RESUMO
The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure and need of higher-level care. From analysis of 203 samples, CRP, IL-6, IL-10 and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS and level of respiratory support (p ≤ 0.001). IL-6 levels of ≥3.27 pg/ml provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37 mg/l of 0.91 and 0.66. Reliable stratification of high-risk cases has significant implications on patient triage, resource management and potentially the initiation of novel therapies in severe patients.
Assuntos
Proteína C-Reativa/metabolismo , COVID-19/diagnóstico , Síndrome da Liberação de Citocina/diagnóstico , Interleucina-6/sangue , Síndrome do Desconforto Respiratório/diagnóstico , SARS-CoV-2/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/sangue , COVID-19/terapia , COVID-19/virologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/terapia , Síndrome da Liberação de Citocina/virologia , Feminino , Hospitalização , Humanos , Interleucina-10/sangue , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Incorporation of routine clinical testing for neutralizing antibodies (NAbs) to interferon (IFN)-ß has remained problematic. With increasing treatment choice for patients, routine NAb testing should be incorporated to aid therapeutic decisions. OBJECTIVE: We sought to improve interpretation of NAb results by combining the luciferase NAb assay (luciferase gene expression assay under control of interferon-stimulated response element) and in-vivo biomarker (myxovirus A protein, MxA) induction in patients with MS. METHODS: Blood samples (serum and PAXGene(®) for RNA) were obtained pre-injection and 12 hours post-injection of IFN-ß from 144 subjects. Sera were tested for NAbs using the luciferase assay. MxA expression was quantified by real-time polymerase chain reaction (PCR). RESULTS: 26% of samples were NAb positive (titre > 20 NU). There was no difference in NAb titres in the pre- or post-dose sera (p = 0.643). MxA expression was inhibited in a dose-dependent fashion in NAb positive samples. Mean MxA level post-IFN-ß: NAb negative 2330 (95% CI 1940-2719), NAb 20-99 NU 1533 (95% CI 741-2324), NAb 100-600 NU 832 (186-1478) and NAb > 600 NU 101 (95% CI 0-224). NAb titre and MxA level correlated strongly: MxA pre- (Spearman r = -0.72, p < 0.0001), MxA post- (Spearman r = -0.79, p < 0.0001) and MxA induction (Spearman r = -0.67, p = 0.0004). CONCLUSION: A single, 12-hour post-injection sample should be used to test for NAbs using the luciferase assay and IFN-ß bioactivity (MxA) in the clinical setting.
Assuntos
Anticorpos Neutralizantes/sangue , Bioensaio/métodos , Monitoramento de Medicamentos/métodos , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Proteínas de Ligação ao GTP/sangue , Proteínas de Ligação ao GTP/genética , Genes Reporter , Humanos , Fatores Imunológicos/imunologia , Interferon beta-1a , Interferon beta/imunologia , Londres , Luciferases/biossíntese , Luciferases/genética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Proteínas de Resistência a Myxovirus , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Elementos de Resposta , Fatores de Tempo , Transfecção , Resultado do Tratamento , Adulto JovemRESUMO
Few regional and seasonal Guillain-Barré syndrome (GBS) clusters have been reported so far. It is unknown whether patients suffering from sporadic GBS differ from GBS clusters with respect to clinical and paraclinical parameters, HLA association and antibody response to glycosphingolipids and Campylobacter jejuni (Cj). We examined 40 consecutive patients with GBS from the greater Munich area in Germany with 14 of those admitted within a period of 3 months in fall 2010 defining a cluster of GBS. Sequencing-based HLA typing of the HLA genes DRB1, DQB1, and DPB1 was performed, and ELISA for anti-glycosphingolipid antibodies was carried out. Clinical and paraclinical findings (Cj seroreactivity, cerebrospinal fluid parameters, and electrophysiology) were obtained and analyzed. GBS cluster patients were characterized by a more severe clinical phenotype with more patients requiring mechanical ventilation and higher frequencies of autoantibodies against sulfatide, GalC and certain ganglioside epitopes (54 %) as compared to sporadic GBS cases (13 %, p = 0.017). Cj seropositivity tended to be higher within GBS cluster patients (69 %) as compared to sporadic cases (46 %, p = 0.155). We noted higher frequencies of HLA class II allele DQB1*05:01 in the cluster cohort (23 %) as compared to sporadic GBS patients (3 %, p = 0.019). Cluster of severe GBS was defined by higher frequencies of autoantibodies against glycosphingolipids. HLA class II allele DQB1*05:01 might contribute to clinical worsening in the cluster patients.
Assuntos
Autoanticorpos/líquido cefalorraquidiano , Glicoesfingolipídeos/imunologia , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/genética , Cadeias beta de HLA-DQ/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Infecções por Campylobacter/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença/genética , Alemanha , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/genética , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: Most professionals in the healthcare environment wear uniforms. For the purpose of this study, we concentrated on nurses' uniforms. In the United Kingdom, many nurses are expected to launder their uniforms at home by using a domestic washing machine that frequently has low-temperature wash cycles. We have investigated whether the use of low-temperature wash cycles results in a microbiologically acceptable product to wear on the wards. METHODS: We have assessed the bioburden on uniforms before and after laundry and the effectiveness of low-temperature wash cycles and ironing on removal of methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii. We did not assess the role of tumble drying. RESULTS: We demonstrate contamination of uniforms by gram-negative bacteria after wash, the removal of MRSA at low-temperature wash cycles in the presence of detergent, and the eradication of gram-negative bacteria after ironing. CONCLUSIONS: Our conclusions are that laundry in a domestic situation at 60°C (140°F) for 10 minutes is sufficient to decontaminate hospital uniforms and reduces the bacterial load by more than 7-log reduction, that items left in the pockets are decontaminated to the same extent, that the addition of either a biological detergent or a nonbiological detergent is beneficial in removing MRSA from experimentally contaminated swatches, and that uniforms become recontaminated with low numbers of principally gram-negative bacteria after laundry but that these are effectively removed by ironing.
Assuntos
Vestuário , Descontaminação , Lavanderia/métodos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Temperatura , Têxteis/microbiologia , Acinetobacter baumannii/isolamento & purificação , Contagem de Colônia Microbiana , Infecção Hospitalar/etiologia , Infecção Hospitalar/prevenção & controle , Detergentes , Humanos , Recursos Humanos de Enfermagem Hospitalar , Reino UnidoRESUMO
Anomalous aortic origin of one of the coronary arteries is uncommon. There have been few reports of the left coronary artery arising from the noncoronary sinus. The occurrence of Prinzmetal's angina in association with anomalous aortic origin is extremely rare. We report a case of such a combination and discuss the diagnostic options and therapeutic decision making.