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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.
Rev Med Suisse ; 17(720-1): 80-84, 2021 Jan 13.
Artículo en Francés | MEDLINE | ID: mdl-33443836

RESUMEN

The main pharmacovigilance updates in 2020 are reviewed. Remdesivir in COVID-19: relatively safe but turns out to be less effective than expected. Hydroxychloroquine in COVID-19 : lack of efficacy and risk of arrhythmias. Cytokines storm in COVID-19: may impact pharmacokinetics. VEGF inhibitors: risk of aneurysm and artery dissection. Tofacitinib: dose-dependant risk of venous thromboembolic events. Ondansetron in the first trimester of pregnancy : a highly debated risk of orofacial cleft defects. Fingolimod : contraindicated during pregnancy due to suspected risk of congenital malformations. Ranitidine: global market withdrawal due to contamination with nitrosamines. Ulipristal for uterine fibroids : market withdrawal due to risk of severe liver injury. Ingenol mebutate : market withdrawal due to paradoxical risk of skin cancers.


Asunto(s)
Farmacovigilancia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Labio Leporino/prevención & control , Contraindicaciones de los Medicamentos , Síndrome de Liberación de Citoquinas/virología , Femenino , Clorhidrato de Fingolimod/efectos adversos , Humanos , Hidroxicloroquina/efectos adversos , Leiomioma/tratamiento farmacológico , Norpregnadienos/uso terapéutico , Farmacocinética , Embarazo , Ranitidina/efectos adversos , Retirada de Medicamento por Seguridad , Neoplasias Cutáneas/inducido químicamente
4.
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
5.
Med Hypotheses ; 147: 110486, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33460992

RESUMEN

On March 11, 2020 the World Health Organization (WHO) declared the state of global pandemic caused by the new SARS-CoV-2 (COVID-19). To date, no antivirals directed against SARS-CoV-2 or effective vaccines to combat the viral infection are available. Severe acute respiratory syndrome caused by SARS-CoV-2 is treated empirically with antivirals, anti-inflammatory, anticoagulants. The approval of an effective vaccine still takes time. In this state, it may be useful to find new therapeutic solutions from drugs already on the market. Recent hypotheses suggest that the use of AT-1 receptor antagonists (ARB) in combination with neprilisin inhibitors (NEPi) could indirectly provide clinical benefits to patients with SARS-CoV-2 and cardiac involvement. In this article we investigate and describe a possible innovative pharmacological approach for the treatment of the most severe stages of COVID-19 infection.


Asunto(s)
Aminobutiratos/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Tetrazoles/administración & dosificación , Valsartán/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina , Antivirales/uso terapéutico , Síndrome de Liberación de Citoquinas/virología , Citocinas/metabolismo , Combinación de Medicamentos , Insuficiencia Cardíaca/virología , Homeostasis , Humanos , Inflamación , Modelos Teóricos , Péptido Natriurético Encefálico/metabolismo , Neprilisina/efectos adversos , Fragmentos de Péptidos/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Organización Mundial de la Salud
6.
Med Hypotheses ; 147: 110504, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33485026

RESUMEN

Declared as a pandemic by the World Health Organization, COVID-19 causes damage to tissues with the cytokine storm. It even causes death in people who are fond of it. In this case, the role of the immune system is vital. In particular, the cycle of melatonin and 5-methoxytryptophol released from the pineal hormone ensures that immunity continues for 24 h. While 5-MTX is active in sunlight, melatonin secretion increases in the dark at night. 5-MTX, like melatonin, has shown antioxidant and immunomodulatory properties in studies. Therefore, people who are sick and those who are not must strictly comply with the 24-h circadian rhythm during this period. We think that it is crucial in terms of being protected from the disease that we should carry out our activities according to the circadian rhythm.


Asunto(s)
/sangre , Ritmo Circadiano , Indoles/sangre , Luz Solar , Antioxidantes/metabolismo , Síndrome de Liberación de Citoquinas/virología , Humanos , Sistema Inmunológico , Indoles/química , Luz , Melatonina/sangre , Glándula Pineal/metabolismo
7.
Int J Antimicrob Agents ; 57(2): 106273, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33370568

RESUMEN

COVID-19 (coronavirus disease 2019), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), emerged in Wuhan, China, and has spread worldwide, resulting in over 73 million cases and more than 1 600 000 deaths as of December 2020. Although the disease is asymptomatic in most cases, some patients develop life-threatening disease characterised by acute respiratory distress syndrome, sepsis, multisystem organ failure (MSOF), extrapulmonary manifestations, thromboembolic disease and associated cytokine release syndrome. The rationale for applying therapeutic plasma exchange (TPE) early in the course of fulminant COVID-19 is the suppression of thromboinflammation and amelioration of microangiopathy, thus preventing the ensuing MSOF. In the course of complicated critical illness due to COVID-19, immune dysregulation may be as important as viral replication itself. Moreover, the natural course of SARS-CoV-2 infection remains obscure, as re-infections and/or recurrently positive real-time PCR results have been reported. Although concerns still exist regarding its potential immunosuppressive effects and safety, TPE shows promise in the management of life-threatening COVID-19 as documented by various pilot studies, which remain to be confirmed by future randomised controlled trials. However, current data suggest that TPE could be an adjunctive rescue therapy in complex COVID-19 critical illness.


Asunto(s)
/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/terapia , Intercambio Plasmático/métodos , /etiología , /terapia , Enfermedad Crítica , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/virología , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Respiración Artificial
8.
Probl Endokrinol (Mosk) ; 66(4): 9-15, 2020 09 01.
Artículo en Ruso | MEDLINE | ID: mdl-33351354

RESUMEN

Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II - to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm¼ in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Síndrome de Liberación de Citoquinas/genética , Antígenos HLA/inmunología , Alelos , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/virología , /inmunología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Humanos , /patogenicidad
9.
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
10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(10): 941-947, 2020 Oct.
Artículo en Chino | MEDLINE | ID: mdl-33148390

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection would stimulate human immune system, trigger the activation and aggregation of various immune cells, and lead to the secretion of a large number of chemokines and cytokines, including interleukin 6 (IL-6), IL-10, granulocyte colony-stimulating factor (G-CSF), interferon γ (IFN-γ), tumor necrosis factor γ (TNF-γ), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 10 (CXCL10) and other cytokines. The development of uncontrolled systemic inflammatory response is a key factor in patients with critical COVID-19. Mild patients have milder inflammation and mild symptoms, but the lung inflammation in critical ones is more severe: the inflammatory factor expression levels are abnormally high; the infiltration of lung inflammatory cells is obvious along with the histopathological changes of viral pneumonia and inflammatory pneumonia. Continuous immunity response causes the accumulation of lung fibrin, permeability change, injury of the pulmonary blood vessels, and ultimately destroys the lung structure and affects ventilation and circulatory function of the lung. Therefore, continuous and severe inflammation is closely related to acute respiratory distress syndrome, multiple organ dysfunction syndrome, and disseminated intravascular coagulation in critical COVID-19 patients, which is the key point for the transition from mild to critical patients.


Asunto(s)
Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/virología , Neumonía Viral/inmunología , Betacoronavirus , Infecciones por Coronavirus/patología , Citocinas , Humanos , Pandemias , Neumonía Viral/patología
11.
Molecules ; 25(22)2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-33207753

RESUMEN

Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) may be beneficial. Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19.


Asunto(s)
Ácido Ascórbico/uso terapéutico , Infecciones por Coronavirus/prevención & control , Síndrome de Liberación de Citoquinas/prevención & control , Suplementos Dietéticos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Selenio/uso terapéutico , Vitamina D/uso terapéutico , Anticuerpos Antivirales/biosíntesis , Betacoronavirus/efectos de los fármacos , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/dietoterapia , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/dietoterapia , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Citocinas/antagonistas & inhibidores , Citocinas/biosíntesis , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/inmunología , Humanos , Sistema Inmunológico/efectos de los fármacos , Factores Inmunológicos/uso terapéutico , Micronutrientes/uso terapéutico , Neumonía Viral/dietoterapia , Neumonía Viral/inmunología , Neumonía Viral/virología , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/virología
12.
Int J Clin Pharmacol Ther ; 58(12): 678-686, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33141018

RESUMEN

Although medication treatment in COVID-19 patients would have no direct effect on the spread of the disease, a shortening of the period of hospitalization by only a few days would release 25 - 30% of critical-care resources. However, there appears to be no well-established medication treatment available that can do this reliably at the present time. Anti-malarials currently being evaluated, i.e., chloroquine and hydroxychloroquine, are not yet established as effective medications, and antiviral agents, including remdesivir, are only weakly active. This position paper report is focused on the modulation of the cytokine storm since it appears to be a major cause of the multi-organ failure in COVID-19. Whereas corticosteroids are not recommended in patients not on mechanical ventilation, immunotherapy with convalescent plasma and intravenous immunoglobulin (IVIG) have been used with some success in COVID-19. There is emerging new evidence that polyvalent immunoglobulins (PVIG) from bovine colostrum given orally can also modulate the immune response. Research using lipopolysaccharide-stimulated peripheral blood mononuclear cells from colorectal cancer patients (a so called micro-cytokine storm) has shown that PVIG block the expression of pro-inflammatory cytokines and stimulate the expression of anti-inflammatory cytokines. We have been able to confirm these results in a similar model using mononuclear cells from healthy subjects and could demonstrate that the modulations produced by PVIG are quantitatively and qualitatively similar to those obtained using human immunoglobulin (IVIG). Both immunoglobulins reduce the lipopolysaccharide-induced increase in inflammatory cytokines, interleukin (IL-) 12/23p40 (-90%), IL-6 (-75%) and TNF-α (-60%) and increased the levels of the anti-inflammatory cytokine, IL-10 (+75%). Evidence is presented that PVIG can produce anti-inflammatory effects similar to these after oral application in patients. Its use is contraindicated in patients with lactose intolerance but is otherwise safe and free of complications in clinical studies including the treatment of infants with gastrointestinal disorders. Conclusion: PVIG appears to be a potential and safe anti-inflammatory agent and can be recommended as a candidate medication for studies in COVID-19 patients.


Asunto(s)
Infecciones por Coronavirus/terapia , Síndrome de Liberación de Citoquinas/terapia , Neumonía Viral/terapia , Animales , Betacoronavirus , Bovinos , Células Cultivadas , Síndrome de Liberación de Citoquinas/virología , Citocinas , Humanos , Inmunización Pasiva , Inmunoglobulinas Intravenosas/uso terapéutico , Leucocitos Mononucleares , Pandemias
13.
F1000Res ; 9: 1078, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33082935

RESUMEN

The pandemic brought on by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has become a global health crisis, with over 22 million confirmed cases and 777,000 fatalities due to coronavirus disease 2019 (COVID-19) reported worldwide. The major cause of fatality in infected patients, now referred to as the "Cytokine Storm Syndrome" (CSS), is a direct result of aberrant immune activation following SARS-CoV2 infection and results in excess release of inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor α (TNF-α), and IL-6, by macrophages, monocytes, and dendritic cells. Single cell analysis has also shown significantly elevated levels of galectin 3 (Gal-3) in macrophages, monocytes, and dendritic cells in patients with severe COVID-19 as compared to mild disease. Inhibition of Gal-3 reduces the release of IL-1, IL-6, and TNF-α from macrophages in vitro, and as such may hold promise in reducing the incidence of CSS. In addition, Gal-3 inhibition shows promise in reducing transforming growth factor ß (TGF-ß) mediated pulmonary fibrosis, likely to be a major consequence in survivors of severe COVID-19. Finally, a key domain in the spike protein of SARS-CoV2 has been shown to bind N-acetylneuraminic acid (Neu5Ac), a process that may be essential to cell entry by the virus. This Neu5Ac-binding domain shares striking morphological, sequence, and functional similarities with human Gal-3. Here we provide an updated review of the literature linking Gal-3 to COVID-19 pathogenesis. Dually targeting galectins and the Neu5Ac-binding domain of SARS-CoV2 shows tentative promise in several stages of the disease: preventing viral entry, modulating the host immune response, and reducing the post-infectious incidence of pulmonary fibrosis.


Asunto(s)
Infecciones por Coronavirus/patología , Síndrome de Liberación de Citoquinas/virología , Galectina 3/inmunología , Neumonía Viral/patología , Betacoronavirus , Humanos , Ácido N-Acetilneuramínico , Pandemias
14.
Mol Med ; 26(1): 97, 2020 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-33121429

RESUMEN

BACKGROUND: COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients' outcome. METHODS: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. RESULTS: The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. CONCLUSIONS: IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.


Asunto(s)
Quimiocina CCL2/sangre , Quimiocina CXCL10/sangre , Infecciones por Coronavirus/complicaciones , Síndrome de Liberación de Citoquinas/complicaciones , Coagulación Intravascular Diseminada/complicaciones , Neumonía Viral/complicaciones , Embolia Pulmonar/complicaciones , Insuficiencia Respiratoria/complicaciones , Proteínas Adaptadoras Transductoras de Señales/sangre , Anciano , Betacoronavirus/patogenicidad , Biomarcadores/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Enfermedad Crítica , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/mortalidad , Síndrome de Liberación de Citoquinas/virología , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/mortalidad , Coagulación Intravascular Diseminada/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Neumonía Viral/virología , Pronóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidad , Embolia Pulmonar/virología , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/virología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
15.
Signal Transduct Target Ther ; 5(1): 235, 2020 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-33037188

RESUMEN

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


Asunto(s)
Apoptosis/inmunología , Betacoronavirus/patogenicidad , Caspasa 8/inmunología , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Necroptosis/inmunología , Neumonía Viral/inmunología , Fibrosis Pulmonar/inmunología , Animales , Caspasa 8/genética , Línea Celular Tumoral , Quimiocina CCL5/genética , Quimiocina CCL5/inmunología , Quimiocina CXCL10/genética , Quimiocina CXCL10/inmunología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/patología , Síndrome de Liberación de Citoquinas/virología , Modelos Animales de Enfermedad , Células Epiteliales/inmunología , Células Epiteliales/patología , Células Epiteliales/virología , Regulación de la Expresión Génica , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-7/genética , Interleucina-7/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Ratones , Ratones Transgénicos , Pandemias , Neumonía Viral/genética , Neumonía Viral/patología , Neumonía Viral/virología , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/virología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
16.
PLoS One ; 15(10): e0240149, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33006999

RESUMEN

From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, non-severe symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos , Melatonina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Piridonas/uso terapéutico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/virología , Bases de Datos Farmacéuticas , Furina/metabolismo , Humanos , Melatonina/farmacología , Pandemias , Piridonas/farmacología
19.
J Allergy Clin Immunol ; 146(3): 518-534.e1, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32896310

RESUMEN

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 presents with a spectrum of clinical manifestations from asymptomatic or mild, self-limited constitutional symptoms to a hyperinflammatory state ("cytokine storm") followed by acute respiratory distress syndrome and death. The objective of this study was to provide an evidence-based review of the associated pathways and potential treatment of the hyperinflammatory state associated with severe acute respiratory syndrome coronavirus 2 infection. Dysregulated immune responses have been reported to occur in a smaller subset of those infected with severe acute respiratory syndrome coronavirus 2, leading to clinical deterioration 7 to 10 days after initial presentation. A hyperinflammatory state referred to as cytokine storm in its severest form has been marked by elevation of IL-6, IL-10, TNF-α, and other cytokines and severe CD4+ and CD8+ T-cell lymphopenia and coagulopathy. Recognition of at-risk patients could permit early institution of aggressive intensive care and antiviral and immune treatment to reduce the complications related to this proinflammatory state. Several reports and ongoing clinical trials provide hope that available immunomodulatory therapies could have therapeutic potential in these severe cases. This review highlights our current state of knowledge of immune mechanisms and targeted immunomodulatory treatment options for the current coronavirus disease 2019 pandemic.


Asunto(s)
Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Síndrome de Liberación de Citoquinas/virología , Inmunomodulación , Interleucina-6/inmunología , Neumonía Viral/inmunología , Neumonía Viral/terapia , Betacoronavirus , Síndrome de Liberación de Citoquinas/inmunología , Humanos , Pandemias , Sepsis/inmunología
20.
Molecules ; 25(19)2020 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-32987757

RESUMEN

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines' synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Péptidos/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Fármacos del Sistema Respiratorio/uso terapéutico , Enfermedad Aguda , Antiinflamatorios/síntesis química , Antivirales/síntesis química , Betacoronavirus/efectos de los fármacos , Betacoronavirus/crecimiento & desarrollo , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/complicaciones , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/virología , Coagulación Intravascular Diseminada/complicaciones , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/virología , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Factores Inmunológicos/síntesis química , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/virología , Pandemias , Péptidos/síntesis química , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Insuficiencia Respiratoria/complicaciones , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/prevención & control , Insuficiencia Respiratoria/virología , Fármacos del Sistema Respiratorio/síntesis química , Relación Estructura-Actividad
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