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1.
Best Pract Res Clin Anaesthesiol ; 35(3): 269-292, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34511219

RESUMO

Coronaviruses belong to the family Coronaviridae order Nidovirales and are known causes of respiratory and intestinal disease in various mammalian and avian species. Species of coronaviruses known to infect humans are referred to as human coronaviruses (HCoVs). While traditionally, HCoVs have been a significant cause of the common cold, more recently, emergent viruses, including severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a global pandemic. Here, we discuss coronavirus disease (COVID-19) biology, pathology, epidemiology, signs and symptoms, diagnosis, treatment, and recent clinical trials involving promising treatments.


Assuntos
Antivirais/administração & dosagem , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2 , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Corticosteroides/administração & dosagem , Alanina/administração & dosagem , Alanina/análogos & derivados , Animais , COVID-19/diagnóstico , COVID-19/imunologia , Coronavirus/efeitos dos fármacos , Coronavirus/imunologia , Tosse/epidemiologia , Tosse/terapia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Fadiga/epidemiologia , Fadiga/terapia , Febre , Cardiopatias/epidemiologia , Cardiopatias/terapia , Humanos , Respiração com Pressão Positiva/métodos , Prognóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Resultado do Tratamento
2.
Viruses ; 13(8)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34452443

RESUMO

The novel coronavirus SARS-CoV-2 is the seventh identified human coronavirus. Understanding the extent of pre-existing immunity induced by seropositivity to endemic seasonal coronaviruses and the impact of cross-reactivity on COVID-19 disease progression remains a key research question in immunity to SARS-CoV-2 and the immunopathology of COVID-2019 disease. This paper describes a panel of lentiviral pseudotypes bearing the spike (S) proteins for each of the seven human coronaviruses (HCoVs), generated under similar conditions optimized for high titre production allowing a high-throughput investigation of antibody neutralization breadth. Optimal production conditions and most readily available permissive target cell lines were determined for spike-mediated entry by each HCoV pseudotype: SARS-CoV-1, SARS-CoV-2 and HCoV-NL63 best transduced HEK293T/17 cells transfected with ACE2 and TMPRSS2, HCoV-229E and MERS-CoV preferentially entered HUH7 cells, and CHO cells were most permissive for the seasonal betacoronavirus HCoV-HKU1. Entry of ACE2 using pseudotypes was enhanced by ACE2 and TMPRSS2 expression in target cells, whilst TMPRSS2 transfection rendered HEK293T/17 cells permissive for HCoV-HKU1 and HCoV-OC43 entry. Additionally, pseudotype viruses were produced bearing additional coronavirus surface proteins, including the SARS-CoV-2 Envelope (E) and Membrane (M) proteins and HCoV-OC43/HCoV-HKU1 Haemagglutinin-Esterase (HE) proteins. This panel of lentiviral pseudotypes provides a safe, rapidly quantifiable and high-throughput tool for serological comparison of pan-coronavirus neutralizing responses; this can be used to elucidate antibody dynamics against individual coronaviruses and the effects of antibody cross-reactivity on clinical outcome following natural infection or vaccination.


Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , COVID-19/imunologia , Coronavirus/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Amplamente Neutralizantes/sangue , Linhagem Celular , Coronavirus Humano 229E/imunologia , Coronavirus Humano 229E/fisiologia , Coronavirus Humano NL63/imunologia , Coronavirus Humano NL63/fisiologia , Coronavirus Humano OC43/imunologia , Coronavirus Humano OC43/fisiologia , Reações Cruzadas , Humanos , Lentivirus/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Testes de Neutralização , Plasmídeos , SARS-CoV-2/fisiologia , Transfecção , Internalização do Vírus
3.
Front Immunol ; 12: 696370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386006

RESUMO

The COVID-19 pandemic is caused by SARS-CoV-2, a novel zoonotic coronavirus. Emerging evidence indicates that preexisting humoral immunity against other seasonal human coronaviruses (HCoVs) plays a critical role in the specific antibody response to SARS-CoV-2. However, current work to assess the effects of preexisting and cross-reactive anti-HCoVs antibodies has been limited. To address this issue, we have adapted our previously reported multiplex assay to simultaneously and quantitatively measure anti-HCoV antibodies. The full mPlex-CoV panel covers the spike (S) and nucleocapsid (N) proteins of three highly pathogenic HCoVs (SARS-CoV-1, SARS-CoV-2, MERS) and four human seasonal strains (OC43, HKU1, NL63, 229E). Combining this assay with volumetric absorptive microsampling (VAMS), we measured the anti-HCoV IgG, IgA, and IgM antibodies in fingerstick blood samples. The results demonstrate that the mPlex-CoV assay has high specificity and sensitivity. It can detect strain-specific anti-HCoV antibodies down to 0.1 ng/ml with 4 log assay range and with low intra- and inter-assay coefficients of variation (%CV). We also estimate multiple strain HCoVs IgG, IgA and IgM concentration in VAMS samples in three categories of subjects: pre-COVID-19 (n=21), post-COVID-19 convalescents (n=19), and COVID-19 vaccine recipients (n=14). Using metric multidimensional scaling (MDS) analysis, HCoVs IgG concentrations in fingerstick blood samples were well separated between the pre-COVID-19, post-COVID-19 convalescents, and COVID-19 vaccine recipients. In addition, we demonstrate how multi-dimensional scaling analysis can be used to visualize IgG mediated antibody immunity against multiple human coronaviruses. We conclude that the combination of VAMS and the mPlex-Cov assay is well suited to performing remote study sample collection under pandemic conditions to monitor HCoVs antibody responses in population studies.


Assuntos
Anticorpos Antivirais/sangue , Coronavirus/imunologia , Reações Cruzadas/imunologia , Imunoensaio/métodos , Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , COVID-19/imunologia , Coronavirus Humano 229E/imunologia , Coronavirus Humano NL63/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Coronavirus Humano OC43/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
4.
Biomed Res Int ; 2021: 6689471, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307666

RESUMO

This article is aimed at analyzing the structure and function of the spike (S) proteins of porcine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV) by applying bioinformatics methods. The physical and chemical properties, hydrophilicity and hydrophobicity, transmembrane region, signal peptide, phosphorylation and glycosylation sites, epitope, functional domains, and motifs of S proteins of porcine enteric coronaviruses were predicted and analyzed through online software. The results showed that S proteins of TGEV, PEDV, SADS-CoV, and PDCoV all contained transmembrane regions and signal peptide. TGEV S protein contained 139 phosphorylation sites, 24 glycosylation sites, and 53 epitopes. PEDV S protein had 143 phosphorylation sites, 22 glycosylation sites, and 51 epitopes. SADS-CoV S protein had 109 phosphorylation sites, 20 glycosylation sites, and 43 epitopes. PDCoV S protein had 124 phosphorylation sites, 18 glycosylation sites, and 52 epitopes. Moreover, TGEV, PEDV, and PDCoV S proteins all contained two functional domains and two motifs, spike_rec_binding and corona_S2. The corona_S2 consisted of S2 subunit heptad repeat 1 (HR1) and S2 subunit heptad repeat 2 (HR2) region profiles. Additionally, SADS-CoV S protein was predicted to contain only one functional domain, the corona_S2. This analysis of the biological functions of porcine enteric coronavirus spike proteins can provide a theoretical basis for the design of antiviral drugs.


Assuntos
Infecções por Coronavirus/epidemiologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Alphacoronavirus/metabolismo , Alphacoronavirus/patogenicidade , Animais , Biologia Computacional/métodos , Coronavirus/imunologia , Coronavirus/ultraestrutura , Bases de Dados Genéticas , Deltacoronavirus/metabolismo , Deltacoronavirus/patogenicidade , Epitopos/imunologia , Vírus da Diarreia Epidêmica Suína/metabolismo , Vírus da Diarreia Epidêmica Suína/patogenicidade , Glicoproteína da Espícula de Coronavírus/metabolismo , Suínos/virologia , Doenças dos Suínos/virologia , Vírus da Gastroenterite Transmissível/metabolismo , Vírus da Gastroenterite Transmissível/patogenicidade
5.
Sci Immunol ; 6(61)2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326184

RESUMO

The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. While antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all seven hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library. Antibody repertoires of 269 recovered COVID-19 patients showed distinct changes compared to 260 unexposed pre-pandemic controls, not limited to binding of SARS-CoV-2 antigens but including binding to antigens from hCoVs and aCoVs with shared motifs to SARS-CoV-2. We isolated broadly reactive monoclonal antibodies from recovered COVID-19 patients that bind a shared motif of SARS-CoV-2, hCoV-OC43, hCoV-HKU1, and several aCoVs, demonstrating that interspecies cross-reactivity can be mediated by a single immunoglobulin. Employing antibody binding data against the entire CoV antigen library allowed accurate discrimination of recovered COVID-19 patients from unexposed individuals by machine learning. Leaving out SARS-CoV-2 antigens and relying solely on antibody binding to other hCoVs and aCoVs achieved equally accurate detection of SARS-CoV-2 infection. The ability to detect SARS-CoV-2 infection without knowledge of its unique antigens solely from cross-reactive antibody responses against other hCoVs and aCoVs suggests a potential diagnostic strategy for the early stage of future pandemics. Creating regularly updated antigen libraries representing the animal coronavirome can provide the basis for a serological assay already poised to identify infected individuals following a future zoonotic transmission event.


Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Infecções por Coronavirus/imunologia , Coronavirus/imunologia , Biblioteca de Peptídeos , Adolescente , Adulto , Idoso , Animais , Infecções por Coronavirus/diagnóstico , Reações Cruzadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Zoonoses
6.
BMC Infect Dis ; 21(1): 544, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107889

RESUMO

BACKGROUND: SARS-CoV-2 is a recently emerged pandemic coronavirus (CoV) capable of causing severe respiratory illness. However, a significant number of infected people present as asymptomatic or pauci-symptomatic. In this prospective assessment of at-risk healthcare workers (HCWs) we seek to determine whether pre-existing antibody or T cell responses to previous seasonal human coronavirus (HCoV) infections affect immunological or clinical responses to SARS-CoV-2 infection or vaccination. METHODS: A cohort of 300 healthcare workers, confirmed negative for SARS-CoV-2 exposure upon study entry, will be followed for up to 1 year with monthly serology analysis of IgM and IgG antibodies against the spike proteins of SARS-CoV-2 and the four major seasonal human coronavirus - HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63. Participants will complete monthly questionnaires that ask about Coronavirus Disease 2019 (COVID-19) exposure risks, and a standardized, validated symptom questionnaire (scoring viral respiratory disease symptoms, intensity and severity) at least twice monthly and any day when any symptoms manifest. SARS-CoV-2 PCR testing will be performed any time participants develop symptoms consistent with COVID-19. For those individuals that seroconvert and/or test positive by SARS-CoV-2 PCR, or receive the SARS-CoV-2 vaccine, additional studies of T cell activation and cytokine production in response to SARS-CoV-2 peptide pools and analysis of Natural Killer cell numbers and function will be conducted on that participant's cryopreserved baseline peripheral blood mononuclear cells (PBMCs). Following the first year of this study we will further analyze those participants having tested positive for COVID-19, and/or having received an authorized/licensed SARS-CoV-2 vaccine, quarterly (year 2) and semi-annually (years 3 and 4) to investigate immune response longevity. DISCUSSION: This study will determine the frequency of asymptomatic and pauci-symptomatic SARS-CoV-2 infection in a cohort of at-risk healthcare workers. Baseline and longitudinal assays will determine the frequency and magnitude of anti-spike glycoprotein antibodies to the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, and may inform whether pre-existing antibodies to these human coronaviruses are associated with altered COVID-19 disease course. Finally, this study will evaluate whether pre-existing immune responses to seasonal HCoVs affect the magnitude and duration of antibody and T cell responses to SARS-CoV-2 vaccination, adjusting for demographic covariates.


Assuntos
COVID-19/imunologia , Pessoal de Saúde/estatística & dados numéricos , SARS-CoV-2/imunologia , Soroconversão , Vacinação/estatística & dados numéricos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Infecções Assintomáticas , Vacinas contra COVID-19/imunologia , Coronavirus/imunologia , Reações Cruzadas , Humanos , Estudos Prospectivos , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia
7.
PLoS Biol ; 19(6): e3001265, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34143766

RESUMO

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Proteínas Virais/imunologia , Anticorpos Antivirais/sangue , COVID-19/patologia , Coronavirus/imunologia , Reações Cruzadas , Epitopos de Linfócito B , Humanos , Epitopos Imunodominantes , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Proteoma/imunologia , Índice de Gravidade de Doença
8.
Science ; 372(6548): 1336-1341, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006597

RESUMO

The identification of CD4+ T cell epitopes is instrumental for the design of subunit vaccines for broad protection against coronaviruses. Here, we demonstrate in COVID-19-recovered individuals a robust CD4+ T cell response to naturally processed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and nucleoprotein (N), including effector, helper, and memory T cells. By characterizing 2943 S-reactive T cell clones from 34 individuals, we found that the receptor-binding domain (RBD) is highly immunogenic and that 33% of RBD-reactive clones and 94% of individuals recognized a conserved immunodominant S346-S365 region comprising nested human leukocyte antigen DR (HLA-DR)- and HLA-DP-restricted epitopes. Using pre- and post-COVID-19 samples and S proteins from endemic coronaviruses, we identified cross-reactive T cells targeting multiple S protein sites. The immunodominant and cross-reactive epitopes identified can inform vaccination strategies to counteract emerging SARS-CoV-2 variants.


Assuntos
Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , Epitopos Imunodominantes , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Coronavirus/imunologia , Reações Cruzadas , Epitopos de Linfócito T/imunologia , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T , Antígenos HLA-DP/imunologia , Antígenos HLA-DR/imunologia , Humanos , Memória Imunológica , Proteínas do Nucleocapsídeo/imunologia , Domínios Proteicos , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Glicoproteína da Espícula de Coronavírus/química , Células T Auxiliares Foliculares/imunologia , Subpopulações de Linfócitos T/imunologia
9.
Int Arch Allergy Immunol ; 182(9): 863-876, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33951640

RESUMO

Coronaviruses (CoVs) were first discovered in the 1960s. Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) has been identified as the cause of COVID-19, which spread throughout China and subsequently, across the world. As COVID-19 causes serious public health concerns across the world, investigating the characteristics of SARS-CoV-2 and its interaction with the host immune responses may provide a clearer picture of how the pathogen causes disease in some individuals. Interestingly, SARS-CoV-2 has 80% sequence homology with SARS-CoV-1 and 96-98% homology with CoVs isolated from bats. Therefore, the experience acquired in SARS and Middle East Respiratory Syndrome (MERS) epidemics may improve our understanding of the immune response and immunopathological changes in COVID-19 patients. In the present paper, we have reviewed the immune responses (including the innate and adaptive immunities) to SARS-CoV, MERS-CoV, and SARS-CoV-2, so as to improve our understanding of the concept of the COVID-19 disease, which will be helpful in developing vaccines and medications for treating the COVID-19 patients.


Assuntos
Infecções por Coronavirus/imunologia , Coronavirus/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade , Imunidade Adaptativa , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Biomarcadores , COVID-19/complicações , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Coronavirus/fisiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Imunidade Inata , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Vacinas Virais/imunologia
10.
Cell Rep ; 35(8): 109164, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33991511

RESUMO

A major goal of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efforts is to elicit antibody responses that confer protection. Mapping the epitope targets of the SARS-CoV-2 antibody response is critical for vaccine design, diagnostics, and development of therapeutics. Here, we develop a pan-coronavirus phage display library to map antibody binding sites at high resolution within the complete viral proteomes of all known human-infecting coronaviruses in patients with mild or moderate/severe coronavirus disease 2019 (COVID-19). We find that the majority of immune responses to SARS-CoV-2 are targeted to the spike protein, nucleocapsid, and ORF1ab and include sites of mutation in current variants of concern. Some epitopes are identified in the majority of samples, while others are rare, and we find variation in the number of epitopes targeted between individuals. We find low levels of SARS-CoV-2 cross-reactivity in individuals with no exposure to the virus and significant cross-reactivity with endemic human coronaviruses (CoVs) in convalescent sera from patients with COVID-19.


Assuntos
COVID-19/imunologia , Epitopos/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas Virais/imunologia , Adulto , Idoso , Anticorpos Antivirais/imunologia , Sítios de Ligação de Anticorpos , COVID-19/virologia , Técnicas de Visualização da Superfície Celular , Coronavirus/imunologia , Reações Cruzadas , Feminino , Células HEK293 , Humanos , Imunidade , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , Poliproteínas/imunologia , Sorologia , Adulto Jovem
11.
Rev. Ciênc. Plur ; 7(2): 196-210, maio 2021. ilus, tab
Artigo em Português | LILACS, BBO - Odontologia | ID: biblio-1283580

RESUMO

Introdução:A população idosa constitui um dos grupos mais vulneráveis à infecção pelo novo coronavírus. Tal fragilidade é ainda mais evidente naqueles que residem em Instituições para Idosos, por apresentar maior risco de contaminação e, ainda, de morbimortalidade. Objetivo: Identificar o impacto da COVID-19 na saúde de pessoas idosas residentes nas Instituições de Longa Permanência. Metodologia:Trata-se de estudo retrospectivo de revisão integrativa da literatura, entre os meses de novembro/2020 e março/2021, sintetizando estudos publicados sobre a temática. A partir do objetivo traçado para este estudo, determinamos quais seriam as questões norteadoras: 1. "Quais medidas estão sendo adotadas para minimizar os efeitos da COVID-19 nas Instituições de Longa Permanência para Idosos?" 2. "Quais os principais impactos causados por essas medidas?". Estes eixos colaboram para a compreensão dos acontecimentos de significativa relevância social. Resultados:As instituições para idosos, como ambientes coletivos, possuem residentes com elevada vulnerabilidade à infecção pelo novo coronavírus. Naqueles idosos acometidos por quadros de demência e outras doenças neurológicas, o isolamento social aprofunda a gravidade da infecção pela COVID-19, dificultando, assim, as atividades relacionadas à atenção e assistência realizadas pelos cuidadores. Ademais, caracteriza-se como medida fundamental a adoção do rastreamento laboratorial precoce para potencializar a prevenção de casos e promover o controle da infecção. Percebe-se ainda uma deficiência referente à construção de um protocolo com medidas de profilaxia e manejo adequado de modo mais direcionado dentro dessas instituições. Conclusão:Torna-se urgente um olhar mais atento às necessidades da população idosa, especialmente dogrupo institucionalizado, de modo a promover políticas de investimento em cuidados de saúde integrais e realizados por equipe multiprofissional (AU).


Introduction:The elderly population is one of the groups most vulnerable to infection by the new coronavirus. Such fragility is even more evident in those who live in Institutions for the Aged, as it presents a higher risk of contamination and, even, of morbidity and mortality. Objective: To identify the impact of COVID-19 on the health of elderly people residing in Long Term Institutions for the Aged. Methodology:This is a retrospective study of integrative literature review, between the months of November/2020 and March/2021, synthesizing published studies on the theme. Based on the objective outlined for this study, we determined what the guiding questions would be: 1. "What measures are being taken to minimize the effects of COVID-19 on Long Term Care Institutions for the Aged?" 2. "What are the main impacts caused by these measures?. These axes contribute to the understanding of events of significant social relevance. Results:Institutions for the aged, as collective environments, have residents with high vulnerability to infection with the new coronavirus. In those aged people affected by dementia and other neurological diseases, social isolation deepens the severity of the infection by COVID-19, thus hampering the activities related to the care and assistance performed by caregivers. In addition, the adoption of early laboratory screening is characterized as a fundamental measure to enhance the prevention of cases and promote infection control. It is also perceived a deficiency regarding the construction of a protocol with prophylaxis measures and adequate management in a more targeted way within these institutions.Conclusions:It is urgent to look more closely at the needs of the aged population, especially the institutionalized group, in order to promote investment policies in comprehensive health care carried out by a multidisciplinary team (AU).


Introducción: la población anciana es uno de los grupos más vulnerables a la infección por el nuevo coronavirus. Tal fragilidad es aún más evidente en quienes viven en Instituciones de Ancianos, ya que presenta un mayor riesgo de contaminación e, incluso, de morbilidad y mortalidad. Objetivo: Identificar el impacto del COVID-19 en la salud de los ancianos que residen en Instituciones de Atención de Larga Duración. Metodología: Se trata de un estudio retrospectivo de revisión integradora de la literatura, entre los meses de noviembre/2020 y marzo/2021, sintetizando los estudios publicados sobre el tema. Con base en el objetivo delineado para este estudio, determinamos cuáles serían las preguntas orientadoras: 1. "¿Qué medidas se están tomando para minimizar los efectos del COVID-19 en las Instituciones de Atención de Larga Duración para el Anciano?" 2. "¿Cuáles son los principales impactos provocados por estas medidas?". Estos ejes contribuyen a la comprensión de hechos de relevancia social significativa.Resultados:Las instituciones para los ancianos, como entornos colectivos, tienen residentes conalta vulnerabilidad a la infección por el nuevo coronavirus. Aquellos ancianos afectados por demencia y otras enfermedades neurológicas, el aislamiento social profundiza la gravedad de la infección por COVID-19, dificultando así las actividades relacionadas con el cuidado y asistencia que realizan los cuidadores. Además, la adopción del cribado precoz de laboratorio se caracteriza por ser una medida fundamental para potenciar la prevención de casos y promover el control de infecciones. También se percibe una deficiencia en la construcción de un protocolo con medidas de profilaxis y manejo adecuado de manera más focalizada dentro de estas instituciones. Conclusiones: Es urgente mirar más de cerca las necesidades de la población anciana, especialmente del grupo institucionalizado, para promover políticas de inversión en la atención integral de salud llevadas a cabo por un equipo multidisciplinario (AU).


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Saúde do Idoso , Assistência de Longa Duração , Coronavirus/imunologia , COVID-19/patologia , Instituição de Longa Permanência para Idosos , Isolamento Social/psicologia , Brasil , Indicadores de Morbimortalidade , Estudos Retrospectivos , Interpretação Estatística de Dados , Infecções por Coronavirus/patologia , Protocolos/métodos , Necessidades e Demandas de Serviços de Saúde
12.
Immunity ; 54(5): 1055-1065.e5, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33945786

RESUMO

Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7+ COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3ß loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Epitopos Imunodominantes/imunologia , SARS-CoV-2/imunologia , Sequência de Aminoácidos , Coronavirus/classificação , Coronavirus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/química , Reações Cruzadas , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Antígeno HLA-B7/química , Antígeno HLA-B7/genética , Antígeno HLA-B7/imunologia , Humanos , Epitopos Imunodominantes/química , Memória Imunológica , Modelos Moleculares , Peptídeos/química , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia
13.
Zoonoses Public Health ; 68(5): 464-473, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33864357

RESUMO

A serological survey of human coronavirus antibodies among villagers in 10 provinces of Thailand was conducted during 2016-2018. Serum samples (n = 364) were collected from participants from the villages and tested for coronavirus antibodies using a human coronavirus IgG ELISA kit. Our results showed that 10.44% (38/364; 21 males and 17 females) of the villagers had antibodies against human coronaviruses. The odds ratio for coronavirus positivity in the villagers in the central region who were exposed to bats was 4.75, 95% CI 1.04-21.70, when compared to that in the non-exposed villagers. The sociodemographics, knowledge, attitudes and practices (KAP) of the villagers were also recorded and analysed by using a quantitative structured questionnaire. Our results showed that 62.36% (227/364) of the villagers had been exposed to bats at least once in the past six months. Low monthly family income was statistically significant in increasing the risk for coronavirus seropositivity among the villagers (OR 2.91, 95% CI 1.13-7.49). In-depth interviews among the coronavirus-positive participants (n = 30) showed that cultural context, local norms and beliefs could influence to bat exposure activities. In conclusion, our results provide baseline information on human coronavirus antibodies and KAP regarding to bat exposure among villagers in Thailand.


Assuntos
Anticorpos Antivirais/sangue , Quirópteros , Infecções por Coronavirus/epidemiologia , Coronavirus/imunologia , Adulto , Idoso , Animais , Quirópteros/virologia , Infecções por Coronavirus/imunologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Tailândia/epidemiologia
15.
Sci Rep ; 11(1): 7554, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824382

RESUMO

A coronavirus antigen microarray (COVAM) was constructed containing 11 SARS-CoV-2, 5 SARS-1, 5 MERS, and 12 seasonal coronavirus recombinant proteins. The array is designed to measure immunoglobulin isotype and subtype levels in serum or plasma samples against each of the individual antigens printed on the array. We probed the COVAM with COVID-19 convalescent plasma (CCP) collected from 99 donors who recovered from a PCR+ confirmed SARS-CoV-2 infection. The results were analyzed using two computational approaches, a generalized linear model (glm) and random forest (RF) prediction model, to classify individual specimens as either Reactive or non-reactive against the SARS-CoV-2 antigens. A training set of 88 pre-COVID-19 specimens (PreCoV) collected in August 2019 and102 positive specimens from SARS-CoV-2 PCR+ confirmed COVID-19 cases was used for these analyses. Results compared with an FDA emergency use authorized (EUA) SARS-CoV2 S1-based total Ig chemiluminescence immunoassay (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and with a SARS-CoV-2 S1-S2 spike-based pseudovirus micro neutralization assay (SARS-CoV-2 reporter viral particle neutralization titration (RVPNT) showed high concordance between the three assays. Three CCP specimens that were negative by the VITROS CoV2T immunoassay were also negative by both COVAM and the RVPNT assay. Concordance between VITROS CoV2T and COVAM was 96%, VITROS CoV2T and RVPNT 93%, and RVPNT and COVAM 91%. The discordances were all weakly reactive samples near the cutoff threshold of the VITROS CoV2T immunoassay. The multiplex COVAM allows CCP to be grouped according to antibody reactivity patterns against 11 SARS-CoV-2 antigens. Unsupervised K-means analysis, via the gap statistics, as well as hierarchical clustering analysis revealed three main clusters with distinct reactivity intensities and patterns. These patterns were not recapitulated by adjusting the VITROS CoV2T or RVPNT assay thresholds. Plasma classified by COVAM reactivity patterns offers potential to improve CCP therapeutic efficacy CoV2T alone. The use of a SARS-CoV-2 antigen array can qualify CCP for administration as a treatment for acute COVID-19, and interrogate vaccine immunogenicity and performance in preclinical, clinical studies, and routine vaccination to identify antibody responses predictive of protection from infection and disease.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/terapia , SARS-CoV-2/imunologia , Imunidade Adaptativa , Coronavirus/imunologia , Humanos , Imunidade Humoral , Imunização Passiva
16.
Science ; 372(6543): 738-741, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33846272

RESUMO

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, prepandemic children had class-switched convergent clones to severe acute respiratory syndrome coronavirus 2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. These results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.


Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Coronavirus/imunologia , Memória Imunológica , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Pré-Escolar , Reações Cruzadas , Ebolavirus/imunologia , Feminino , Sangue Fetal/imunologia , Genes de Imunoglobulinas , Humanos , Switching de Imunoglobulina , Imunoglobulina D/genética , Imunoglobulina D/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Imunoglobulina M/genética , Imunoglobulina M/imunologia , Lactente , Linfonodos/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos B/imunologia , Hipermutação Somática de Imunoglobulina , Baço/imunologia , Adulto Jovem
17.
Cell Transplant ; 30: 963689721993769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33840257

RESUMO

Until July 29th, the number of confirmed coronavirus (COVID-19) cases worldwide has risen to over 16 million, within which 655 k deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerges as the 11th global pandemic disease, showing the highest infectivity and lowest infection fatality rate. In this review, we compare the immunopathology among SARS-CoV, Middle East respiratory syndrome coronavirus, and SARS-CoV2. SARS-CoV2 is similar to SARS-CoV; it can cause lymphocytopenia and a rising granulocyte count. Here we point out the human body and concentrated society make for an excellent incubator for virus evolution. Most research energies put into developing the SARS-CoV2 vaccine are trying to block virus infection. Sixty-five percent of severe patients die with multiple organ failure, inflammation, and cytokine storm, which indicates that the patient's immune system maintains functionality. Finding a way to trigger the specific T cell subset and plasmablast in our body is the best shot to get away with SARS-CoV2.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Animais , COVID-19/patologia , Coronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/patologia
18.
J Infect Dis ; 224(1): 49-59, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-33755731

RESUMO

BACKGROUND: We investigated frequency of reinfection with seasonal human coronaviruses (HCoVs) and serum antibody response following infection over 8 years in the Household Influenza Vaccine Evaluation (HIVE) cohort. METHODS: Households were followed annually for identification of acute respiratory illness with reverse-transcription polymerase chain reaction-confirmed HCoV infection. Serum collected before and at 2 time points postinfection were tested using a multiplex binding assay to quantify antibody to seasonal, severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins and SARS-CoV-2 spike subdomains and N protein. RESULTS: Of 3418 participants, 40% were followed for ≥3 years. A total of 1004 HCoV infections were documented; 303 (30%) were reinfections of any HCoV type. The number of HCoV infections ranged from 1 to 13 per individual. The mean time to reinfection with the same type was estimated at 983 days for 229E, 578 days for HKU1, 615 days for OC43, and 711 days for NL63. Binding antibody levels to seasonal HCoVs were high, with little increase postinfection, and were maintained over time. Homologous, preinfection antibody levels did not significantly correlate with odds of infection, and there was little cross-response to SARS-CoV-2 proteins. CONCLUSIONS: Reinfection with seasonal HCoVs is frequent. Binding anti-spike protein antibodies do not correlate with protection from seasonal HCoV infection.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavirus , Características da Família , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Síndrome Respiratória Aguda Grave/epidemiologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , COVID-19/virologia , Coinfecção/epidemiologia , Coronavirus/classificação , Coronavirus/genética , Coronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/virologia , Estimativa de Kaplan-Meier , Michigan/epidemiologia , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Reinfecção/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Estações do Ano , Estudos Soroepidemiológicos , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Carga Viral
19.
Front Immunol ; 12: 573078, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692778

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV), first discovered in 2017, is a porcine enteric coronavirus that can cause acute diarrhea syndrome (SADS) in piglets. Here, we studied the role of SADS-CoV nucleocapsid (N) protein in innate immunity. Our results showed that SADS-CoV N protein could inhibit type I interferon (IFN) production mediated by Sendai virus (Sev) and could block the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3). Simultaneously, the IFN-ß promoter activity mediated by TANK binding kinase 1 (TBK1) or its upstream molecules in the RLRs signal pathway was inhibited by SADS-CoV N protein. Further investigations revealed that SADS-CoV N protein could counteract interaction between TNF receptor-associated factor 3 (TRAF3) and TBK1, which led to reduced TBK1 activation and IFN-ß production. Our study is the first report of the interaction between SADS-CoV N protein and the host antiviral innate immune responses, and the mechanism utilized by SADS-CoV N protein provides a new insight of coronaviruses evading host antiviral innate immunity.


Assuntos
Alphacoronavirus/metabolismo , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Interferon beta/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Fator 3 Associado a Receptor de TNF/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Alphacoronavirus/imunologia , Animais , Linhagem Celular , Coronavirus/imunologia , Coronavirus/metabolismo , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Quinase I-kappa B/imunologia , Quinase I-kappa B/metabolismo , Imunidade Inata , Fator Regulador 3 de Interferon/imunologia , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/biossíntese , Interferon beta/imunologia , Interferon beta/metabolismo , NF-kappa B/imunologia , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Suínos , Fator 3 Associado a Receptor de TNF/imunologia , Fator 3 Associado a Receptor de TNF/metabolismo
20.
mBio ; 12(2)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653891

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the CoV disease 2019 (COVID-19) pandemic, enters host cells via the interaction of its receptor-binding domain (RBD) of the spike protein with host angiotensin-converting enzyme 2 (ACE2). Therefore, the RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of an RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling Helicobacter pylori-bullfrog ferritin nanoparticles as an antigen delivery system. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. Sixteen- to 20-month-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss, or clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious virus in nasal washes and lungs as well as of viral RNA in respiratory organs. This study demonstrates that spike RBD-nanoparticles are an effective protein vaccine candidate against SARS-CoV-2.


Assuntos
COVID-19/prevenção & controle , Nanopartículas/química , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Virais/uso terapêutico , Enzima de Conversão de Angiotensina 2/química , Animais , Celulose/química , Coronavirus/imunologia , Coronavirus/patogenicidade , Furões , Ferritinas , SARS-CoV-2/imunologia , Vacinas Virais/química
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