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1.
J Ovarian Res ; 14(1): 28, 2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33550983

RESUMEN

Improving early diagnosis along with timely and effective treatment of COVID-19 are urgently needed. However, at present, the mechanisms underlying disease spread and development, defined prognosis, and immune status of patients with COVID-19 remain to be determined. Patients with severe disease state exhibit a hyperinflammatory response associated with cytokine storm syndrome, hypercoagulability, and depressed cell-mediated immunity. These clinical manifestations, sharing similar pathogenesis, have been well-studied in patients with advanced ovarian cancer. The present review suggests treatment approaches for COVID-19 based on strategies used against ovarian cancer, which shares similar immunopathology and associated coagulation disorders.The chronicization of the hyperinflammatory cytokine storm in patients with severe COVID-19 highlights a defective resistance phase that leads to aspecific chronic inflammation, associated with oxidative stress, which impairs specific T-cell response, induces tissue and endothelial damage, and thrombosis associated with systemic effects that lead to severe multi-organ failure and death. These events are similar to those observed in advanced ovarian cancer which share similar pathogenesis mediated primarily by Interleukin-6, which is, as well demonstrated in ovarian cancer, the key cytokine driving the immunopathology, related systemic symptoms, and patient prognosis.Consistent with findings in other disease models with similar immunopathology, such as advanced ovarian cancer, treatment of severe COVID-19 infection should target inflammation, oxidative stress, coagulation disorders, and immunodepression to improve patient outcome. Correctly identifying disease stages, based on available laboratory data, and developing a specific protocol for each phase is essential for effective treatment.


Asunto(s)
/complicaciones , Síndrome de Liberación de Citoquinas/etiología , Interleucina-6/metabolismo , Neoplasias Ováricas/metabolismo , Corticoesteroides/uso terapéutico , Aspirina/uso terapéutico , /metabolismo , /terapia , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/prevención & control , Femenino , Humanos , Inmunización Pasiva , Inflamación/tratamiento farmacológico , Inflamación/virología , Interleucina-6/inmunología , Necrosis , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/inmunología , Estrés Oxidativo
2.
BMC Infect Dis ; 21(1): 19, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407229

RESUMEN

BACKGROUND: Exotoxins secreted from Staphylococcus aureus or Streptococcus pyogenes act as superantigens that induce systemic release of inflammatory cytokines and are a common cause of toxic shock syndrome (TSS). However, little is known about TSS caused by coagulase-negative staphylococci (CoNS) and the underlying mechanisms. Here, we present a rare case of TSS caused by Staphylococcus simulans (S. simulans). CASE PRESENTATION: We report the case of a 75-year-old woman who developed pneumococcal pneumonia and bacteremia from S. simulans following an influenza infection. The patient met the clinical criteria for probable TSS, and her symptoms included fever of 39.5 °C, diffuse macular erythroderma, conjunctival congestion, vomiting, diarrhea, liver dysfunction, and disorientation. Therefore, the following treatment was initiated for bacterial pneumonia complicating influenza A with suspected TSS: meropenem (1 g every 8 h), vancomycin (1 g every 12 h), and clindamycin (600 mg every 8 h). Blood cultures taken on the day after admission were positive for CoNS, whereas sputum and pharyngeal cultures grew Streptococcus pneumoniae (Geckler group 4) and methicillin-sensitive S. aureus, respectively. However, exotoxins thought to cause TSS, such as TSS toxin-1 and various enterotoxins, were not detected. The patient's therapy was switched to cefazolin (2 g every 8 h) and clindamycin (600 mg every 8 h) for 14 days based on microbiologic test results. She developed desquamation of the fingers on hospital day 8 and was diagnosed with TSS. Conventional exotoxins, such as TSST-1, and S. aureus enterotoxins were not detected in culture samples. The serum levels of inflammatory cytokines, such as neopterin and IL-6, were high. CD8+ T cells were activated in peripheral blood. Vß2+ population activation, which is characteristic for TSST-1, was not observed in the Vß usage of CD8+ T cells in T cell receptor Vß repertoire distribution analysis. CONCLUSIONS: We present a case of S. simulans-induced TSS. Taken together, we speculate that no specific exotoxins are involved in the induction of TSS in this patient. A likely mechanism is uncontrolled cytokine release (i.e., cytokine storm) induced by non-specific immune reactions against CoNS proliferation.


Asunto(s)
Síndrome de Liberación de Citoquinas/complicaciones , Choque Séptico/complicaciones , Infecciones Estafilocócicas/complicaciones , Staphylococcus aureus/aislamiento & purificación , Staphylococcus/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Anciano , Antibacterianos/administración & dosificación , Cultivo de Sangre , Cefazolina/administración & dosificación , Clindamicina/administración & dosificación , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Citocinas/sangre , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Choque Séptico/tratamiento farmacológico , Esputo/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Resultado del Tratamiento
3.
Med Hypotheses ; 146: 110473, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33385879

RESUMEN

Severe forms of the Coronavirus disease 2019 (COVID-19) are characterized by an enhanced inflammatory syndrome called "cytokine storm" that produces an aberrant release of high amounts of cytokines, chemokines, and other proinflammatory mediators. The pathogenetic role of the "cytokine storm" has been confirmed by the efficacy of immunosuppressive drugs such as corticosteroids along with antiviral drugs in the treatment of the severe forms of this disease. Phenylmethimazole (C10) is a derivative of methimazole with anti-inflammatory properties. Studies performed both in vitro and in vivo have shown that C10 is able to block the production of multiple cytokines, chemokines, and other proinflammatory molecules involved in the pathogenesis of inflammation. Particularly, C10 is effective in reducing the increased secretion of cytokines in animal models of endotoxic shock. We hypothesize that these effects are not limited to the endotoxic shock, but can also be applied to any disease characterized by the presence of a "cytokine storm". Therefore, C10 may be a potential drug to be used alternatively or in association with the corticosteroids or other immunosuppressive agents in the severe forms of COVID-19 as well as other viral diseases that induce a "cytokine storm". Preclinical and clinical studies have to be performed to confirm this hypothesis.


Asunto(s)
/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Metimazol/análogos & derivados , Tionas/farmacología , Animales , Antiinflamatorios/farmacología , Antivirales/farmacología , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/antagonistas & inhibidores , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Metimazol/farmacología , Ratones , Pandemias , Choque Séptico/tratamiento farmacológico , Choque Séptico/inmunología , Investigación en Medicina Traslacional
4.
Immunotherapy ; 13(4): 289-295, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33397150

RESUMEN

In COVID-19, the inflammatory cytokine-release syndrome is associated with the progression of the disease. Itolizumab is a monoclonal antibody that recognizes human CD6 expressed in activated T cells. The antibody has shown to be safe and efficacious in the treatment of moderate to severe psoriasis. Its effect is associated with the reduction of pro-inflammatory cytokines release, including IFN-γ, IL-6 and TNF-α. Here, we report the outcome of three severe and critically ill COVID-19 patients treated with itolizumab as part of an expanded access protocol. Itolizumab was able to reduce IL-6 concentrations in all the patients. Two of the three patients showed respiratory and radiological improvement and were fully recovered. We hypothesize this anti-inflammatory therapy in addition to antiviral and anticoagulant therapy could reduce COVID-19 associated morbidity and mortality.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedad Crítica , Síndrome de Liberación de Citoquinas/patología , Quimioterapia Combinada , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
5.
Arch Pharm Res ; 44(1): 84-98, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33398691

RESUMEN

Unexpected viral infections outbreaks, significantly affect human health, leading to increased mortality and life disruption. Among them is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a deadly pandemic, calling for intense research efforts on its pathogenicity mechanism and development of therapeutic strategies. In the SARS-CoV-2 cytokine storm, systemic inflammation has been associated with severe illness and mortality. Recent studies have demonstrated special pro-resolving lipids mediators (SPMs) lipoxins, resolvins, maresins, and protectins as potential therapeutic options for abnormal viral-triggered inflammation. Pro-resolving lipids mediators have shown great promise for the treatment of Herpes simplex virus, respiratory syncytial virus, human immunodeficiency virus, and hepatitis C virus. Based on this, studies are being conducted on their therapeutic effects in SARS-CoV-2 infection. In this review, we discussed SPMs and reviewed evidence from recent studies on SPMs as therapeutic options for viral infections, including SARS-CoV2. Based on our analysis of the previous study, we argue that SPMs are a potential treatment for SARS-CoV-2 infection and other viral infections. We expect further research on how SPMs modulate viral-triggered inflammation through G-protein-coupled receptors (GPCRs), and chemical stability and druggability of SPMs.


Asunto(s)
/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/metabolismo , Lipoxinas/metabolismo , Animales , Ácidos Grasos Insaturados/administración & dosificación , Ácidos Grasos Insaturados/metabolismo , Humanos , Lipoxinas/administración & dosificación , Receptores Acoplados a Proteínas G/metabolismo
6.
Arch Pharm Res ; 44(1): 99-116, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33398692

RESUMEN

The novel beta coronavirus (SARS-CoV-2, designated as COVID-19) that is responsible for severe acute respiratory syndrome has devastated the global economy and health care system. Since COVID-19 changed the definition of "normal" in ordinary life around the world, the development of effective therapeutics and preventive measures is desperately needed to fight SARS-CoV-2 infection and restore normalcy. A clear understanding of COVID-19 pathogenesis is crucial in providing the scientific rationale necessary to develop anti-COVID19 drugs and vaccines. According to the most recently published literature, COVID-19 pathogenesis was postulated to occur in three sequential phases: pulmonary, proinflammatory, and prothrombic. Herein, virus-host interactions, potential pathogenic mechanisms, and clinical manifestations are described for each phase. Additionally, based on this pathogenesis model, various therapeutic strategies involving current clinical trials are presented with an explanation of their modes of action and example drugs. This review is a thorough, updated summary of COVID-19 pathogenesis and the therapeutic options available for this disease.


Asunto(s)
/metabolismo , /metabolismo , Inmunidad Innata/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Animales , Antivirales/administración & dosificación , Antivirales/metabolismo , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/metabolismo , Humanos , Inmunidad Innata/fisiología , Mediadores de Inflamación/antagonistas & inhibidores
7.
Biomolecules ; 11(1)2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33445810

RESUMEN

The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal consequences. Although several factors of this infection and its consequences are not completely clear, the presence and involvement of specific chemokines is undoubtedly crucial for the development and progression of COVID-19. Cytokine storm and the often-resulting cytokine release syndrome (CRS) are pathophysiological hallmarks in COVID-19 infections related to its most severe and fatal cases. In this hyperinflammatory event, chemokines and other cytokines are highly upregulated and are therefore not fulfilling their beneficial function in the host response anymore but causing harmful effects. Here, we present the recent views on the involvement of chemokines and selected cytokines in COVID-19 and the therapeutics currently in clinical development targeting or interfering with them, discussing their potentials in the treatment of COVID-19 infections.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/inmunología , /tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Humanos
8.
PLoS One ; 16(1): e0243964, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33507958

RESUMEN

OBJECTIVE: Test whether high dose corticosteroid pulse therapy (HDCPT) with either methylprednisolone or dexamethasone is associated with increased survival in COVID-19 patients at risk of hyper-inflammatory response. Provide some initial diagnostic criteria using laboratory markers to stratify these patients. METHODS: This is a prospective observational study, 318 met the inclusion criteria. 64 patients (20.1%) were treated with HDCPT by using at least 1.5mg/kg/24h of methylprednisolone or dexamethasone equivalent. A multivariate Cox regression (controlling for co-morbidities and other therapies) was carried out to determine whether HDCPT (among other interventions) was associated with decreased mortality. We also carried out a 30-day time course analysis of laboratory markers between survivors and non-survivors, to identify potential markers for patient stratification. RESULTS: HDCPT showed a statistically significant decrease in mortality (HR = 0.087 [95% CI 0.021-0.36]; P < 0.001). 30-day time course analysis of laboratory marker tests showed marked differences in pro-inflammatory markers between survivors and non-survivors. As diagnostic criteria to define the patients at risk of developing a COVID-19 hyper-inflammatory response, we propose the following parameters (IL-6 > = 40 pg/ml, and/or two of the following: C-reactive protein > = 100 mg/L, D-dimer > = 1000 ng/ml, ferritin > = 500 ng/ml and lactate dehydrogenase > = 300 U/L). CONCLUSIONS: HDCPT can be an effective intervention to increase COVID-19 survival rates in patients at risk of developing a COVID-19 hyper-inflammatory response, laboratory marker tests can be used to stratify these patients who should be given HDCPT. This study is not a randomized clinical trial (RCT). Future RCTs should be carried out to confirm the efficacy of HDCPT to increase the survival rates of COVID-19.


Asunto(s)
Corticoesteroides/administración & dosificación , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Adulto , Anciano , /mortalidad , Síndrome de Liberación de Citoquinas/inmunología , Dexametasona/farmacología , Femenino , Hospitalización , Humanos , Inflamación/inmunología , Inflamación/prevención & control , Masculino , Metilprednisolona/farmacología , Persona de Mediana Edad , Estudios Prospectivos , España/epidemiología , Tasa de Supervivencia
9.
Theranostics ; 11(1): 316-329, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33391477

RESUMEN

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure. Cytokine storm refers to a set of clinical conditions caused by excessive immune reactions and has been recognized as a leading cause of severe COVID-19. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Recent studies have shown that impaired response of type-1 IFNs in early stage of COVID-19 infection played a major role in the development of cytokine storm, and various cytokines such as IL-6 and IL-1 were involved in severe COVID-19. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory therapy in severe COVID-19. Several approaches are currently being used to treat the observed cytokine storm associated with COVID-19, and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib. Although a number of studies have been conducted on anti-inflammatory treatments for severe COVID-19, no specific recommendations have been made on which drugs should be used for which patients and when. In this review, we provide an overview of cytokine storm in COVID-19 and treatments currently being used to address it. In addition, we discuss the potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19.


Asunto(s)
Antiinflamatorios/uso terapéutico , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/metabolismo , Inmunosupresores/uso terapéutico , Antiinflamatorios/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Azetidinas/farmacología , Azetidinas/uso terapéutico , /inmunología , Ensayos Clínicos como Asunto , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Citocinas/antagonistas & inhibidores , Citocinas/inmunología , Humanos , Inmunosupresores/farmacología , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Quinasas Janus/antagonistas & inhibidores , Quinasas Janus/metabolismo , Purinas/farmacología , Purinas/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Factores de Transcripción STAT/antagonistas & inhibidores , Factores de Transcripción STAT/metabolismo , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Resultado del Tratamiento
10.
PLoS One ; 16(1): e0245924, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33481950

RESUMEN

SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis in animal models and clinical trials. Here we show that aspiration of the GU-rich ssRNA oligonucleotide ORN06 into mouse lungs induces all of the above COVID-19-like symptoms. Men tend to have more severe COVID-19 symptoms than women, and in the aspirated ORN06 model, male mice tended to have more severe symptoms than female mice. Intraperitoneal injections of SAP starting from day 1 post ORN06 aspiration attenuated the ORN06-induced increase in the number of inflammatory cells and formation of clot-like aggregates in the mouse lung fluid, reduced ORN06-increased alveolar wall thickness and accumulation of exudates in the alveolar airspace, and attenuated an ORN06-induced upregulation of the inflammatory cytokines IL-1ß, IL-6, IL-12p70, IL-23, and IL-27 in serum. SAP also reduced D-dimer levels in the lung fluid. In human peripheral blood mononuclear cells, SAP attenuated ORN06-induced extracellular accumulation of IL-6. Together, these results suggest that aspiration of ORN06 is a simple model for both COVID-19 as well as cytokine storm in general, and that SAP is a potential therapeutic for diseases with COVID-19-like symptoms and/or a cytokine storm.


Asunto(s)
/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Componente Amiloide P Sérico/uso terapéutico , Animales , /patología , Síndrome de Liberación de Citoquinas/complicaciones , Síndrome de Liberación de Citoquinas/patología , Modelos Animales de Enfermedad , Femenino , Humanos , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Neumonía/complicaciones , Neumonía/patología , Componente Amiloide P Sérico/administración & dosificación
11.
Biomaterials ; 267: 120389, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33130319

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.


Asunto(s)
/complicaciones , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , ADN/sangre , Desoxirribonucleasa I/uso terapéutico , Portadores de Fármacos/administración & dosificación , Nanopartículas/administración & dosificación , Neutrófilos/efectos de los fármacos , Sepsis/tratamiento farmacológico , Animales , /inmunología , Síndrome de Liberación de Citoquinas/etiología , Desoxirribonucleasa I/administración & dosificación , Dexametasona/uso terapéutico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Trampas Extracelulares/efectos de los fármacos , Humanos , Indoles , Masculino , Ratones , Ratones Endogámicos C57BL , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/prevención & control , FN-kappa B/sangre , Neutrófilos/enzimología , Peroxidasa/sangre , Polietilenglicoles , Poliglactina 910 , Polímeros , Sepsis/etiología , Sepsis/inmunología
12.
Carbohydr Polym ; 254: 117232, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33357843

RESUMEN

The pandemic coronavirus disease 2019 (COVID-19), caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading globally. Clinical observations found that systemic symptoms caused by SARS-CoV-2 infection are attenuated when using the anticoagulant agent heparin, indicating that heparin may play other roles in managing COVID-19, in addition to prevention of pulmonary thrombosis. Several biochemical studies show strong binding of heparin and heparin-like molecules to the Spike protein, which resulted in inhibition of viral infection to cells. The clinical observations and in vitro studies argue for a potential multiple-targeting effects of heparin. However, adverse effects of heparin administration and some of the challenges using heparin therapy for SARS-CoV-2 infection need to be considered. This review discusses the pharmacological mechanisms of heparin regarding its anticoagulant, anti-inflammatory and direct antiviral activities, providing current evidence concerning the effectiveness and safety of heparin therapy for this major public health emergency.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticoagulantes/uso terapéutico , Antivirales/uso terapéutico , Heparina/uso terapéutico , /efectos de los fármacos , Animales , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Humanos , Pandemias
13.
Cytokine ; 138: 155393, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33333393

RESUMEN

COVID-19 is a public health emergency of international concern with millions confirmed cases globally including in Indonesia with more than two hundred thousand confirmed cases to date COVID-19. (1) COVID-19 has wide clinical manifestation ranging from asymptomatic, acute respiratory illness, respiratory failure that necessitates mechanical ventilation and support in an ICU, to MODS. (2) Several comorbidities have been demonstrated to be associated with the development of severe outcomes from COVID-19 infection, such as hypertension, diabetes, cardiovascular disease, dyslipidemia, thyroid disease, and pulmonary disease. (3)-(5) Severe COVID-19 is associated with increased plasma concentrations of IL-6, resulting in cytokine storm. (6) Tocilizumab, an interleukin-6 inhibitor, might alleviates the cytokine storm, prevents significant lungs and organs damage, thus improving clinical outcomes. (7) Therefore, tocilizumab, might be one of the promising therapies for severe COVID-19. (8) However there were limited studies regarding the efficacy in COVID-19 patients, especially with control group. We would like to report our experience in using tocilizumab as treatment in severe COVID-19 patients in Indonesia, which is the first in Indonesia to the best of our knowledge.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Interleucina-6/antagonistas & inhibidores , Femenino , Humanos , Indonesia , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
14.
Nutrition ; 81: 110900, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32738510

RESUMEN

The new coronavirus associated with severe acute respiratory syndrome (SARS-CoV-2), surprisingly, does not affect only the lungs. The severe response to SARS-CoV-2 appears to include a "cytokine storm," which indicates a state of hyperinflammation and subsequent dysfunction of multiple organs and tissues in the most severe cases. This could be the reason why populations at the highest risk for death from the SARS-CoV-2 infection-induced disease (coronavirus disease 2019 [COVID-19]) are those suffering from chronic low-grade inflammation, but prone to hyperinflammation. This includes individuals of advanced age and those with obesity, type 2 diabetes, hypertension, and metabolic syndrome. Inflammation resolution is strongly dependent on lipid mediators, the specialized pro-resolution mediators (SPMs). ω-3 polyunsaturated fatty acids (ω-3 PUFAs) are precursors of very potent SPMs, including resolvins, protectins, and maresins. Additionally, they are associated with a less aggressive inflammatory initiation, after competing with ω-6 fatty acids for eicosanoid synthesis. Therefore, it makes sense to consider the use of ω-3 PUFAs for clinical management of COVID-19 patients. ω-3 PUFAs may be given by oral, enteral, or parenteral routes; however, the parenteral route favors faster incorporation into plasma phospholipids, blood cells, and tissues. Here, we discuss these aspects to propose the parenteral infusion of ω-3 PUFAs as adjuvant immunopharmacotherapy for hospitalized patients with COVID-19.


Asunto(s)
/tratamiento farmacológico , Aceites de Pescado/administración & dosificación , /epidemiología , Quimioterapia Adyuvante , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/inmunología , Ácidos Grasos Omega-3/administración & dosificación , Humanos , Inflamación/dietoterapia , Inflamación/inmunología , Infusiones Parenterales , Modelos Biológicos , Fenómenos Fisiológicos de la Nutrición , Pandemias
15.
Front Endocrinol (Lausanne) ; 11: 569241, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33362713

RESUMEN

The clinical hallmarks of infections caused by critical respiratory viruses consist of pneumonia, which can progress to acute lung injury (ALI), and systemic manifestations including hypercoagulopathy, vascular dysfunction, and endotheliitis. The disease outcome largely depends on the immune response produced by the host. The bio-molecular mechanisms underlying certain dire consequences of the infection partly arise from an aberrant production of inflammatory molecules, an event denoted as "cytokine storm". Therefore, in addition to antiviral therapies, molecules able to prevent the injury caused by cytokine excess are under investigation. In this perspective, taking advantage of melanocortin peptides and their receptors, components of an endogenous modulatory system that exerts marked anti-inflammatory and immunomodulatory influences, could be an effective therapeutic strategy to control disease evolution. Exploiting the melanocortin system using natural or synthetic ligands can form a realistic basis to counteract certain deleterious effects of respiratory virus infections. The central and peripheral protective actions exerted following melanocortin receptor activation could allow dampening the harmful events that trigger the cytokine storm and endothelial dysfunction while sustaining the beneficial signals required to elicit repair mechanisms. The long standing evidence for melanocortin safety encourages this approach.


Asunto(s)
/tratamiento farmacológico , Receptores de Melanocortina/agonistas , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Antiinflamatorios/uso terapéutico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/etiología , Citocinas/metabolismo , Humanos , Hormonas Estimuladoras de los Melanocitos/metabolismo , Infecciones del Sistema Respiratorio/etiología , Infecciones del Sistema Respiratorio/metabolismo
16.
Eur Cytokine Netw ; 31(3): 81-93, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-33361013

RESUMEN

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.


Asunto(s)
Anticuerpos/uso terapéutico , Síndrome de Liberación de Citoquinas , Interleucina-6/antagonistas & inhibidores , Pandemias , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , /sangre , /tratamiento farmacológico , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/mortalidad , Humanos , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/sangre
17.
Front Immunol ; 11: 598444, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33362782

RESUMEN

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.


Asunto(s)
/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , FN-kappa B/antagonistas & inhibidores , Inhibidores de Proteasoma/farmacología , /efectos de los fármacos , Animales , /patología , Síndrome de Liberación de Citoquinas/patología , Citocinas/sangre , Modelos Animales de Enfermedad , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H5N1 del Virus de la Influenza A/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/tratamiento farmacológico , /inmunología
18.
Molecules ; 25(24)2020 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-33322757

RESUMEN

SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19.


Asunto(s)
/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Pandemias , Fitoquímicos/uso terapéutico , Polifenoles/uso terapéutico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Antivirales/uso terapéutico , China/epidemiología , Síndrome de Liberación de Citoquinas/epidemiología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/epidemiología , Polifenoles/química
19.
Eur Rev Med Pharmacol Sci ; 24(23): 12527-12535, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33336773

RESUMEN

Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Miocarditis/inmunología , /metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antioxidantes/uso terapéutico , Apoptosis , Factor Natriurético Atrial/uso terapéutico , Azetidinas/uso terapéutico , Compuestos de Bencilo/uso terapéutico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Glucocorticoides/uso terapéutico , Glicoproteínas/uso terapéutico , Humanos , Hipoxia/metabolismo , Hipoxia/terapia , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Isquemia Miocárdica/metabolismo , Miocarditis/metabolismo , Miocarditis/terapia , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Terapia por Inhalación de Oxígeno , Respiración Artificial , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Inhibidores de Tripsina/uso terapéutico , Inhibidores del factor de Necrosis Tumorales/uso terapéutico , alfa-Metiltirosina/uso terapéutico
20.
BMJ Open ; 10(11): e039951, 2020 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-33191263

RESUMEN

INTRODUCTION: About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive). METHODS AND ANALYSIS: Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm). ETHICS AND DISSEMINATION: The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions. TRIAL REGISTRATION NUMBER: NCT04357860.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , /tratamiento farmacológico , Adolescente , Adulto , Anciano , Betacoronavirus , Ensayos Clínicos Fase II como Asunto , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Pandemias , Neumonía Viral/inmunología , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial , Adulto Joven
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