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1.
Proc Natl Acad Sci U S A ; 118(23)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34016708

RESUMO

The SARS-CoV-2 pandemic has caused a surge in research exploring all aspects of the virus and its effects on human health. The overwhelming publication rate means that researchers are unable to keep abreast of the literature. To ameliorate this, we present the CoronaCentral resource that uses machine learning to process the research literature on SARS-CoV-2 together with SARS-CoV and MERS-CoV. We categorize the literature into useful topics and article types and enable analysis of the contents, pace, and emphasis of research during the crisis with integration of Altmetric data. These topics include therapeutics, disease forecasting, as well as growing areas such as "long COVID" and studies of inequality. This resource, available at https://coronacentral.ai, is updated daily.


Assuntos
COVID-19 , Aprendizado de Máquina , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Pandemias , SARS-CoV-2/metabolismo , Síndrome Respiratória Aguda Grave , Animais , COVID-19/epidemiologia , COVID-19/metabolismo , COVID-19/terapia , COVID-19/transmissão , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/transmissão
3.
Acta Med Indones ; 53(1): 86-95, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33818411

RESUMO

The global widespread mortality after the emergence of SARS-CoV-2 infection in China, has become a critical concern all around the world. Convalescent plasma (CP) therapy is one of the methods elevating the survival rate for COVID-19 infection cases. This technique, as a practicable therapy, was used in previous viral outbreaks including influenza, SARS and MERS. In CP therapy, the blood plasma is collected from persons rehabilitated from that specific infection in order to develop a passive immunity in other patients. Therefore, this review aimed to point out the role of CP therapy in aforementioned viral infections and illustrate different factors influencing the efficacy of CP therapy.


Assuntos
COVID-19/terapia , Infecções por Coronavirus/terapia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/terapia , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Humanos , Imunização Passiva/métodos , Resultado do Tratamento
4.
Cell Transplant ; 30: 963689721996217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33845643

RESUMO

COVID-19 has spread worldwide, including the United States, United Kingdom, and Italy, along with its site of origin in China, since 2020. The virus was first found in the Wuhan seafood market at the end of 2019, with a controversial source. The clinical symptoms of COVID-19 include fever, cough, and respiratory tract inflammation, with some severe patients developing an acute and chronic lung injury, such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). It has already claimed approximately 300 thousand human lives and the number is still on the rise; the only way to prevent the infection is to be safe till vaccines and reliable treatments develop. In previous studies, the use of mesenchymal stem cells (MSCs) in clinical trials had been proven to be effective in immune modulation and tissue repair promotion; however, their efficacy in treating COVID-19 remains underestimated. Here, we report the findings from past experiences of SARS and MSCs, and how SARS could also induce PF. Such studies may help to understand the rationale for the recent cell-based therapies for COVID-19.


Assuntos
COVID-19/complicações , Transplante de Células-Tronco Mesenquimais , Fibrose Pulmonar/etiologia , Animais , COVID-19/sangue , COVID-19/patologia , COVID-19/terapia , Coronavirus/isolamento & purificação , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Fibrose Pulmonar/sangue , Fibrose Pulmonar/patologia , Fibrose Pulmonar/terapia , Sistema Renina-Angiotensina , SARS-CoV-2/isolamento & purificação , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/terapia , Fator de Crescimento Transformador beta/sangue
5.
Trials ; 22(1): 188, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673845

RESUMO

OBJECTIVE: To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. METHOD: We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. RESULTS: A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). CONCLUSION: Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.


Assuntos
COVID-19/terapia , Ensaios Clínicos como Assunto , Influenza Humana/terapia , Medicina Tradicional Chinesa , Sistema de Registros/normas , Síndrome Respiratória Aguda Grave/terapia , Humanos , Vírus da Influenza A Subtipo H1N1 , Saúde Pública , SARS-CoV-2
6.
Biomed J ; 44(1): 86-93, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33602634

RESUMO

Coronavirus disease 2019 (COVID-19) outbreak is proving to be an unprecedented disaster that lays its dark shadow on global health, economics and personal freedom. Severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) epidemics provide scientific data that is useful in better understanding and resolution of COVID-19. Similarities among SARS-CoV, MERS-CoV and SARS-CoV-2 have been investigated in the light of available data. SARS-CoV, MERS-CoV and SARS-CoV-2 evolved in bats and have positive-sense RNA genomes of 27.9 kb, 30.1 kb and 29.9 kb, respectively. Molecular and serological tools used for diagnosis of SARS and MERS patients resemble COVID-19 diagnostic tools. Stability and longevity data of SARS and MERS epidemics contribute in the current pandemic precaution policies. Trials to produce vaccines for SARS-CoV and MERS-CoV failed, therefore different strategies were employed for SARS-CoV2 vaccines production and during the past period antiviral agents, Convalescent plasma and monoclonal antibodies provide potential treatments for sever patients. The mortality rate caused by the SARS-CoV and MERS-CoV reached 15% and 37%, respectively. The first declarations about mortality rate of SARS-CoV-2 was around 2-4% but now this rate differed globally and reached more than 13% in some countries. A realistic COVID-19 outbreak scenario suggest that the pandemic might last for three years with fluctuation in the number of infected cases, unless vaccination process goes faster and/or antiviral drug is discovered.


Assuntos
COVID-19/epidemiologia , Infecções por Coronavirus/epidemiologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/epidemiologia , Adulto , Fatores Etários , Idoso , COVID-19/mortalidade , COVID-19/terapia , Comorbidade , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/terapia , Caracteres Sexuais
7.
J Immunol ; 206(7): 1569-1575, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33547169

RESUMO

The IL-1 receptor antagonist, anakinra, may represent a therapeutic option for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19). In this study, COVID-19 ARDS patients admitted to the Azienda Socio Sanitaria Territoriale of Lecco, Italy, between March 5th to April 15th, 2020, and who had received anakinra off-label were retrospectively evaluated and compared with a cohort of matched controls who did not receive immunomodulatory treatment. The primary end point was survival at day 28. The population consisted of 112 patients (56 treated with anakinra and 56 controls). Survival at day 28 was obtained in 69 patients (61.6%) and was significantly higher in anakinra-treated patients than in the controls (75.0 versus 48.2%, p = 0.007). When stratified by continuous positive airway pressure support at baseline, anakinra-treated patients' survival was also significant compared with the controls (p = 0.008). Univariate analysis identified anakinra usage (odds ratio, 3.2; 95% confidence interval, 1.47-7.17) as a significant survival predictor. This was not supported by multivariate modeling. The rate of infectious-related adverse events was similar between groups. In conclusion, anakinra improved overall survival and invasive ventilation-free survival and was well tolerated in patients with ARDS associated with COVID-19.


Assuntos
COVID-19 , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Respiração Artificial , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave , Idoso , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/terapia , Intervalo Livre de Doença , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/antagonistas & inibidores , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/virologia , Taxa de Sobrevida
8.
J Bras Nefrol ; 43(1): 132-134, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33599679

RESUMO

This patient was a 73-year-old man who initially came to our service with acute respiratory failure secondary to COVID-19. Soon after hospitalization, he was submitted to orotracheal intubation and placed in the prone position to improve hypoxia, due to severe acute respiratory syndrome (SARS). On the third day of hospitalization, he developed acute oliguric kidney injury and volume overload. The nephrology service was activated to obtain deep venous access for renal replacement therapy (RRT). The patient could not be placed in the supine position due to significant hypoxemia. A 50-cm Permcath (MAHURKARTM, Covidien, Massachusetts, USA) was inserted through the left popliteal vein. This case report describes a possible challenging scenario that the interventional nephrologist may encounter when dealing with patients with COVID-19 with respiratory impairment in the prone position.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , COVID-19/complicações , Cuidados Críticos/métodos , Posicionamento do Paciente , Veia Poplítea , Terapia de Substituição Renal/métodos , Insuficiência Respiratória/complicações , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/complicações , Idoso , COVID-19/terapia , COVID-19/virologia , Evolução Fatal , Hospitalização , Humanos , Intubação Intratraqueal/métodos , Masculino , Decúbito Ventral , Insuficiência Respiratória/terapia , Síndrome Respiratória Aguda Grave/terapia
9.
Mil Med Res ; 8(1): 13, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593415

RESUMO

BACKGROUND: Until January 18, 2021, coronavirus disease-2019 (COVID-19) has infected more than 93 million individuals and has caused a certain degree of panic. Viral pneumonia caused by common viruses such as respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses have been more common in children. However, the incidence of COVID-19 in children was significantly lower than that in adults. The purpose of this study was to describe the clinical manifestations, treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak. METHODS: Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study. A total of 64 children with COVID-19 were defined as the COVID-19 cohort, of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort. Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort. The epidemiologic, clinical, and laboratory findings were compared by Kolmogorov-Smirnov test, t-test, Mann-Whitney U test and Contingency table method. Drug usage, immunotherapy, blood transfusion, and need for oxygen support were collected as the treatment indexes. Mortality, intensive care needs and symptomatic duration were collected as the outcome indicators. RESULTS: Compared with the viral pneumonia cohort, children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19 (53/64 vs. 23/284), were of older median age (6.3 vs. 3.2 years), and had a higher proportion of ground-glass opacity (GGO) on computed tomography (18/40 vs. 0/38, P < 0.001). Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases (1/40 vs. 38/284, P = 0.048), and lower cases with high fever (3/40 vs. 167/284, P < 0.001), requiring intensive care (1/40 vs. 32/284, P < 0.047) and with shorter symptomatic duration (median 5 vs. 8 d, P < 0.001). The proportion of cases with evaluated inflammatory indicators, biochemical indicators related to organ or tissue damage, D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort (P < 0.05). No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs (lopinavir-ritonavir, ribavirin, and arbidol) as compared with duration in 39 children without antiviral therapy [median 10 vs. 9 d, P = 0.885]. CONCLUSION: The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia. Lopinavir-ritonavir, ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19. During the COVID-19 outbreak, attention also must be given to children with infection by other pathogens infection.


Assuntos
COVID-19/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Adolescente , COVID-19/fisiopatologia , COVID-19/terapia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/fisiopatologia , Síndrome Respiratória Aguda Grave/terapia , Índice de Gravidade de Doença
11.
Emergencias (Sant Vicenç dels Horts) ; 33(1): 42-58, feb. 2021. tab, ilus, mapas
Artigo em Espanhol | IBECS | ID: ibc-202135

RESUMO

La incidencia y el impacto de la COVID-19 (Coronavirus Disease 2019) en Latinoamérica y España, en particular en sus servicios de urgencias hospitalarios (SUH), independientemente de la diversidad de los conceptos y definiciones de casos confirmados o sospechosos empleados ha sido, es, y, desgraciadamente a medio plazo, va a seguir siendo enorme, sostenida e imprevisible. En este escenario global, un grupo multinacional de expertos y representantes del Grupo de Trabajo Latinoamericano para la mejora de la atención del paciente con Infección en Urgencias (GT-LATINFURG), compuesto por 13 Sociedades y Asociaciones Científicas que integran la Federación Latinoamericana de Medicina de Emergencias (FLAME), junto con la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES),ha elaborado diversos documentos técnicos y de opinión destinados a los profesionales de los Sistemas de Urgencias y Emergencias de nuestros países. El objetivo de este artículo es ofrecer unas pautas o recomendaciones consensuadas para facilitar la actuación de los SUH en relación los puntos que los miembros del grupo han considerado más interesantes o clave en relación a: la necesidad de reorganizar los SUH, triaje, disponibilidad de pruebas complementarias habituales y otras como biomarcadores, la identificación del paciente con COVID-19 a través de criterios clínicos, analíticos, radiológicos y microbiológicos, así como factores de riesgo, pronóstico y de mortalidad que puedan ayudara detectar rápidamente a los pacientes graves a su llegada a los dispositivos de Urgencias y Emergencias de los hospitales en nuestro entorno


The incidence of the coronavirus disease 2019 (COVID-19) in Latin America and Spain and its impact particularly on hospital emergency departments have been great, sustained, and unpredictable. Unfortunately, this situation will continue in the medium term, regardless of the diverse concepts and definitions used to identify cases or hypotheses about the role of staff. In the context of the worldwide pandemic, a multinational group of experts from the Latin American Working Group to Improve Care for Patients With Infection (GT-LATINFURG) has drafted various opinion papers for use by emergency care systems in the member countries. The GT-LATINFURG is comprised of representatives from the 13 scientific associations affiliated with the Latin American Federation for Emergency Medicine (FLAME). Experts from the Spanish Society of Emergency Medicine (SEMES) also participated. The present consensus statement offers protocols and recommendations to facilitate the work of hospital emergency departments with regard to key issues the group identified, namely, the need for reorganization, triage, and routine test availability. Additional issues discussed include biomarkers; clinical, laboratory, radiologic, and microbiologic criteria for identifying patients with COVID-19; and risk and prognostic factors for mortality that emergency staff can use to quickly detect severe cases in our settings


Assuntos
Humanos , Infecções por Coronavirus/terapia , Tratamento de Emergência/normas , Síndrome Respiratória Aguda Grave/terapia , Vírus da SARS/isolamento & purificação , Padrões de Prática Médica , Pandemias/prevenção & controle , Melhoria de Qualidade/normas , Índice de Gravidade de Doença , Testes de Função Respiratória/métodos , América Latina/epidemiologia
12.
Science ; 371(6531): 823-829, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33495307

RESUMO

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/metabolismo , Anticorpos Antivirais/genética , Anticorpos Antivirais/metabolismo , Afinidade de Anticorpos , Sítios de Ligação , Sítios de Ligação de Anticorpos , Anticorpos Amplamente Neutralizantes/genética , Anticorpos Amplamente Neutralizantes/metabolismo , COVID-19/prevenção & controle , COVID-19/terapia , Técnicas de Visualização da Superfície Celular , Evolução Molecular Direcionada , Epitopos/imunologia , Humanos , Imunização Passiva , Fragmentos Fc das Imunoglobulinas/imunologia , Camundongos Endogâmicos BALB C , Domínios Proteicos , Engenharia de Proteínas , Receptores de Coronavírus/metabolismo , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/terapia , Glicoproteína da Espícula de Coronavírus/metabolismo
13.
Viruses ; 13(1)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33477902

RESUMO

Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike's receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Mapeamento de Epitopos , Epitopos/imunologia , Humanos , Imunização Passiva/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , SARS-CoV-2/genética , Síndrome Respiratória Aguda Grave/terapia , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Virais/imunologia , Internalização do Vírus/efeitos dos fármacos
14.
Theranostics ; 11(3): 1207-1231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391531

RESUMO

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.


Assuntos
Antivirais/uso terapêutico , COVID-19/terapia , Infecções por Coronavirus/terapia , Síndrome Respiratória Aguda Grave/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Animais , COVID-19/mortalidade , Carbamatos/uso terapêutico , Infecções por Coronavirus/mortalidade , Modelos Animais de Doenças , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Imidazóis/uso terapêutico , Imunização Passiva/métodos , Pirrolidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome Respiratória Aguda Grave/mortalidade , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivados , Valina/uso terapêutico
15.
Ann Emerg Med ; 77(1): 19-31, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32788066

RESUMO

STUDY OBJECTIVE: To synthesize the evidence regarding the infection risk associated with different modalities of oxygen therapy used in treating patients with severe acute respiratory infection. Health care workers face significant risk of infection when treating patients with a viral severe acute respiratory infection. To ensure health care worker safety and limit nosocomial transmission of such infection, it is crucial to synthesize the evidence regarding the infection risk associated with different modalities of oxygen therapy used in treating patients with severe acute respiratory infection. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2000, to April 1, 2020, for studies describing the risk of infection associated with the modalities of oxygen therapy used for patients with severe acute respiratory infection. The study selection, data extraction, and quality assessment were performed by independent reviewers. The primary outcome measure was the infection of health care workers with a severe acute respiratory infection. Random-effect models were used to synthesize the extracted data. RESULTS: Of 22,123 citations, 50 studies were eligible for qualitative synthesis and 16 for meta-analysis. Globally, the quality of the included studies provided a very low certainty of evidence. Being exposed or performing an intubation (odds ratio 6.48; 95% confidence interval 2.90 to 14.44), bag-valve-mask ventilation (odds ratio 2.70; 95% confidence interval 1.31 to 5.36), and noninvasive ventilation (odds ratio 3.96; 95% confidence interval 2.12 to 7.40) were associated with an increased risk of infection. All modalities of oxygen therapy generate air dispersion. CONCLUSION: Most modalities of oxygen therapy are associated with an increased risk of infection and none have been demonstrated as safe. The lowest flow of oxygen should be used to maintain an adequate oxygen saturation for patients with severe acute respiratory infection, and manipulation of oxygen delivery equipment should be minimized.


Assuntos
Infecção Hospitalar/transmissão , Transmissão de Doença Infecciosa do Paciente para o Profissional , Oxigenoterapia , Síndrome Respiratória Aguda Grave/transmissão , Infecção Hospitalar/terapia , Humanos , Oxigenoterapia/efeitos adversos , Fatores de Risco , Síndrome Respiratória Aguda Grave/terapia
16.
Ann Allergy Asthma Immunol ; 126(4): 321-337, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33310180

RESUMO

OBJECTIVE: To review the virology, immunology, epidemiology, clinical manifestations, and treatment of the following 3 major zoonotic coronavirus epidemics: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). DATA SOURCES: Published literature obtained through PubMed database searches and reports from national and international public health agencies. STUDY SELECTIONS: Studies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19, with a focus on patients with asthma, allergy, and primary immunodeficiency. RESULTS: Although SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies on nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not seem to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive. It is recommended that effective therapies, including inhaled corticosteroids and biologic therapy, be continued to maintain disease control. There are no reports of COVID-19 among patients with primary innate and T-cell deficiencies. The presentation of COVID-19 among patients with primary antibody deficiencies is variable, with some experiencing mild clinical courses, whereas others experiencing a fatal disease. The landscape of treatment for COVID-19 is rapidly evolving, with both antivirals and immunomodulators demonstrating efficacy. CONCLUSION: Further data are needed to better understand the role of asthma, allergy, and primary immunodeficiency on COVID-19 infection and outcomes.


Assuntos
COVID-19/epidemiologia , COVID-19/patologia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , COVID-19/terapia , COVID-19/transmissão , Criança , Pré-Escolar , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/transmissão , Adulto Jovem
17.
FASEB J ; 35(1): e21197, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33368679

RESUMO

SARS-CoV and SARS-CoV-2 encode four structural and accessory proteins (spike, envelope, membrane and nucleocapsid proteins) and two polyproteins (pp1a and pp1ab). The polyproteins are further cleaved by 3C-like cysteine protease (3CLpro ) and papain-like protease (PLpro ) into 16 nonstructural proteins (nsps). PLpro is released from nsp3 through autocleavage, and then it cleaves the sites between nsp1/2, between nsp2/3 and between nsp3/4 with recognition motif of LXGG, and the sites in the C-terminus of ubiquitin and of protein interferon-stimulated gene 15 (ISG15) with recognition motif of RLRGG. Alone or together with SARS unique domain (SUD), PLpro can stabilize an E3 ubiquitin ligase, the ring-finger, and CHY zinc-finger domain-containing 1 (RCHY1), through domain interaction, and thus, promote RCHY1 to ubiquitinate its target proteins including p53. However, a dilemma appears in terms of PLpro roles. On the one hand, the ubiquitination of p53 is good for SARS-CoV because the ubiquitinated p53 cannot inhibit SARS-CoV replication. On the other hand, the ubiquitination of NF-κB inhibitor (IκBα), TNF receptor-associated factors (TRAFs), and stimulator of interferon gene (STING), and the ISGylation of targeted proteins are bad for SARS-CoV because these ubiquitination and ISGylation initiate the innate immune response and antiviral state. This mini-review analyzes the dilemma and provides a snapshot on how the viral PLpro smartly manages its roles to avoid its simultaneously contradictory actions, which could shed lights on possible strategies to deal with SARS-CoV-2 infections.


Assuntos
COVID-19/virologia , Proteases Semelhantes à Papaína de Coronavírus/fisiologia , Vírus da SARS/fisiologia , SARS-CoV-2/fisiologia , Síndrome Respiratória Aguda Grave/virologia , COVID-19/imunologia , COVID-19/terapia , Proteases Semelhantes à Papaína de Coronavírus/genética , Genes Virais , Interações Hospedeiro-Patógeno , Humanos , Terapia de Alvo Molecular , NF-kappa B/metabolismo , Domínios Proteicos , Processamento de Proteína Pós-Traducional , Vírus da SARS/genética , SARS-CoV-2/genética , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/terapia , Especificidade por Substrato , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Proteínas Virais/metabolismo , Replicação Viral
18.
BMC Pulm Med ; 20(1): 317, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287790

RESUMO

BACKGROUND: The COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia. METHODS: We plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and ß risk of 20 percent. DISCUSSION: This study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences. FUNDING AND REGISTRATION: The trial is funded by the Belgian Health Care Knowledge Center KCE # COV201004 TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT04558476. Registered 14 September 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04558476.


Assuntos
COVID-19/terapia , Respiração Artificial , Síndrome Respiratória Aguda Grave/terapia , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Bélgica , COVID-19/mortalidade , Ensaios Clínicos Fase II como Assunto , Humanos , Imunização Passiva , Unidades de Terapia Intensiva , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome Respiratória Aguda Grave/mortalidade , Fatores de Tempo , Resultado do Tratamento
19.
Monaldi Arch Chest Dis ; 90(4)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33305555

RESUMO

The novel coronavirus (SARS-CoV-2) has distinct clinical manifestations that can vary from an asymptomatic condition to severe acute respiratory failure. Phenotypes are attributable to different pathophysiological mechanisms and require different treatment strategies. The assessment and identification of different phenotypes can guide therapy configurations such as oxygen therapy, non-invasive ventilation, airway management, and tracheal intubation. Further studies are essential to provide information on the influence of phenotypes in the decision of rehabilitation strategies. The sequelae left in the respiratory system of COVID-19 survivors and its limitations will be a challenge for rehabilitation services worldwide. Lung injuries are directly related to the phenotypes presented, and depending on the degree of these injuries, rehabilitation strategies can be targeted. We believe that differentiating patients, according to their respective phenotypes, can improve decision-making in treatment and individualized rehabilitation.


Assuntos
COVID-19/epidemiologia , COVID-19/reabilitação , Medicina Física e Reabilitação/métodos , SARS-CoV-2/genética , Manuseio das Vias Aéreas/métodos , COVID-19/terapia , COVID-19/virologia , Tomada de Decisão Clínica , Humanos , Intubação Intratraqueal/métodos , Ventilação não Invasiva/métodos , Oxigênio/uso terapêutico , Fenótipo , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/virologia
20.
Front Immunol ; 11: 567710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178193

RESUMO

The serological responses to both SARS-CoV-1 and SARS-CoV-2 virus have some unique characteristics that suggest cross-reactive priming by other human coronaviruses (hCoVs). The early kinetics and magnitude of these responses are, in some cases, associated with worse clinical outcomes in SARS and COVID-19. Cross-reactive hCoV antibody responses have been detected in both SARS and COVID-19 patients. There is also evidence that pre-existing T cell immunity to common cold coronaviruses can prime the response to SARS-CoV-2. Studies in non-human primates show that SARS-CoV-1 S-protein vaccine-induced antibodies are associated with acute lung injury in macaques challenged with SARS-CoV-1. Here we discuss the potential of cross-reactive immunity to drive the immunopathogenesis of COVID-19 and its implications for current efforts to develop immune-based therapies and vaccines.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Animais , Anticorpos Facilitadores , Linfócitos T CD4-Positivos/imunologia , COVID-19/prevenção & controle , COVID-19/terapia , COVID-19/virologia , Reações Cruzadas , Humanos , Memória Imunológica , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/virologia , Vacinas Virais/imunologia
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