an immediate intense anti-inflammatory treatment.


Assuntos
Alarminas/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Animais , COVID-19/virologia , Comorbidade , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Humanos , Inflamação/imunologia , Inflamação/virologia , Prognóstico , Índice de Gravidade de Doença
5.
Front Immunol ; 12: 668507, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33981314

RESUMO

SARS-COV-2 virus is responsible for the ongoing devastating pandemic. Since the early phase of the pandemic, the "cytokine-storm" appeared a peculiar aspect of SARS-COV-2 infection which, at least in the severe cases, is responsible for respiratory treat damage and subsequent multi-organ failure. The efforts made in the last few months elucidated that the cytokine-storm results from a complex network involving cytokines/chemokines/infiltrating-immune-cells which orchestrate the aberrant immune response in COVID-19. Clinical and experimental studies aimed at depicting a potential "immune signature" of SARS-COV-2, identified three main "actors," namely the cytokine IL-6, the chemokine CXCL10 and the infiltrating immune cell type macrophages. Although other cytokines, chemokines and infiltrating immune cells are deeply involved and their role should not be neglected, based on currently available data, IL-6, CXCL10, and infiltrating macrophages could be considered prototype factors representing each component of the immune system. It rapidly became clear that a strong and continuous interplay among the three components of the immune response is mandatory in order to produce a severe clinical course of the disease. Indeed, while IL-6, CXCL10 and macrophages alone would not be able to fully drive the onset and maintenance of the cytokine-storm, the establishment of a IL-6/CXCL10/macrophages axis is crucial in driving the sequence of events characterizing this condition. The present review is specifically aimed at overviewing current evidences provided by both in vitro and in vivo studies addressing the issue of the interplay among IL-6, CXCL10 and macrophages in the onset and progression of cytokine storm. SARS-COV-2 infection and the "cytokine storm."


Assuntos
COVID-19/imunologia , Quimiocina CXCL10/imunologia , Síndrome da Liberação de Citocina/imunologia , Interleucina-6/imunologia , Macrófagos/imunologia , COVID-19/complicações , COVID-19/virologia , Quimiocinas/imunologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Citocinas/imunologia , Humanos , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia
6.
Oxid Med Cell Longev ; 2021: 6648199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968298

RESUMO

Introduction: Mortality among critically ill COVID-19 patients remains relatively high despite different potential therapeutic modalities being introduced recently. The treatment of critically ill patients is a challenging task, without identified credible predictors of mortality. Methods: We performed an analysis of 160 consecutive patients with confirmed COVID-19 infection admitted to the Respiratory Intensive Care Unit between June 23, 2020, and October 2, 2020, in University Hospital Center Bezanijska kosa, Belgrade, Serbia. Patients on invasive, noninvasive ventilation and high flow oxygen therapy with moderate to severe ARDS, according to the Berlin definition of ARDS, were selected for the study. Demographic data, past medical history, laboratory values, and CT severity score were analyzed to identify predictors of mortality. Univariate and multivariate logistic regression models were used to assess potential predictors of mortality in critically ill COVID-19 patients. Results: The mean patient age was 65.6 years (range, 29-92 years), predominantly men, 68.8%. 107 (66.9%) patients were on invasive mechanical ventilation, 31 (19.3%) on noninvasive, and 22 (13.8%) on high flow oxygen therapy machine. The median total number of ICU days was 10 (25th to 75th percentile: 6-18), while the median total number of hospital stay was 18 (25th to 75th percentile: 12-28). The mortality rate was 60% (96/160). Univariate logistic regression analysis confirmed the significance of age, CRP, and lymphocytes at admission to hospital, serum albumin, D-dimer, and IL-6 at admission to ICU, and CT score. Serum albumin, D-dimer, and IL-6 at admission to ICU were independently associated with mortality in the final multivariate analysis. Conclusion: In the present study of 160 consecutive critically ill COVID-19 patients with moderate to severe ARDS, IL-6, serum albumin, and D-dimer at admission to ICU, accompanied by chest CT severity score, were marked as independent predictors of mortality.


Assuntos
Transtornos da Coagulação Sanguínea/complicações , COVID-19/complicações , COVID-19/mortalidade , Síndrome da Liberação de Citocina/complicações , Oxigenoterapia/métodos , Síndrome do Desconforto Respiratório/complicações , SARS-CoV-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/virologia , COVID-19/epidemiologia , COVID-19/terapia , Cuidados Críticos , Estado Terminal , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Unidades de Terapia Intensiva , Interleucina-6/sangue , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Respiração Artificial , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/virologia , Sérvia/epidemiologia , Albumina Sérica Humana/análise , Índice de Gravidade de Doença , Resultado do Tratamento
7.
BMC Infect Dis ; 21(1): 398, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926377

RESUMO

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.


Assuntos
COVID-19/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Idoso , Aspartato Aminotransferases/sangue , COVID-19/epidemiologia , COVID-19/terapia , China/epidemiologia , Comorbidade , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Feminino , Ferritinas/sangue , Humanos , Incidência , Contagem de Linfócitos , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de Risco
8.
Eur Rev Med Pharmacol Sci ; 25(6): 2802-2807, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33829465

RESUMO

Since November 2019, SARS Coronavirus 2 disease (COVID-19) pandemic has spread through more than 195 nations worldwide. Though the coronavirus infection affects all age and sex groups, the mortality is skewed towards the elderly population and the cause of death is mostly acute respiratory distress syndrome (ARDS). There are data suggesting the role of excessive immune activation and cytokine storm as the cause of lung injury in COVID-19. The excessive immune activation and cytokine storm usually occurs due to an imbalance in redox homeostasis of the individuals. Considering the antioxidant and free radical scavenging action of N acetyl cysteine (NAC), its use might be useful in COVID-19 patients by decreasing the cytokine storm consequently decreasing the disease severity. Therefore, we reviewed all the available resources pertaining to the role of reactive oxygen species (ROS) in cytokine storm and the mechanism of action of NAC in preventing ROS. We also reviewed the use of NAC in COVID-19.


Assuntos
Acetilcisteína/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , COVID-19/imunologia , COVID-19/virologia , Síndrome da Liberação de Citocina/virologia , Humanos , Prognóstico
9.
BMC Pediatr ; 21(1): 181, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865340

RESUMO

BACKGROUND: Early diagnostic indicators and the identification of possible progression to severe or critical COVID-19 in children are unknown. To investigate the immune characteristics of early SARS-CoV-2 infection in children and possible key prognostic factors for early identification of critical COVID-19, a retrospective study including 121 children with COVID-19 was conducted. Peripheral blood lymphocyte subset counts, T cell-derived cytokine concentrations, inflammatory factor concentrations, and routine blood counts were analyzed statistically at the initial presentation. RESULTS: The T lymphocyte subset and natural killer cell counts decreased with increasing disease severity. Group III (critical cases) had a higher Th/Tc ratio than groups I and II (common and severe cases); group I had a higher B cell count than groups II and III. IL-6, IL-10, IFN-γ, SAA, and procalcitonin levels increased with increasing disease severity. Hemoglobin concentration, and RBC and eosinophil counts decreased with increasing disease severity. Groups II and III had significantly lower lymphocyte counts than group I. T, Th, Tc, IL-6, IL-10, RBC, and hemoglobin had relatively high contribution and area under the curve values. CONCLUSIONS: Decreased T, Th, Tc, RBC, hemoglobin and increased IL-6 and IL-10 in early SARS-CoV-2 infection in children are valuable indices for early diagnosis of severe disease. The significantly reduced Th and Tc cells and significantly increased IL-6, IL-10, ferritin, procalcitonin, and SAA at this stage in children with critical COVID-19 may be closely associated with the systemic cytokine storm caused by immune dysregulation.


Assuntos
COVID-19/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Adolescente , Linfócitos B/citologia , Criança , Pré-Escolar , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Feminino , Humanos , Imunidade , Lactente , Células Matadoras Naturais/citologia , Contagem de Linfócitos , Masculino , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/citologia
10.
Mol Biol Rep ; 48(3): 2917-2928, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33837899

RESUMO

The renin-angiotensin-aldosterone system and its metabolites play an important role in homeostasis of body, especially the cardiovascular system. In this study, we discuss the imbalance of multiple systems during the infection and the importance of therapeutic choice, dosing, and laboratory monitoring of cardiac and anti-coagulant therapies in COVID-19 patients. The crosstalk between angiotensin, kinin-kallikrein system, as well as inflammatory and coagulation systems plays an essential role in COVID-19. Cardiac complications and coagulopathies imply the crosstalks between the mentioned systems. We believe that the blockage of bradykinin can be a good option in the management of COVID-19 and CVD in patients and that supportive treatment of respiratory and cardiologic complications is needed in COVID-19 patients. Ninety-one percent of COVID-19 patients who were admitted to hospital with a prolonged aPTT were positive for lupus anticoagulant, which increases the risk of thrombosis and prolonged aPTT. Therefore, the question that is posed at this juncture is whether it is safe to use the prophylactic dose of heparin particularly in those with elevated D-dimer levels. It should be noted that timing is of high importance in anti-coagulant therapy; therefore, we should consider the level of D-dimer, fibrinogen, drug-drug interactions, and risk factors during thromboprophylaxis administration. Fibrinogen is an independent predictor of resistance to heparin and should be considered before thromboprophylaxis. Alteplase and Futhan might be a good choice to assess the condition of heparin resistance. Finally, the treatment option, dosing, and laboratory monitoring of anticoagulant therapy are critical decisions in COVID-19 patients.


Assuntos
COVID-19 , SARS-CoV-2 , Trombose , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Bradicinina/sangue , COVID-19/complicações , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Inflamação/imunologia , Inflamação/virologia , Calicreínas/sangue , Sistema Renina-Angiotensina/imunologia , Sistema Renina-Angiotensina/fisiologia , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Trombose/virologia
11.
Iran J Immunol ; 18(1): 54-64, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33787514

RESUMO

BACKGROUND: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients. OBJECTIVE: To investigate and compare the serum levels of different cytokines in COVID-19 patients with different clinical severity. METHODS: Concentrations of serum cytokines, including IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and GM-CSF, were measured in 61 COVID-19 patients and 31 normal controls with ELISA. We investigated the correlation between the levels of these cytokines and clinical severity, CRP level, neutrophil and lymphocyte count in patients with COVID-19. RESULTS: Our data indicated that the levels of IL-1ß, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF, but not IL-10 were significantly increased in COVID-19 patients compared to normal controls. Statistical analysis showed that the level of IL-1ß, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF were higher in severe COVID-19 than those of mild cases. The concentrations of all mentioned cytokines were negatively associated with the absolute count of lymphocytes, and positively correlated with the CRP level and the absolute count of neutrophils. CONCLUSION: The current study suggests that high levels of various cytokines correlate with the disease severity and immunopathogenesis of COVID-19.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/sangue , SARS-CoV-2/imunologia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/virologia , Estudos de Casos e Controles , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Irã (Geográfico) , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/virologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença
12.
Iran J Immunol ; 18(1): 65-73, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33787515

RESUMO

BACKGROUND: The role of cytokine storm in the immunopathogenesis of coronavirus disease 2019 (COVID-19) has been implicated. OBJECTIVE: To determine the association of microRNA (miRNA)-10b and serum levels of IL-2 and IL-8 in patients with COVID-19. METHODS: Blood samples were obtained from 33 COVID-19 patients and 29 healthy subjects. After RNA extraction and cDNA synthesis, the transcript level of miR-10b was determined by Real-time PCR. In addition, the serum levels of IL-2 and IL-8 were measured in subjects using ELISA. RESULTS: The patient group comprised of 33 patients with COVID-19 (62.4 ± 3.7 years old), 13 (39%) males and 20 (61%) females. In the control group, 29 subjects (56.6 ± 1.6 years old), 9 (31%) males and 20 (69%) females, were included. The expression of miR-10b was significantly downregulated in the peripheral blood of COVID-19 patients in comparison to the healthy controls (fold change= 0.12, P< 0.0001). The levels of IL-2 (P< 0.001) and IL-8 (P< 0.001) were significantly increased in the serum samples of COVID-19 patients compared to the healthy subjects. The expression level of miR-10b was correlated significantly with the serum levels of IL-2 and IL-8 as well as with the age of patients, ESR and CRP levels. CONCLUSIONS: miR-10b is downregulated in the COVID-19 patients and might result in increased levels of IL-2 and IL-8, hence contributing to cytokine storm.


Assuntos
COVID-19/sangue , MicroRNA Circulante/sangue , Interleucina-2/sangue , Interleucina-8/sangue , MicroRNAs/sangue , SARS-CoV-2/patogenicidade , Idoso , Biomarcadores/sangue , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Estudos de Casos e Controles , MicroRNA Circulante/genética , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , SARS-CoV-2/imunologia
13.
Iran J Immunol ; 18(1): 1-12, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33787510

RESUMO

Severe Acute Respiratory Syndrome (SARS) associated with SARS-CoV-2, causes a severe form of the respiratory illness known as Coronavirus Disease-19 (COVID-19). COVID-19 has emerged as a worldwide pandemic with a high number of fatalities. Approximately 112,654,202 people have been infected so far with this disease which has led to the death of more than one point seven million (2,496,749) till 24th Feb, 2021. Measures to counter this disease have led to a global economic slowdown. Multiple drug trials are ongoing and several putative candidates for vaccination against the virus have been approved and are in the pipeline. Many studies have also characterized the immunological profile of patients infected with COVID-19. Some studies suggest that the severity of the COVID-19 infection is directly associated with the cytokine storm. In this review, we aim to compile the available knowledge and describe the nature of immune responses in patients infected with COVID-19 in different age groups, comorbidity, and immune-compromised state and their association with disease severity.


Assuntos
Imunidade Adaptativa , COVID-19/imunologia , Imunidade Inata , SARS-CoV-2/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Fatores Etários , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/terapia , COVID-19/virologia , Vacinas contra COVID-19/uso terapêutico , Comorbidade , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Interações Hospedeiro-Patógeno , Humanos , Imunidade Humoral , Imunidade Inata/efeitos dos fármacos , Hospedeiro Imunocomprometido , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
14.
Viruses ; 13(3)2021 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673529

RESUMO

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.2020, irrespective of type of article, country, or region. Joanna Briggs Institute's design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1ß, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Histamina/administração & dosagem , Imunoglobulinas/administração & dosagem , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Síndrome da Liberação de Citocina/virologia , Bases de Dados Factuais , Regulação para Baixo/efeitos dos fármacos , Reposicionamento de Medicamentos , Humanos , Imunidade , Produção de Droga sem Interesse Comercial , SARS-CoV-2/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
15.
Front Immunol ; 12: 629193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732251

RESUMO

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Índice de Gravidade de Doença , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Humanos , Inflamação/imunologia , Influenza Humana/sangue , Influenza Humana/virologia , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/virologia
17.
Pan Afr Med J ; 38: 34, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777302

RESUMO

Since December 2019, the world has experienced the emergence in China of a new infection called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This infection quickly has progressed to a global pandemic since March 2020, with very high human-to-human transmission rate. Besides lung injury, COVID-19 is also associated with cardio and neurovascular complications. Herein, we report the case of a 77-year-old female who presented with non-severe COVID-19 and multiple ischemic strokes secondary to an extensive carotid thrombosis. The ischemic stroke was supposed to have been caused by the cytokine storm related to COVID-19. The possibility of hemorrhagic transformation, based on the assessment of bleeding score, limited the use of anticoagulation, and probably explained the stroke recurrence and poor outcome in our patient. The pathogenic mechanism and the management of this complex situation are still lacking and further studies are needed.


Assuntos
COVID-19/complicações , Trombose das Artérias Carótidas/etiologia , Síndrome da Liberação de Citocina/virologia , AVC Isquêmico/etiologia , Idoso , Síndrome da Liberação de Citocina/fisiopatologia , Feminino , Humanos , Recidiva
18.
Virulence ; 12(1): 918-936, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33757410

RESUMO

The coronavirus disease 19 (COVID-19) caused by the novel coronavirus known as SARS-CoV-2 has caused a global public health crisis. As of 7 January 2021, 87,640,402 confirmed cases and 1,891,692 mortalities have been reported worldwide. Studies focusing on the epidemiological and clinical characteristics of COVID-19 patients have suggested a dysregulated immune response characterized by lymphopenia and cytokine storm in these patients. The exaggerated immune response induced by the cytokine storm causes septic shock, acute respiratory distress syndrome (ARDS), and/or multiple organs failure, which increases the fatality rate of patients with SARS-CoV-2 infection. Herein, we review the recent research progress on epidemiology, clinical features, and system pathology in COVID-19. Moreover, we summarized the recent therapeutic strategies, which are either approved, under clinical trial, and/or under investigation by the local or global health authorities. We assume that treatments should focus on the use of antiviral drugs in combination with immunomodulators as well as treatment of the underlying comorbidities.


Assuntos
COVID-19/imunologia , COVID-19/patologia , SARS-CoV-2/patogenicidade , Imunidade Adaptativa , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Humanos , Imunidade Inata , Fatores Imunológicos/uso terapêutico , Linfopenia/tratamento farmacológico , Linfopenia/imunologia , Linfopenia/patologia , Linfopenia/virologia , SARS-CoV-2/imunologia , Carga Viral
19.
Ann Transplant ; 26: e929279, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33707409

RESUMO

Coronavirus disease 19 (COVID-19) has been an ongoing pandemic since December 2019. Unfortunately, kidney transplant recipients are a high-risk group during the disease course, and scientific data are still limited in this patient group. Beyond the dosage of immunosuppressive drugs, pharmacological immunosuppression may also alter the infection response in the COVID-19 course. The effects of immunosuppressive agents on the development and process of infection should not be decided only by determining how potent they are and how much they suppress the immune system; it is also thought that the direct effect of the virus, increased oxidative stress, and cytokine storm play a role in the pathogenesis of COVID-19 disease. There are data about immunosuppressive drugs like calcineurin inhibitors (CNI) or mammalian target of rapamycin inhibitors (mTORi) therapy related to their beneficial effects during any infection course. Limited data suggest that the use of CNI or mTORi may have beneficial effects on the process. In this hypothetical review, the probable impacts of CNI and mTORi on the pathogenesis of the COVID-19 were investigated.


Assuntos
COVID-19/imunologia , Inibidores de Calcineurina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Complicações Pós-Operatórias/imunologia , Inibidores de Proteínas Quinases/uso terapêutico , Imunidade Adaptativa/efeitos dos fármacos , COVID-19/diagnóstico , Inibidores de Calcineurina/farmacologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Síndrome da Liberação de Citocina/virologia , Rejeição de Enxerto/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Hospedeiro Imunocomprometido , Imunossupressores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/virologia , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores
20.
J Int Med Res ; 49(3): 3000605211002695, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33745336

RESUMO

Over the past several decades, studies have demonstrated the existence of bi-directional relationships between periodontal disease and systemic conditions. Periodontitis is a polymicrobial and multifactorial disease involving both host and environmental factors. Tissue destruction is primarily associated with hyperresponsiveness of the host resulting in release of inflammatory mediators. Pro-inflammatory cytokines play a major role in bacterial stimulation and tissue destruction. In addition, these cytokines are thought to underlie the associations between periodontitis and systemic conditions. Current research suggests that increased release of cytokines from host cells, referred to as the cytokine storm, is associated with disease progression in patients with coronavirus disease 2019 (COVID-19). An intersection between periodontitis and pulmonary disease is biologically plausible. Hence, we reviewed the evidence linking COVID-19, cytokines, and periodontal disease. Plaque control is essential to prevent exchange of bacteria between the mouth and the lungs, reducing the risk of lung disease. Understanding these associations may help identify individuals at high risk and deliver appropriate care at early stages.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Placa Dentária/imunologia , Interações Hospedeiro-Patógeno/imunologia , Periodontite/imunologia , SARS-CoV-2/patogenicidade , Estresse Psicológico/imunologia , COVID-19/complicações , COVID-19/genética , COVID-19/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/virologia , Placa Dentária/complicações , Placa Dentária/genética , Placa Dentária/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Padrões Moleculares Associados a Patógenos/imunologia , Padrões Moleculares Associados a Patógenos/metabolismo , Periodontite/complicações , Periodontite/genética , Periodontite/virologia , SARS-CoV-2/imunologia , Transdução de Sinais , Estresse Psicológico/complicações , Estresse Psicológico/genética , Estresse Psicológico/virologia , Dente/imunologia , Dente/patologia , Dente/virologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
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