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1.
Circulation ; 143(1): 78-88, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33166178

RESUMEN

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with substantial cardiovascular implications. Although infection with SARS-CoV-2 is usually mild in children, some children later develop a severe inflammatory disease that can have manifestations similar to toxic shock syndrome or Kawasaki disease. This syndrome has been defined by the US Centers for Disease Control and Prevention as multisystem inflammatory syndrome in children. Although the prevalence is unknown, >600 cases have been reported in the literature. Multisystem inflammatory syndrome in children appears to be more common in Black and Hispanic children in the United States. Multisystem inflammatory syndrome in children typically occurs a few weeks after acute infection and the putative etiology is a dysregulated inflammatory response to SARS-CoV-2 infection. Persistent fever and gastrointestinal symptoms are the most common symptoms. Cardiac manifestations are common, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, and conduction abnormalities. Severe cases can present as vasodilatory or cardiogenic shock requiring fluid resuscitation, inotropic support, and in the most severe cases, mechanical ventilation and extracorporeal membrane oxygenation. Empirical treatments have aimed at reversing the inflammatory response using immunomodulatory medications. Intravenous immunoglobulin, steroids, and other immunomodulatory agents have been used frequently. Most patients recover within days to a couple of weeks and mortality is rare, although the medium- and long-term sequelae, particularly cardiovascular complications, are not yet known. This review describes the published data on multisystem inflammatory syndrome in children, focusing on cardiac complications, and provides clinical considerations for cardiac evaluation and follow-up.


Asunto(s)
Enfermedades Cardiovasculares , Síndrome de Respuesta Inflamatoria Sistémica , /sangre , /tratamiento farmacológico , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Niño , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Masculino , Esteroides/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología
2.
Curr Med Chem ; 28(2): 284-307, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32900341

RESUMEN

The COVID-19 pandemic continues to wreak havoc worldwide due to the lack of risk assessment, rapid spreading ability, and propensity to precipitate severe disease in comorbid conditions. In an attempt to fulfill the demand for prophylactic and treatment measures to intercept the ongoing outbreak, the drug development process is facing several obstacles and renaissance in clinical trials, including vaccines, antivirals, immunomodulators, plasma therapy, and traditional medicines. This review outlines the overview of SARS-CoV-2 infection, significant recent findings, and ongoing clinical trials concerning current and future therapeutic interventions for the management of advancing pandemic of the century.


Asunto(s)
Antivirales/uso terapéutico , /tratamiento farmacológico , /terapia , Ensayos Clínicos como Asunto , Humanos , Inmunización Pasiva , Factores Inmunológicos/uso terapéutico , Medicina Tradicional , Pandemias
3.
Trends Parasitol ; 37(1): 11-14, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33153921

RESUMEN

In recent months, the parasitology research community has been tasked with investigation of the influence of parasite coinfection on coronavirus disease 2019 (COVID-19) outcomes. Herein, we share our approach to analyze the effect of the trematode Fasciola hepatica as a modulator of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of COVID-19 pathology.


Asunto(s)
/terapia , Coinfección , Fascioliasis , Proteínas del Helminto/uso terapéutico , Animales , Modulación Antigénica , /parasitología , Fasciola hepatica/metabolismo , Humanos , Inmunidad Innata , Factores Inmunológicos/uso terapéutico , Inflamación/prevención & control , /prevención & control
4.
Rheumatology (Oxford) ; 60(1): 399-407, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33020836

RESUMEN

OBJECTIVES: The Janus kinase (JAK) inhibitor baricitinib may block viral entry into pneumocytes and prevent cytokine storm in patients with SARS-CoV-2 pneumonia. We aimed to assess whether baricitinib improved pulmonary function in patients treated with high-dose corticosteroids for moderate to severe SARS-CoV-2 pneumonia. METHODS: This observational study enrolled patients with moderate to severe SARS-CoV-2 pneumonia [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) <200 mmHg] who received lopinavir/ritonavir and HCQ plus either corticosteroids (CS group, n = 50) or corticosteroids and baricitinib (BCT-CS group, n = 62). The primary end point was the change in oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 from hospitalization to discharge. Secondary end points included the proportion of patients requiring supplemental oxygen at discharge and 1 month later. Statistics were adjusted by the inverse propensity score weighting (IPSW). RESULTS: A greater improvement in SpO2/FiO2 from hospitalization to discharge was observed in the BCT-CS vs CS group (mean differences adjusted for IPSW, 49; 95% CI: 22, 77; P < 0.001). A higher proportion of patients required supplemental oxygen both at discharge (62.0% vs 25.8%; reduction of the risk by 82%, OR adjusted for IPSW, 0.18; 95% CI: 0.08, 0.43; P < 0.001) and 1 month later (28.0% vs 12.9%, reduction of the risk by 69%, OR adjusted for IPSW, 0.31; 95% CI: 0.11, 0.86; P = 0.024) in the CS vs BCT-CS group. CONCLUSIONS: . In patients with moderate to severe SARS-CoV-2 pneumonia a combination of baricitinib with corticosteroids was associated with greater improvement in pulmonary function when compared with corticosteroids alone. TRIAL REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967).


Asunto(s)
Azetidinas/uso terapéutico , Glucocorticoides/uso terapéutico , Hipoxia/terapia , Inhibidores de las Cinasas Janus/uso terapéutico , Metilprednisolona/uso terapéutico , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Anciano , Antivirales/uso terapéutico , /fisiopatología , Estudios de Cohortes , Combinación de Medicamentos , Quimioterapia Combinada , Endotelio Vascular , Inhibidores Enzimáticos/uso terapéutico , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Hidroxicloroquina/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Interferon beta-1b/uso terapéutico , Lopinavir/uso terapéutico , Pulmón/irrigación sanguínea , Masculino , Persona de Mediana Edad , Oximetría , Estudios Prospectivos , Ritonavir/uso terapéutico , Índice de Severidad de la Enfermedad
5.
Neurology ; 96(1): e111-e120, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33106389

RESUMEN

OBJECTIVE: To investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets. METHODS: Using original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations. RESULTS: In both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates. CONCLUSIONS: All investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS.


Asunto(s)
Evaluación de la Discapacidad , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud/normas , Reproducibilidad de los Resultados , Adulto , Conjuntos de Datos como Asunto , Femenino , Humanos , Interferón beta-1a/uso terapéutico , Masculino , Persona de Mediana Edad , Natalizumab/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
J Med Virol ; 93(2): 831-842, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32672860

RESUMEN

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-ß (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Síndrome de Liberación de Citoquinas/prevención & control , Factores Inmunológicos/uso terapéutico , /patogenicidad , Administración Intravenosa , Adulto , Temperatura Corporal/efectos de los fármacos , Proteína C-Reactiva/metabolismo , /mortalidad , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/mortalidad , Síndrome de Liberación de Citoquinas/virología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Interferón beta/efectos adversos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Receptores de Interleucina-6/antagonistas & inhibidores , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/inmunología , Frecuencia Respiratoria/efectos de los fármacos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
7.
Transplantation ; 105(1): 56-60, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33141805

RESUMEN

As in the general population with coronavirus 2019 (COVID-19) infection, therapeutic interventions in solid organ transplant (SOT) recipients have evolved over time. The preceding 6 months of the pandemic can be divided into 2 main therapeutic eras: the early era and the later era. The first era was characterized by the widespread use of drugs such as hydroxychloroquine with or without azithromycin, lopinavir-ritonavir, and tocilizumab. More recently, with the publication of larger trials, there has been increasing use of remdesivir, dexamethasone, and convalescent plasma, with the rapid proliferation of clinical trials including a wide variety of investigational and repurposed agents with antiviral or immunomodulatory effects. This overview focuses on what is known about the effects of different therapies in SOT recipients with COVID-19, mainly from case series and, more recently, larger multicenter registries; as well as outlining the information that will be needed to optimize management and outcomes in SOT recipients with COVID-19 in the future.


Asunto(s)
/terapia , Trasplante de Órganos , Anticuerpos Monoclonales Humanizados/uso terapéutico , /inmunología , Humanos , Hidroxicloroquina/uso terapéutico , Tolerancia Inmunológica , Inmunización Pasiva , Factores Inmunológicos/uso terapéutico
9.
Inflamm Bowel Dis ; 27(1): 25-33, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-32830267

RESUMEN

BACKGROUND: There are scarce data about SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD). Our aim was to analyze the incidence, clinical presentation, and severity of SARS-CoV-2 infection in patients with IBD. METHODS: This is a cross-sectional, observational study. We contacted all the patients being treated at our IBD unit to identify those patients with suspected or confirmed SARS-CoV-2 infection, following the World Health Organization case definition. Data were obtained by patient electronical medical records and by phone interview. RESULTS: Eighty-two of 805 patients with IBD (10.2%; 95% confidence interval [CI], 8.3-12.5) were diagnosed as having confirmed (28 patients, 3.5%; 95% CI, 2.4-5.0) or suspected (54 patients, 6.7%) infection. Patient age was 46 ± 14 years, 44 patients were female (53.7%), 17.3% were smokers, 51.2% had Crohn disease (CD), and 39.0% had comorbidities. Digestive symptoms were reported in 41 patients (50.0%), with diarrhea as the most common (42.7%). One patient (1.2%) was diagnosed with IBD flare-up during SARS-CoV-2 infection. Twenty-two patients (26.8%) temporarily withdrew from their IBD treatment because of COVID-19. Most of the patients had mild disease (79.3%), and 1 patient died (1.2%). In the multivariate analysis, the presence of dyspnea was associated with moderate to severe infection (odds ratio, 5.3; 95% CI, 1.6-17.7; P = 0.01) and myalgias (odds ratio, 4.8; 95% CI, 1.3-17.9; P = 0.02) were related to a milder clinical course. Immunosuppression was not related to severity. CONCLUSIONS: SARS-CoV-2 infection in patients with IBD is not rare. Dyspnea is associated with a more severe infection. Therapy for IBD, including immunomodulators and biologic therapy, is not related to a greater severity of COVID-19, and SARS-CoV-2 infections do not appear to be related to IBD flare-ups.


Asunto(s)
/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Adulto , Terapia Biológica/métodos , Estudios Transversales , Disnea/etiología , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Factores Inmunológicos/uso terapéutico , Incidencia , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , España/epidemiología
10.
Am J Med ; 134(1): 16-22, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32771461

RESUMEN

Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This article outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy, and 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed will undoubtedly refine and clarify their individual roles; however, we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.


Asunto(s)
Atención Ambulatoria , /terapia , Anticoagulantes/uso terapéutico , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéutico , Oxígeno/uso terapéutico
11.
J Vasc Surg ; 73(1): 13-17, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32425326

RESUMEN

Objective: The primary purpose of the study was to investigate and to summarize the registered trials that listed COVID-19 as the primary condition. Methods: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS-CoV-2 and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. Results: Of 124 registered trials, 56 (45.2%) were listed as recruiting. The majority (85 [68.5%]) were classified as interventional, 37 (29.8%) as observational, and one (0.8%) each as either expanded access: individual patients|treatment investigational new drug/protocol or expanded access: intermediate-size population|treatment investigational new drug/protocol. There were 67 (54.0%) trials that listed drug as the type of study. Immunologic and antiviral trials were the most common, representing approximately 30% and 21%, respectively. When immunologic and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Antimalarial agents are represented in 7.5% of trials. Approximately 14% of trials involved traditional Chinese medicine. The study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID-19. Conclusions: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, whereas some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within ClinicalTrials.gov, patients, family members, health care professionals, and researchers can search and find ongoing and future trials for COVID-19.


Asunto(s)
Antivirales/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Ensayos Clínicos como Asunto , Factores Inmunológicos/uso terapéutico , /efectos de los fármacos , Antivirales/efectos adversos , /epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/virología , Interacciones Huésped-Patógeno , Humanos , Factores Inmunológicos/efectos adversos , Sistema de Registros , Proyectos de Investigación , Estudios Retrospectivos , Resultado del Tratamiento
12.
Int J Dermatol ; 60(1): 53-59, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33252832

RESUMEN

BACKGROUND: To retrospectively review the outcomes of two rare cutaneous diseases, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to question the practice of averaging the mortality rate on the assumption that they are one disease. METHODS: A retrospective chart review of all patients diagnosed with SJS and TEN by a dermatologist between January 1, 2000, and January 1, 2020, at our institution was performed. Seventy-one patients were identified (21 pediatric and 50 adults). Pathology slides from 32 adult patients (64%) were evaluated by a blinded board-certified dermatopathologist. RESULTS: Of the adult patients, 31 had SJS, two had SJS-TEN overlap, and 17 had TEN. All 21 patients in the pediatric group were diagnosed with SJS mainly caused by Mycoplasma. Mortality rates were 6.5% for SJS among adults and 35.3% for TEN. Chemotherapy-induced TEN is a trigger with 50% mortality. CONCLUSIONS: SJS was more common in adults and pediatric cases than TEN (3:1) and had a much better prognosis and outcome. Combining and averaging the mortality rates of TEN and SJS are not advised as SJS is mainly a mucocutaneous disorder with good prognosis versus TEN, a systemic toxicity of multiple organs with deep skin detachment.


Asunto(s)
Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/mortalidad , Adolescente , Adulto , Factores de Edad , Antibacterianos/efectos adversos , Antiinflamatorios/uso terapéutico , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Infecciones por Mycoplasma/complicaciones , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Esteroides/uso terapéutico , Síndrome de Stevens-Johnson/patología , Síndrome de Stevens-Johnson/terapia , Adulto Joven
13.
Int J Dermatol ; 60(1): 44-52, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32686136

RESUMEN

BACKGROUND: Toxic epidermal necrolysis (TEN) is a life-threatening severe cutaneous adverse reaction. Data on pediatric TEN is limited. METHODS: Case records of 44 children, 1 month-12 years with a diagnosis of TEN (>30% body surface area [%BSA] detachment) admitted to a tertiary pediatric intensive care unit (PICU) between 2009 and 2018 were analyzed retrospectively. The primary outcome was mortality, and secondary outcomes were organ dysfunction, length of stay (LOS), and long-term sequelae. RESULTS: Median (IQR) age was 6.5 (3.6, 8.0) years, and 25 (57%) were boys. Median (IQR) %BSA involved, SCORTEN score, and PRISM-III were 65% (45, 80); 2 (2, 3) and 13 (10, 16), respectively. Antiepileptics (n = 24, 54.6%) and antimicrobials (n = 8, 18.2%) were the most common offending agents. Twenty-four (54.5%) children had culture positive sepsis. Immunomodulatory therapy was provided in 35 (79.5%) and conservative management in nine (20.5%) children. Intravenous immunoglobulin (IVIG) was given in 22 (50%), steroids in three (6.8%), and both IVIG and steroids in 10 (22.7%) children. Respiratory failure (n = 14, 31.8%) was the commonest organ failure. Mortality was 15.9% (n = 7), and median (IQR) PICU-LOS in survivors was 8 (4, 11.75) days. There was no association between IVIG, steroids, or conservative management with mortality or LOS. Ocular sequelae (n = 20, 54.1%) were the most common long-term complication followed by skin (18, 40.1%). CONCLUSION: Immunomodulation with IVIG or steroids was not associated with any mortality benefit as compared to conservative management alone. Further research is required to determine the most effective treatment in pediatric TEN.


Asunto(s)
Cuidados Críticos , Síndrome de Stevens-Johnson/terapia , Antiinflamatorios/uso terapéutico , Niño , Preescolar , Tratamiento Conservador , Dexametasona/uso terapéutico , Oftalmopatías/etiología , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Inmunomodulación , Lactante , Unidades de Cuidado Intensivo Pediátrico , Tiempo de Internación , Masculino , Metilprednisolona/uso terapéutico , Insuficiencia Respiratoria/etiología , Estudios Retrospectivos , Sepsis/microbiología , Índice de Severidad de la Enfermedad , Esteroides/uso terapéutico , Síndrome de Stevens-Johnson/complicaciones , Síndrome de Stevens-Johnson/mortalidad , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
14.
JCI Insight ; 6(1)2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33232303

RESUMEN

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.


Asunto(s)
/inmunología , /mortalidad , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Biomarcadores , /terapia , Calgranulina B/genética , Calgranulina B/inmunología , Estudios de Casos y Controles , Quimiocina CCL2/genética , Quimiocina CCL2/inmunología , Quimiocina CXCL9/genética , Quimiocina CXCL9/inmunología , Inhibidores Enzimáticos/uso terapéutico , Femenino , Ferritinas/genética , Ferritinas/inmunología , Perfilación de la Expresión Génica , Humanos , Hidroxicloroquina/uso terapéutico , Factores Inmunológicos/uso terapéutico , Interferón Tipo I/genética , Interferón Tipo I/inmunología , Interferón gamma/genética , Interferón gamma/inmunología , Proteína 1 Similar al Receptor de Interleucina-1/genética , Proteína 1 Similar al Receptor de Interleucina-1/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-15/genética , Interleucina-15/inmunología , Interleucina-2/genética , Interleucina-2/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Lactoferrina/genética , Lactoferrina/inmunología , Lipocalina 2/genética , Lipocalina 2/inmunología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Persona de Mediana Edad , Análisis Multivariante , FN-kappa B/genética , FN-kappa B/inmunología
16.
Brain Dev ; 43(2): 230-233, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33082059

RESUMEN

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum, emerging related to encephalitis, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Among RESLES, mild encephalitis/encephalopathy with reversible splenial lesion (MERS) has been defined as a distinct clinicoradiologic syndrome associated with viral infections. CASE PRESENTATION: We report two children with multisystem inflammatory syndrome-children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who developed RESLES during the disease course. Encephalopathy was the main central nervous system symptom. Both of the children showed a rapid recovery, and brain magnetic resonance imaging revealed complete resolution of the splenial lesion within 1 week. CONCLUSION: The complete resolution of the splenial lesion and rapid recovery from encephalopathy in RESLES associated with SARS CoV-2 were similar to observed in MERS.


Asunto(s)
Encefalopatías/diagnóstico por imagen , Cuerpo Calloso/diagnóstico por imagen , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico por imagen , Encefalopatías/tratamiento farmacológico , Encefalopatías/fisiopatología , /tratamiento farmacológico , Niño , Disnea/fisiopatología , Electroencefalografía , Exantema/fisiopatología , Femenino , Fiebre/fisiopatología , Glucocorticoides/uso terapéutico , Alucinaciones/fisiopatología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Metilprednisolona/uso terapéutico , Trastornos Neurocognitivos/diagnóstico por imagen , Trastornos Neurocognitivos/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Taquipnea/fisiopatología
17.
Ann Hematol ; 100(1): 1-10, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33009935

RESUMEN

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection with high mortality rate usually seen in the context of immunosuppression. Although cases have been reported largely in patients with HIV/AIDS, following the use of monoclonal antibodies and occasionally in haematological malignancies, there is no review to date of patients with smouldering or treated myeloma who developed PML. Here, we conducted a literature search of PML cases in patients with multiple myeloma (MM), analyse patient and disease characteristics and describe the possible mechanisms that could lead to the development of PML. The lack of data and case reports until 2010 may indicate that PML in MM is underdiagnosed. Simultaneously, with an expanding field of new therapeutic options, patients with MM live longer, albeit continually immunosuppressed, and at risk of opportunistic infections. Emerging new treatments for PML in the horizon render the need to look out for this complication mandatory, and more case reports are needed to enrich our knowledge in this field.


Asunto(s)
Huésped Inmunocomprometido/efectos de los fármacos , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/inmunología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/inmunología , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Humanos , Huésped Inmunocomprometido/fisiología , Factores Inmunológicos/metabolismo , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Leucoencefalopatía Multifocal Progresiva/metabolismo , Mieloma Múltiple/metabolismo
18.
Mod Rheumatol Case Rep ; 5(1): 101-107, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33019894

RESUMEN

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed Pneumocystis jirovecii infection so treatment with intravenous trimethoprim-sulfamethoxazole was initiated. Due to RP-ILD worsening, immunosuppressive therapy was intensified using methylprednisolone pulses, cyclophosphamide, tofacitinib and intravenous immunoglobulin without response. She developed severe hypoxemic respiratory failure, pneumomediastinum and pneumothorax, further complicated with severe RP-ILD and cervical subcutaneous emphysema. Three real-time RT-PCR for SARS-CoV-2 were made with a negative result. In addition, she was complicated with a secondary hemophagocytic lymphohistiocytosis and a fourth real-time PCR for SARS-CoV-2 performed in BAS sample was positive. Despite aggressive treatment of RP-ILD due to anti-MDA5 JDM, there was no improvement of respiratory failure in the following days and patient developed refractory septic shock and died. Anti-MDA5 JDM patients with RP-ILD have a poor prognosis with a high mortality rate. For this reason, intensive immunosuppressive therapy is essential including the use of promising drugs such as tofacitinib. COVID-19 in children with underlying health conditions like anti-MDA5 JDM may still be at risk for disease and severe complications.


Asunto(s)
/complicaciones , Dermatomiositis/complicaciones , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/complicaciones , Linfohistiocitosis Hemofagocítica/etiología , Neumonía por Pneumocystis/complicaciones , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Autoanticuerpos/inmunología , Broncoscopía , Niño , Ciclofosfamida/uso terapéutico , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/inmunología , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Huésped Inmunocomprometido , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Helicasa Inducida por Interferón IFIH1/inmunología , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/terapia , Linfohistiocitosis Hemofagocítica/inmunología , Enfisema Mediastínico/etiología , Metilprednisolona/uso terapéutico , Piperidinas/uso terapéutico , Neumonía por Pneumocystis/inmunología , Neumotórax/etiología , Pirimidinas/uso terapéutico , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Choque Séptico/etiología , Enfisema Subcutáneo/etiología , Tomografía Computarizada por Rayos X , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico
19.
Immunology ; 162(1): 30-43, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32935333

RESUMEN

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, a novel coronavirus strain. Some studies suggest that COVID-19 could be an immune-related disease, and failure of effective immune responses in initial stages of viral infection could contribute to systemic inflammation and tissue damage, leading to worse disease outcomes. T cells can act as a double-edge sword with both pro- and anti-roles in the progression of COVID-19. Thus, better understanding of their roles in immune responses to SARS-CoV-2 infection is crucial. T cells primarily react to the spike protein on the coronavirus to initiate antiviral immunity; however, T-cell responses can be suboptimal, impaired or excessive in severe COVID-19 patients. This review focuses on the multifaceted roles of T cells in COVID-19 pathogenesis and rationalizes their significance in eliciting appropriate antiviral immune responses in COVID-19 patients and unexposed individuals. In addition, we summarize the potential therapeutic approaches related to T cells to treat COVID-19 patients. These include adoptive T-cell therapies, vaccines activating T-cell responses, recombinant cytokines, Th1 activators and Th17 blockers, and potential utilization of immune checkpoint inhibitors alone or in combination with anti-inflammatory drugs to improve antiviral T-cell responses against SARS-CoV-2.


Asunto(s)
/inmunología , Inmunidad Celular , Inmunoterapia , Pulmón/inmunología , Linfocitos T/inmunología , Traslado Adoptivo , Animales , Antivirales/uso terapéutico , /virología , Interacciones Huésped-Patógeno , Humanos , Inmunidad Celular/efectos de los fármacos , Factores Inmunológicos/uso terapéutico , Pulmón/efectos de los fármacos , Pulmón/virología , /patogenicidad , Linfocitos T/efectos de los fármacos , Linfocitos T/trasplante , Linfocitos T/virología
20.
Nutrients ; 12(12)2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33297491

RESUMEN

There are limited proven therapies for COVID-19. Vitamin C's antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6-24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients' vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.


Asunto(s)
Deficiencia de Ácido Ascórbico/tratamiento farmacológico , Ácido Ascórbico/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Vitaminas/uso terapéutico , Administración Intravenosa , Administración Oral , Antiinflamatorios/uso terapéutico , Deficiencia de Ácido Ascórbico/complicaciones , /virología , Quimioterapia Adyuvante , Cuidados Críticos , Hospitalización , Humanos , Factores Inmunológicos/uso terapéutico , Unidades de Cuidados Intensivos , Estado Nutricional , Pandemias , Respiración Artificial , Infecciones del Sistema Respiratorio/etiología , Infecciones del Sistema Respiratorio/virología , Sepsis/etiología , Sepsis/virología
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