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2.
BMC Pulm Med ; 20(1): 269, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066765

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects. METHODS: We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA). RESULTS: The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group. CONCLUSIONS: This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients.


Assuntos
Dióxido de Carbono/metabolismo , Infecções por Coronavirus/metabolismo , Eritrócitos/metabolismo , Hipóxia/metabolismo , Óxido Nítrico/metabolismo , Oxigênio/metabolismo , Pneumonia Viral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Betacoronavirus , Gasometria , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Feminino , Citometria de Fluxo , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pressão Parcial , Projetos Piloto , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/metabolismo , Vasodilatação , Adulto Jovem
3.
A A Pract ; 14(9): e01287, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32909713

RESUMO

Methemoglobinemia is a rare disorder of the blood in which there is an increase in methemoglobin, which occurs when hemoglobin is present in the oxidized form. Methemoglobin impairs hemoglobin's ability to transport oxygen, produces functional anemia, and leads to tissue hypoxia. We report the successful management of a case of refractory hypoxia due to acutely acquired methemoglobinemia in a patient undergoing treatment for coronavirus disease 2019 (COVID-19) pneumonia. The cause of methemoglobinemia in this patient remains unknown. Hypoxia and methemoglobinemia did not respond to methylene blue and required administration of packed red blood cell transfusions.


Assuntos
Infecções por Coronavirus/complicações , Hipóxia/etiologia , Metemoglobinemia/complicações , Pneumonia Viral/complicações , Insuficiência Respiratória/etiologia , Lesão Renal Aguda/complicações , Lesão Renal Aguda/terapia , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Corynebacterium , Infecções por Corynebacterium/complicações , Infecções por Corynebacterium/terapia , Síndrome da Liberação de Citocina/complicações , Inibidores Enzimáticos/uso terapêutico , Transfusão de Eritrócitos , Hematínicos/uso terapêutico , Humanos , Hidroxocobalamina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Hipóxia/terapia , Masculino , Metemoglobinemia/terapia , Azul de Metileno/uso terapêutico , Pandemias , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/terapia , Pneumonia Viral/tratamento farmacológico , Terapia de Substituição Renal , Insuficiência Respiratória/terapia , Choque Séptico/complicações
4.
Nat Commun ; 11(1): 4883, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985528

RESUMO

Early stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement. Although speculated that such paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. Herein, a mathematical model demonstrates that the large amount of pulmonary venous admixture observed in patients with early COVID-19 can be reasonably explained by a combination of pulmonary embolism, ventilation-perfusion mismatching in the noninjured lung, and normal perfusion of the relatively small fraction of injured lung. Although underlying perfusion heterogeneity exacerbates existing shunt and ventilation-perfusion mismatch in the model, the reported hypoxemia severity in early COVID-19 patients is not replicated without either extensive perfusion defects, severe ventilation-perfusion mismatch, or hyperperfusion of nonoxygenated regions.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Hipóxia/etiologia , Hipóxia/fisiopatologia , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Modelos Biológicos , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Circulação Pulmonar/fisiologia , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Humanos , Hipóxia/terapia , Pneumopatias/terapia , Conceitos Matemáticos , Modelos Cardiovasculares , Oxigenoterapia , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Tempo , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Relação Ventilação-Perfusão/fisiologia
5.
BMJ Open Respir Res ; 7(1)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32963028

RESUMO

Reviews of COVID-19 CT imaging along with postmortem lung biopsies and autopsies indicate that the majority of patients with COVID-19 pulmonary involvement have secondary organising pneumonia (OP) or its histological variant, acute fibrinous and organising pneumonia, both well-known complications of viral infections. Further, many publications on COVID-19 have debated the puzzling clinical characteristics of 'silent hypoxemia', 'happy hypoxemics' and 'atypical ARDS', all features consistent with OP. The recent announcement that RECOVERY, a randomised controlled trial comparing dexamethasone to placebo in COVID-19, was terminated early due to excess deaths in the control group further suggests patients present with OP given that corticosteroid therapy is the first-line treatment. Although RECOVERY along with other cohort studies report positive effects with corticosteroids on morbidity and mortality of COVID-19, treatment approaches could be made more effective given that secondary OP often requires prolonged duration and/or careful and monitored tapering of corticosteroid dose, with 'pulse' doses needed for the well-described fulminant subtype. Increasing recognition of this diagnosis will thus lead to more appropriate and effective treatment strategies in COVID-19, which may lead to a further reduction of need for ventilatory support and improved survival.


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumonia em Organização Criptogênica/diagnóstico , Erros de Diagnóstico , Hipóxia/fisiopatologia , Pulmão/diagnóstico por imagem , Pneumonia Viral/fisiopatologia , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pneumonia em Organização Criptogênica/tratamento farmacológico , Pneumonia em Organização Criptogênica/etiologia , Pneumonia em Organização Criptogênica/fisiopatologia , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Hipóxia/etiologia , Pulmão/patologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Tomografia Computadorizada por Raios X
6.
Life Sci ; 259: 118389, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898522

RESUMO

AIMS: Adenosine triphosphate (ATP) is released at a high concentration in the tumor microenvironment. The overexpression of ectonucleotidases in non-small-cell lung cancer (NSCLC), metabolizing ΑΤP to the immunosuppressive adenosine, is studied. MATERIALS AND METHODS: We examined the expression of the ectonucleotidases CD73 and CD39 in NSCLC in parallel with immunological parameters and markers of hypoxia and anaerobic metabolism. In vitro experiments with A549 and H1299 lung cancer cell lines were also conducted. RESULTS: CD73 and CD39 were not expressed by normal bronchial and alveolar epithelium. In contrast, these were overexpressed by cancer cells, cancer-associated fibroblasts (CAFs), and tumor-infiltrating lymphocytes (TILs). High CD73 cancer cell expression was directly linked with lactate dehydrogenase LDH5 and with hypoxia-inducible factor HIF1α expression by cancer cells. The expression of CD39 by CAFs was directly linked with PD-L1 expression by cancer cells. A significant abundance of FOXP3+ and PD-1+ TILs was noted in tumors with high CD73 and CD39 stroma expression. In in vitro experiments, hypoxia and acidity induced CD73 mRNA and protein levels in cancer cell lines. Exposure of cancer cell lines to adenosine induced the expression of PD-L1 and LDHA mRNA and protein levels. CONCLUSION: Ectonucleotidases are up-regulated in cancer cells, CAFs, and TILs in lung tumors. Such overexpression is linked with regulatory TIL-phenotype and PD-L1 up-regulation by cancer cells. Overexpression of LDH5 is up-regulated by adenosine, creating a vicious cycle, as the high amounts of ATP produced by LDH5-mediated anaerobic glycolysis promote the production of adenosine by a tumor microenvironment rich in ectonucleotidases.


Assuntos
5'-Nucleotidase/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Hipóxia/etiologia , Neoplasias Pulmonares/metabolismo , Adenosina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia/metabolismo , Tolerância Imunológica , Neoplasias Pulmonares/enzimologia , Masculino , Pessoa de Meia-Idade
7.
BMJ Case Rep ; 13(8)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747596
8.
BMC Med ; 18(1): 260, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814566

RESUMO

BACKGROUND: The current target oxygen saturation range for patients with COVID-19 recommended by the National Institutes of Health is 92-96%. MAIN BODY: This article critically examines the evidence guiding current target oxygen saturation recommendation for COVID-19 patients, and raises important concerns in the extrapolation of data from the two studies stated to be guiding the recommendation. Next, it examines the influence of hypoxia on upregulation of ACE2 (target receptor for SARS-CoV-2 entry) expression, with supporting transcriptomic analysis of a publicly available gene expression profile dataset of human renal proximal tubular epithelial cells cultured in normoxic or hypoxic conditions. Finally, it discusses potential implications of specific clinical observations and considerations in COVID-19 patients on target oxygen saturation, such as diffuse systemic endothelitis and microthrombi playing an important pathogenic role in the wide range of systemic manifestations, exacerbation of hypoxic pulmonary vasoconstriction in the setting of pulmonary vascular endothelitis/microthrombi, the phenomenon of "silent hypoxemia" with some patients presenting to the hospital with severe hypoxemia disproportional to symptoms, and overburdened health systems and public health resources in many parts of the world with adverse implications on outpatient monitoring and early institution of oxygen supplementation. CONCLUSIONS: The above factors and analyses, put together, call for an urgent exploration and re-evaluation of target oxygen saturation in COVID-19 patients, both in the inpatient and outpatient settings. Until data from such trials become available, where possible, it may be prudent to target an oxygen saturation at least at the upper end of the recommended 92-96% range in COVID-19 patients both in the inpatient and outpatient settings (in patients that are normoxemic at pre-COVID baseline). Home pulse oximetry, tele-monitoring, and earlier institution of oxygen supplementation for hypoxemic COVID-19 outpatients could be beneficial, where public health resources allow for their implementation.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Hipóxia/prevenção & controle , Oxigênio/sangue , Pneumonia Viral/sangue , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Humanos , Hipóxia/sangue , Hipóxia/diagnóstico , Hipóxia/etiologia , Oximetria , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto , Telemedicina
10.
Neuroradiol J ; 33(5): 374-376, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32757827

RESUMO

We are reporting the imaging findings of the rare entity of critical illness-associated cerebral microbleeds in a COVID-19-positive 66-year-old woman with hypoxic respiratory failure, who was eventually intubated and ventilated. Multiple scattered cerebral microhaemorrhages diffusely distributed in the juxtacortical white matter and internal capsule region, sparing the deep and periventricular white matter, basal ganglia, thalami and cortex were seen, which is a unique imaging finding in critically ill patients with respiratory failure and hypoxemia requiring mechanical ventilation. The mechanism underlying these microhaemorrhages relates to the endpoint of critical illness, rather than a specific underlying disease.


Assuntos
Edema Encefálico/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idoso , Betacoronavirus , Edema Encefálico/complicações , Hemorragia Cerebral/complicações , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Estado Terminal , Feminino , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Angiografia por Ressonância Magnética , Imagem por Ressonância Magnética , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Tomografia Computadorizada por Raios X
11.
Aging (Albany NY) ; 12(16): 15954-15961, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32826388

RESUMO

The COVID-19 pandemic has caused monumental mortality, and there are still no adequate therapies. Most severely ill COVID-19 patients manifest a hyperactivated immune response, instigated by interleukin 6 (IL6) that triggers a so called "cytokine storm" and coagulopathy. Hypoxia is also associated with COVID-19. So far overlooked is the fact that both IL6 and hypoxia depress the abundance of a key anticoagulant, Protein S. We speculate that the IL6-driven cytokine explosion plus hypoxemia causes a severe drop in Protein S level that exacerbates the thrombotic risk in COVID-19 patients. Here we highlight a mechanism by which the IL6-hypoxia curse causes a deadly hypercoagulable state in COVID-19 patients, and we suggest a path to therapy.


Assuntos
Infecções por Coronavirus , Síndrome da Liberação de Citocina , Hipóxia , Pandemias , Pneumonia Viral , Proteína S , Trombofilia/imunologia , Anticoagulantes/metabolismo , Anticoagulantes/farmacologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/virologia , Gerenciamento Clínico , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Hipóxia/imunologia , Interleucina-6/sangue , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Proteína S/metabolismo , Proteína S/farmacologia , Índice de Gravidade de Doença
12.
Acta Neuropathol Commun ; 8(1): 147, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847628

RESUMO

We document the neuropathologic findings of a 73-year old man who died from acute cerebellar hemorrhage in the context of relatively mild SARS-CoV2 infection. The patient developed sudden onset of headache, nausea, and vomiting, immediately followed by loss of consciousness on the day of admission. Emergency medical services found him severely hypoxemic at home, and the patient suffered a cardiac arrest during transport to the emergency department. The emergency team achieved return of spontaneous circulation after over 17 min of resuscitation. A chest radiograph revealed hazy bilateral opacities; and real-time-PCR for SARS-CoV-2 on the nasopharyngeal swab was positive. Computed tomography of the head showed a large right cerebellar hemorrhage, with tonsillar herniation and intraventricular hemorrhage. One day after presentation, he was transitioned to comfort care and died shortly after palliative extubation. Autopsy performed 3 h after death showed cerebellar hemorrhage and acute infarcts in the dorsal pons and medulla. Remarkably, there were microglial nodules and neuronophagia bilaterally in the inferior olives and multifocally in the cerebellar dentate nuclei. This constellation of findings has not been reported thus far in the context of SARS-CoV-2 infection.


Assuntos
Infartos do Tronco Encefálico/patologia , Doenças Cerebelares/patologia , Infecções por Coronavirus/patologia , Hemorragias Intracranianas/patologia , Microglia/patologia , Neurônios/patologia , Fagocitose , Pneumonia Viral/patologia , Idoso , Betacoronavirus , Infartos do Tronco Encefálico/complicações , Infartos do Tronco Encefálico/diagnóstico por imagem , Doenças Cerebelares/complicações , Doenças Cerebelares/diagnóstico por imagem , Núcleos Cerebelares/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Cefaleia/etiologia , Parada Cardíaca/etiologia , Humanos , Hipóxia/etiologia , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/diagnóstico por imagem , Masculino , Bulbo/diagnóstico por imagem , Bulbo/patologia , Núcleo Olivar/patologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Tegmento Pontino/diagnóstico por imagem , Tegmento Pontino/patologia , Tomografia Computadorizada por Raios X
13.
Lancet ; 396(10251): 603-611, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32822564

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection. METHODS: We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study-a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed. FINDINGS: Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14-28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00-0·48]) compared with infection with wild-type virus only. INTERPRETATION: The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines. FUNDING: National Medical Research Council Singapore.


Assuntos
Infecções por Coronavirus/virologia , Deleção de Genes , Genoma Viral/genética , Pneumonia Viral/virologia , Adulto , Idoso , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Pessoa de Meia-Idade , Fases de Leitura Aberta , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Terapia Respiratória , Índice de Gravidade de Doença , Singapura/epidemiologia , Replicação Viral
15.
Crit Care Med ; 48(11): e1079-e1086, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32826432

RESUMO

OBJECTIVES: An ongoing outbreak of coronavirus disease 2019 is spreading globally. Acute hypoxemic respiratory failure is the most common complication of coronavirus disease 2019. However, the clinical effectiveness of early high-flow nasal oxygen treatment in patients with coronavirus disease 2019 with acute hypoxemic respiratory failure has not been explored. This study aimed to analyze the effectiveness of high-flow nasal oxygen treatment and to identify the variables predicting high-flow nasal oxygen treatment failure in coronavirus disease 2019 patients with acute hypoxemic respiratory failure. DESIGN: A multicenter, retrospective cohort study. SETTING: Three tertiary hospitals in Wuhan, China. PATIENTS: Forty-three confirmed coronavirus disease 2019 adult patients with acute hypoxemic respiratory failure treated with high-flow nasal oxygen. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean age of the enrolled patients was 63.0 ± 9.7 years; female patients accounted for 41.9%. High-flow nasal oxygen failure (defined as upgrading respiratory support to positive pressure ventilation or death) was observed in 20 patients (46.5%), of which 13 (30.2%) required endotracheal intubation. Patients with high-flow nasal oxygen success had a higher median oxygen saturation (96.0% vs 93.0%; p < 0.001) at admission than those with high-flow nasal oxygen failure. High-flow nasal oxygen failure was more likely in patients who were older (p = 0.030) and male (p = 0.037), had a significant increase in respiratory rate and a significant decrease in the ratio of oxygen saturation/FIO2 to respiratory rate index within 3 days of high-flow nasal oxygen treatment. In a multivariate logistic regression analysis model, male and lower oxygen saturation at admission remained independent predictors of high-flow nasal oxygen failure. The hospital mortality rate of the cohort was 32.5%; however, the hospital mortality rate in patients with high-flow nasal oxygen failure was 65%. CONCLUSIONS: High-flow nasal oxygen may be effective for treating coronavirus disease 2019 patients with mild to moderate acute hypoxemic respiratory failure. However, high-flow nasal oxygen failure was associated with a poor prognosis. Male and lower oxygenation at admission were the two strong predictors of high-flow nasal oxygen failure.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Hipóxia/terapia , Intubação Intratraqueal/métodos , Pneumonia Viral/terapia , Adulto , Idoso , Estudos de Coortes , Infecções por Coronavirus/complicações , Feminino , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Respiração com Pressão Positiva , Insuficiência Respiratória/terapia , Estudos Retrospectivos
17.
Med Hypotheses ; 143: 110142, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32759013

RESUMO

BACKGROUND: Pulmonary hypertension is a significant complication for some patients with COVID-19 pneumonia, especially those requiring intensive care. Tachyphylaxis to the current therapy, inhaled nitric oxide (iNO), is also common. In vitro, folic acid directly increases nitric oxide (NO) production and extends its duration of action; effects which could be of benefit in reversing pulmonary hypertension and severe hypoxaemia. Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). HYPOTHESIS: A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion. We therefore hypothesise that folic acid, 5 mg or greater, is a useful therapeutic option for pulmonary hypertension and/or refractory severe hypoxaemia, in patients with severe COVID-19 associated pneumonia in whom NO therapy is considered, with a very low risk of adverse effects.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Ácido Fólico/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/metabolismo , Pandemias , Pneumonia Viral/complicações , Administração por Inalação , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Ativação Enzimática/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Humanos , Hipertensão Pulmonar/complicações , Hipóxia/tratamento farmacológico , Hipóxia/etiologia , Camundongos , Óxido Nítrico/administração & dosagem , Óxido Nítrico/uso terapêutico , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Taquifilaxia
19.
BMJ Case Rep ; 13(7)2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641442

RESUMO

We report on a patient with coronavirus disease 2019 (COVID-19) and decompensated cirrhosis who experienced a favourable outcome of severe immune thrombocytopaenic purpura (ITP) after administration of intravenous immunoglobulin and high-dose dexamethasone. The present case suggests that it is reasonable to evoke ITP in case of profound thrombocytopaenia in a patient with COVID-19.


Assuntos
Infecções por Coronavirus , Glucocorticoides/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Cirrose Hepática Alcoólica , Obesidade , Pandemias , Pneumonia Viral , Púrpura Trombocitopênica Idiopática , Adulto , Betacoronavirus/isolamento & purificação , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Humanos , Hipóxia/diagnóstico , Hipóxia/etiologia , Fatores Imunológicos/administração & dosagem , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/epidemiologia , Masculino , Obesidade/diagnóstico , Obesidade/epidemiologia , Oxigenoterapia/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/fisiopatologia , Púrpura Trombocitopênica Idiopática/terapia , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
20.
N Engl J Med ; 383(5): 426-439, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32726529

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).


Assuntos
Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano , Infecções Respiratórias/prevenção & controle , Adolescente , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hipóxia/etiologia , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Doenças do Recém-Nascido/prevenção & controle , Injeções Intramusculares , Nanopartículas , Distribuição de Poisson , Gravidez , Terceiro Trimestre da Gravidez , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano/imunologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Vacinação , Proteínas Virais de Fusão/imunologia , Adulto Jovem
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