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1.
Sci Rep ; 11(1): 12948, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155232

RESUMO

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.


Assuntos
Adenocarcinoma/etiologia , COVID-19/complicações , Carcinogênese/genética , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Neoplasias Pancreáticas/etiologia , Vírus da SARS , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/complicações , COVID-19/genética , COVID-19/metabolismo , COVID-19/virologia , Caspase 3/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Influenza Humana/genética , Influenza Humana/metabolismo , Influenza Humana/virologia , PTEN Fosfo-Hidrolase/genética , Mapas de Interação de Proteínas , Risco , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais/genética , Proteína Smad3/genética , Regulação para Cima/genética
2.
Sci Rep ; 11(1): 12948, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: covidwho-1279894

RESUMO

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.


Assuntos
Adenocarcinoma/etiologia , COVID-19/complicações , Carcinogênese/genética , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Neoplasias Pancreáticas/etiologia , Vírus da SARS , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/complicações , COVID-19/genética , COVID-19/metabolismo , COVID-19/virologia , Caspase 3/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Influenza Humana/genética , Influenza Humana/metabolismo , Influenza Humana/virologia , PTEN Fosfo-Hidrolase/genética , Mapas de Interação de Proteínas , Risco , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais/genética , Proteína Smad3/genética , Regulação para Cima/genética
3.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1224028

RESUMO

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman's correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.


Assuntos
COVID-19/sangue , Galectinas/sangue , Osteopontina/sangue , Pneumonia/sangue , Síndrome Respiratória Aguda Grave/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores/metabolismo , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Feminino , Humanos , Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Rim/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Curva ROC , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Adulto Jovem
4.
Mol Cells ; 44(6): 384-391, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: covidwho-1259762

RESUMO

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Interações Hospedeiro-Patógeno/imunologia , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Dexametasona/uso terapêutico , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamação , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interleucinas/genética , Interleucinas/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Transdução de Sinais , Análise de Sobrevida
5.
Mol Cells ; 44(6): 384-391, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34098591

RESUMO

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Interações Hospedeiro-Patógeno/imunologia , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Dexametasona/uso terapêutico , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamação , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interleucinas/genética , Interleucinas/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Transdução de Sinais , Análise de Sobrevida
6.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067072

RESUMO

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman's correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.


Assuntos
COVID-19/sangue , Galectinas/sangue , Osteopontina/sangue , Pneumonia/sangue , Síndrome Respiratória Aguda Grave/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores/metabolismo , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Feminino , Humanos , Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Rim/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Curva ROC , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Adulto Jovem
7.
Pan Afr Med J ; 38: 159, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1145704

RESUMO

Introduction: the new coronavirus (COVID-19) that emerged from Wuhan, Hubei Province of China in December 2019, causing severe acute respiratory syndrome (SARS) has fast spread across the entire globe, with most countries struggling to slow and reduce the spread of the virus through rapid screening, testing, isolation, case management, contact tracing, implementing social distancing and lockdowns. This has been shown to be a major factor in countries that have been successful in containing COVID-19 transmission. Early detection of cases is important, and the use of geospatial technology can support to detect and easily identify potential hotspots that will require timely response. The use of spatial analysis with geographic information systems (GIS) had proved to be effective in providing timely and effective solutions in supporting epidemic response and pandemics over the years. It has developed and evolved rapidly with a complete technological tool for representing data, model construction, visualization and platform construction among others. Methods: we conducted a geospatial analysis to develop a web mapping application using ArcMap and ArcGIS online to guide and support active case search of potential COVID-19 cases, within 500m radius of COVID-19 confirmed cases to improve detection and testing of suspected cases. Results: the web mapping application tool guides the active case search teams in the field, with clear boundaries on the houses to be visited within 500-meter radius of confirmed positive cases, to conduct active case search of all cases of severe acute respiratory illnesses (SARI), acute respiratory illnesses (ARI), pneumonia etc, to detect and test for COVID-19 towards containing the pandemic. Conclusion: the use of GIS and spatial statistical tools have become an important and valuable tool in decision-making and, more importantly, guiding health care professional and other stakeholders in the response being carried out in a more coherent and easy manner. It has proven to be effective in supporting the active case search process to rapidly detect, test and isolate cases during the process, towards containing the COVID-19 pandemic.


Assuntos
COVID-19/epidemiologia , Sistemas de Informação Geográfica , Saúde Pública , COVID-19/diagnóstico , Estudos Transversais , Humanos , Síndrome Respiratória Aguda Grave/virologia , Análise Espacial , Zimbábue/epidemiologia
8.
Pan Afr Med J ; 38: 159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995766

RESUMO

Introduction: the new coronavirus (COVID-19) that emerged from Wuhan, Hubei Province of China in December 2019, causing severe acute respiratory syndrome (SARS) has fast spread across the entire globe, with most countries struggling to slow and reduce the spread of the virus through rapid screening, testing, isolation, case management, contact tracing, implementing social distancing and lockdowns. This has been shown to be a major factor in countries that have been successful in containing COVID-19 transmission. Early detection of cases is important, and the use of geospatial technology can support to detect and easily identify potential hotspots that will require timely response. The use of spatial analysis with geographic information systems (GIS) had proved to be effective in providing timely and effective solutions in supporting epidemic response and pandemics over the years. It has developed and evolved rapidly with a complete technological tool for representing data, model construction, visualization and platform construction among others. Methods: we conducted a geospatial analysis to develop a web mapping application using ArcMap and ArcGIS online to guide and support active case search of potential COVID-19 cases, within 500m radius of COVID-19 confirmed cases to improve detection and testing of suspected cases. Results: the web mapping application tool guides the active case search teams in the field, with clear boundaries on the houses to be visited within 500-meter radius of confirmed positive cases, to conduct active case search of all cases of severe acute respiratory illnesses (SARI), acute respiratory illnesses (ARI), pneumonia etc, to detect and test for COVID-19 towards containing the pandemic. Conclusion: the use of GIS and spatial statistical tools have become an important and valuable tool in decision-making and, more importantly, guiding health care professional and other stakeholders in the response being carried out in a more coherent and easy manner. It has proven to be effective in supporting the active case search process to rapidly detect, test and isolate cases during the process, towards containing the COVID-19 pandemic.


Assuntos
COVID-19/epidemiologia , Sistemas de Informação Geográfica , Saúde Pública , COVID-19/diagnóstico , Estudos Transversais , Humanos , Síndrome Respiratória Aguda Grave/virologia , Análise Espacial , Zimbábue/epidemiologia
9.
Nature ; 594(7862): 246-252, 2021 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1180252

RESUMO

The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1-10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-ß pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2.


Assuntos
COVID-19/metabolismo , Interações Hospedeiro-Patógeno , Proteoma/metabolismo , Proteômica , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/metabolismo , Animais , Antivirais/farmacologia , Autofagia/efeitos dos fármacos , COVID-19/imunologia , COVID-19/virologia , Linhagem Celular , Conjuntos de Dados como Assunto , Avaliação Pré-Clínica de Medicamentos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inibidores de Metaloproteinases de Matriz/farmacologia , Fosforilação , Mapas de Interação de Proteínas , Inibidores de Proteínas Quinases/farmacologia , Processamento de Proteína Pós-Traducional , Proteoma/química , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Fator de Crescimento Transformador beta/metabolismo , Ubiquitinação , Proteínas Virais/química , Proteínas Virais/metabolismo , Proteínas Viroporinas/metabolismo
10.
Clin Lab ; 67(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: covidwho-1190628

RESUMO

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is the cause of the third pneumonia-like outbreak of coronaviruses in humans during the 21st century. The status of the host immune system is a critical factor that affects the severity and outcomes of COVID-19. In particular, antibody responses are an indicator of the anti-viral defense; so, a delayed or inappropriate induction of these responses would correlate with a defect in the viral clearance. METHODS: This is a rapid synthesis of literature investigating antibody responses in patients with the severe acute respiratory syndrome (SARS) and COVID-19. RESULTS: Lessons learned from severe acute respiratory syndrome (SARS), along with the direct evidence of antibody responses in COVID-19, pose the potentials of dynamic antibody responses for screening and prognostic purposes in COVID-19. Also, neutralizing antibodies extracted from recovered patients and monoclonal antibodies targeting cytokines offer therapeutic support for COVID-19. CONCLUSIONS: Altogether, the dynamics of antibody responses help to determine the effectiveness of treatments for COVID-19. Of note, it might be helpful for the evaluation of the efficacy of immunotherapy and vaccination - the dreams for the future of COVID-19. Further studies are necessary to investigate the possibility and efficacy of antibody extraction from animal subjects. Finally, numerous factors affect antibody response such as race, nutrition status, and virus mutations in viral infections, which need to be considered in the context of COVID-19.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , Biomarcadores/sangue , COVID-19/sangue , Humanos , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/virologia
11.
Epidemiol Infect ; 149: e96, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: covidwho-1182771

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and Middle East respiratory syndrome coronavirus. We examined laboratory animal and human studies. The literature on infective dose, transmission and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severe symptoms. Higher viral load measures did not reflect coronavirus disease 2019 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Our review suggests that it is small, perhaps about 100 particles. Further work is also required on the relationship between routes of transmission, infective dose, co-infection and outcomes.


Assuntos
COVID-19/transmissão , SARS-CoV-2/patogenicidade , Carga Viral , Adenoviridae/patogenicidade , Animais , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Chlorocebus aethiops , Controle de Doenças Transmissíveis , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Cricetinae , Enterovirus/patogenicidade , Furões , Humanos , Macaca mulatta , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Orthomyxoviridae/patogenicidade , Vírus Sinciciais Respiratórios/patogenicidade , Rhinovirus/patogenicidade , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Viroses/epidemiologia , Viroses/transmissão , Viroses/virologia
12.
Nature ; 594(7862): 246-252, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33845483

RESUMO

The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1-10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-ß pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2.


Assuntos
COVID-19/metabolismo , Interações Hospedeiro-Patógeno , Proteoma/metabolismo , Proteômica , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/metabolismo , Animais , Antivirais/farmacologia , Autofagia/efeitos dos fármacos , COVID-19/imunologia , COVID-19/virologia , Linhagem Celular , Conjuntos de Dados como Assunto , Avaliação Pré-Clínica de Medicamentos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inibidores de Metaloproteinases de Matriz/farmacologia , Fosforilação , Mapas de Interação de Proteínas , Inibidores de Proteínas Quinases/farmacologia , Processamento de Proteína Pós-Traducional , Proteoma/química , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Fator de Crescimento Transformador beta/metabolismo , Ubiquitinação , Proteínas Virais/química , Proteínas Virais/metabolismo , Proteínas Viroporinas/metabolismo
13.
Clin Lab ; 67(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33865266

RESUMO

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is the cause of the third pneumonia-like outbreak of coronaviruses in humans during the 21st century. The status of the host immune system is a critical factor that affects the severity and outcomes of COVID-19. In particular, antibody responses are an indicator of the anti-viral defense; so, a delayed or inappropriate induction of these responses would correlate with a defect in the viral clearance. METHODS: This is a rapid synthesis of literature investigating antibody responses in patients with the severe acute respiratory syndrome (SARS) and COVID-19. RESULTS: Lessons learned from severe acute respiratory syndrome (SARS), along with the direct evidence of antibody responses in COVID-19, pose the potentials of dynamic antibody responses for screening and prognostic purposes in COVID-19. Also, neutralizing antibodies extracted from recovered patients and monoclonal antibodies targeting cytokines offer therapeutic support for COVID-19. CONCLUSIONS: Altogether, the dynamics of antibody responses help to determine the effectiveness of treatments for COVID-19. Of note, it might be helpful for the evaluation of the efficacy of immunotherapy and vaccination - the dreams for the future of COVID-19. Further studies are necessary to investigate the possibility and efficacy of antibody extraction from animal subjects. Finally, numerous factors affect antibody response such as race, nutrition status, and virus mutations in viral infections, which need to be considered in the context of COVID-19.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , Biomarcadores/sangue , COVID-19/sangue , Humanos , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/virologia
14.
Epidemiol Infect ; 149: e96, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33849679

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and Middle East respiratory syndrome coronavirus. We examined laboratory animal and human studies. The literature on infective dose, transmission and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severe symptoms. Higher viral load measures did not reflect coronavirus disease 2019 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Our review suggests that it is small, perhaps about 100 particles. Further work is also required on the relationship between routes of transmission, infective dose, co-infection and outcomes.


Assuntos
COVID-19/transmissão , SARS-CoV-2/patogenicidade , Carga Viral , Adenoviridae/patogenicidade , Animais , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Chlorocebus aethiops , Controle de Doenças Transmissíveis , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Cricetinae , Enterovirus/patogenicidade , Furões , Humanos , Macaca mulatta , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Orthomyxoviridae/patogenicidade , Vírus Sinciciais Respiratórios/patogenicidade , Rhinovirus/patogenicidade , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Viroses/epidemiologia , Viroses/transmissão , Viroses/virologia
15.
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
16.
Front Immunol ; 12: 629193, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1140644

RESUMO

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Índice de Gravidade de Doença , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Humanos , Inflamação/imunologia , Influenza Humana/sangue , Influenza Humana/virologia , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/virologia
18.
J Neurovirol ; 27(2): 348-353, 2021 04.
Artigo em Inglês | MEDLINE | ID: covidwho-1111382

RESUMO

This study was designed to evaluate whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can directly target the central nervous system (CNS). We present four patients suffering from the loss of consciousness and seizure during the clinical course of COVID-19 infection. In addition to positive nasopharyngeal swab tests, SARS-CoV-2 has been detected in their cerebrospinal fluid. This report indicates the neuroinvasive potential of SARS-CoV-2, suggesting the ability of this virus to spread from the respiratory tract to the CNS.


Assuntos
COVID-19/complicações , Líquido Cefalorraquidiano/virologia , SARS-CoV-2/isolamento & purificação , Convulsões/virologia , Síndrome Respiratória Aguda Grave/virologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Pharmacol Ther ; 224: 107825, 2021 08.
Artigo em Inglês | MEDLINE | ID: covidwho-1117458

RESUMO

Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities. Results from several studies suggest that CoVs localize in mitochondria and interact with mitochondrial protein translocation machinery to target their encoded products to mitochondria. Coronaviruses encode a number of proteins; this process is essential for viral replication through inhibiting degradation of viral proteins and host misfolded proteins including those in mitochondria. These viruses seem to maintain their replication by altering mitochondrial dynamics and targeting mitochondrial-associated antiviral signaling (MAVS), allowing them to evade host innate immunity. Coronaviruses infections such as COVID-19 are more severe in aging patients. Since endogenous melatonin levels are often dramatically reduced in the aged and because it is a potent anti-inflammatory agent, melatonin has been proposed to be useful in CoVs infections by altering proteasomal and mitochondrial activities. Melatonin inhibits mitochondrial fission due to its antioxidant and inhibitory effects on cytosolic calcium overload. The collective data suggests that melatonin may mediate mitochondrial adaptations through regulating both mitochondrial dynamics and biogenesis. We propose that melatonin may inhibit SARS-CoV-2-induced cell damage by regulating mitochondrial physiology.


Assuntos
COVID-19/tratamento farmacológico , Melatonina/farmacologia , Mitocôndrias/patologia , Idoso , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , COVID-19/complicações , COVID-19/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Feminino , Humanos , Melatonina/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/virologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/virologia , Replicação Viral
20.
Nat Commun ; 12(1): 1653, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: covidwho-1132073

RESUMO

SARS-CoV-2 emerged in late 2019 and caused a pandemic, whereas the closely related SARS-CoV was contained rapidly in 2003. Here, an experimental set-up is used to study transmission of SARS-CoV and SARS-CoV-2 through the air between ferrets over more than a meter distance. Both viruses cause a robust productive respiratory tract infection resulting in transmission of SARS-CoV-2 to two of four indirect recipient ferrets and SARS-CoV to all four. A control pandemic A/H1N1 influenza virus also transmits efficiently. Serological assays confirm all virus transmission events. Although the experiments do not discriminate between transmission via small aerosols, large droplets and fomites, these results demonstrate that SARS-CoV and SARS-CoV-2 can remain infectious while traveling through the air. Efficient virus transmission between ferrets is in agreement with frequent SARS-CoV-2 outbreaks in mink farms. Although the evidence for virus transmission via the air between humans under natural conditions is absent or weak for SARS-CoV and SARS-CoV-2, ferrets may represent a sensitive model to study interventions aimed at preventing virus transmission.


Assuntos
Microbiologia do Ar , COVID-19/transmissão , Furões/virologia , Vírus da SARS , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/transmissão , Aerossóis , Substituição de Aminoácidos , Pelo Animal/virologia , Animais , COVID-19/virologia , Modelos Animais de Doenças , Feminino , Fômites/virologia , Vírus da Influenza A Subtipo H1N1 , Modelos Biológicos , Infecções por Orthomyxoviridae/transmissão , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/genética , Síndrome Respiratória Aguda Grave/virologia , Fatores de Tempo , Carga Viral , Zoonoses Virais/transmissão , Zoonoses Virais/virologia , Eliminação de Partículas Virais
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