RESUMO
Tragic events such as pandemics can be remembered as well as foreshadowed by works of art. Paintings by the artists Edvard Munch and John Singer Sargent (1918-19) tell us in real time what it was like to be stricken by the Spanish flu. Paintings by Edward Hopper (1940s and '50s) foretell the lockdown and social distancing of today's COVID-19 pandemic.
Assuntos
Infecções por Coronavirus , Influenza Pandêmica, 1918-1919 , Medicina nas Artes , Pandemias , Pneumonia Viral , COVID-19 , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Pessoas Famosas , História do Século XX , Humanos , Influenza Humana/epidemiologia , Pneumonia Viral/epidemiologia , I Guerra MundialRESUMO
SARS-CoV-2 infection is mild in the majority of individuals but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed "trained immunity," by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections through epigenetic, transcriptional, and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole-microorganism vaccines may represent an important tool for reducing susceptibility to and severity of SARS-CoV-2.
Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Imunomodulação , Pneumonia Viral/imunologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/fisiologia , Animais , Vacina BCG/imunologia , COVID-19 , Ensaios Clínicos como Assunto , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Humanos , Imunidade Inata/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Linfopenia/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/patologia , Replicação ViralRESUMO
Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.
Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Animais , Betacoronavirus/classificação , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , SARS-CoV-2 , Vacinas Virais/imunologia , Tratamento Farmacológico da COVID-19RESUMO
SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers-individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease-present a unique opportunity to reveal human genetic determinants of infection and disease.
Assuntos
Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Predisposição Genética para Doença , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Fatores Etários , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Resistência à Doença , Estudos de Associação Genética , Doenças Genéticas Inatas/imunologia , Variação Genética , Genoma Humano , Interações Hospedeiro-Patógeno , Humanos , Infecções/genética , Infecções/imunologia , Infecções/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , SARS-CoV-2RESUMO
Viruses are a constant threat to global health as highlighted by the current COVID-19 pandemic. Currently, lack of data underlying how the human host interacts with viruses, including the SARS-CoV-2 virus, limits effective therapeutic intervention. We introduce Viral-Track, a computational method that globally scans unmapped single-cell RNA sequencing (scRNA-seq) data for the presence of viral RNA, enabling transcriptional cell sorting of infected versus bystander cells. We demonstrate the sensitivity and specificity of Viral-Track to systematically detect viruses from multiple models of infection, including hepatitis B virus, in an unsupervised manner. Applying Viral-Track to bronchoalveloar-lavage samples from severe and mild COVID-19 patients reveals a dramatic impact of the virus on the immune system of severe patients compared to mild cases. Viral-Track detects an unexpected co-infection of the human metapneumovirus, present mainly in monocytes perturbed in type-I interferon (IFN)-signaling. Viral-Track provides a robust technology for dissecting the mechanisms of viral-infection and pathology.
Assuntos
Infecções por Coronavirus/fisiopatologia , Interações Hospedeiro-Patógeno , Pneumonia Viral/fisiopatologia , Software , Animais , Betacoronavirus/isolamento & purificação , COVID-19 , Coinfecção/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Interferons/imunologia , Pulmão/patologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , SARS-CoV-2 , Sensibilidade e Especificidade , Análise de Sequência de RNA , Índice de Gravidade de Doença , Análise de Célula ÚnicaRESUMO
Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide "megapools," circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in â¼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in â¼40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating "common cold" coronaviruses and SARS-CoV-2.
Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Epitopos de Linfócito T , Pneumonia Viral/imunologia , Betacoronavirus/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19 , Vacinas contra COVID-19 , Convalescença , Infecções por Coronavirus/sangue , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Reações Cruzadas , Humanos , Leucócitos Mononucleares/imunologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , Proteínas Virais/metabolismo , Vacinas Virais/imunologiaRESUMO
Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA-positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China, we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain because of low virus genetic variation early in the pandemic. Our results illustrate how the timing, size, and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required, because the number of cases imported from other countries has increased.
Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Teorema de Bayes , COVID-19 , China/epidemiologia , Infecções por Coronavirus/virologia , Monitoramento Epidemiológico , Humanos , Funções Verossimilhança , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , ViagemRESUMO
SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.
Assuntos
Convalescença , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Adulto , Anticorpos Antivirais/imunologia , Infecções Assintomáticas , Betacoronavirus/imunologia , COVID-19 , Infecções por Coronavirus/patologia , Feminino , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , SARS-CoV-2RESUMO
The ongoing pandemic of a new human coronavirus, SARS-CoV-2, has generated enormous global concern. We and others in China were involved in the initial genome sequencing of the virus. Herein, we describe what genomic data reveal about the emergence SARS-CoV-2 and discuss the gaps in our understanding of its origins.
Assuntos
Betacoronavirus/genética , Quirópteros/virologia , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Pneumonia Viral/virologia , Animais , Animais Selvagens , COVID-19 , China , Infecções por Coronavirus/transmissão , DNA Ambiental , Genoma Viral , Pandemias , Pneumonia Viral/transmissão , SARS-CoV-2 , Análise de Sequência de RNA , Zoonoses/virologiaRESUMO
The SARS-CoV-2 pandemic has posed a significant challenge for risk evaluation and mitigation among cancer patients. Susceptibility to and severity of COVID-19 in cancer patients has not been studied in a prospective and broadly applicable manner. CAPTURE is a pan-cancer, longitudinal immune profiling study designed to address this knowledge gap.
Assuntos
Infecções por Coronavirus/complicações , Monitorização Imunológica/métodos , Neoplasias/complicações , Pneumonia Viral/complicações , Anticorpos Antivirais/imunologia , COVID-19 , Infecções por Coronavirus/imunologia , Humanos , Estudos Longitudinais , Neoplasias/imunologia , Neoplasias/virologia , Pandemias , Pneumonia Viral/imunologiaRESUMO
Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.
Assuntos
Infecções por Coronavirus/sangue , Metabolômica , Pneumonia Viral/sangue , Proteômica , Adulto , Aminoácidos/metabolismo , Biomarcadores/sangue , COVID-19 , Análise por Conglomerados , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Metabolismo dos Lipídeos , Aprendizado de Máquina , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Índice de Gravidade de DoençaRESUMO
Researchers around the globe have been mounting, accelerating, and redeploying efforts across disciplines and organizations to tackle the SARS-CoV-2 outbreak. However, humankind continues to be afflicted by numerous other devastating diseases in increasing numbers. Here, we outline considerations and opportunities toward striking a good balance between maintaining and redefining research priorities.
Assuntos
Pesquisa Biomédica , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Pesquisa Biomédica/economia , COVID-19 , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Ciência de Dados/instrumentação , Ciência de Dados/métodos , Atenção à Saúde , Humanos , Invenções , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/prevenção & controle , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , PesquisaRESUMO
Understanding which arms of the immune response are responsible for protection against SARS-CoV-2 infection is key to predicting long-term immunity and to inform vaccine design. Two studies in this issue of Cell collectively suggest that, although SARS-CoV-2 infection may blunt long-lived antibody responses, immune memory might still be achieved through virus-specific memory T cells.
Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Linfócitos T , Linfócitos B , Betacoronavirus , COVID-19 , SARS-CoV-2RESUMO
In this issue of Cell, Korber et al. found that a SARS-CoV-2 variant in the spike protein D614G rapidly became dominant around the world. Although clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , Humanos , Mutação , SARS-CoV-2RESUMO
The emergence of SARS-CoV-2 has driven a global research effort to identify medical countermeasures at an unprecedented pace. In this issue of Cell, Cao et al. identify thousands of SARS-CoV-2 neutralizing antibodies from convalescent donors. The authors improve our understanding of immunity against the coronavirus spike glycoprotein and detail novel pathways to rapidly identify and characterize protective monoclonal antibodies.
Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Anticorpos Antivirais , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2RESUMO
Vaccines save millions of lives from infectious diseases caused by viruses and bacteria. As the world awaits safe and effective COVID-19 vaccines, we celebrate the progresses made and highlight challenges ahead in vaccines and the science behind them.
Assuntos
Controle de Doenças Transmissíveis , Doenças Transmissíveis/imunologia , Vacinas/imunologia , Adjuvantes Imunológicos/administração & dosagem , COVID-19 , Vacinas contra COVID-19 , Ensaios Clínicos como Assunto , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/parasitologia , Doenças Transmissíveis/virologia , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Uso de Medicamentos , Humanos , Imunidade Coletiva , Pandemias/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Vacinação , Vacinas/administração & dosagem , Vacinas Virais/química , Vacinas Virais/imunologiaRESUMO
The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.
Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Viagem , Betacoronavirus/isolamento & purificação , COVID-19 , Connecticut/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Monitoramento Epidemiológico , Humanos , Funções Verossimilhança , Pandemias , Filogenia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , SARS-CoV-2 , Viagem/legislação & jurisprudência , Estados Unidos/epidemiologia , Washington/epidemiologiaRESUMO
Infectious diseases prevalent in humans and animals are caused by pathogens that once emerged from other animal hosts. In addition to these established infections, new infectious diseases periodically emerge. In extreme cases they may cause pandemics such as COVID-19; in other cases, dead-end infections or smaller epidemics result. Established diseases may also re-emerge, for example by extending geographically or by becoming more transmissible or more pathogenic. Disease emergence reflects dynamic balances and imbalances, within complex globally distributed ecosystems comprising humans, animals, pathogens, and the environment. Understanding these variables is a necessary step in controlling future devastating disease emergences.
Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , COVID-19 , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Demografia , Meio Ambiente , Interações Hospedeiro-Patógeno , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissãoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.
Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , Autoanticorpos/sangue , Betacoronavirus/isolamento & purificação , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Feminino , Humanos , Imunidade Humoral , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/patologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Análise de Componente Principal , Proteoma/análise , SARS-CoV-2 , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" or "down" conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2's therapeutic potential in treating COVID-19.