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1.
Emerg Microbes Infect ; 10(1): 266-276, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33522893

RESUMEN

SARS-CoV-2 has claimed 2,137,908 lives in more than a year. Some COVID-19 patients experience sudden and rapid deterioration with the onset of fatal cytokine storm syndrome (CSS), which have increased interest in CSS's mechanisms, diagnosis and therapy. Although the prototypic concept of CSS was first proposed 116 years ago, we have only begun to study and understand CSS for less than 30 years. Actually, diseases under CSS umbrella include familial/primary and secondary hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome (MAS), infection-associated hemophagocytic syndrome, cytokine release syndrome (CRS), and cytokine storm (CS). Hematologic malignancies and autoimmune diseases that cause CSS are named malignancy-associated hemophagocytic syndrome (MAHS) and MAS, respectively. In-depth research on the pathogenesis of HLH/CSS has greatly increased the number of patients that were able to be definitively diagnosed with HLH/CSS. However, it should be emphasized that HLH/CSS diagnosis is difficult at the early stages due to the non-specific clinical signs and symptoms, which tends to result in missed and incorrect diagnoses. Therefore, clinicians should not only possess extensive clinical experience to ensure high sensitivity to the characteristics of HLH/CSS but must also be familiar with HLH-2004/2009 diagnostic criteria, and HScore methods. The paper concisely comment evolution of CSS classifications, cytokines associated with CSS, evolution of CSS diagnostic criteria and importance of the correct identification of hemophagocytes in diagnosing CSS, which is timely and may benefit clinicians familiar HLH-2004/2009 diagnostic criteria, and HScore methods. In addition, clinicians must also understand that there are some limitations to these diagnostic criteria. Abbreviations: aBMT: autologous bone marrow transplantation; CAR-T: chimeric antigen receptor-engineered T-cell; COVID-19: coronavirus disease 2019; CSS: cytokine storm syndrome; HLH: hemophagocytic lymphohistiocytosis; MAS: macrophage activation syndrome; CRS: cytokine release syndrome; CS: cytokine storm; MAHS: malignancy-associated hemophagocytic syndrome; IAHS: infection-associated hemophagocytic syndrome; fHLH/pHLH: familial/primary hemophagocytic lymphohistiocytosis; sHLH: secondary hemophagocytic lymphohistiocytosis; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TCR-T, T-cell receptor-engineered T-cell.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/inmunología , Animales , /genética , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/virología , Citocinas/genética , Citocinas/inmunología , Humanos , /fisiología
2.
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
3.
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
4.
Eur Rev Med Pharmacol Sci ; 25(1): 556-566, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33506949

RESUMEN

A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a current outbreak of infection termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 is currently a global pandemic that may cause close to half a billion deaths around the world. Until now, there is no effective treatment for COVID-19. Quinacrine (Qx) has been used since the 1930s as preventive antimalarial compound. It is a recognized small molecule inhibitor of RNA virus replication, with known anti-prion activity, and identified as a potent Ebola virus inhibitor both in vitro and in vivo. Recently, Qx has showed anti-SARS-CoV-2 activity. Herein, we review the potential mechanisms associated with quinacrine as an antiviral compound.


Asunto(s)
Antivirales/farmacología , Quinacrina/farmacología , Animales , Antivirales/administración & dosificación , Antivirales/efectos adversos , Línea Celular , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/prevención & control , Citocinas/inmunología , Humanos , Ratones , Quinacrina/administración & dosificación , Quinacrina/efectos adversos , Replicación Viral/efectos de los fármacos
5.
Nature ; 590(7844): 29-31, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33469204
6.
Med Hypotheses ; 146: 110415, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33422363

RESUMEN

COVID-19 is characterized by two major clinical phases, the SARS-CoV-2 infection of target cells and tissues, and a deep inflammatory state, known as "cytokine storm", caused by activation of pro-inflammatory genes, such as NF-kB, STAT-3, IL-6, IL-8, IL-1ß. Among possible anti-inflammatory agents, the "microRNA targeting" should be carefully considered, since it is well known that microRNAs are deeply involved in the expression of cytokines, chemokines and growth factors. The working general hypothesis is that targeting the microRNA network might be important for the development of therapeutic approaches to counteract the COVID-19 induction of inflammatory response. This hypothesis is based on several publications demonstrating the use of miRNA mimics for inhibitory effects on the production of proteins characterizing the COVID-19 "cytokine storm".


Asunto(s)
/terapia , Síndrome de Liberación de Citoquinas/terapia , MicroARNs/genética , Modelos Biológicos , Regiones no Traducidas 3'/genética , Antiinflamatorios/farmacología , /inmunología , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/inmunología , Humanos , Inflamación/genética , Inflamación/inmunología , Inflamación/terapia , MicroARNs/uso terapéutico , Imitación Molecular , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/genética
7.
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
8.
Biosens Bioelectron ; 176: 112942, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33401144

RESUMEN

2019 novel coronavirus (2019-nCoV) with strong contagion in the crowd, has ravaged worldwide and severely impacts the human health and epidemic prevention system, by producing a series of significant stress reactions in the body to induce further cytokine storm. Transcription factors (TFs) served as essential DNA binding proteins play an integral role in regulating cytokine storm, and the detection of it in the human coronavirus environment provides especially valuable approaches to diagnosis and treatment of 2019-nCoV and development of antiviral drugs. In this work, an entropy-driven electrochemiluminescence (ECL) biosensor was constructed for ultra-sensitive bioassay of NF-κB p50. The strategy primarily capitalizing the splendid double-stranded DNA (dsDNA) binding properties of transcription factors, employing GOAu-Ru composite material as ECL emitter, utilizing entropy-driven reactions for signal amplification method, offered a repeatable proposal for TFs detection. In the absence of TFs, the released DNA1 further went in the entropy-driven reaction, contributing to an "ECL off" state. However, in the presence of TFs, the dsDNA avoided being digested, which blocked DNA1 for participating in the entropy-driven reaction, and the system exhibited an "ECL on" state. Most importantly, the ECL bioanalytical method denoted broad application prospects for NF-κB p50 detection with a lower detection limit (9.1 pM).


Asunto(s)
Técnicas Biosensibles/métodos , Síndrome de Liberación de Citoquinas/inmunología , Subunidad p50 de NF-kappa B/análisis , Técnicas Biosensibles/estadística & datos numéricos , Síndrome de Liberación de Citoquinas/etiología , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/estadística & datos numéricos , Entropía , Humanos , Límite de Detección , Mediciones Luminiscentes/métodos , Mediciones Luminiscentes/estadística & datos numéricos , Pandemias , Sensibilidad y Especificidad
9.
Immunol Lett ; 231: 28-34, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33421440

RESUMEN

Clinical symptoms of COVID-19 include fever, cough, and fatigue which may progress to acute respiratory distress syndrome (ARDS). The main hematological laboratory findings associated with the severe form of disease are represented by lymphopenia and eosinopenia which mostly occur in the elderly population characterized by cardiovascular comorbidities and immunosenescence. Besides, increased levels of D-dimer, procalcitonin, and C reactive protein (CRP) seem to be powerful prognostic biomarkers helping to predict the onset of coagulopathy. The host immune response to SARS-CoV-2 can lead to an aberrant inflammatory response or "cytokine storm" which contributes to the severity of illness. At immunological level, patients affected by a severe form of COVID-19 show poor clinical trajectories characterized by differential "immunotypes" for which T cell response seems to play a critical role in understanding pathogenic mechanisms of disease. Also, patients with mild to severe COVID-19 displayed macrophage activation syndrome (MAS), very low human leukocyte antigen D related (HLA-DR) expression with a parallel reduction of CD04+ lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Corticosteroids resulted the best therapy for the immune dysregulation whereas repurposing of tocilizumab (IL-6 receptor antagonist) appears to have mixed results in patients with COVID-19. Besides, anticoagulative therapy was associated with reduced in-hospital mortality and need of intubation among COVID-19 patients. Furthermore, the beneficial use of intravenous immunoglobulin (IVIG) and passive immunotherapy with convalescent plasma needs to be validated in large controlled clinical trials. In this review, we summarize the main hematological parameters with a prognostic value in COVID-19 and the basis of immunological reactivity during COVID-19, with a focus on ongoing clinical trials evaluating immune targets as possible therapeutic strategies.


Asunto(s)
/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/prevención & control , Inmunoterapia/métodos , /inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticoagulantes/uso terapéutico , /diagnóstico , Síndrome de Liberación de Citoquinas/inmunología , Reposicionamiento de Medicamentos , Quimioterapia Combinada/métodos , Glucocorticoides/uso terapéutico , Mortalidad Hospitalaria , Humanos , Inmunización Pasiva/métodos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
10.
Sci Rep ; 11(1): 1930, 2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33479353

RESUMEN

SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes. In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we identified the genes associated with the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We then analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) and created a DS-SARS-CoV-2 network. We detected COVID-19 protective and risk factors among HSA21 genes and interactors and/or DS deregulated genes that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome. Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells. However, as the anti-viral interferon I signaling is also upregulated in DS, this might increase the initial anti-viral response, inhibiting viral genome release, viral replication and viral assembly. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.


Asunto(s)
/genética , Síndrome de Down/genética , /epidemiología , /metabolismo , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Down/epidemiología , Síndrome de Down/inmunología , Síndrome de Down/virología , Redes Reguladoras de Genes , Interacciones Microbiota-Huesped , Humanos , Inflamación/inmunología , Pandemias , Factores Protectores , Factores de Riesgo , /aislamiento & purificación , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Transcriptoma/genética
11.
Life Sci ; 269: 119010, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33454368

RESUMEN

The COVID-19 is a novel infectious disease caused by SARS-CoV-2 and is known as a pandemic emergency that has led to a high rate of mortality throughout the world. Evidence has indicated that hyperinflammatory responses triggered by SARS-CoV-2 are the main cause of pathogenicity in the severe cases of patients who have died during the current viral disease. Monocytes and macrophages as the most important cells of the innate arm of the immune system play a substantial part in the body's defense against viral infections. They mainly respond to the microbial antigens by producing inflammatory mediators to remove pathogens and repair tissue injury. Nevertheless, aberrant alterations in their function such as cytokine storm can be so harmful to the host in the acute respiratory distress syndrome cases caused by SARS-CoV-2. Moreover, inflammatory responses stimulated by SARS-CoV-2 have affected the other vital organs of the body including the heart. As cardiovascular complications in COVID-19 patients have been reported in several studies. During the infection, monocytes and macrophages may be involved in the hypersensitive and exacerbated reactions that contribute to the tissue damage, especially lung injury resulted in its dysfunction and respiratory disorder. In this review, we discuss both advantageous and disadvantageous about the pathological potential of monocytes and macrophages during the infection of SARS-CoV-2 to clarify their mutual effects on immune processing as a fist line defender in the current disease.


Asunto(s)
/complicaciones , Macrófagos/inmunología , Monocitos/inmunología , Animales , /virología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Humanos , /virología , /aislamiento & purificación
12.
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
13.
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
14.
Life Sci ; 267: 118923, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33358906

RESUMEN

Such testing and trying time probably never seen before in the human history. The novel coronavirus disease abbreviated as COVID-19 is the ongoing health crisis which entered into human life in late December 2019. The ease of transmission between humans and the undetectability in early stage makes COVID-19 frightening and unprecedented. The disease is characterised by pneumonia progressing to breathing difficulty, acute respiratory distress syndrome (ARDS) and multi-organ failure. Clinical studies suggest excessive release of inflammatory mediators leads to cytokine storm, a phenomenon which appears to be potentially life-threatening in COVID-19. Across the globe, when the world authorities are grappling to contain the virus, our review provides a glimpse on structure, pathophysiology of the virus and further sheds light on various clinical complications associated with the disease in order to open up/raise new horizons to explore various possible theoretical targets for COVID-19. The review also portrays a question and debates: Can targeting cytokine storm can be a feasible approach to combat COVID-19?


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/inmunología , /inmunología , Antivirales/uso terapéutico , Síndrome de Liberación de Citoquinas/fisiopatología , Humanos , Mediadores de Inflamación/metabolismo , Interleucinas/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo
15.
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
16.
Clin Immunol ; 223: 108652, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33333256

RESUMEN

The outbreak of COVID-19 reminds us that the emerging and reemerging respiratory virus infections pose a continuing threat to human life. Cytokine storm syndromes of viral origin seem to have a common pathogenesis of the imbalanced immune response with the exaggerated inflammatory reaction combined with the reduction and functional exhaustion of T cells. Immunomodulatory therapy is gaining interest in COVID-19, but this strategy has received less attention in other respiratory viral infections than it deserved. In this review we suggest that based on the similarities of the immune dysfunction in the severe cases of different respiratory viral infections, some lessons from the immunomodulatory therapy of COVID-19 (particularly regarding the choice of an immunomodulatory drug, the selection of patients and optimal time window for this kind of therapy) could be applied for some cases of severe influenza infection and probably for some future outbreaks of novel severe respiratory viral infections.


Asunto(s)
/inmunología , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Inmunoterapia/métodos , Gripe Humana/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Orthomyxoviridae/fisiología , Virus del SRAS/fisiología , Síndrome Respiratorio Agudo Grave/inmunología , Citocinas/metabolismo , Humanos , Inmunomodulación , Inflamación
17.
Respir Physiol Neurobiol ; 283: 103548, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32956843

RESUMEN

BACKGROUND: Globally, the current medical emergency for novel coronavirus 2019 (COVID-19) leads to respiratory distress syndrome and death. PURPOSE: This review highlighted the effect of COVID-19 on systemic multiple organ failure syndromes. This review is intended to fill a gap in information about human physiological response to COVID-19 infections. This review may shed some light on other potential mechanisms and approaches in COVID -19 infections towards systemic multiorgan failure syndromes. FINDING: SARS-CoV-2 intervened mainly in the lung with progression to pneumonia and acute respiratory distress syndrome (ARDS) via the angiotensin-converting enzyme 2(ACE2) receptor. Depending on the viral load, infection spread through the ACE2 receptor further to various organs such as heart, liver, kidney, brain, endothelium, GIT, immune cell, and RBC (thromboembolism). This may be aggravated by cytokine storm with the extensive release of proinflammatory cytokines from the deregulating immune system. CONCLUSION: The widespread and vicious combinations of cytokines with organ crosstalk contribute to systemic hyper inflammation and ultimately lead to multiple organ dysfunction (Fig. 1). This comprehensive study comprises various manifestations of different organs in COVID-19 and may assist the clinicians and scientists pertaining to a broad approach to fight COVID 19.


Asunto(s)
Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Insuficiencia Multiorgánica/inmunología , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/inmunología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/fisiopatología , Arritmias Cardíacas/inmunología , Arritmias Cardíacas/fisiopatología , Betacoronavirus/metabolismo , Infecciones por Coronavirus/fisiopatología , Síndrome de Liberación de Citoquinas/fisiopatología , Citocinas/inmunología , Endotelio Vascular/metabolismo , Eritrocitos/metabolismo , Enfermedades Gastrointestinales/inmunología , Enfermedades Gastrointestinales/fisiopatología , Tracto Gastrointestinal/metabolismo , Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/fisiopatología , Humanos , Inflamación/inmunología , Riñón/metabolismo , Hígado/metabolismo , Hepatopatías/inmunología , Hepatopatías/fisiopatología , Pulmón/metabolismo , Insuficiencia Multiorgánica/fisiopatología , Miocardio/metabolismo , Pandemias , Neumonía Viral/fisiopatología , Tromboembolia/inmunología , Tromboembolia/fisiopatología , Carga Viral
18.
Eur Rev Med Pharmacol Sci ; 24(23): 12500-12509, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33336769

RESUMEN

OBJECTIVE: Since the emergence of coronavirus disease (COVID-19), the death toll has been increasing daily. Many risk factors are associated with a high mortality rate in COVID-19. Establishment of a common pathway among these risk factors could improve our understanding of COVID-19 severity and mortality. This review aims at establishing this common pathway and its possible effect on COVID-19 mortality. MATERIALS AND METHODS: The current review was executed in five consecutive stages starting from determining the risk factors of COVID-19 mortality and trying to find a common pathway among them depending on the available literature. This was followed by proposing a mechanism explaining how this common pathway could increase the mortality. Finally, its potential role in managing COVID-19 was proposed. RESULTS: This review identified this common pathway to be a low baseline of reduced glutathione (i.e., GSH) level. In particular, this review provided an in-depth discussion regarding the pathophysiology by which COVID-19 leads to GSH depletion, tissue damage, and acute respiratory distress syndrome. In addition, the current review demonstrated how GSH depletion could result in failure of the immune system and rendering the end organs vulnerable to damage from the oxidative stress. CONCLUSIONS: This preclinical study shows that GSH depletion may have a central role in COVID-19 mortality and pathophysiology. Therefore, elevating the GSH level in tissues may decrease the severity and mortality rates of COVID-19.


Asunto(s)
/mortalidad , Síndrome de Liberación de Citoquinas/inmunología , Glutatión/metabolismo , Lesión Pulmonar Aguda/metabolismo , Factores de Edad , Antioxidantes/metabolismo , Apoptosis , /metabolismo , Síndrome de Liberación de Citoquinas/metabolismo , Diabetes Mellitus/epidemiología , Diabetes Mellitus/metabolismo , Glutatión/inmunología , Humanos , Hipertensión/epidemiología , Hipertensión/metabolismo , Macrófagos/inmunología , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/metabolismo , Obesidad/epidemiología , Obesidad/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factores de Riesgo , Fumar/epidemiología , Fumar/metabolismo
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.
Mediators Inflamm ; 2020: 8829674, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33343232

RESUMEN

Coronavirus disease 2019 (COVID-19) is a virus-induced respiratory disease that may progress to acute respiratory distress syndrome (ARDS) and is triggered by immunopathological mechanisms that cause excessive inflammation and leukocyte dysfunction. Neutrophils play a critical function in the clearance of bacteria with specific mechanisms to combat viruses. The aim of this review is to highlight the current advances in the pathways of neutrophilic inflammation against viral infection over the past ten years, focusing on the production of neutrophil extracellular traps (NETs) and its impact on severe lung diseases, such as COVID-19. We focused on studies regarding hyperinflammation, cytokine storms, neutrophil function, and viral infections. We discuss how the neutrophil's role could influence COVID-19 symptoms in the interaction between hyperinflammation (overproduction of NETs and cytokines) and the clearance function of neutrophils to eliminate the viral infection. We also propose a more in-depth investigation into the neutrophil response mechanism targeting NETosis in the different phases of COVID-19.


Asunto(s)
/inmunología , Inflamación/inmunología , Neutrófilos/inmunología , /complicaciones , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Trampas Extracelulares/inmunología , Trampas Extracelulares/virología , Interacciones Microbiota-Huesped/inmunología , Humanos , Inmunidad Innata , Inflamación/etiología , Inflamación/virología , Mediadores de Inflamación/inmunología , Pulmón/inmunología , Pulmón/virología , Modelos Inmunológicos , Neutrófilos/virología , Pandemias , /inmunología , /inmunología , /patogenicidad
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