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1.
J Exp Med ; 218(3)2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33211088

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Betacoronavirus/inmunología , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Animales , Anticuerpos Monoclonales de Origen Murino/inmunología , Anticuerpos Monoclonales de Origen Murino/farmacología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/farmacología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/farmacología , Línea Celular , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Femenino , Humanos , Mesocricetus , Ratones , Ratones Endogámicos BALB C , Neumonía Viral/inmunología , Neumonía Viral/terapia
2.
Biosens Bioelectron ; 171: 112679, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33069957

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Técnicas Biosensibles/instrumentación , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/sangre , Neumonía Viral/sangre , Anticuerpos Antivirales/inmunología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/inmunología , Pruebas con Sangre Seca , Diseño de Equipo , Fluorescencia , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Dispositivos Laboratorio en un Chip , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/inmunología , Sensibilidad y Especificidad
3.
Biosens Bioelectron ; 171: 112709, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33075724

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Técnicas Biosensibles/instrumentación , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/sangre , Espectroscopía Dieléctrica/instrumentación , Neumonía Viral/sangre , Anticuerpos Antivirales/inmunología , Técnicas Biosensibles/economía , Técnicas de Laboratorio Clínico/economía , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/economía , Infecciones por Coronavirus/inmunología , Espectroscopía Dieléctrica/economía , Impedancia Eléctrica , Diseño de Equipo , Humanos , Proteínas Inmovilizadas/inmunología , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/inmunología , Sensibilidad y Especificidad , Glicoproteína de la Espiga del Coronavirus/inmunología , Factores de Tiempo
4.
Ann Med ; 53(1): 34-42, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-32808808

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Neumonía Viral/inmunología , Estudios de Casos y Controles , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Técnicas para Inmunoenzimas/métodos , Masculino , Pandemias , Estudios Retrospectivos
5.
Respir Physiol Neurobiol ; 283: 103548, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32956843

RESUMEN

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.


Asunto(s)
Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Insuficiencia Multiorgánica/inmunología , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/inmunología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/fisiopatología , Arritmias Cardíacas/inmunología , Arritmias Cardíacas/fisiopatología , Betacoronavirus/metabolismo , Infecciones por Coronavirus/fisiopatología , Síndrome de Liberación de Citoquinas/fisiopatología , Citocinas/inmunología , Endotelio Vascular/metabolismo , Eritrocitos/metabolismo , Enfermedades Gastrointestinales/inmunología , Enfermedades Gastrointestinales/fisiopatología , Tracto Gastrointestinal/metabolismo , Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/fisiopatología , Humanos , Inflamación/inmunología , Riñón/metabolismo , Hígado/metabolismo , Hepatopatías/inmunología , Hepatopatías/fisiopatología , Pulmón/metabolismo , Insuficiencia Multiorgánica/fisiopatología , Miocardio/metabolismo , Pandemias , Neumonía Viral/fisiopatología , Tromboembolia/inmunología , Tromboembolia/fisiopatología , Carga Viral
6.
Methods Mol Biol ; 2225: 25-38, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33108655

RESUMEN

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.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Plantas/inmunología , Neumonía Viral/prevención & control , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/biosíntesis , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Vectores Genéticos , Humanos , Plantas/genética , Neumonía Viral/inmunología , Neumonía Viral/transmisión , Neumonía Viral/virología
7.
Rev Paul Pediatr ; 39: e2020217, 2021.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-32876096

RESUMEN

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.


Asunto(s)
Infecciones por Coronavirus , Síndrome Mucocutáneo Linfonodular , Pandemias , Neumonía Viral , Síndrome de Respuesta Inflamatoria Sistémica/virología , Betacoronavirus/aislamiento & purificación , Niño , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/fisiopatología , Manejo de la Enfermedad , Humanos , Síndrome Mucocutáneo Linfonodular/epidemiología , Síndrome Mucocutáneo Linfonodular/terapia , Síndrome Mucocutáneo Linfonodular/virología , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/fisiopatología
8.
Vet Microbiol ; 252: 108918, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33191000

RESUMEN

Porcine haemagglutinating encephalomyelitis virus (PHEV) is a member of coronavirus that causes acute infectious disease and high mortality in piglets. The transcription factor IRF3 is a central regulator of type I interferon (IFN) innate immune signalling. Here, we report that PHEV infection of RAW264.7 cells results in strong suppression of IFN-ß production in the early stage. A comparative analysis of the upstream effector of IFN-ß transcription demonstrated that deactivation of IRF3, but not p65 or ATF-2 proteins, is uniquely attributed to failure of early IFN-ß induction. Moreover, the RIG-I/MDA5/MAVS/TBK1-dependent protective response that regulates the IRF3 pathway is not disrupted by PHEV and works well underlying the deactivated IRF3-mediated IFN-ß inhibition. After challenge with poly(I:C), a synthetic analogue of dsRNA used to stimulate IFN-ß secretion in the TLR-controlled pathway, we show that PHEV and poly(I:C) regulate IFN-ß-induction via two different pathways. Collectively, our findings reveal that deactivation of IRF3 is a specific mechanism that contributes to termination of type I IFN signalling during early infection with PHEV independent of the conserved RIG-I/MAVS/MDA5/TBK1-mediated innate immune response.


Asunto(s)
Betacoronavirus 1/inmunología , Infecciones por Coronavirus/veterinaria , Factor 3 Regulador del Interferón/genética , Interferón beta/inmunología , Animales , Betacoronavirus 1/genética , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Inmunidad Innata , Factor 3 Regulador del Interferón/inmunología , Ratones , Poli I-C/farmacología , Células RAW 264.7 , Transducción de Señal/inmunología
9.
Virology ; 552: 43-51, 2021 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-33059319

RESUMEN

This study focused on intestinal restitution including phenotype switching of absorptive enterocytes and the abundance of different enterocyte subtypes in weaned pigs after porcine epidemic diarrhea virus (PEDV) infection. At 10 days post-PEDV-inoculation, the ratio of villus height to crypt depth in both jejunum and ileum had restored, and the PEDV antigen was not detectable. However, enterocytes at the villus tips revealed epithelial-mesenchymal transition (EMT) in the jejunum in which E-cadherin expression decreased while expression of N-cadherin, vimentin, and Snail increased. Additionally, there was reduced expression of actin in microvilli and Zonula occludens-1 (ZO-1) in tight junctions. Moreover, the protein concentration of transforming growth factor ß1 (TGFß1), which mediates EMT and cytoskeleton alteration, was increased. We also found a decreased number of Peyer's patch M cells in the ileum. These results reveal incomplete restitution of enterocytes in the jejunum and potentially impaired immune surveillance in the ileum after PEDV infection.


Asunto(s)
Infecciones por Coronavirus/veterinaria , Enterocitos/patología , Transición Epitelial-Mesenquimal , Gastroenteritis Porcina Transmisible/patología , Ganglios Linfáticos Agregados/patología , Virus de la Diarrea Epidémica Porcina/patogenicidad , Animales , Cadherinas/metabolismo , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Gastroenteritis Porcina Transmisible/inmunología , Gastroenteritis Porcina Transmisible/virología , Íleon/inmunología , Íleon/patología , Mucosa Intestinal/patología , Yeyuno/inmunología , Yeyuno/patología , Microvellosidades/patología , Porcinos , Uniones Estrechas/patología , Factor de Crecimiento Transformador beta1/metabolismo , Destete
10.
Recurso de Internet en Portugués | LIS - Localizador de Información en Salud | ID: lis-48002

RESUMEN

O plano de imunização contra a Covid-19 será apresentado aos brasileiros em breve, em evento. Nesta quarta-feira (9), o ministro Eduardo Pazuello recebeu o documento - que passará ainda por uma revisão técnica final antes de ser enviado ao Supremo Tribunal Federal (STF).


Asunto(s)
Infecciones por Coronavirus/inmunología , Vacunación Masiva , Política de Salud
11.
Viruses ; 12(12)2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33271762

RESUMEN

The emergence of SARS-CoV-2 in 2019 has caused a major health and economic crisis around the globe. Gaining knowledge about its attributes and interactions with human host cells is crucial. Non-coding RNAs (ncRNAs) are involved in the host cells' innate antiviral immune response. In RNA interference, microRNAs (miRNAs) may bind to complementary sequences of the viral RNA strand, forming an miRNA-induced silencing complex, which destroys the viral RNA, thereby inhibiting viral protein expression. There are several targets for human miRNAs on SARS-CoV-2's RNA, most of which are in the 5' and 3' untranslated regions. Mutations of the viral genome causing the creation or loss of miRNA binding sites may have crucial effects on SARS-CoV-2 pathogenicity. In addition to mediating immunity, the ncRNA landscape of host cells further influences their susceptibility to virus infection, as certain miRNAs are essential in the regulation of cellular receptors that are necessary for virus invasion. Conversely, virus infection also changes the host ncRNA expression patterns, possibly augmenting conditions for viral replication and dissemination. Hence, ncRNAs typically upregulated in SARS-CoV-2 infection could be useful biomarkers for disease progression and severity. Understanding these mechanisms could provide further insight into the pathogenesis and possible treatment options against COVID-19.


Asunto(s)
Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Coronavirus/patogenicidad , ARN no Traducido/metabolismo , Animales , Antivirales/metabolismo , Antivirales/uso terapéutico , Coronavirus/genética , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/genética , Humanos , Evasión Inmune/genética , Mutación , Interferencia de ARN , ARN no Traducido/genética , ARN no Traducido/uso terapéutico , ARN Viral/genética
12.
Avian Dis ; 64(4): 451-456, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33347551

RESUMEN

Major histocompatibility complex (MHC) congenic chicken lines have been used as a model to study infectious bronchitis virus (IBV) immune responses in chickens. Zinc (Zn) and manganese (Mn) are trace minerals that act as enzyme cofactors in cellular reactions. In addition, Zn is an important modulator of immune responses, especially in the respiratory tract. Zinc and Zn + Mn amino acid complex supplements were tested to alleviate the effects of an IBV challenge using relatively resistant and susceptible MHC congenic chicken lines. Prior to the challenge with IBV, the amino acid-bound supplements induced better weight gain in the IBV-resistant chicken line (331/B2) compared to the birds fed with the sulfate-delivered supplements. No body weight differences were detected between IBV-challenged and unchallenged 331/B2 birds supplemented with Zn in amino acid complex. A reduction of respiratory signs was observed in 335/B19 birds fed with the diet supplemented with Zn in amino acid complexes at 4 dpi. Compared to the sulfate-bound trace minerals, 331/B2 chickens fed with the amino acid-bound supplements presented milder clinical sign trends at 6 dpi and less severe airsacculitis at 14 dpi. The total antibody response in serum in 331/B2 birds fed with the amino acid-bound Zn ration was the highest among all groups tested. Both amino acid-delivered trace mineral supplements induced a slightly higher antibody response than the sulfate-bound ration in both chicken lines. This experiment provides insights into the effect of Zn and Mn on the immunity of chickens with known different susceptibilities to IBV.


Asunto(s)
Infecciones por Coronavirus/veterinaria , Suplementos Dietéticos , Virus de la Bronquitis Infecciosa , Enfermedades de las Aves de Corral/dietoterapia , Aminoácidos/administración & dosificación , Alimentación Animal/análisis , Animales , Animales Congénicos , Anticuerpos Antivirales/sangre , Pollos/genética , Pollos/inmunología , Infecciones por Coronavirus/dietoterapia , Infecciones por Coronavirus/inmunología , Susceptibilidad a Enfermedades/veterinaria , Haplotipos , Virus de la Bronquitis Infecciosa/inmunología , Complejo Mayor de Histocompatibilidad , Manganeso/administración & dosificación , Enfermedades de las Aves de Corral/genética , Enfermedades de las Aves de Corral/inmunología , Zinc/administración & dosificación
14.
Rev. esp. quimioter ; 33(6): 392-398, dic. 2020. tab
Artículo en Español | IBECS | ID: ibc-FGT-6023

RESUMEN

Los coronavirus (CoVs) son un amplio grupo de virus en el que se encuentra el SARS-CoV-2 (familia Coronaviridae, subfamilia Coronavirinae, género Betacoronavirus y subgénero Sarbecovirus). Sus principales proteínas estructurales son la de membrana (M), la de envoltura (E), la nucleocápside (N) y la espicular (S). La respuesta inmune frente a SARS-CoV-2 implica la vertiente celular y humoral, con anticuerpos neutralizantes potencialmente defensivos fundamentalmente dirigidos frente al antígeno S. Aunque los datos de seroprevalencia se asumen muy frecuentemente como marcadores de protección, no necesariamentelo son. En España se estima que al menos cuatro quintas partes de la población deberían estar inmuno-protegidas para asegurar la inmunidad de grupo. Dada la alta tasa de letalidad por COVID-19, la adquisición de esta protección únicamente mediante el contagio natural no es asumible y se debe abogar por otras medidas como puede ser la inmunización masiva. En la actualidad existen varios prototipos de vacunas (que incluyen virus vivos, vectores virológicos, péptidos y proteínas y ácidos nucleicos) en diversas etapas de evaluación clínica. Se prevé que en breve alguna de estas nuevas vacunas se encuentre ya disponible en el mercado. En este texto se revisan aspectos relacionados con estos asuntos


The coronavirus are a wide group of viruses among that the SARS-CoV-2 is included (family Coronaviridae, subfamily Coronavirinae, genus Betacoronavirus and subgenus Sarbecovirus). Its main structural proteins are the membrane (M), the envelope (E), the nucleocapsid (N) and spike (S). The immune response to SARS-CoV-2 involves the cellular and the humoral sides, with neutralizing antibodies fundamentally directed against the S antigen. Although the seroprevalence data are frequently assumed as protection markers, no necessarily they are. In Spain, it is estimated that, to assure the herd immunity, at least four-fifths of the population should be immunoprotected. Due the high fatality rate of COVID-19, the acquisition of the protection only by the natural infection it not assumable and other measures as the mass immunization are required. Currently, there are several vaccine prototypes (including life virus, viral vectors, peptides and proteins and nucleic acid) in different phase of clinical evaluation. Foreseeably, some of these news vaccines would be soon commercially available. In this text, aspects related to these issues are reviewed


Asunto(s)
Humanos , Infecciones por Coronavirus/prevención & control , Neumonía Viral/prevención & control , Betacoronavirus/inmunología , Vacunación , Vacunas Virales/inmunología , Pandemias , Anticuerpos Antivirales/inmunología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Ensayos Clínicos como Asunto/clasificación , Reacciones Cruzadas/inmunología , Inmunidad Colectiva/inmunología , Inmunización , Pruebas de Neutralización/métodos , Proteínas Estructurales Virales
15.
Rev. Hosp. Ital. B. Aires (2004) ; 40(4): 233-236, dic. 2020. ilus
Artículo en Español | LILACS | ID: biblio-1145604

RESUMEN

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)


Asunto(s)
Humanos , Neumonía Viral/epidemiología , Encuestas Epidemiológicas/estadística & datos numéricos , Infecciones por Coronavirus/epidemiología , Argentina , Neumonía Viral/inmunología , Estudios Seroepidemiológicos , Muestreo Aleatorio Simple , Prevalencia , Infecciones por Coronavirus/inmunología , Betacoronavirus/inmunología
16.
Int J Mol Sci ; 21(22)2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33233817

RESUMEN

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.


Asunto(s)
Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Factores Inmunológicos/farmacología , Inflamación/tratamiento farmacológico , Luminol/análogos & derivados , Neumonía Viral/tratamiento farmacológico , Aminación , Animales , Antivirales/química , Betacoronavirus/inmunología , Chlorocebus aethiops , Infecciones por Coronavirus/inmunología , Citocinas/inmunología , Femenino , Humanos , Factores Inmunológicos/química , Inflamación/inmunología , Luminol/química , Luminol/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Pandemias , Neumonía Viral/inmunología , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Poli(ADP-Ribosa) Polimerasa-1/inmunología , Especies Reactivas de Oxígeno/inmunología , Células Vero
17.
MMWR Morb Mortal Wkly Rep ; 69(47): 1762-1766, 2020 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-33237893

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Personal de Hospital/estadística & datos numéricos , Neumonía Viral/inmunología , Adulto , Infecciones por Coronavirus/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Estados Unidos/epidemiología
18.
PLoS Biol ; 18(11): e3001000, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33166303

RESUMEN

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.


Asunto(s)
Betacoronavirus/inmunología , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Farmacorresistencia Viral/inmunología , Neumonía Viral/inmunología , Neumonía Viral/virología , Vacunas Virales/inmunología , Infecciones por Coronavirus/prevención & control , Humanos , Pandemias , Factores de Riesgo
19.
Mol Med ; 26(1): 103, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33167852

RESUMEN

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.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Inmunidad Innata , Neumonía Viral/inmunología , Animales , Bradiquinina/metabolismo , Humanos , Calicreínas/metabolismo , Modelos Inmunológicos , Pandemias , Sistema Renina-Angiotensina
20.
BMC Infect Dis ; 20(1): 818, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33167900

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/inmunología , Pulmón/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/inmunología , Adolescente , Adulto , Anciano , Betacoronavirus/genética , Niño , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Proteínas de la Nucleocápside/inmunología , Pandemias , Fosfoproteínas , Neumonía Viral/epidemiología , Neumonía Viral/virología , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esputo/virología , Tomografía Computarizada por Rayos X , Adulto Joven
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