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1.
J Trop Pediatr ; 67(1)2021 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-33787904

RESUMEN

LAY SUMMARY: Clinical and laboratory parameters of multisystem inflammatory syndrome in children (MIS-C) mimic Kawasaki disease (KD). KD has been described in association with dengue, scrub typhus and leptospirosis. However, MIS-C with concomitant infection has rarely been reported in literature. A 14-year-old-girl presented with fever and rash with history of redness of eyes, lips and tongue. Investigations showed anemia, lymphopenia, thrombocytosis with elevated erythrocyte sedimentation rate, C-reactive protein, pro-brain natriuretic peptide, Interleukin-6, ferritin and d-dimer. Scrub typhus immunoglobulin M was positive. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) level was also elevated. A diagnosis of MIS-C with concomitant scrub typhus was proffered. Child received azithromycin, intravenous immunoglobulin and methylprednisolone. After an afebrile period of 2.5 days, child developed unremitting fever and rash. Repeat investigations showed anemia, worsening lymphopenia, thrombocytopenia, transaminitis, hypertriglyceridemia, hyperferritinemia and hypofibrinogenemia which were consistent with a diagnosis of macrophage activation syndrome (MAS). KD, MIS-C and MAS represent three distinct phenotypes of hyperinflammation seen in children during coronavirus disease pandemic. Several tropical infections may mimic or coexist with MIS-C which can be a diagnostic challenge for the treating physician. Identification of coexistence or differentiation between the two conditions is important in countries with high incidence of tropical infections to guide appropriate investigations and treatment.


Asunto(s)
/complicaciones , Síndrome de Activación Macrofágica/diagnóstico , Tifus por Ácaros/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica , Adolescente , Azitromicina/uso terapéutico , Biomarcadores/sangre , /diagnóstico , Niño , Femenino , Fiebre/etiología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome de Activación Macrofágica/complicaciones , Síndrome de Activación Macrofágica/tratamiento farmacológico , Síndrome de Activación Macrofágica/inmunología , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Pandemias , Tifus por Ácaros/complicaciones , Tifus por Ácaros/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/inmunología
2.
Indian J Ophthalmol ; 69(4): 989-991, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33727475

RESUMEN

Ocular manifestations of COVID-19 are still being studied. Posterior segment involvement in viral entities is either direct viral involvement or a delayed immune response to the antigen. A 22-year-old woman presented with history of perceiving absolute inferior scotoma in the right eye for 4 days and history of fever and sore throat 10 days ago. Fundus examination revealed disc edema and vessel tortuosity. Humphreys Field Analyzer confirmed inferior field defect and Optical Coherence Tomography showed superior, nasal and inferior retinal nerve fiber layer thickening in the right eye. Patient was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR) testing. Patient received three doses of injection methylprednisolone over 3 days. There was subjective resolution of scotoma reported 3 weeks posttreatment. We bring forward the first reported case of parainfectious optic neuritis associated with COVID-19.


Asunto(s)
/diagnóstico , Infecciones Virales del Ojo/diagnóstico , Papiledema/diagnóstico , Escotoma/diagnóstico , Campos Visuales/fisiología , /tratamiento farmacológico , Infecciones Virales del Ojo/tratamiento farmacológico , Infecciones Virales del Ojo/virología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Metilprednisolona/uso terapéutico , Papiledema/tratamiento farmacológico , Papiledema/virología , Escotoma/tratamiento farmacológico , Escotoma/virología , Tomografía de Coherencia Óptica , Agudeza Visual , Pruebas del Campo Visual , Adulto Joven
3.
Indian J Ophthalmol ; 69(4): 992-994, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33727476

RESUMEN

COVID-19 is a respiratory virus, which has affected various organ systems as well. Here we report a neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery.


Asunto(s)
Adenoma/diagnóstico , Infecciones Virales del Ojo/diagnóstico , Apoplejia Hipofisaria/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Adenoma/tratamiento farmacológico , Adenoma/virología , Infecciones Virales del Ojo/tratamiento farmacológico , Infecciones Virales del Ojo/virología , Glucocorticoides/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Apoplejia Hipofisaria/tratamiento farmacológico , Apoplejia Hipofisaria/virología , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/virología
4.
Medicine (Baltimore) ; 100(12): e25170, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761694

RESUMEN

RATIONALE: The immunologic syndrome induced by severe acute coronavirus disease 2019 (COVID-19) is yet not fully understood. Typical patterns of clinical and laboratory features match secondary hemophagocytic lymphohistiocytosis (sHLH). However, the optimal approach to COVID-19 patients testing positive for sHLH is still unclear. PATIENT CONCERNS: Three patients with COVID-19 are reviewed. All showed hyperinflammation and cytokine storm, necessitating intensive care treatment including mechanical ventilation. DIAGNOSIS: Secondary hemophagocytic lymphohistiocytosis due to severe COVID-19; diagnosed via HScore. INTERVENTIONS: A treatment regimen of methylprednisolone, pentaglobin, and anakinra was developed and administered. OUTCOMES: One patient survived the ICU stay. Two other patients, in whom sHLH was diagnosed too late, deceased. LESSONS: A routine screening of COVID-19 patients for secondary HLH by using the HScore is feasible; especially those patients deteriorating clinically with no sufficient response to shock management might be at particular high risk. A stepwise therapeutic approach comprising corticosteroids, immunoglobulins and anakinra, accompanied by immunoadsorption, may dampen cytokine storm effects, and potentially reduce mortality.


Asunto(s)
/complicaciones , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/etiología , Anciano , Antiinflamatorios/uso terapéutico , /terapia , Terapia Combinada , Cuidados Críticos , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Diagnóstico Tardío , Resultado Fatal , Femenino , Humanos , Inmunoglobulina A/uso terapéutico , Inmunoglobulina M/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Linfohistiocitosis Hemofagocítica/diagnóstico , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Respiración Artificial
5.
BMJ Case Rep ; 14(3)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33762287

RESUMEN

SARS-CoV-2 infection has recently been related to a spectrum of hyper-inflammatory states in children. There is a striking similarity between these hyper-inflammatory states and Kawasaki disease (KD). We present an interesting case of KD recurrence in a 10-year-old child, who had previously developed KD at 4 years of age. His symptoms included fever, maculopapular rash and altered sensorium. Investigations showed noticeably elevated inflammatory markers, and an echocardiography revealed dilated coronary arteries. SARS-CoV-2 IgG antibodies were positive. The child responded dramatically to intravenous immunoglobulin and intravenous methylprednisolone. It is possible that SARS-CoV-2 infection triggered the recurrence of KD in this child who might have been genetically predisposed to KD.


Asunto(s)
/complicaciones , Síndrome Mucocutáneo Linfonodular/etiología , Antiinflamatorios/uso terapéutico , Anticuerpos Antivirales/aislamiento & purificación , Niño , Ecocardiografía/métodos , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Masculino , Metilprednisolona/uso terapéutico , Síndrome Mucocutáneo Linfonodular/terapia , Síndrome Mucocutáneo Linfonodular/virología , Recurrencia , Resultado del Tratamiento
6.
Infect Dis (Lond) ; 53(4): 291-302, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33620019

RESUMEN

BACKGROUND: There is an urgent need to reduce mortality of COVID-19. We examined if corticosteroids and tocilizumab reduce risk for death in patients with severe pneumonia caused by SARS-CoV-2. METHODS: A retrospective cohort study was performed in a single university hospital. All adult patients admitted with confirmed severe COVID-19 pneumonia from 9 March to 9 April 2020 were included. Severe pneumonia was defined as multi-lobar or bilateral pneumonia and a ratio of oxygen saturation by pulse oximetry to the fraction of inspired oxygen (SpFi)<315. All patients received antiviral and antibiotic treatment. From March 26, patients also received immunomodulatory treatment with corticosteroids (methylprednisolone 250 mg/day for 3 days), or tocilizumab or both. In-hospital mortality in the entire cohort and in a 1:1 matched cohort sub-analysis was evaluated. RESULTS: 255 patients were included, 118 received only antiviral and antibiotic treatment while 137, admitted after March 26, also received immunomodulators. In-hospital mortality of patients on immunomodulatory treatment was significantly lower than in those without [47/137(34.3%) vs. 69/118(58.5%), (p < .001)]. The risk of death was 0.44 (CI, 0.26-0.76) in patients receiving corticosteroids alone and 0.292 (CI, 0.18-0.47) in those treated with corticosteroids and tocilizumab. In the sub-analysis with 202 matched patients, the risk of death was 0.356 (CI 0.179-0.707) in patients receiving corticosteroids alone and 0.233 (0.124-0.436) in those treated with the combination. CONCLUSIONS: Combined treatment with corticosteroids and tocilizumab reduced mortality with about 25% in patients with severe COVID-19 pneumonia. Corticosteroids alone also resulted in lower in-hospital mortality rate compared to patients receiving only antiviral and antibiotic treatment. Corticosteroids alone or combined with tocilizumab may be considered in patients with severe COVID-19 pneumonia.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Mortalidad Hospitalaria , Metilprednisolona/uso terapéutico , Anciano , Femenino , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España
7.
BMC Nephrol ; 22(1): 75, 2021 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-33639869

RESUMEN

BACKGROUND: Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection. CASE PRESENTATION: The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome. CONCLUSION: Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.


Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , /complicaciones , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/etiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/fisiopatología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Niño , Ciclofosfamida/uso terapéutico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Riñón/patología , Riñón/fisiología , Metilprednisolona/uso terapéutico , Plasmaféresis , Prednisona/uso terapéutico , Recurrencia , Vejiga Urinaria/fisiopatología , Reflujo Vesicoureteral/fisiopatología
8.
Artículo en Inglés | MEDLINE | ID: mdl-33614199

RESUMEN

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is the cause of the COVID-19 pandemic [5]. SARS-Cov-2 demonstrates partial resemblance to SARS-CoV and MERS-CoV in phylogenetic analysis, clinical manifestations, and pathological findings [6, 7]. Reports emerging from China have described ataxia as a neurological symptom of the SARS-CoV-2 infection [5]. Opsoclonus consists of back-to-back multidirectional conjugate saccades without an inter-saccadic interval [8]. Myoclonus is defined as a sudden, brief, "shock-like", nonepileptic involuntary movement [9], which has been described as a symptom of SARS-CoV-2 infection [10]. Opsoclonus-Myoclonus-Ataxia syndrome (OMAS) associated COVID-19 infection has been reported recently [1112].


Asunto(s)
/fisiopatología , Síndrome de Opsoclonía-Mioclonía/fisiopatología , Adulto , Clonazepam/uso terapéutico , GABAérgicos/uso terapéutico , Humanos , Masculino , Metilprednisolona/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Síndrome de Opsoclonía-Mioclonía/tratamiento farmacológico , Síndrome de Opsoclonía-Mioclonía/etiología , Pronóstico , Recuperación de la Función , Resultado del Tratamiento , Ácido Valproico/uso terapéutico
9.
Emerg Microbes Infect ; 10(1): 291-304, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33538646

RESUMEN

Effective treatments for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Dexamethasone has been shown to confer survival benefits to certain groups of hospitalized patients, but whether glucocorticoids such as dexamethasone and methylprednisolone should be used together with antivirals to prevent a boost of SARS-CoV-2 replication remains to be determined. Here, we show the beneficial effect of methylprednisolone alone and in combination with remdesivir in the hamster model of SARS-CoV-2 infection. Treatment with methylprednisolone boosted RNA replication of SARS-CoV-2 but suppressed viral induction of proinflammatory cytokines in human monocyte-derived macrophages. Although methylprednisolone monotherapy alleviated body weight loss as well as nasal and pulmonary inflammation, viral loads increased and antibody response against the receptor-binding domain of spike protein attenuated. In contrast, a combination of methylprednisolone with remdesivir not only prevented body weight loss and inflammation, but also dampened viral protein expression and viral loads. In addition, the suppressive effect of methylprednisolone on antibody response was alleviated in the presence of remdesivir. Thus, combinational anti-inflammatory and antiviral therapy might be an effective, safer and more versatile treatment option for COVID-19. These data support testing of the efficacy of a combination of methylprednisolone and remdesivir for the treatment of COVID-19 in randomized controlled clinical trials.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Metilprednisolona/uso terapéutico , /efectos de los fármacos , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Alanina/farmacología , Alanina/uso terapéutico , Animales , Anticuerpos Antivirales/sangre , Antivirales/farmacología , /virología , Citocinas/biosíntesis , Citocinas/inmunología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Macrófagos/inmunología , Macrófagos/virología , Masculino , Mesocricetus , Metilprednisolona/farmacología , ARN Viral , Sistema Respiratorio/patología , Sistema Respiratorio/virología , Glicoproteína de la Espiga del Coronavirus/inmunología , Carga Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacos
10.
J Neuroimmunol ; 353: 577521, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33607505

RESUMEN

BACKGROUND: Serious neurological complications of SARS-CoV-2 are increasingly being recognized. CASE: We report a novel case of HHV6 myelitis with parainfectious MOG-IgG in the setting of COVID-19-induced lymphopenia and hypogammaglobulinemia. The patient experienced complete neurological recovery with gancyclovir, high dose corticosteroids, and plasma exchange. To our knowledge, this is the first case of HHV6 reactivation in the central nervous system in the setting of COVID19 infection and the first case of MOG-IgG myelitis in the setting of SARS-CoV-2 and HHV6 coinfection. CONCLUSION: Patients with neurological manifestations in the setting of COVID19-related immunodeficiency should be tested for opportunistic infections including HHV6. Viral infection is a known trigger for MOG-IgG and therefore this antibody should be checked in patients with SARS-CoV-2 associated demyelination.


Asunto(s)
/complicaciones , Coinfección/complicaciones , Linfopenia/virología , Mielitis Transversa/virología , Infecciones por Roseolovirus/inmunología , Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Coinfección/inmunología , Ganciclovir/uso terapéutico , Herpesvirus Humano 6 , Humanos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Mielitis Transversa/inmunología , Mielitis Transversa/terapia , Intercambio Plasmático/métodos , Infecciones por Roseolovirus/tratamiento farmacológico , Activación Viral/inmunología
11.
J Neuroimmunol ; 353: 577523, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33640717

RESUMEN

OBJECTIVE: To report a unique case and literature review of post COVID-19 associated transverse myelitis and dysautonomia with abnormal MRI and CSF findings. BACKGROUND: Coronavirus disease have been reported to be associated with several neurological manifestations such as stroke, Guillain-Barré syndrome, meningoencephalitis amongst others. There are only few reported cases of transverse myelitis with the novel coronavirus (n-CoV-2) and only one reported case identifying dysautonomia in COVID-19 patient. Here, we identify a COVID-19 patient diagnosed with acute transverse myelitis in addition to dysautonomia following with complete resolution of symptoms. METHOD: A retrospective chart review of a patient diagnosed with post SARS-CoV-2 infection acute transverse myelitis and dysautonomia, and a review of literature of all the reported cases of transverse myelitis and COVID-19, from December 1st, 2019 till December 25th, 2020, was performed. CONCLUSION: To our knowledge, this is the first reported case of transverse myelitis and dysautonomia in a patient with SARS-CoV-2 infection, who responded to intravenous methyl prednisone and bromocriptine. Follow-up imaging of the spine showed complete resolution of the lesion. Further studies would be recommended to identify the underlying correlation between COVID-19 and transverse myelitis.


Asunto(s)
/complicaciones , Mielitis Transversa/virología , Disautonomías Primarias/virología , Médula Espinal/patología , Adulto , Antiinflamatorios/uso terapéutico , Bromocriptina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Humanos , Masculino , Metilprednisolona/uso terapéutico , Mielitis Transversa/tratamiento farmacológico , Mielitis Transversa/patología
12.
Medicine (Baltimore) ; 100(6): e24627, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578576

RESUMEN

RATIONALE: Steroid-resistant nephrotic syndrome (SRNS) is a special kidney disease. SRNS is characterized by steroid-resistant, clinical variability, and genetic heterogeneity. Patients with SRNS often may eventually need renal transplantation. PATIENT CONCERNS: A 10-month-old Chinese male infant presented with oliguria, renal dysfunction, hypertension, and anemia. DIAGNOSES: Combined with clinical manifestations, laboratory testing and sequencing results, the patient was diagnosed as SRNS. INTERVENTIONS: Combined intravenous methylprednisolone and cefoperazone sulbactam did not improve the patient's condition. Thus, SRNS associated with hereditary nephrotic syndrome was strongly suspected. Genetic testing for hereditary renal disease of the patient revealed 2 novel heterozygous mutations in the Nucleoporin 93 (NUP93) gene, which were predicted pathogenic and harmful by bioinformatic softwares of SIFT, PolyPhen_2 and REVEL. OUTCOMES: As general physical health deterioration and renal dysfunction, the patient died of a severe infection. LESSONS: The novel NUP93 heterozygous mutations identified in the current study broadened the genetic spectrum of SRNS and further deepened our insight into pathogenic mutations of NUP93 to improve disease diagnosis.


Asunto(s)
Síndrome Nefrótico/diagnóstico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Cefoperazona/administración & dosificación , Cefoperazona/uso terapéutico , Resultado Fatal , Asesoramiento Genético , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Humanos , Lactante , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/genética
13.
JAMA ; 325(9): 855-864, 2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33523115

RESUMEN

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.


Asunto(s)
/terapia , Glucocorticoides/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Metilprednisolona/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Adolescente , /tratamiento farmacológico , Niño , Preescolar , Terapia Combinada , Femenino , Fiebre/etiología , Francia , Glucocorticoides/efectos adversos , Humanos , Unidades de Cuidado Intensivo Pediátrico , Tiempo de Internación , Masculino , Metilprednisolona/efectos adversos , Puntaje de Propensión , Recurrencia , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Resultado del Tratamiento
14.
Eur J Endocrinol ; 184(2): 277-287, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33539318

RESUMEN

Background: Tripterygium glycosides (TG) has been used to treat a spectrum of inflammatory and autoimmune diseases. Our preliminary studies have shown that TG is effective in the treatment of active Graves' ophthalmopathy (GO). Objective: We aimed to compare the efficacy and tolerability of TG with intravenous methylprednisolone (iv.MP) in patients with active moderate-to-severe GO. Methods: This study was an observer-masked, single-centre, block-randomised trial. Patients with active moderate-to-severe GO were randomly assigned to receive iv.MP (500 mg once per week for 6 weeks followed by 250 mg per week for 6 weeks) or with TG (20 mg tablet three times per day for 24 weeks). The primary endpoints were the overall response rate and the patients' quality of life at 12 and 24 weeks. Results: In this study, 161 patients were enrolled and randomised from 2015 to 2019. A total of 79 were randomly assigned to receive iv.MP and 82 to receive TG. A greater overall response rate was found in the TG group compared with the iv.MP group at week 24 (90.2% vs 68.4%, P = 0.000). Similarly, the patients' quality of life of the TG group showed a significantly higher response than the iv.MP group at week 24 (89.02% vs 72.15%, P = 0.001). The TG therapy showed a better CAS response than the iv.MP (91.5% vs 70.9% improved, P < 0.05), and up to 91.2% of patients were inactive. Also, the TG group showed a significantly higher improved rate of diplopia, proptosis, visual acuity, soft tissue involved and the decrease of eye muscle motility than the iv.MP group at week 24. Significantly more patients in the iv.MP group than the TG group experienced adverse events. Conclusion: Compared with iv.MP treatment, TG therapy is more effective and safer for patients with active moderate to severe GO.


Asunto(s)
Glicósidos/uso terapéutico , Oftalmopatía de Graves/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Tripterygium , Administración Intravenosa , Adulto , Antitiroideos/uso terapéutico , Diplopía/fisiopatología , Exoftalmia/fisiopatología , Dolor Ocular/fisiopatología , Femenino , Glucocorticoides/uso terapéutico , Enfermedad de Graves/tratamiento farmacológico , Oftalmopatía de Graves/fisiopatología , Humanos , Hipotiroidismo/tratamiento farmacológico , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Músculos Oculomotores/fisiopatología , Índice de Severidad de la Enfermedad , Método Simple Ciego , Tiroxina/uso terapéutico , Resultado del Tratamiento , Agudeza Visual/fisiología
15.
BMC Infect Dis ; 21(1): 163, 2021 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-33563218

RESUMEN

BACKGROUND: Many studies have been published about critically ill coronavirus disease 2019 (COVID-19) during the early phases of the pandemic but the characteristic or survival of critically ill Japanese patients have not yet been investigated. We sought to investigate the characteristics, inflammatory laboratory finding trends, and outcomes among critically ill Japanese patients who were admitted to the intensive care unit (ICU) with the first wave of COVID-19. METHODS: A retrospective observational study was performed in a single institution in the center of Tokyo. Laboratory-confirmed COVID-19 patients admitted to the ICU from March 19 to April 30, 2020 were included. Trends for significant inflammatory laboratory findings were analyzed. In-hospital death, days of mechanical ventilation or oxygen supplementation, days of ICU or hospital stay were followed until May 26, 2020. RESULTS: Twenty-four patients were included. Median age was 57.5 years, and 79% were male. The neutrophil-to-lymphocyte ratio was elevated to a median of 10.1 on admission and peaked on Day 10 of illness. Seventeen patients were intubated on Day 11 of illness and received mechanical ventilation. One patient underwent extracorporeal membrane oxygenation. The majority (88%) received systemic steroids, including 16 patients who received high dose methylprednisolone (500-1000 mg). Favipiravir was used in 38% of patients. Two patients, including 1 who refused intensive care, died. Eighteen patients were discharged. Median length of ICU and hospital stay for all patients was 6 and 22 days, respectively. Median length of ventilator dependency was 7 days. Four patients underwent a tracheostomy and received prolonged ventilation for more than 21 days. One patient receiving mechanical ventilation died. All survivors discontinued ventilator use. CONCLUSIONS: Mortality was remarkably low in our single institutional study. Three survivors received mechanical ventilation for more than 3 weeks. Trends of clinically significant laboratory markers reflected the clinical course of COVID-19.


Asunto(s)
/fisiopatología , /terapia , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Proteína C-Reactiva/análisis , /mortalidad , Enfermedad Crítica , Oxigenación por Membrana Extracorpórea , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Recuento de Leucocitos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Respiración Artificial , Estudios Retrospectivos , Tokio
16.
Respiration ; 100(2): 116-126, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33486496

RESUMEN

BACKGROUND: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. OBJECTIVE: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. METHODS: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. RESULTS: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6-16 days), which was significantly longer than that in the control group (8 days [2-12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). CONCLUSIONS: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04273321.


Asunto(s)
/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Hospitalización , Metilprednisolona/uso terapéutico , Faringe/química , ARN Viral/aislamiento & purificación , Esparcimiento de Virus , Adulto , Anciano , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Complejo CD3 , Linfocitos T CD8-positivos , /terapia , Progresión de la Enfermedad , Intervención Médica Temprana , Oxigenación por Membrana Extracorpórea , Femenino , Humanos , Células Asesinas Naturales , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Habitaciones de Pacientes , Faringe/virología , Modelos de Riesgos Proporcionales , Respiración Artificial , Método Simple Ciego , Subgrupos de Linfocitos T , Linfocitos T , Factores de Tiempo , Resultado del Tratamiento
17.
Intern Med ; 60(1): 123-130, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33390469

RESUMEN

Case 1: A 65-year-old man with novel coronavirus infection (COVID-19) complicated with acute respiratory failure. On admission, the patient was started on favipiravir and corticosteroid. However, due to a lack of significant improvement, he was introduced to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Although iliopsoas hematoma occurred as a complication, the patient recovered. Case 2: A 49-year-old man with COVID-19 had been started on favipiravir and corticosteroid. Due to progressive respiratory failure, the patient underwent mechanical ventilation and ECMO. The patient recovered without complications. We successfully treated these severe cases with a multimodal combination of pharmacological and non-pharmacological supportive therapy.


Asunto(s)
Corticoesteroides/uso terapéutico , Amidas/uso terapéutico , Antivirales/uso terapéutico , Oxigenación por Membrana Extracorpórea , Metilprednisolona/uso terapéutico , Pirazinas/uso terapéutico , Respiración Artificial , Anciano , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/virología
18.
Rev Iberoam Micol ; 38(1): 16-18, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33500209

RESUMEN

BACKGROUND: Patients with severe viral pneumonia are likely to receive high-dose immunomodulatory drugs to prevent clinical worsening. Aspergillus species have been described as frequent secondary pneumonia agents in severely ill influenza patients receiving steroids. COVID-19 patients admitted to Intensive Care Unit (ICU) are receiving steroids as part of their treatment and they share clinical characteristics with other patients with severe viral pneumonias. COVID-19 patients receiving steroids should be considered a putative risk group of invasive aspergillosis. CASE REPORT: We are reporting a SARS-CoV-2/Aspergillus section Fumigati coinfection in an elderly intubated patient with a history of pulmonary embolism treated with corticosteroids. The diagnosis was made following the ad hoc definitions described for patients admitted to ICU with severe influenza, including clinical criteria (fever for 3 days refractory to the appropriate antibiotic therapy, dyspnea, pleural friction rub, worsening of respiratory status despite antibiotic therapy and need of ventilator support), a radiological criterion (pulmonary infiltrate) and a mycological criterion (several positive galactomannan tests on serum with ratio ≥0.5). In addition, Aspergillus section Fumigati DNA was found in serum and blood samples. These tests were positive 4 weeks after the patient was admitted to the ICU. The patient received voriconazole and after two month in ICU his respiratory status improved; he was discharged after 6 weeks of antifungal treatment. CONCLUSIONS: Severely ill COVID-19 patients would be considered a new aspergillosis risk group. Galactomannan and Aspergillus DNA detection would be useful methods for Aspergillus infection diagnosis as they allow avoiding the biosafety issues related to these patients.


Asunto(s)
Aspergillus fumigatus/aislamiento & purificación , /tratamiento farmacológico , Coinfección/diagnóstico , Inmunocompetencia , Inmunosupresores/efectos adversos , Aspergilosis Pulmonar Invasiva/complicaciones , Metilprednisolona/efectos adversos , /aislamiento & purificación , Acetaminofén/uso terapéutico , Anciano , Antiinfecciosos/uso terapéutico , Líquido del Lavado Bronquioalveolar/microbiología , /terapia , Coinfección/microbiología , Coinfección/terapia , Coinfección/virología , Terapia Combinada , Diagnóstico Diferencial , Quimioterapia Combinada , Enoxaparina/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Inmunosupresores/uso terapéutico , Intubación Intratraqueal , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/microbiología , Aspergilosis Pulmonar Invasiva/terapia , Masculino , Mananos/sangre , Metilprednisolona/uso terapéutico , Nasofaringe/virología , Neumonía por Mycoplasma/diagnóstico , Pseudomonas aeruginosa/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Respiración Artificial , Staphylococcus aureus/aislamiento & purificación , Tráquea/microbiología
20.
Trials ; 22(1): 43, 2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33430891

RESUMEN

OBJECTIVES: The aim of this study is to assess the effectiveness and safety of glucocorticoid infusion pulse therapy to improve the clinical outcomes of patients with COVID-19 pneumonia with elevated inflammatory biomarkers. TRIAL DESIGN: A parallel-group quadruple-blind (participant, intervention provider, outcome assessor and data manager), randomised controlled trial. PARTICIPANTS: All patients admitted to hospital due to COVID-19 pneumonia will be considered eligible. Potential candidates will be identified and consecutively included in the emergency room or in the COVID-19 admission wards of two hospitals in Spain: Complejo Hospitalario de Navarra (Pamplona) and Hospital Moisès Broggi (Sant Joan Despí, Barcelona). Inclusion criteria are: 1) age ≥18 years old; 2) diagnosis of SARS-CoV-2 pneumonia confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal swabs or sputum in accordance with the recommendations of the Spanish Ministry of Health; 3) history of symptoms compatible with COVID-19 ≥7 days; 4) hospital admission; 5) at least one of the following: C-reactive protein (CRP) >60 mg/dL, interleukin-6 (IL-6) >40 pg/mL, and/or ferritin >1000 µg/L; and 6) provision of informed consent. Exclusion criteria are: 1) allergy or contraindication to any of the drugs under study; 2) oxygen saturation (SpO2) <90% (in air ambient) or partial pressure of oxygen in arterial blood (PaO2) <60 mmHg (in ambient air) or PaO2/FiO2 <300 mmHg; 3) ongoing treatment with glucocorticoids, or other immunosuppressants, including biologics for another indication; 4) decompensated diabetes mellitus; 5) uncontrolled hypertension; 6) psychotic or manic disorder; 7) active cancer; 8) pregnancy or breastfeeding; 9) clinical or biochemical suspicion (procalcitonin >0.5 ng/mL) of active infection other than with SARS-CoV-2; 10) management as an outpatient; 11) conservative or palliative management; 12) participation in another clinical trial; or 13) any major uncontrolled medical, psychological, psychiatric, geographic or social problem that contraindicates the patient's participation in the trial or hinders proper follow-up and adherence to the protocol and evaluation of study outcomes. INTERVENTION AND COMPARATOR: Eligible patients will be randomised to receive standard of care plus methylprednisolone (intervention group) or standard of care plus placebo (control group). Intervention group: standard of care at the discretion of the researcher, including lopinavir/ritonavir (200/50 mg, 2 tablets twice daily, per os, for 7 to 14 days) ± remdesivir (a single intravenous loading dose of 200 mg on day 1 followed by once-daily intravenous maintenance doses of 100 mg from day 2 to 5), or no drug treatment, + methylprednisolone (once-daily intravenous infusion of 120 mg on days 1, 2 and 3). CONTROL GROUP: standard of care at the discretion of the researcher, including lopinavir/ritonavir (200/50 mg, 2 tablets every 12 hours, per os, for 7 to 14 days) ± remdesivir (a single intravenous loading dose of 200 mg on day 1 followed by once-daily intravenous maintenance doses of 100 mg from day 2 to 5), or no drug treatment, + placebo (once-daily intravenous infusion of 100 mL of 0.9% saline on days 1, 2 and 3). MAIN OUTCOMES: The primary outcome is the proportion of patients with treatment failure at 14 days after randomisation, defined as: 1) death, 2) need for admission to an intensive care unit (ICU), 3) initiation of mechanical ventilation, 4) SpO2 falling to <90% (in ambient air) or PaO2 <60 mmHg (in ambient air) or PaO2FiO2 <300 mmHg, not explained by a cause other than COVID-19, and/or 5) decrease in PaO2 ≥15% from baseline, together with laboratory and radiological deterioration. RANDOMISATION: Treatment will be allocated by block randomisation stratified by patient age (< or ≥ 75 years of age). For this purpose, we will use the R randomizeR package using two block sizes (4 and 6) with random permutation. The randomisation sequence will be generated by a unit (the Navarrabiomed Clinical Trials Platform) independent from the researchers who will recruit patients and implement the protocol. BLINDING (MASKING): The study will be quadruple-blinded, specifically, with blinding of patients, intervention providers, outcome assessors and data managers. The pharmacy at each participating hospital will prepare indistinguishable bags of methylprednisolone or placebo (0.9% saline) for patients of the experimental and placebo groups, respectively. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with treatment failure (primary endpoint) is currently unknown. Assuming an absolute difference of 25% in the primary outcome between the two groups (35% in the control group and 10% in the intervention group), we estimate that 60 patients (30 per group) are required to detect this difference with a two-tailed type I error of 0.05 and a type II error of 0.2. Estimating a loss to follow-up of 20%, we should recruit a total sample size of 72 patients (36 per group). TRIAL STATUS: The Spanish Agency of Medicines and Medical Devices (AEMPS) and the Ethics Committee of the University Hospital La Princesa approved version 7.0 of the protocol on 30 April 2020 as a low intervention clinical trial. Subsequently, the protocol has been amended by researchers and re-approved by AEMPS and the same ethics committee on 1 July 2020 (version 8.0) and on 28 August 2020 (version 9.0). Currently, the trial is in the recruitment phase. Recruitment began on 28 May 2020 and is expected to be completed by February 2021. TRIAL REGISTRATION: This study protocol was registered on the eudract.ema.europa.eu on 5 May 2020 (title "Early treatment of COVID-19 pneumonia with glucocorticoids. Randomized controlled clinical trial"; EudraCT Number: 2020-001827-15 ) and on clinicaltrials.gov on 19 June 2020 (title: "Glucocorticoids in COVID-19 (CORTIVID)"; identifier: NCT04438980 ). FULL PROTOCOL: The full protocol (version 9.0) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Proteína C-Reactiva/metabolismo , Método Doble Ciego , Ferritinas/metabolismo , Hospitalización , Humanos , Infusiones Intravenosas , Interleucina-6/metabolismo , Quimioterapia por Pulso , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
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