Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.324
Filtrar
1.
J Exp Med ; 218(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33211088

RESUMO

SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.


Assuntos
Anticorpos Monoclonais Murinos , Anticorpos Neutralizantes , Anticorpos Antivirais , Betacoronavirus/imunologia , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Animais , Anticorpos Monoclonais Murinos/imunologia , Anticorpos Monoclonais Murinos/farmacologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , Linhagem Celular , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia Viral/imunologia , Pneumonia Viral/terapia
2.
Biosens Bioelectron ; 171: 112679, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33069957

RESUMO

The 2019 SARS CoV-2 (COVID-19) pandemic has illustrated the need for rapid and accurate diagnostic tests. In this work, a multiplexed grating-coupled fluorescent plasmonics (GC-FP) biosensor platform was used to rapidly and accurately measure antibodies against COVID-19 in human blood serum and dried blood spot samples. The GC-FP platform measures antibody-antigen binding interactions for multiple targets in a single sample, and has 100% selectivity and sensitivity (n = 23) when measuring serum IgG levels against three COVID-19 antigens (spike S1, spike S1S2, and the nucleocapsid protein). The GC-FP platform yielded a quantitative, linear response for serum samples diluted to as low as 1:1600 dilution. Test results were highly correlated with two commercial COVID-19 antibody tests, including an enzyme linked immunosorbent assay (ELISA) and a Luminex-based microsphere immunoassay. To demonstrate test efficacy with other sample matrices, dried blood spot samples (n = 63) were obtained and evaluated with GC-FP, yielding 100% selectivity and 86.7% sensitivity for diagnosing prior COVID-19 infection. The test was also evaluated for detection of multiple immunoglobulin isotypes, with successful detection of IgM, IgG and IgA antibody-antigen interactions. Last, a machine learning approach was developed to accurately score patient samples for prior COVID-19 infection, using antibody binding data for all three COVID-19 antigens used in the test.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas de Laboratório Clínico , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Anticorpos Antivirais/imunologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Teste em Amostras de Sangue Seco , Desenho de Equipamento , Fluorescência , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Dispositivos Lab-On-A-Chip , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Sensibilidade e Especificidade
3.
Biosens Bioelectron ; 171: 112709, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33075724

RESUMO

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was classified as a pandemic by the World Health Organization and has caused over 550,000 deaths worldwide as of July 2020. Accurate and scalable point-of-care devices would increase screening, diagnosis, and monitoring of COVID-19 patients. Here, we demonstrate rapid label-free electrochemical detection of SARS-CoV-2 antibodies using a commercially available impedance sensing platform. A 16-well plate containing sensing electrodes was pre-coated with receptor binding domain (RBD) of SARS-CoV-2 spike protein, and subsequently tested with samples of anti-SARS-CoV-2 monoclonal antibody CR3022 (0.1 µg/ml, 1.0 µg/ml, 10 µg/ml). Subsequent blinded testing was performed on six serum specimens taken from COVID-19 and non-COVID-19 patients (1:100 dilution factor). The platform was able to differentiate spikes in impedance measurements from a negative control (1% milk solution) for all CR3022 samples. Further, successful differentiation and detection of all positive clinical samples from negative control was achieved. Measured impedance values were consistent when compared to standard ELISA test results showing a strong correlation between them (R2=0.9). Detection occurs in less than five minutes and the well-based platform provides a simplified and familiar testing interface that can be readily adaptable for use in clinical settings.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas de Laboratório Clínico , Infecções por Coronavirus/sangue , Espectroscopia Dielétrica/instrumentação , Pneumonia Viral/sangue , Anticorpos Antivirais/imunologia , Técnicas Biossensoriais/economia , Técnicas de Laboratório Clínico/economia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/economia , Infecções por Coronavirus/imunologia , Espectroscopia Dielétrica/economia , Impedância Elétrica , Desenho de Equipamento , Humanos , Proteínas Imobilizadas/imunologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de Tempo
4.
Ann Med ; 53(1): 34-42, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32808808

RESUMO

BACKGROUND: Studies have demonstrated the diagnostic efficiency of antibody testing in COVID-19 infection. There is limited data on the IgM/IgG changes in asymptomatic and discharged patients with reoccurring positive nucleic acid test (RPNAT). This study aims to investigate these IgM/IgG changes. METHODS: There were 111 patients with positive nucleic acid test (NAT) and 40 suspected patients enrolled in the study. The serum SARS-CoV-2 specific IgM/IgG antibody levels were retrospectively analysed with the disease progress in asymptomatic and RPNAT patients. RESULTS: The best overall performance was found by combining the IgM, IgG, and CT; 95.1% sensitivity and 75% specificity. This was tested in 111 RT-PCR positive cases. The median IgM and IgG levels were lower in the asymptomatic group compared to the symptomatic group (p < .01). Among 15 RPNAT cases, the IgM levels of the RPNAT group at the time of discharge (IgM2.79, IQR: 0.95-5.37) and retest (IgM 2.35, IQR: 0.88-8.65) were significantly higher than those of the non-reoccurring positive nucleic acid test group (Non-RPNAT) (IgM on discharge: 0.59, IQR: 0.33-1.22, IgG on retest: 0.92, IQR: 0.51-1.58). CONCLUSION: Serum SARS-CoV-2 specific IgM/IgG antibody levels remained at a low level during hospitalisation for asymptomatic patients. Elevated IgM levels may have implications in the identification of RPNAT patients before discharge. Key messages This study determined the IgM/IgG changes in asymptomatic and RPNAT patients. The rate of serum SARS-CoV-2 specific IgM/IgG antibody levels increase in the asymptomatic group was lower than in the symptomatic group during hospitalisation. The IgM level did not decrease significantly at discharge in the RPNAT patients, and was higher than that of the Non-RPNAT group on discharge. These results highlight the importance of timely monitoring of IgM levels to identify RPNAT patients before discharge.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pneumonia Viral/imunologia , Estudos de Casos e Controles , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Técnicas Imunoenzimáticas/métodos , Masculino , Pandemias , Estudos Retrospectivos
5.
Respir Physiol Neurobiol ; 283: 103548, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956843

RESUMO

BACKGROUND: Globally, the current medical emergency for novel coronavirus 2019 (COVID-19) leads to respiratory distress syndrome and death. PURPOSE: This review highlighted the effect of COVID-19 on systemic multiple organ failure syndromes. This review is intended to fill a gap in information about human physiological response to COVID-19 infections. This review may shed some light on other potential mechanisms and approaches in COVID -19 infections towards systemic multiorgan failure syndromes. FINDING: SARS-CoV-2 intervened mainly in the lung with progression to pneumonia and acute respiratory distress syndrome (ARDS) via the angiotensin-converting enzyme 2(ACE2) receptor. Depending on the viral load, infection spread through the ACE2 receptor further to various organs such as heart, liver, kidney, brain, endothelium, GIT, immune cell, and RBC (thromboembolism). This may be aggravated by cytokine storm with the extensive release of proinflammatory cytokines from the deregulating immune system. CONCLUSION: The widespread and vicious combinations of cytokines with organ crosstalk contribute to systemic hyper inflammation and ultimately lead to multiple organ dysfunction (Fig. 1). This comprehensive study comprises various manifestations of different organs in COVID-19 and may assist the clinicians and scientists pertaining to a broad approach to fight COVID 19.


Assuntos
Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Insuficiência de Múltiplos Órgãos/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Lesão Renal Aguda/imunologia , Lesão Renal Aguda/fisiopatologia , Arritmias Cardíacas/imunologia , Arritmias Cardíacas/fisiopatologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/imunologia , Endotélio Vascular/metabolismo , Eritrócitos/metabolismo , Gastroenteropatias/imunologia , Gastroenteropatias/fisiopatologia , Trato Gastrointestinal/metabolismo , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Inflamação/imunologia , Rim/metabolismo , Fígado/metabolismo , Hepatopatias/imunologia , Hepatopatias/fisiopatologia , Pulmão/metabolismo , Insuficiência de Múltiplos Órgãos/fisiopatologia , Miocárdio/metabolismo , Pandemias , Pneumonia Viral/fisiopatologia , Tromboembolia/imunologia , Tromboembolia/fisiopatologia , Carga Viral
6.
Methods Mol Biol ; 2225: 25-38, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108655

RESUMO

Various systems exist for the robust production of recombinant proteins. However, only a few systems are optimal for human vaccine protein production. Plant-based transient protein expression systems offer an advantageous alternative to costly mammalian cell culture-based systems and can perform posttranslational modifications due to the presence of an endomembrane system that is largely similar to that of the animal cell. Technological advances in expression vectors for transient expression in the last two decades have produced new plant expression systems with the flexibility and speed that cannot be matched by those based on mammalian or insect cell culture. The rapid and high-level protein production capability of transient expression systems makes them the optimal system to quickly and versatilely develop and produce vaccines against viruses such as 2019-nCoV that have sudden and unpredictable outbreaks. Here, expression of antiviral subunit vaccines in Nicotiana benthamiana plants via transient expression is demonstrated.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Plantas/imunologia , Pneumonia Viral/prevenção & controle , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/biossíntese , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Vetores Genéticos , Humanos , Plantas/genética , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia
7.
Rev Paul Pediatr ; 39: e2020217, 2021.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32876096

RESUMO

OBJECTIVE: To analyze the current scientific literature to document, in an integrative review, the main findings that correlate Kawasaki disease (KD) to COVID-19. DATA SOURCES: The search was carried out in June 2020 in the following databases: Biblioteca Virtual em Saúde (BVS), periódico da CAPES and U.S National Library of Medicine (PubMed). The combination of descriptors used was [(COVID-19 OR SARS-CoV-2) AND (Kawasaki disease)], and the inclusion criteria stipulated were studies published from January 2019 to June 2020, without restriction of language or location, and available online in full. News, editorials, comments, and letters, as well as duplicates and articles that did not answer the guiding question were excluded. DATA SYNTHESIS: A total of 97 articles were identified, of which seven comprised this review. The association of KD to the new coronavirus appears to trigger a severe clinical condition of vasculitis. Different from the usual, in this inflammatory syndrome, patients are older, and prevalence is higher in children from African or Caribbean ancestry; clinical and laboratory manifestations are also atypical, with a predominance of abdominal complaints and exaggerated elevation of inflammatory markers. In addition, there was a greater report of rare complications and greater resistance to the recommended treatment for KD. CONCLUSIONS: Pediatric COVID-19 and its potential association to severe KD, still unfamiliar to health professionals, reinforces the importance of testing patients with vasculitis for the new coronavirus and the need to wage high surveillance and preparation of the health system during the current pandemic.


Assuntos
Infecções por Coronavirus , Síndrome de Linfonodos Mucocutâneos , Pandemias , Pneumonia Viral , Síndrome de Resposta Inflamatória Sistêmica/virologia , Betacoronavirus/isolamento & purificação , Criança , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Gerenciamento Clínico , Humanos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/terapia , Síndrome de Linfonodos Mucocutâneos/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia
9.
J Transl Med ; 18(1): 457, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272291

RESUMO

BACKGROUND: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis. METHODS: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared. RESULTS: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1ß, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-ß), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation. CONCLUSION: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.


Assuntos
/diagnóstico , Imunidade Inata/fisiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Idoso , Idoso de 80 Anos ou mais , /terapia , Cuidados Críticos , Feminino , França/epidemiologia , Humanos , Imunofenotipagem , Ativação Linfocitária/fisiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Prognóstico , Respiração Artificial , Índice de Gravidade de Doença
10.
Rev. Hosp. Ital. B. Aires (2004) ; 40(4): 233-236, dic. 2020. ilus
Artigo em Espanhol | LILACS | ID: biblio-1145604

RESUMO

Entre el 1 y el 26 de junio se llevó a cabo el estudio de investigación "Encuesta de infección por coronavirus tipo 2 del síndrome respiratorio agudo grave (SARS-CoV-2), nivel comunitario en habitantes de un barrio vulnerable urbano de la ciudad de Buenos Aires", que determinó que un 54,3% de los habitantes del barrio presentaban anticuerpos inmunoglobulina tipo G para SARS-CoV-2. El objetivo de este artículo es proporcionar un ejemplo de un muestreo probabilístico que fue utilizado para estimar la prevalencia de seropositividad en este estudio. (AU)


Between 1st and 26th of june, a research named "Survey of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), community level in inhabitants of a marginal urban neighborhood of the city of Buenos Aires" was carried on. The study showed that 54.3% of the that 54.3% of the people of the neighborhood had antibodies immunoglobulin type G for SARS-CoV-2. The objective of this article is to provide an example of a probability sampling carried out in the study, to measuring the prevalence of seropositivity. (AU)


Assuntos
Humanos , Pneumonia Viral/epidemiologia , Inquéritos Epidemiológicos/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Argentina , Pneumonia Viral/imunologia , Estudos Soroepidemiológicos , Amostragem Aleatória Simples , Prevalência , Infecções por Coronavirus/imunologia , Betacoronavirus/imunologia
11.
Int J Mol Sci ; 21(22)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233817

RESUMO

At least since March 2020, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic and the multi-organ coronavirus disease 2019 (COVID-19) are keeping a firm grip on the world. Although most cases are mild, older patients and those with co-morbidities are at increased risk of developing a cytokine storm, characterized by a systemic inflammatory response leading to acute respiratory distress syndrome and organ failure. The present paper focuses on the small molecule MP1032, describes its mode of action, and gives rationale why it is a promising option for the prevention/treatment of the SARS-CoV-2-induced cytokine storm. MP1032 is a phase-pure anhydrous polymorph of 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt that exhibits good stability and bioavailability. The physiological action of MP1032 is based on a multi-target mechanism including localized, self-limiting reactive oxygen species (ROS) scavenging activities that were demonstrated in a model of lipopolysaccharide (LPS)-induced joint inflammation. Furthermore, its immune-regulatory and PARP-1-modulating properties, coupled with antiviral effects against SARS-CoV-2, have been demonstrated in various cell models. Preclinical efficacy was elucidated in LPS-induced endotoxemia, a model with heightened innate immune responses that shares many similarities to COVID-19. So far, during oral clinical development with three-month daily administrations, no serious adverse drug reactions occurred, highlighting the outstanding safety profile of MP1032.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/farmacologia , Inflamação/tratamento farmacológico , Luminol/análogos & derivados , Pneumonia Viral/tratamento farmacológico , Aminação , Animais , Antivirais/química , Betacoronavirus/imunologia , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Feminino , Humanos , Fatores Imunológicos/química , Inflamação/imunologia , Luminol/química , Luminol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pandemias , Pneumonia Viral/imunologia , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/imunologia , Espécies Reativas de Oxigênio/imunologia , Células Vero
12.
MMWR Morb Mortal Wkly Rep ; 69(47): 1762-1766, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33237893

RESUMO

Most persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), develop virus-specific antibodies within several weeks, but antibody titers might decline over time. Understanding the timeline of antibody decline is important for interpreting SARS-CoV-2 serology results. Serum specimens were collected from a convenience sample of frontline health care personnel at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again approximately 60 days later to assess this timeline. The percentage of participants who experienced seroreversion, defined as an antibody signal-to-threshold ratio >1.0 at baseline and <1.0 at the follow-up visit, was assessed. Overall, 194 (6.0%) of 3,248 participants had detectable antibodies to SARS-CoV-2 at baseline (1). Upon repeat testing approximately 60 days later (range = 50-91 days), 146 (93.6%) of 156 participants experienced a decline in antibody response indicated by a lower signal-to-threshold ratio at the follow-up visit, compared with the baseline visit, and 44 (28.2%) experienced seroreversion. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response. Whether decay in these antibodies increases risk for reinfection and disease remains unanswered. However, these results suggest that serology testing at a single time point is likely to underestimate the number of persons with previous SARS-CoV-2 infection, and a negative serologic test result might not reliably exclude prior infection.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Recursos Humanos em Hospital/estatística & dados numéricos , Pneumonia Viral/imunologia , Adulto , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estados Unidos/epidemiologia
13.
PLoS Biol ; 18(11): e3001000, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33166303

RESUMO

Although less common than the evolution of antimicrobial drug resistance, vaccine resistance can and has evolved. How likely is it that COVID-19 vaccines currently in development will be undermined by viral evolution? We argue that this can be determined by repurposing samples that are already being collected as part of clinical trials. Such information would be useful for prioritizing investment among candidate vaccines and maximizing the potential long-term impact of COVID-19 vaccines.


Assuntos
Betacoronavirus/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Farmacorresistência Viral/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vacinas Virais/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias , Fatores de Risco
14.
Mol Med ; 26(1): 103, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167852

RESUMO

The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Pneumonia Viral/imunologia , Animais , Bradicinina/metabolismo , Humanos , Calicreínas/metabolismo , Modelos Imunológicos , Pandemias , Sistema Renina-Angiotensina
15.
BMC Infect Dis ; 20(1): 818, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167900

RESUMO

BACKGROUND: To explore the kinetic changes in virology, specific antibody response and imaging during the clinical course of COVID-19. METHODS: This observational study enrolled 20 patients with COVID-19, who were hospitalized between January 20-April 6, 2020, in the two COVID-19 designated hospitals of Zhoushan, Zhejiang and Rushan, Shandong, China, The laboratory findings, imaging, serum response to viral infection, and viral RNA level in the throat and stool samples were assessed from onset to recovery phase in patients with COVID-19. RESULTS: SARS-COV-2 RNA was positive as early as day four. It remained positive until day 55 post-onset in the sputum-throat swabs and became negative in most cases (55%) within 14 days after onset. Lymphocytopenia occurred in 40% (8/20) of patients during the peak infection period and returned to normal at week five. The most severe inflammation in the lungs appeared in week 2 or 3 after onset, and this was completely absorbed between week 6 and 8 in 85.7% of patients. All patients had detectable antibodies to the receptor binding domain (RBD), and 95% of these patients had IgG to viral N proteins. The antibody titer peaked at week four. Anti-S IgM was positive in 7 of 20 patients after week three. CONCLUSIONS: All COVID-19 patients in this study were self-limiting and recovered well though it may take as long as 6-8 weeks. Our findings on the kinetic changes in imaging, serum response to viral infection and viral RNA level may help understand pathogenesis and define clinical course of COVID-19.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/imunologia , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/imunologia , Adolescente , Adulto , Idoso , Betacoronavirus/genética , Criança , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , Pandemias , Fosfoproteínas , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Escarro/virologia , Tomografia Computadorizada por Raios X , Adulto Jovem
16.
BMJ Case Rep ; 13(11)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168542

RESUMO

Renal transplant (RT) recipients are at increased risk for infectious complications. The clinical course of COVID-19 has been described in several RT recipients with varying clinical outcomes. Most present with pulmonary manifestations, however extrapulmonary presentations are not uncommon. Also, the timing and efficacy of seroconversion in transplant recipients is not well known. This report describes the duration of viral shedding and timing of seroconversion in a young adult RT recipient with COVID-19 who presented with severe diarrhoea and acute kidney injury requiring dialysis. She developed anti-SARS-CoV-2 IgG antibody after 5 weeks despite persistently shedding the virus in the nasopharynx until 6 weeks after symptom onset. Further studies are needed to determine if immunosuppressed patients have prolonged viral shedding and are still contagious despite seroconversion.


Assuntos
Lesão Renal Aguda/complicações , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Transplante de Rim , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Soroconversão , Eliminação de Partículas Virais/imunologia , Lesão Renal Aguda/imunologia , Lesão Renal Aguda/terapia , Adulto , Betacoronavirus/imunologia , Feminino , Humanos , Rim/imunologia , Rim/cirurgia , Pandemias , Diálise Renal/métodos , Transplantados , Adulto Jovem
19.
R I Med J (2013) ; 103(10): 24-26, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33172223

RESUMO

To date, there have only been a few reports of reinfections in COVID-19 patients. The possibility of being reinfected with COVID-19 is poorly understood. In this case report, we describe an individual who was initially diagnosed in April 2020 with COVID-19. Seven months later, he presented again to the hospital with shortness of breath and was found to have COVID-19 reinfection. We also summarize a list of all known cases of COVID-19 reinfection at this time.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Idoso , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico , Humanos , Masculino , Pandemias , Recidiva , Índice de Gravidade de Doença
20.
Sci Rep ; 10(1): 19395, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173052

RESUMO

An incomplete understanding of the molecular mechanisms behind impairment of lung pathobiology by COVID-19 complicates its clinical management. In this study, we analyzed the gene expression pattern of cells obtained from biopsies of COVID-19-affected patient and compared to the effects observed in typical SARS-CoV-2 and SARS-CoV-infected cell-lines. We then compared gene expression patterns of COVID-19-affected lung tissues and SARS-CoV-2-infected cell-lines and mapped those to known lung-related molecular networks, including hypoxia induced responses, lung development, respiratory processes, cholesterol biosynthesis and surfactant metabolism; all of which are suspected to be downregulated following SARS-CoV-2 infection based on the observed symptomatic impairments. Network analyses suggest that SARS-CoV-2 infection might lead to acute lung injury in COVID-19 by affecting surfactant proteins and their regulators SPD, SPC, and TTF1 through NSP5 and NSP12; thrombosis regulators PLAT, and EGR1 by ORF8 and NSP12; and mitochondrial NDUFA10, NDUFAF5, and SAMM50 through NSP12. Furthermore, hypoxia response through HIF-1 signaling might also be targeted by SARS-CoV-2 proteins. Drug enrichment analysis of dysregulated genes has allowed us to propose novel therapies, including lung surfactants, respiratory stimulants, sargramostim, and oseltamivir. Our study presents a distinct mechanism of probable virus induced lung damage apart from cytokine storm.


Assuntos
Infecções por Coronavirus/genética , Infecções por Coronavirus/metabolismo , Perfilação da Expressão Gênica , Pulmão/metabolismo , Terapia de Alvo Molecular , Pneumonia Viral/genética , Pneumonia Viral/metabolismo , Surfactantes Pulmonares/metabolismo , Biologia de Sistemas , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Epigênese Genética , Humanos , Pulmão/efeitos dos fármacos , Especificidade de Órgãos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Proteínas Virais/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA