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1.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 55(5): 286-288, sept.-oct. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-192478

RESUMO

INTRODUCCIÓN: El síndrome de tormenta de citoquinas (STC) es una complicación muy grave de los pacientes con infección por SARS-CoV-2. El tratamiento y la evolución no están bien definidos. Nuestro objetivo es describir sus características clínicas, los tratamientos empleados y su evolución clínica. PACIENTES Y MÉTODO: Estudio retrospectivo observacional de pacientes consecutivos ingresados en el período comprendido entre el 23 de marzo y el 12 de abril de 2020 con infección por SARS-CoV-2 confirmada, con neumonía por estudio radiológico o tomografía de tórax, que cumplían criterios de STC y que recibieron tratamiento. Clasificamos a los pacientes en los que recibieron solo pulsos de glucocorticoides (GC), o pulsos de GC y tocilizumab. Determinamos niveles séricos de ferritina, PCR y dímeros-D. La variable final fue la supervivencia. RESULTADOS: Veintiún pacientes con una edad de 83 años (80-88 años). La ferritina media fue de 1.056 microg/L (317-3.553), la PCR de 115,8mg/dL (22-306) y los dímeros-D de 2,9mg/L (0,45-17,5). Todos los pacientes recibieron pulsos de GC y en 2 casos simultáneamente tocilizumab. El tiempo medio de seguimiento fue de 13,7 días (8-21). La mortalidad global fue del 38,1% (8/21pacientes). Los 2 pacientes que recibieron tocilizumab fallecieron. Los fallecidos presentaron niveles significativamente más elevados de ferritina (1.254 vs. 925microg/L; p = 0,045) y PCR (197,6 vs. 76mg/dL; p = 0,007). Al final del seguimiento se observó una disminución en los parámetros bioquímicos con ferritina de 727microg/L, PCR de 27mg/dl y dímeros-D de 1,18mg/L. En 13/21 pacientes (61,9%) el STC se controló sin necesidad de añadir otros tratamientos. CONCLUSIONES: La mortalidad del STC por SARS-CoV-2 es alta a pesar del tratamiento. Una mayor respuesta inflamatoria se asoció con una mayor mortalidad. Aunque parece que el uso precoz de pulsos de GC puede controlarlo, pudiendo disminuir la necesidad de uso de otros tratamientos, con el diseño del estudio y sus limitaciones, no se puede establecer esta conclusión


INTRODUCTION: Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defiREVned. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. PATIENTS AND METHOD: Retrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. RESULTS: 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925microg/L; P=.045) and CRP (197.6 vs. 76mg / dL; P=.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg/L, CRP of 27mg/dl and D-dimers of 1.18mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. CONCLUSIONS: STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished


Assuntos
Humanos , Masculino , Feminino , Idoso de 80 Anos ou mais , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Vírus da SARS/patogenicidade , Citocinas/efeitos adversos , Inflamação/fisiopatologia , Glucocorticoides/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos Retrospectivos , Infecções por Coronavirus/epidemiologia , Epidemias , Mediadores da Inflamação/imunologia , Inflamação/imunologia , Ferritinas/efeitos dos fármacos , Linfo-Histiocitose Hemofagocítica/imunologia
2.
Front Immunol ; 11: 565521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013930

RESUMO

Neurological disorders caused by neuroviral infections are an obvious pathogenic manifestation. However, non-neurotropic viruses or peripheral viral infections pose a considerable challenge as their neuropathological manifestations do not emerge because of primary infection. Their secondary or bystander pathologies develop much later, like a syndrome, during and after the recovery of patients from the primary disease. Massive inflammation caused by peripheral viral infections can trigger multiple neurological anomalies. These neurological damages may range from a general cognitive and motor dysfunction up to a wide spectrum of CNS anomalies, such as Acute Necrotizing Hemorrhagic Encephalopathy, Guillain-Barré syndrome, Encephalitis, Meningitis, anxiety, and other audio-visual disabilities. Peripheral viruses like Measles virus, Enteroviruses, Influenza viruses (HIN1 series), SARS-CoV-1, MERS-CoV, and, recently, SARS-CoV-2 are reported to cause various neurological manifestations in patients and are proven to be neuropathogenic even in cellular and animal model systems. This review presents a comprehensive picture of CNS susceptibilities toward these peripheral viral infections and explains some common underlying themes of their neuropathology in the human brain.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Inflamação Neurogênica/complicações , Inflamação Neurogênica/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/complicações , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/virologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Modelos Animais de Doenças , Humanos , Microglia/imunologia , Microglia/virologia , Inflamação Neurogênica/virologia , Pandemias , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia
4.
Nat Rev Immunol ; 20(10): 615-632, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32887954

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most formidable challenge to humanity in a century. It is widely believed that prepandemic normalcy will never return until a safe and effective vaccine strategy becomes available and a global vaccination programme is implemented successfully. Here, we discuss the immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies. On the basis of these principles, we examine the current COVID-19 vaccine candidates, their strengths and potential shortfalls, and make inferences about their chances of success. Finally, we discuss the scientific and practical challenges that will be faced in the process of developing a successful vaccine and the ways in which COVID-19 vaccine strategies may evolve over the next few years.


Assuntos
Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Vacinas Virais/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Vetores Genéticos/química , Vetores Genéticos/imunologia , Humanos , Imunidade Coletiva/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Esquemas de Imunização , Imunogenicidade da Vacina , Segurança do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
5.
Nat Rev Immunol ; 20(10): 594-602, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913283

RESUMO

The COVID-19 pandemic is shining a spotlight on the field of immunology like never before. To appreciate the diverse ways in which immunologists have contributed, Nature Reviews Immunology invited the president of the International Union of Immunological Societies and the presidents of 15 other national immunology societies to discuss how they and their members responded following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


Assuntos
Infecções por Coronavirus/epidemiologia , Cooperação Internacional , Pandemias , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Sociedades Científicas/organização & administração , Antivirais/síntese química , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Relações Comunidade-Instituição , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Saúde Global/tendências , Humanos , Educação de Pacientes como Assunto/organização & administração , Equipamento de Proteção Individual/provisão & distribução , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/virologia , Distância Social , Vacinas Virais/biossíntese
6.
Signal Transduct Target Ther ; 5(1): 212, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963228

RESUMO

The outbreaks of severe acute respiratory syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV and SARS-CoV-2, respectively, have posed severe threats to global public health and the economy. Treatment and prevention of these viral diseases call for the research and development of human neutralizing monoclonal antibodies (NMAbs). Scientists have screened neutralizing antibodies using the virus receptor-binding domain (RBD) as an antigen, indicating that RBD contains multiple conformational neutralizing epitopes, which are the main structural domains for inducing neutralizing antibodies and T-cell immune responses. This review summarizes the structure and function of RBD and RBD-specific NMAbs against SARS-CoV and SARS-CoV-2 currently under development.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus/química , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Epitopos/química , Epitopos/imunologia , Epitopos/metabolismo , Humanos , Modelos Moleculares , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Estrutura Secundária de Proteína , Receptores Virais/química , Receptores Virais/imunologia , Receptores Virais/metabolismo , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Vírion/imunologia , Vírion/ultraestrutura
7.
Adv Rheumatol ; 60(1): 50, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962761

RESUMO

The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself.Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena.Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Fatores Etários , Animais , Formação de Anticorpos , Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/etiologia , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Humanos , Imunidade Inata , Inflamação/imunologia , Pulmão/patologia , Linfopenia/imunologia , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Índice de Gravidade de Doença , Fatores Sexuais , Internalização do Vírus
8.
PLoS Pathog ; 16(9): e1008798, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32903279

RESUMO

COVID-19, caused by SARS-CoV-2, is significantly more severe in adults than in children. The biological reasons for this difference remain to be elucidated. We have compared the most recent virological and immunological data related to COVID-19 between adults and children and contrasted this with earlier data from severe acute respiratory syndrome (SARS) caused by the related SARS-CoV-1 in 2003. Based on these available data, a number of hypotheses are proposed to explain the difference in COVID-19 clinical outcomes between adults and children. NF-kB may be a key factor that could explain the severe clinical manifestations of COVID-19 in adults as well as rare complications associated with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in paediatric COVID-19 patients.


Assuntos
Fatores Etários , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , NF-kappa B/metabolismo , Pneumonia Viral/imunologia , Adulto , Betacoronavirus/imunologia , Criança , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/imunologia
9.
Front Immunol ; 11: 1979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973803

RESUMO

The new pandemic virus SARS-CoV-2 emerged in China and spread around the world in <3 months, infecting millions of people, and causing countries to shut down public life and businesses. Nearly all nations were unprepared for this pandemic with healthcare systems stretched to their limits due to the lack of an effective vaccine and treatment. Infection with SARS-CoV-2 can lead to Coronavirus disease 2019 (COVID-19). COVID-19 is respiratory disease that can result in a cytokine storm with stark differences in morbidity and mortality between younger and older patient populations. Details regarding mechanisms of viral entry via the respiratory system and immune system correlates of protection or pathogenesis have not been fully elucidated. Here, we provide an overview of the innate immune responses in the lung to the coronaviruses MERS-CoV, SARS-CoV, and SARS-CoV-2. This review provides insight into key innate immune mechanisms that will aid in the development of therapeutics and preventive vaccines for SARS-CoV-2 infection.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pneumonia Viral/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Idoso , Idoso de 80 Anos ou mais , Animais , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Feminino , Humanos , Evasão da Resposta Imune , Masculino , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Mucosa Respiratória/imunologia , Síndrome Respiratória Aguda Grave/virologia
10.
Front Immunol ; 11: 2037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983152

RESUMO

Coronaviruses were first discovered in the 1960s and are named due to their crown-like shape. Sometimes, but not often, a coronavirus can infect both animals and humans. An acute respiratory disease, caused by a novel coronavirus (severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 previously known as 2019-nCoV) was identified as the cause of coronavirus disease 2019 (COVID-19) as it spread throughout China and subsequently across the globe. As of 14th July 2020, a total of 13.1 million confirmed cases globally and 572,426 deaths had been reported by the World Health Organization (WHO). SARS-CoV-2 belongs to the ß-coronavirus family and shares extensive genomic identity with bat coronavirus suggesting that bats are the natural host. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2), as that for SARS-CoV, the coronavirus associated with the SARS outbreak in 2003. It mainly spreads through the respiratory tract with lymphopenia and cytokine storms occuring in the blood of subjects with severe disease. This suggests the existence of immunological dysregulation as an accompanying event during severe illness caused by this virus. The early recognition of this immunological phenotype could assist prompt recognition of patients who will progress to severe disease. Here we review the data of the immune response during COVID-19 infection. The current review summarizes our understanding of how immune dysregulation and altered cytokine networks contribute to the pathophysiology of COVID-19 patients.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Animais , Quirópteros/virologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interleucina-6/sangue , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo
11.
Front Immunol ; 11: 2033, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922406

RESUMO

Immune dysfunction and aberrant cytokine storms often lead to rapid exacerbation of the disease during late infection stages in SARS-CoV and MERS-CoV patients. However, the underlying immunopathology mechanisms are not fully understood, and there has been little progress in research regarding the development of vaccines, anti-viral drugs, and immunotherapy. The newly discovered SARS-CoV-2 (2019-nCoV) is responsible for the third coronavirus pandemic in the human population, and this virus exhibits enhanced pathogenicity and transmissibility. SARS-CoV-2 is highly genetically homologous to SARS-CoV, and infection may result in a similar clinical disease (COVID-19). In this review, we provide detailed knowledge of the pathogenesis and immunological characteristics of SARS and MERS, and we present recent findings regarding the clinical features and potential immunopathogenesis of COVID-19. Host immunological characteristics of these three infections are summarised and compared. We aim to provide insights and scientific evidence regarding the pathogenesis of COVID-19 and therapeutic strategies targeting this disease.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pneumonia Viral/patologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Humanos , Pandemias , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/patologia
12.
Clin Immunol ; 219: 108555, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32771488

RESUMO

Respiratory failure and acute kidney injury (AKI) are associated with high mortality in SARS-CoV-2-associated Coronavirus disease 2019 (COVID-19). These manifestations are linked to a hypercoaguable, pro-inflammatory state with persistent, systemic complement activation. Three critical COVID-19 patients recalcitrant to multiple interventions had skin biopsies documenting deposition of the terminal complement component C5b-9, the lectin complement pathway enzyme MASP2, and C4d in microvascular endothelium. Administration of anti-C5 monoclonal antibody eculizumab led to a marked decline in D-dimers and neutrophil counts in all three cases, and normalization of liver functions and creatinine in two. One patient with severe heart failure and AKI had a complete remission. The other two individuals had partial remissions, one with resolution of his AKI but ultimately succumbing to respiratory failure, and another with a significant decline in FiO2 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19.


Assuntos
Lesão Renal Aguda/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/patogenicidade , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Lesão Renal Aguda/complicações , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/virologia , Adulto , Betacoronavirus/imunologia , Biomarcadores/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complemento C4b/antagonistas & inibidores , Complemento C5/antagonistas & inibidores , Complexo de Ataque à Membrana do Sistema Complemento/antagonistas & inibidores , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Imunidade Humoral/efeitos dos fármacos , Masculino , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/imunologia , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/patologia , Pandemias , Fragmentos de Peptídeos/antagonistas & inibidores , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia
13.
Viruses ; 12(8)2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784685

RESUMO

Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette-Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Animais , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Modelos Animais , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/virologia , Vacinas de DNA/imunologia , Vacinas Virais/administração & dosagem
14.
Open Vet J ; 10(2): 164-177, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32821661

RESUMO

Viruses are having great time as they seem to have bogged humans down. Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and novel coronavirus (COVID-19) are the three major coronaviruses of present-day global human and animal health concern. COVID-19 caused by SARS-CoV-2 is identified as the newest disease, presumably of bat origin. Different theories on the evolution of viruses are in circulation, yet there is no denying the fact that the animal source is the skeleton. The whole world is witnessing the terror of the COVID-19 pandemic that is following the same path of SARS and MERS, and seems to be more severe. In addition to humans, several species of animals are reported to have been infected with these life-threatening viruses. The possible routes of transmission and their zoonotic potentialities are the subjects of intense research. This review article aims to overview the link of all these three deadly coronaviruses among animals along with their phylogenic evolution and cross-species transmission. This is essential since animals as pets or food are said to pose some risk, and their better understanding is a must in order to prepare a possible plan for future havoc in both human and animal health. Although COVID-19 is causing a human health hazard globally, its reporting in animals are limited compared to SARS and MERS. Non-human primates and carnivores are most susceptible to SARS-coronavirus and SARS-CoV-2, respectively, whereas the dromedary camel is susceptible to MERS-coronavirus. Phylogenetically, the trio viruses are reported to have originated from bats and have special capacity to undergo mutation and genomic recombination in order to infect humans through its reservoir or replication host. However, it is difficult to analyze how the genomic pattern of coronaviruses occurs. Thus, increased possibility of new virus-variants infecting humans and animals in the upcoming days seems to be the biggest challenge for the future of the world. One health approach is portrayed as our best way ahead, and understanding the animal dimension will go a long way in formulating such preparedness plans.


Assuntos
Betacoronavirus/classificação , Infecções por Coronavirus/veterinária , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Pandemias/veterinária , Pneumonia Viral/veterinária , Vírus da SARS/classificação , Síndrome Respiratória Aguda Grave/veterinária , Animais , Animais Selvagens , Betacoronavirus/genética , Camelídeos Americanos/virologia , Camelus/virologia , Gatos , Quirópteros/virologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Suscetibilidade a Doenças/veterinária , Cães , Eutérios/virologia , Furões/virologia , Humanos , Leões/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Filogenia , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Primatas/virologia , Cães Guaxinins/virologia , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/transmissão , Serpentes/virologia , Tigres/virologia , Viverridae/virologia
15.
Nat Rev Immunol ; 20(10): 633-643, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32782358

RESUMO

Antibody-dependent enhancement (ADE) is a mechanism by which the pathogenesis of certain viral infections is enhanced in the presence of sub-neutralizing or cross-reactive non-neutralizing antiviral antibodies. In vitro modelling of ADE has attributed enhanced pathogenesis to Fcγ receptor (FcγR)-mediated viral entry, rather than canonical viral receptor-mediated entry. However, the putative FcγR-dependent mechanisms of ADE overlap with the role of these receptors in mediating antiviral protection in various viral infections, necessitating a detailed understanding of how this diverse family of receptors functions in protection and pathogenesis. Here, we discuss the diversity of immune responses mediated upon FcγR engagement and review the available experimental evidence supporting the role of FcγRs in antiviral protection and pathogenesis through ADE. We explore FcγR engagement in the context of a range of different viral infections, including dengue virus and SARS-CoV, and consider ADE in the context of the ongoing SARS-CoV-2 pandemic.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Anticorpos Facilitadores/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Receptores de IgG/imunologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/efeitos adversos , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Dengue/tratamento farmacológico , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores de IgG/antagonistas & inibidores , Receptores de IgG/genética , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais , Internalização do Vírus/efeitos dos fármacos
16.
Infection ; 48(5): 665-669, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32737833

RESUMO

Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic by the end of March 2020. In contrast to the 2002-2003 SARS-CoV outbreak, which had a higher pathogenicity and lead to higher mortality rates, SARSCoV-2 infection appears to be much more contagious. Moreover, many SARS-CoV-2 infected patients are reported to develop low-titer neutralizing antibody and usually suffer prolonged illness, suggesting a more effective SARS-CoV-2 immune surveillance evasion than SARS-CoV. This paper summarizes the current state of art about the differences and similarities between the pathogenesis of the two coronaviruses, focusing on receptor binding domain, host cell entry and protease activation. Such differences may provide insight into possible intervention strategies to fight the pandemic.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Catepsinas/genética , Catepsinas/imunologia , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Ativação Enzimática/imunologia , Humanos , Evasão da Resposta Imune , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/enzimologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Ligação Proteica , Domínios Proteicos , Vírus da SARS/imunologia , Serina Endopeptidases/genética , Serina Endopeptidases/imunologia , Síndrome Respiratória Aguda Grave/enzimologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/patologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Internalização do Vírus , Replicação Viral
17.
Zool Res ; 41(5): 503-516, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32772513

RESUMO

As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( Macaca mulatta) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b + and CD8 + cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b + cells, and persistent infiltration of CD8 + cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.


Assuntos
Envelhecimento/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Macaca mulatta/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Fatores Etários , Envelhecimento/metabolismo , Animais , Betacoronavirus/fisiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Inflamação/imunologia , Inflamação/veterinária , Inflamação/virologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macaca mulatta/virologia , Doenças dos Macacos/imunologia , Doenças dos Macacos/virologia , Pandemias/veterinária , Pneumonia Viral/veterinária , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/veterinária , Síndrome Respiratória Aguda Grave/virologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Carga Viral/imunologia , Carga Viral/veterinária , Replicação Viral/imunologia
18.
J Transl Med ; 18(1): 297, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746922

RESUMO

BACKGROUND: The severe acute respiratory syndrome virus SARS-CoV-2, a close relative of the SARS-CoV virus, is the cause of the recent COVID-19 pandemic affecting, to date, over 14 million individuals across the globe and demonstrating relatively high rates of infection and mortality. A third virus, the H5N1, responsible for avian influenza, has caused infection with some clinical similarities to those in COVID-19 infections. Cytokines, small proteins that modulate immune responses, have been directly implicated in some of the severe responses seen in COVID-19 patients, e.g. cytokine storms. Understanding the immune processes related to COVID-19, and other similar infections, could help identify diagnostic markers and therapeutic targets. METHODS: Here we examine data of cytokine, immune cell types, and disease associations captured from biomedical literature associated with COVID-19, Coronavirus in general, SARS, and H5N1 influenza, with the objective of identifying potentially useful relationships and areas for future research. RESULTS: Cytokine and cell-type associations captured from Medical Subject Heading (MeSH) terms linked to thousands of PubMed records, has identified differing patterns of associations between the four corpuses of publications (COVID-19, Coronavirus, SARS, or H5N1 influenza). Clustering of cytokine-disease co-occurrences in the context of Coronavirus has identified compelling clusters of co-morbidities and symptoms, some of which already known to be linked to COVID-19. Finally, network analysis identified sub-networks of cytokines and immune cell types associated with different manifestations, co-morbidities and symptoms of Coronavirus, SARS, and H5N1. CONCLUSION: Systematic review of research in medicine is essential to facilitate evidence-based choices about health interventions. In a fast moving pandemic the approach taken here will identify trends and enable rapid comparison to the literature of related diseases.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Pneumopatias/imunologia , Pneumonia Viral/imunologia , Publicações , Análise por Conglomerados , Comorbidade , Síndrome da Liberação de Citocina/virologia , Citocinas/imunologia , Células-Tronco Hematopoéticas/citologia , Humanos , Sistema Imunitário , Virus da Influenza A Subtipo H5N1 , Influenza Humana/imunologia , Pandemias , PubMed , Síndrome Respiratória Aguda Grave/imunologia
19.
Front Immunol ; 11: 1949, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849654

RESUMO

After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Pneumonia Viral/imunologia , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/imunologia , Animais , Apresentação do Antígeno/imunologia , Antivirais/uso terapêutico , Betacoronavirus/química , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Citocinas/biossíntese , Genoma Viral , Humanos , Evasão da Resposta Imune , Imunização Passiva/métodos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/química , Pandemias , Filogenia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Vírus da SARS/química , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Linfócitos T/imunologia , Replicação Viral
20.
Cells ; 9(9)2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32854433

RESUMO

Coronaviruses (CoVs) are a diverse family of the enveloped human and animal viruses reported as causative agents for respiratory and intestinal infections. The high pathogenic potential of human CoVs, including SARS-CoV, MERS-CoV and SARS-CoV-2, is closely related to the invasion mechanisms underlying the attachment and entry of viral particles to the host cells. There is increasing evidence that sialylated compounds of cellular glycocalyx can serve as an important factor in the mechanism of CoVs infection. Additionally, the sialic acid-mediated cross-reactivity with the host immune lectins is known to exert the immune response of different intensity in selected pathological stages. Here, we focus on the last findings in the field of glycobiology in the context of the role of sialic acid in tissue tropism, viral entry kinetics and immune regulation in the CoVs infections.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Citocinas/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Ácido N-Acetilneuramínico/metabolismo , Pneumonia Viral/imunologia , Vírus da SARS/fisiologia , Síndrome Respiratória Aguda Grave/imunologia , Animais , Infecções por Coronavirus/virologia , Humanos , Camundongos , Pandemias , Pneumonia Viral/virologia , Receptores de Reconhecimento de Padrão/metabolismo , Síndrome Respiratória Aguda Grave/virologia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Receptores Toll-Like/metabolismo , Internalização do Vírus
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