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1.
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
/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 , Síndrome Respiratória Aguda Grave/imunologia , Índice de Gravidade de Doença , /sangue , /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
3.
Sci Signal ; 14(673)2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33688079

RESUMO

IL-1ß is a key mediator of the cytokine storm linked to high morbidity and mortality from COVID-19, and IL-1ß blockade with anakinra and canakinumab during COVID-19 infection has entered clinical trials. Using mass cytometry of human peripheral blood mononuclear cells, we identified effector memory CD4+ T cells and CD4-CD8low/-CD161+ T cells, specifically those positive for the chemokine receptor CCR6, as the circulating immune subtypes with the greatest response to IL-1ß. This response manifested as increased phosphorylation and, thus, activation of the proinflammatory transcription factor NF-κB and was also seen in other subsets, including CD11c+ myeloid dendritic cells, classical monocytes, two subsets of natural killer cells (CD16-CD56brightCD161- and CD16-CD56dimCD161+), and lineage- (Lin-) cells expressing CD161 and CD25. IL-1ß also induced a rapid but less robust increase in the phosphorylation of the kinase p38 as compared to that of NF-κB in most of these immune cell subsets. Prolonged IL-1ß stimulation increased the phosphorylation of the transcription factor STAT3 and to a lesser extent that of STAT1 and STAT5 across various immune cell types. IL-1ß-induced production of IL-6 likely led to the activation of STAT1 and STAT3 at later time points. Interindividual heterogeneity and inhibition of STAT activation by anakinra raise the possibility that assays measuring NF-κB phosphorylation in response to IL-1ß in CCR6+ T cell subtypes could identify those patients at higher risk of cytokine storm and most likely to benefit from IL-1ß-neutralizing therapies.


Assuntos
/imunologia , Interleucina-1beta/sangue , Subpopulações de Linfócitos T/imunologia , /sangue , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Citometria de Fluxo , Humanos , Interleucina-1beta/farmacologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Monócitos/classificação , Monócitos/imunologia , Monócitos/metabolismo , NF-kappa B/sangue , Pandemias , Fosforilação , Receptores CCR6/sangue , Fatores de Transcrição STAT/sangue , Fatores de Transcrição STAT/imunologia , Transdução de Sinais/imunologia , Subpopulações de Linfócitos T/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/sangue
5.
Front Immunol ; 12: 613422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679753

RESUMO

Hyper-inflammatory responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major cause of disease severity and death. Predictive prognosis biomarkers to guide therapeutics are critically lacking. Several studies have indicated a "cytokine storm" with the release of interleukin-1 (IL-1), IL-6, and IL-8, along with tumor necrosis factor alpha (TNFα) and other inflammatory mediators. Here, we proposed to assess the relationship between IL-6 and outcomes of patients with coronavirus disease 2019 (COVID-19). Our cohort consisted of 46 adult patients with PCR-proven SARS-CoV-2 infection admitted in a COVID-19 ward of the Hospital de Braga (HB) from April 7 to May 7, 2020, whose IL-6 levels were followed over time. We found that IL-6 levels were significantly different between the disease stages. Also, we found a significant negative correlation between IL-6 levels during stages IIb and III, peripheral oxygen saturation (SpO2), and partial pressure of oxygen in arterial blood (PaO2), showing that IL-6 correlates with respiratory failure. Compared to the inflammatory markers available in the clinic routine, we found a positive correlation between IL-6 and C-reactive protein (CRP). However, when we assessed the predictive value of these two markers, IL-6 behaves as a better predictor of disease progression. In a binary logistic regression, IL-6 level was the most significant predictor of the non-survivors group, when compared to age and CRP. Herein, we present IL-6 as a relevant tool for prognostic evaluation, mainly as a predictor of outcome.


Assuntos
Síndrome da Liberação de Citocina , Interleucina-6/sangue , /metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , /mortalidade , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue
7.
Cardiol Rev ; 29(1): 43-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32947478

RESUMO

The novel coronavirus (severe acute respiratory syndrome CoV-2 [SARS-CoV-2]), also known as COVID-19, is a single-stranded enveloped RNA virus that created a Public Health Emergency of International Concern in January 2020, with a global case burden of over 15 million in just 7 months. Infected patients develop a wide range of clinical manifestations-typically presenting with fever, cough, myalgia, and fatigue. Severely ill patients may fall victim to acute respiratory distress syndrome, acute heart injuries, neurological manifestations, or complications due to secondary infections. These critically ill patients are also found to have disrupted coagulation function, predisposing them to consumptive coagulopathies, and both venous and thromboembolic complications. Common laboratory findings include thrombocytopenia, elevated D-dimer, fibrin degradation products, and fibrinogen, all of which have been associated with greater disease severity. Many cases of pulmonary embolism have been noted, along with deep vein thrombosis, ischemic stroke, myocardial infarction, and systemic arterial embolism. The pathogenesis of coronavirus has not been completely elucidated, but the virus is known to cause excessive inflammation, endothelial injury, hypoxia, and disseminated intravascular coagulation, all of which contribute to thrombosis formation. These patients are also faced with prolonged immobilization while staying in the hospital or intensive care unit. It is important to have a high degree of suspicion for thrombotic complications as patients may rapidly deteriorate in severe cases. Evidence suggests that prophylaxis with anticoagulation may lead to a lower risk of mortality, although it does not eliminate the possibility. The risks and benefits of anticoagulation treatment should be considered in each case. Patients should be regularly evaluated for bleeding risks and thrombotic complications.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Embolia/sangue , Trombose/sangue , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/metabolismo , /tratamento farmacológico , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/metabolismo , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/metabolismo , Coagulação Intravascular Disseminada/prevenção & controle , Embolia/etiologia , Embolia/metabolismo , Embolia/prevenção & controle , Endotélio Vascular/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Hipóxia/metabolismo , Imobilização , Inflamação/sangue , Inflamação/etiologia , Inflamação/metabolismo , /etiologia , /prevenção & controle , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Guias de Prática Clínica como Assunto , Embolia Pulmonar/sangue , Embolia Pulmonar/etiologia , Embolia Pulmonar/metabolismo , Embolia Pulmonar/prevenção & controle , Índice de Gravidade de Doença , Trombocitopenia/sangue , Trombocitopenia/etiologia , Trombose/etiologia , Trombose/metabolismo , Trombose/prevenção & controle , Trombose Venosa/sangue , Trombose Venosa/etiologia , Trombose Venosa/metabolismo
8.
Eur Cytokine Netw ; 31(3): 81-93, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33361013

RESUMO

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.


Assuntos
Anticorpos/uso terapêutico , Síndrome da Liberação de Citocina , Interleucina-6/antagonistas & inibidores , Pandemias , Fator de Necrose Tumoral alfa/antagonistas & inibidores , /sangue , /tratamento farmacológico , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/mortalidade , Humanos , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue
9.
PLoS One ; 15(12): e0244628, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382773

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has spread around the world. High Interleukin-6 (IL-6) levels in COVID-19 patients suggest that a cytokine storm may play a major role in the pathophysiology and are considered as a relevant parameter in predicting most severe course of disease. The aim of this study was to assess repeated IL-6 levels in critically ill COVID-19 patients admitted to our Intensive Care Unit (ICU) and to evaluate their relationship with patient's severity and outcome. METHODS: We conducted a retrospective study on patients admitted to the ICU with a diagnosis of COVID-19 between March 10 (i.e. the date of the first admitted patients) and April 30, 2020. Demographic, clinical and laboratory data were collected at admission. On the day of IL-6 blood concentration measurement, we also collected results of D-Dimers, C-Reactive Protein, white blood cells and lymphocytes count, lactate dehydrogenase (LDH) and ferritin as well as microbiological samples, whenever present. RESULTS: Of a total of 65 patients with COVID-19 admitted to our ICU we included 41 patients with repeated measure of IL-6. There was a significant difference in IL-6 levels between survivors and non-survivors over time (p = 0.001); moreover, non survivors had a significantly higher IL-6 maximal value when compared to survivors (720 [349-2116] vs. 336 [195-646] pg/mL, p = 0.01). The IL-6 maximal value had a significant predictive value of ICU mortality (AUROC 0.73 [95% CI 0.57-0.89]; p = 0.01). CONCLUSIONS: Repeated measurements of IL-6 can help clinicians in identifying critically ill COVID-19 patients with the highest risk of poor prognosis.


Assuntos
/sangue , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/mortalidade , Interleucina-6/sangue , Estado Terminal , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
10.
Front Immunol ; 11: 598404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329592

RESUMO

Background: Bacterial sepsis has been used as a prototype to understand the pathogenesis of severe coronavirus disease 2019 (COVID-19). In addition, some management programs for critically ill COVID-19 patients are also based on experience with bacterial sepsis. However, some differences may exist between these two types of sepsis. Methods: This retrospective study investigated whether there are differences in the immune system status of these two types of sepsis. A total of 64 bacterial sepsis patients and 43 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sepsis were included in this study. Demographic data were obtained from medical records. Laboratory results within 24 h after the diagnosis of sepsis were provided by the clinical laboratory. Results: The results of blood routine (neutrophil, lymphocyte, and monocyte counts), infection biomarkers (C-reactive protein, ferritin, and procalcitonin levels), lymphocyte subset counts (total T lymphocyte, CD4+ T cell, CD8+ T cell, B cell, and NK cell counts), and lymphocyte subset functions (the proportions of PMA/ionomycin-stimulated IFN-γ positive cells in CD4+, CD8+ T cells, and NK cells) were similar in bacterial sepsis patients and SARS-CoV-2 sepsis patients. Cytokine storm was milder, and immunoglobulin and complement protein levels were higher in SARS-CoV-2 sepsis patients. Conclusions: There are both similarities and differences in the immune system status of bacterial sepsis and SARS-CoV-2 sepsis. Our findings do not support blocking the cytokine storm or supplementing immunoglobulins in SARS-CoV-2 sepsis, at least in the early stages of the disease. Treatments for overactivation of the complement system and lymphocyte depletion may be worth exploring further.


Assuntos
Infecções Bacterianas , Síndrome da Liberação de Citocina , Subpopulações de Linfócitos , Sepse , Adulto , Idoso , Infecções Bacterianas/sangue , Infecções Bacterianas/imunologia , /imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/imunologia , Feminino , Humanos , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , /metabolismo , Sepse/sangue , Sepse/imunologia
11.
Mol Med Rep ; 22(6): 4485-4491, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33173966

RESUMO

In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome­CoV­2 and the disease CoV disease­19 (COVID­19). Patients with COVID­19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID­19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID­19 may aid in the development of treatments and may improve patient prognosis.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Anticorpos Antivirais/imunologia , Complexo Antígeno-Anticorpo/imunologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Microambiente Celular , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Testes Diagnósticos de Rotina , Endotélio Vascular/patologia , Testes Hematológicos , Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas/patologia , Humanos , Hipoalbuminemia/etiologia , Fígado/fisiopatologia , Pulmão/fisiopatologia , Linfopenia/etiologia , Linfopenia/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/terapia , Traumatismo por Reperfusão/etiologia , Trombocitopenia/etiologia , Trombocitopenia/fisiopatologia , Trombofilia/etiologia
12.
Trials ; 21(1): 934, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213529

RESUMO

OBJECTIVES: Zilucoplan (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms that lead to improvement in lung oxygenation parameters. The purpose of this study is to investigate the efficacy and safety of Zilucoplan in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure. TRIAL DESIGN: This is a phase 2 academic, prospective, 2:1 randomized, open-label, multi-center interventional study. PARTICIPANTS: Adult patients (≥18y old) will be recruited at specialized COVID-19 units and ICUs at 9 Belgian hospitals. The main eligibility criteria are as follows: 1) Inclusion criteria: a. Recent (≥6 days and ≤16 days) SARS-CoV-2 infection. b. Chest CT scan showing bilateral infiltrates within the last 2 days prior to randomisation. c. Acute hypoxia (defined as PaO2/FiO2 below 350 mmHg or SpO2 below 93% on minimal 2 L/min supplemental oxygen). d. Signs of cytokine release syndrome characterized by either high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those. 2) Exclusion criteria: e. Mechanical ventilation for more than 24 hours prior to randomisation. f. Active bacterial or fungal infection. g. History of meningococcal disease (due to the known high predisposition to invasive, often recurrent meningococcal infections of individuals deficient in components of the alternative and terminal complement pathways). INTERVENTION AND COMPARATOR: Patients in the experimental arm will receive daily 32,4 mg Zilucoplan subcutaneously and a daily IV infusion of 2g of the antibiotic ceftriaxone for 14 days (or until hospital discharge, whichever comes first) in addition to standard of care. These patients will receive additional prophylactic antibiotics until 14 days after the last Zilucoplan dose: hospitalized patients will receive a daily IV infusion of 2g of ceftriaxone, discharged patients will switch to daily 500 mg of oral ciprofloxacin. The control group will receive standard of care and a daily IV infusion of 2g of ceftriaxone for 1 week (or until hospital discharge, whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19. MAIN OUTCOMES: The primary endpoint is the improvement of oxygenation as measured by mean and/or median change from pre-treatment (day 1) to post-treatment (day 6 and 15 or at discharge, whichever comes first) in PaO2/FiO2 ratio, P(A-a)O2 gradient and a/A PO2 ratio. (PAO2= Partial alveolar pressure of oxygen, PaO2=partial arterial pressure of oxygen, FiO2=Fraction of inspired oxygen). RANDOMISATION: Patients will be randomized in a 2:1 ratio (Zilucoplan: control). Randomization will be done using an Interactive Web Response System (REDCap). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 81 patients will be enrolled: 54 patients will be randomized to the experimental arm and 27 patients to the control arm. TRIAL STATUS: ZILU-COV protocol Version 4.0 (June 10 2020). Participant recruitment started on June 23 2020 and is ongoing. Given the uncertainty of the pandemic, it is difficult to predict the anticipated end date. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on May 11th, 2020 (ClinicalTrials.gov Identifier: NCT04382755 ) and on EudraCT (Identifier: 2020-002130-33 ). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Complemento C5/antagonistas & inibidores , Infecções por Coronavirus/complicações , Hipóxia/tratamento farmacológico , Pneumonia Viral/complicações , Insuficiência Respiratória/tratamento farmacológico , Doença Aguda , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bélgica/epidemiologia , Betacoronavirus/isolamento & purificação , Estudos de Casos e Controles , Ceftriaxona/administração & dosagem , Ceftriaxona/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/tratamento farmacológico , Quimioterapia Combinada , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Oxigênio/sangue , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Estudos Prospectivos , Segurança , Resultado do Tratamento
15.
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
16.
Virus Res ; 289: 198171, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32979474

RESUMO

BACKGROUND: Innate and adaptive immune responses have been evaluated in infected patients with COVID-19. The severity of the disease has been supposed to be associated with some profile not reported with other bacterial and viral pneumonia. We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors. METHODS: A prospective cohort with moderate and severe cases of COVID-19 infection from June to July 2020. Blood samples from patients were collected regularly to evaluate IFN-γ, TNF-α, IL-4, IL-6, and IL-10. Clinical, laboratory, radiological data, and outcomes were recorded. The outcome variable was in-hospital death, survival, mechanical ventilation, and admission at the intensive care unit. Data are presented in median and interquartile range [IQR]. RESULTS: We evaluated the Th1 and Th2 responses according to evolution, distinguishing possible predictive markers. The IFN-γ median of 323 pg/mL [IQR 166-570] was found in patients who died and 208 pg/mL [IQR 155-392] in the survival group (p = 0.017). IFN-γ was also higher in the early stages of the disease (394 pg/mL [IQR 229-575] against 162 pg/mL [IQR 117-259], p < 0.001). IL-4 that was increased in late-stage (182 pg/mL [IQR 162-199] against 131 pg/mL [IQR 124-152], p < 0.001) but not associated with mortality. Also, death was also related to male gender (relative risk = 1.5 [95 % confidence interval = 1.1-2.0]). CONCLUSION: Our results suggest that the activation of the host immune response between Th1 or Th2 in COVID-19 infection may be related to the final result between discharge or death. This implies an attempt to control cytokines, such as IFN-γ, with combined therapies for clinical treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Interferon gama/fisiologia , Pandemias , Pneumonia Viral/mortalidade , Idoso , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Citocinas/sangue , Progressão da Doença , Feminino , Mortalidade Hospitalar , Humanos , Imunidade Inata , Pacientes Internados/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Prognóstico , Estudos Prospectivos , Respiração Artificial , Fatores de Risco , Células Th1/imunologia , Células Th2/imunologia
17.
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
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
20.
Med Sci Monit ; 26: e926393, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914767

RESUMO

BACKGROUND The aim of this study was to determine the effect of C-reactive protein (CRP), lymphocytes (LYM), and the ratio of CRP to LYM (CRP/LYM) on assessing the prognosis of COVID-19 severity at early stages of disease. MATERIAL AND METHODS A total of 108 hospitalized patients diagnosed with COVID-19 in Zhongnan Hospital of Wuhan University from January 17, 2020 to March 12, 2020 were enrolled. Data of demographic parameters, clinical characteristics, laboratory indicators, clinical manifestation, and outcome of disease were collected. The patients were divided into a severe group and a non-severe group according to diagnosis and classification, which followed the guidelines and management of the Chinese National Health Council COVID-19. The receiver-operating characteristic (ROC) analysis and comparison of ROC curves were used for the laboratory findings for assessment of COVID-19 severity. RESULTS Of the 108 patients, 42 patients (38.9%) were male and 24 patients (22.2%) were considered severe cases, with the mean age of 51.0 years old. Males and patients with comorbidities were more likely to become severe cases. CRP increased and LYM decreased in the severe group.The results for the areas under the curve (AUC) of CRP/LYM and CRP used to assess severe COVID-19 were 0.787 (95% CI 0.698-0.860, P<0.0001) and 0.781 (95% CI 0.693-0.856, P<0.0001), respectively; both results were better than that of LYM. The associated criterion value of CRP/LYM was calculated, with an excellent sensitivity of 95.83%. CONCLUSIONS The effect of CRP/LYM and CRP on the assessment for severe COVID-19 may be superior to LYM alone. CRP/LYM is a highly sensitive indicator to assess the severity of COVID-19 in the early stage of disease.


Assuntos
Betacoronavirus , Proteína C-Reativa/análise , Infecções por Coronavirus/sangue , Contagem de Linfócitos , Pandemias , Pneumonia Viral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Progressão da Doença , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
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