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1.
Circulation ; 143(1): 78-88, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33166178

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Síndrome de Resposta Inflamatória Sistêmica , /sangue , /tratamento farmacológico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Criança , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Esteroides/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia
2.
Pediatr Emerg Care ; 37(1): 44-47, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33181794

RESUMO

ABSTRACT: Pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS) is infrequent, but children might present as a life-threatening disease. In a systematic quantitative review, we analyzed 11 studies of PIMS-TS, including 468 children reported before July 1, 2020. We found a myriad of clinical features, but we were able to describe common characteristics: previously healthy school-aged children, persistent fever and gastrointestinal symptoms, lymphopenia, and high inflammatory markers. Clinical syndromes such as myocarditis and Kawasaki disease were present in only one third of cases each one. Pediatric intensive care unit admission was frequent, although length of stay was less than 1 week, and mortality was low. Most patients received immunoglobulin or steroids, although the level of evidence for that treatment is low. The PIMS-ST was recently described, and the detailed quantitative pooled data will increase clinicians' awareness, improve diagnosis, and promptly start treatment. This analysis also highlights the necessity of future collaborative studies, given the heterogeneous nature of the PIMS-TS.


Assuntos
/complicações , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , /epidemiologia , /terapia , Criança , Terapia Combinada , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/etiologia , Miocardite/epidemiologia , Miocardite/etiologia , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia
5.
Rheumatology (Oxford) ; 60(1): 399-407, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020836

RESUMO

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).


Assuntos
Azetidinas/uso terapêutico , Glucocorticoides/uso terapêutico , Hipóxia/terapia , Inibidores de Janus Quinases/uso terapêutico , Metilprednisolona/uso terapêutico , Oxigenoterapia/estatística & dados numéricos , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Antivirais/uso terapêutico , /fisiopatologia , Estudos de Coortes , Combinação de Medicamentos , Quimioterapia Combinada , Endotélio Vascular , Inibidores Enzimáticos/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Pulmão/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Oximetria , Estudos Prospectivos , Ritonavir/uso terapêutico , Índice de Gravidade de Doença
6.
Int J Dermatol ; 60(1): 53-59, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33252832

RESUMO

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.


Assuntos
Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/mortalidade , Adolescente , Adulto , Fatores Etários , Antibacterianos/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções por Mycoplasma/complicações , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Esteroides/uso terapêutico , Síndrome de Stevens-Johnson/patologia , Síndrome de Stevens-Johnson/terapia , Adulto Jovem
7.
Int J Dermatol ; 60(1): 44-52, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32686136

RESUMO

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.


Assuntos
Cuidados Críticos , Síndrome de Stevens-Johnson/terapia , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Tratamento Conservador , Dexametasona/uso terapêutico , Oftalmopatias/etiologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunomodulação , Lactente , Unidades de Terapia Intensiva Pediátrica , Tempo de Internação , Masculino , Metilprednisolona/uso terapêutico , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Sepse/microbiologia , Índice de Gravidade de Doença , Esteroides/uso terapêutico , Síndrome de Stevens-Johnson/complicações , Síndrome de Stevens-Johnson/mortalidade , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
9.
Brain Dev ; 43(2): 230-233, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33082059

RESUMO

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.


Assuntos
Encefalopatias/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico por imagem , Encefalopatias/tratamento farmacológico , Encefalopatias/fisiopatologia , /tratamento farmacológico , Criança , Dispneia/fisiopatologia , Eletroencefalografia , Exantema/fisiopatologia , Feminino , Febre/fisiopatologia , Glucocorticoides/uso terapêutico , Alucinações/fisiopatologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Transtornos Neurocognitivos/diagnóstico por imagem , Transtornos Neurocognitivos/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Taquipneia/fisiopatologia
10.
Mod Rheumatol Case Rep ; 5(1): 101-107, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019894

RESUMO

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.


Assuntos
/complicações , Dermatomiosite/complicações , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Pneumonia por Pneumocystis/complicações , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Autoanticorpos/imunologia , Broncoscopia , Criança , Ciclofosfamida/uso terapêutico , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/terapia , Linfo-Histiocitose Hemofagocítica/imunologia , Enfisema Mediastínico/etiologia , Metilprednisolona/uso terapêutico , Piperidinas/uso terapêutico , Pneumonia por Pneumocystis/imunologia , Pneumotórax/etiologia , Pirimidinas/uso terapêutico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Choque Séptico/etiologia , Enfisema Subcutâneo/etiologia , Tomografia Computadorizada por Raios X , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
11.
J Frailty Aging ; 10(1): 70-71, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33331625

RESUMO

COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, showed higher severity and lethality in male older adults . There are currently no specific treatments. Studies are evaluating the efficacy of monoclonal antibodies against interleukin-6 receptor. Here we present the case of a 98-years old man admitted to our COVID-Hospital with acute respiratory failure. Comprehensive geriatric assessment showed no signs of frailty. First-line therapy with hydroxychloroquine and anticoagulants was not effective. Patient was administered intravenous monoclonal antibodies, and he showed remarkable clinical improvement. This case suggests that age alone should not preclude access to new therapeutic approaches. Comprehensive, multisciplinary, multidomain approaches are needed to develop patient-tailored treatments against COVID-19.


Assuntos
Anticorpos Monoclonais/uso terapêutico , /terapia , Idoso de 80 Anos ou mais , Hospitalização , Humanos , Hidroxicloroquina , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Receptores de Interleucina-6
12.
Medicine (Baltimore) ; 99(50): e23607, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327330

RESUMO

RATIONALE: Stiff-person syndrome (SPS) is an uncommon neurological disorder with autoimmune features. Here, we report a 60-year-old man with SPS associated with critical illness polyneuropathy (CIP). CIP was diagnosed during an episode of acute respiratory failure secondary to muscular rigidity and spasms, which has rarely been reported in this condition. The overlapping of CIP and SPS complicated the case. PATIENT CONCERNS: A 60-year-old man presented with gradual onset of cramps, stiffness, and rigidity in his lower limbs 1 year before admission, which eventually led to inability to stand and walk. The persistent nature of his symptoms progressed to frequent acute episodes of dyspnea and he was admitted to intensive care unit (ICU). DIAGNOSIS: SPS had been diagnosed after 2 tests of electromyography (EMG) and the detection of an elevated anti-GAD65 antibody titer. During the first EMG, low or absent compound muscle action potentials (CMAP), and sensory nerve action potentials (SNAP) were shown. Therefore, the diagnosis of SPS coexisting with CIP was made. INTERVENTIONS: Symptomatic treatment was initiated with oral clonazepam (0.5 mg Bid) and baclofen (5 mg Bid). Intravenous immunoglobulin (IVIG) (0.4 g/kg/d) was administered for the patient for 5 days after admission. We observed a significant clinical improvement during the administration period, and the patient became ambulatory. OUTCOMES: On follow-up, the patient reported complete relief of his pain and rigidity. LESSONS: We report this special case to address the varied clinical features of SPS. Electrophysiological testing is an important diagnostic approach. Accurate recognition of the disease ensures that the patients can be given appropriate treatment without delay.


Assuntos
Polineuropatias/diagnóstico , Insuficiência Respiratória/etiologia , Rigidez Muscular Espasmódica/diagnóstico , Baclofeno/administração & dosagem , Baclofeno/uso terapêutico , Clonazepam/administração & dosagem , Clonazepam/uso terapêutico , Diagnóstico Diferencial , Eletromiografia , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/uso terapêutico , Polineuropatias/complicações , Rigidez Muscular Espasmódica/complicações
13.
Medicine (Baltimore) ; 99(52): e23714, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350751

RESUMO

INTRODUCTION: Kawasaki disease (KD) is the leading cause of acquired heart abnormalities during childhood. The infiltration of CD8+ T cells plays an essential role in the formation of coronary aneurysms. Follicular cytotoxic T (Tfc) cells are a newly defined subset of CD8+ T cells that express CXC-chemokine receptor 5. The role of Tfc cells in KD is unclear. However, in this report, we present 2 KD children with sustained coronary artery aneurysms (CAA), and we found that their peripheral C-X-C Chemokine Receptor 5+ T cells contained quite amounts of CD4 negative cells. Importantly, these cells have never been reported in KD. PATIENTS CONCERNS: Case 1 was a 3-year-old boy with a complaint of continuous fever for 6 days and conjunctival injection for 3 days. Case 2 was a 6-month-old boy who was hospitalized because of persistent fever for 5 days, rashes and conjunctival injection for 1 day. DIAGNOSIS: Case 1 was diagnosed with KD according to typical symptoms and signs including fever over 5 days, conjunctival injection, rashes, swelling cervical lymph nodes and a strawberry tongue. Case 2 had atypical symptoms including persistent fever for 5 days, rashes and conjunctival injection, and he was diagnosed with KD based on the echocardiographic findings. INTERVENTION: Both the 2 patients received intravenous immunoglobulin and oral aspirin. Besides, case 1 was given the second infusion of intravenous immunoglobulin, intravenous prednisolone and low-molecular-weight heparin. OUTCOMES: The CAA of case 1 did not regress until the 12th month after disease onset. The CAA of patient 2 began to regress at the third month after disease onset. During the months from disease onset to the recent follow-up, no cardiovascular events had occurred. CONCLUSIONS: We speculate that Tfc cells may be associated with the formation of CAA. Further studies with larger sample size and functional analysis of these cells are needed.


Assuntos
Aneurisma Coronário/diagnóstico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Administração Oral , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Pré-Escolar , Aneurisma Coronário/complicações , Aneurisma Coronário/tratamento farmacológico , Aneurisma Coronário/metabolismo , Diagnóstico Diferencial , Febre/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/metabolismo , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Linfócitos T Citotóxicos/metabolismo
14.
Sci China Life Sci ; 63(12): 1833-1849, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33355886

RESUMO

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients' outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.


Assuntos
Anticorpos Antivirais/biossíntese , /imunologia , /imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/biossíntese , Anticorpos Neutralizantes/uso terapêutico , Infecções Assintomáticas , /isolamento & purificação , China , Desenvolvimento de Medicamentos/tendências , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade Humoral , Imunização Passiva , Imunoglobulinas Intravenosas/uso terapêutico , Modelos Imunológicos , Pandemias , /prevenção & controle , Soroconversão
15.
BMJ Case Rep ; 13(12)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298501

RESUMO

An 11-year-old boy presented with features resembling those described in health alerts on Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), including persistent fever, haemodynamic instability and abdominal pain. Laboratory tests, including raised inflammatory markers, D-dimer, troponin and a coagulopathy, were consistent with PIMS-TS. Our patient required transfer to the paediatric intensive care unit; an echocardiography revealed left ventricular dysfunction. He was treated with intravenous immunoglobulins (Igs), corticosteroids and aspirin, with full resolution of clinical symptoms. A follow-up echocardiogram 1 month after discharge was unremarkable.Three SARS-CoV-2 PCRs on respiratory samples, taken over the initial 4-day period, were negative, as was a SARS-CoV-2 PCR on faeces 1 month after presentation; titres of IgG were clearly elevated. The negative PCRs in the presence of elevated titres of IgG suggest that the inflammatory syndrome might have developed in a late phase of COVID-19 infection when the virus was no longer detectable in the upper airway.


Assuntos
/diagnóstico , /isolamento & purificação , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Corticosteroides/uso terapêutico , Aspirina/uso terapêutico , Criança , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Unidades de Terapia Intensiva Pediátrica , Masculino , Avaliação de Sintomas , Resultado do Tratamento
16.
Med Hypotheses ; 144: 110263, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254568

RESUMO

In recent months, there are increasing reports of a Kawasaki disease-like syndrome in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed 'Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS)' in the UK. Debate is ongoing regarding the nature of these pro-inflammatory syndromes. We herein propose that the platelet count may, at least in part, be able to help us differentiate between the two aforementioned syndromes. In a recent report, compared to a historical 'classical' Kawasaki disease (KD) cohort, patients with PIMS-TS had significantly lower platelet counts (188 vs 383 g/L, p < 0.0001). A possible explanation for this is their difference in underlying immunopathogenesis. In KD, the fundamental pathogenesis is thought to be immune complex-mediated, hence, the use of intravenous immunoglobulin (IVIg) which competes with the immunoglobulin Fc receptors (FcRs) on inflammatory cells, preventing the activation of these cells and thereby ameliorating the inflammatory response. If left untreated, these immune complexes activates the inflammatory cells (including monocytes and neutrophils), which also results in recruitment of platelets, resulting in the thrombocytosis we commonly see in KD. These immune complexes may also bind to platelets directly via FcRs on platelet membranes. In contrast, in viral-associated hyperinflammatory syndromes (e.g. PIMS-TS or MIS-C), there are mediators being secreted in the process of eradication of the virus (mainly to stimulate CD8+ cells to kill viral infected cells), which would inadvertently suppress bone marrow function and activate platelets, culminating in thrombocytopenia.


Assuntos
/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Plaquetas/metabolismo , /diagnóstico , Criança , Diagnóstico Diferencial , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Inflamação , Modelos Teóricos , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Trombocitopenia/complicações , Reino Unido
17.
S D Med ; 73(10): 458-460, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33264524

RESUMO

This report describes a rare case of an 87-year-old woman presenting to a rural emergency department with ataxia. Throughout her admission, she developed areflexia and ophthalmoplegia consistent with a diagnosis of Miller Fisher syndrome. The patient underwent a rapid recovery after receiving treatment with intravenous immunoglobulin (IVIg) for a duration of five days and a two-month period of outpatient physical therapy.


Assuntos
Síndrome de Miller Fisher , Oftalmoplegia , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Miller Fisher/complicações , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/terapia , Oftalmoplegia/etiologia , South Dakota
18.
Int J Clin Pharmacol Ther ; 58(12): 678-686, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33141018

RESUMO

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.


Assuntos
Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/terapia , Pneumonia Viral/terapia , Animais , Betacoronavirus , Bovinos , Células Cultivadas , Síndrome da Liberação de Citocina/virologia , Citocinas , Humanos , Imunização Passiva , Imunoglobulinas Intravenosas/uso terapêutico , Leucócitos Mononucleares , Pandemias
20.
BMC Infect Dis ; 20(1): 786, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087047

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has infected people in many countries worldwide. Discovering an effective treatment for this disease, particularly in severe cases, has become the subject of intense scientific investigation. Therefore, the objective of this study was to evaluate the efficacy of intravenous immunoglobulin (IVIg) in patients with severe COVID-19 infection. METHODS: This study was conducted as a randomized placebo-controlled double-blind clinical trial. Fifty-nine patients with severe COVID-19 infection who did not respond to initial treatments were randomly assigned into two groups. One group received IVIg (human)-four vials daily for 3 days (in addition to initial treatment), while the other group received a placebo. Patients' demographic, clinical, and select laboratory test results, as well as the occurrence of in-hospital mortality, were recorded. RESULTS: Among total study subjects, 30 patients received IVIg and 29 patients received a placebo. Demographics, clinical characteristics, and laboratory tests were not statistically different (P > 0.05) between the two groups. The in-hospital mortality rate was significantly lower in the IVIg group compared to the control group (6 [20.0%] vs. 14 [48.3%], respectively; P = 0.022). Multivariate regression analysis demonstrated that administration of IVIg did indeed have a significant impact on mortality rate (aOR = 0.003 [95% CI: 0.001-0.815]; P = 0.042). CONCLUSIONS: Our study demonstrated that the administration of IVIg in patients with severe COVID-19 infection who did not respond to initial treatment could improve their clinical outcome and significantly reduce mortality rate. Further multicenter studies with larger sample sizes are nonetheless required to confirm the appropriateness of this medication as a standard treatment. TRIAL REGISTRATION: A study protocol was registered at the Iranian Registry of Clinical Trials ( www.IRCT.ir ), number IRCT20200501047259N1 . It was registered retrospectively on May 17th, 2020.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Adulto , Idoso , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Método Duplo-Cego , Feminino , Mortalidade Hospitalar , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
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