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1.
Crit Care ; 26(1): 10, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983614

RESUMO

BACKGROUND: Research on the duration of infectivity of ICU patients with COVID-19 has been sparse. Tests based on Reverse Transcriptase polymerase chain reaction (RT-PCR) detect both live virus and non-infectious viral RNA. We aimed to determine the duration of infectiousness based on viral culture of nasopharyngeal samples of patients with COVID-19. METHODS: Prospective observational study in adult intensive care units with a diagnosis of COVID-19 Pneumonia. Patients had repeated nasopharyngeal sampling performed after day 10 of ICU admission. Culture positive rate (based on viral culture on Vero cells in a level 4 lab) and Cycle threshold from RT-PCR were measured. RESULTS: Nine patients of the 108 samples (8.3%, 95% CI 3.9-15.2%) grew live virus at a median of 13 days (interquartile range 11-19) after their initial positive test. 74.1% of patients were RT-PCR positive but culture negative, and the remaining (17.6%) were RT-PCR and culture negative. Cycle threshold showed excellent ability to predict the presence of live virus, with a Ct < 25 with an AUC of 0.90 (95% CI 0.83-0.97, p < 0.001). The specificity of a Ct > 25 to predict negative viral culture was 100% (95% CI 70-100%). CONCLUSION: 8.3% of our ICU patients with COVID-19 grew live virus at a median of 13 days post-initial positive RT-PCR test. Severity of illness, use of mechanical ventilation, and time between tests did not predict the presence of live virus. Cycle threshold of > 25 had the best ability to determine the lack of live virus in these patents.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , COVID-19/terapia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Nasofaringe/virologia , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação
2.
PLoS One ; 17(1): e0262258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34986156

RESUMO

Although patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, influenza B and respiratory syncytial virus (RSV) show comparable or very similar manifestations, the therapeutic approaches of these respiratory viral infections are different, which requires an accurate diagnosis. Recently, the novel multiplex real-time reverse transcription-polymerase chain reaction assay AMPLIQUICK® Respiratory Triplex (BioSynex SA, Illkirch-Graffenstaden, France) allows simultaneous detection and differentiation of SARS-CoV-2, influenza A, influenza B, and RSV in respiratory tract samples. We herein evaluated the performance of the AMPLIQUICK® Respiratory Triplex for the detection of the four viruses in respiratory specimens, using Allplex™ Respiratory Panel 1 and 2019-nCoV assays (Seegene, Seoul, Korea) as reference comparator assays. A total of 359 archived predetermined respiratory samples, including 83, 145, 19 and 95 positive specimens for SARS-CoV-2, influenza A, influenza B and RSV respectively, were included. The AMPLIQUICK® Respiratory Triplex showed high concordance with the reference assays, with an overall agreement for SARS-CoV-2, influenza A, influenza B, and RSV at 97.6%, 98.8%, 98.3% and 100.0%, respectively, and high κ values ranging from 0.93 to 1.00, indicating an almost perfect agreement between assays. Furthermore, high correlations of cycle threshold (Ct) values were observed for positive samples of the four viruses between the AMPLIQUICK® Respiratory Triplex and comparator assays, with an overall high agreement between Ct values assessed by Bland-Altman analyses. In conclusion, these observations demonstrate that the multiplex AMPLIQUICK® Respiratory Triplex is a reliable assay for the qualitative detection and differentiation of SARS-CoV-2, influenza A, influenza B, and RSV in respiratory specimens, which may prove useful for streamlining diagnostics during the winter influenza-seasons.


Assuntos
COVID-19/diagnóstico , Influenza Humana/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções por Vírus Respiratório Sincicial/diagnóstico , COVID-19/virologia , Humanos , Influenza Humana/virologia , Técnicas de Diagnóstico Molecular , Nasofaringe/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Estudos Retrospectivos , Sensibilidade e Especificidade
3.
J Cardiovasc Med (Hagerstown) ; 23(1): 1-11, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34091532

RESUMO

2020 marked the 20th anniversary of the discovery of the angiotensin-converting enzyme 2 (ACE2). This major event that changed the way we see the renin-angiotensin system today could have passed quietly. Instead, the discovery that ACE2 is a major player in the severe acute respiratory syndrome coronavirus 2 pandemic has blown up the literature regarding this enzyme. ACE2 connects the classical arm renin-angiotensin system, consisting mainly of angiotensin II peptide and its AT1 receptor, with a protective arm, consisting mainly of the angiotensin 1-7 peptide and its Mas receptor. In this brief article, we have reviewed the literature to describe how ACE2 is a key protective arm enzyme in the function of many organs, particularly in the context of brain and cardiovascular function, as well as in renal, pulmonary and digestive homeostasis. We also very briefly review and refer to recent literature to present an insight into the role of ACE2 in determining the course of coronavirus diseases 2019.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Sistema Renina-Angiotensina/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Angiotensinas/fisiologia , Animais , COVID-19/complicações , COVID-19/metabolismo , COVID-19/virologia , Humanos , Camundongos , Especificidade de Órgãos , Ratos , Receptores de Angiotensina/fisiologia , Sistema Renina-Angiotensina/efeitos dos fármacos , SARS-CoV-2/metabolismo
4.
Virology ; 566: 114-121, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902730

RESUMO

This communication summarizes the presentations given at the 1st international conference of the World Society for Virology (WSV) held virtually during 16-18 June 2021, under the theme of tackling global viral epidemics. The purpose of this biennial meeting is to foster international collaborations and address important viral epidemics in different hosts. The first day included two sessions exclusively on SARS-CoV-2 and COVID-19. The other two days included one plenary and three parallel sessions each. Last not least, 16 sessions covered 140 on-demand submitted talks. In total, 270 scientists from 49 countries attended the meeting, including 40 invited keynote speakers.


Assuntos
COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Congressos como Assunto , SARS-CoV-2 , Humanos , Sociedades Científicas , Virologia
5.
MAbs ; 14(1): 2005507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34923915

RESUMO

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a serious public health crisis worldwide, and considering the novelty of the disease, preventative and therapeutic measures alike are urgently needed. To accelerate such efforts, the development of JS016, a neutralizing monoclonal antibody directed against the SARS-CoV-2 spike protein, was expedited from a typical 12- to 18-month period to a 4-month period. During this process, transient Chinese hamster ovary cell lines are used to support preclinical, investigational new drug-enabling toxicology research, and early Chemistry, Manufacturing and Controls development; mini-pool materials to supply Phase 1 clinical trials; and a single-clone working cell bank for late-stage and pivotal clinical trials were successively adopted. Moreover, key process performance and product quality investigations using a series of orthogonal and state-of-the-art techniques were conducted to demonstrate the comparability of products manufactured using these three processes, and the results indicated that, despite observed variations in process performance, the primary and high-order structures, purity and impurity profiles, biological and immunological functions, and degradation behaviors under stress conditions were largely comparable. The study suggests that, in particular situations, this strategy can be adopted to accelerate the development of therapeutic biopharmaceuticals and their access to patients.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/uso terapêutico , Afinidade de Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Células CHO , COVID-19/prevenção & controle , COVID-19/virologia , Cromatografia Líquida de Alta Pressão/métodos , Dicroísmo Circular , Células Clonais , Cricetinae , Cricetulus , Humanos , Imunoglobulina G/química , Imunoglobulina G/imunologia , Imunoglobulina G/uso terapêutico , Ponto Isoelétrico , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo
6.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34930824

RESUMO

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous loss worldwide. Although viral spike (S) protein binding of angiotensin-converting enzyme 2 (ACE2) has been established, the functional consequences of the initial receptor binding and the stepwise fusion process are not clear. By utilizing a cell-cell fusion system, in complement with a pseudoviral infection model, we found that the spike engagement of ACE2 primed the generation of S2' fragments in target cells, a key proteolytic event coupled with spike-mediated membrane fusion. Mutagenesis of an S2' cleavage site at the arginine (R) 815, but not an S2 cleavage site at arginine 685, was sufficient to prevent subsequent syncytia formation and infection in a variety of cell lines and primary cells isolated from human ACE2 knock-in mice. The requirement for S2' cleavage at the R815 site was also broadly shared by other SARS-CoV-2 spike variants, such as the Alpha, Beta, and Delta variants of concern. Thus, our study highlights an essential role for host receptor engagement and the key residue of spike for proteolytic activation, and uncovers a targetable mechanism for host cell infection by SARS-CoV-2.


Assuntos
Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Fusão de Membrana , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , COVID-19/virologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Ligação Proteica , Proteólise , Internalização do Vírus
7.
J Autoimmun ; 126: 102779, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34915422

RESUMO

Severe Acute Respiratory Coronavirus (SARS-CoV-2) has been emerging in the form of different variants since its first emergence in early December 2019. A new Variant of Concern (VOC) named the Omicron variant (B.1.1.529) was reported recently. This variant has a large number of mutations in the S protein. To date, there exists a limited information on the Omicron variant. Here we present the analyses of mutation distribution, the evolutionary relationship of Omicron with previous variants, and probable structural impact of mutations on antibody binding. Our analyses show the presence of 46 high prevalence mutations specific to Omicron. Twenty-three of these are localized within the spike (S) protein and the rest localized to the other 3 structural proteins of the virus, the envelope (E), membrane (M), and nucleocapsid (N). Phylogenetic analysis showed that the Omicron is closely related to the Gamma (P.1) variant. The structural analyses showed that several mutations are localized to the region of the S protein that is the major target of antibodies, suggesting that the mutations in the Omicron variant may affect the binding affinities of antibodies to the S protein.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/virologia , SARS-CoV-2/genética , Sítios de Ligação , COVID-19/imunologia , Humanos , Mutação , Filogenia , Estrutura Terciária de Proteína , Glicoproteína da Espícula de Coronavírus/genética
9.
J Med Virol ; 94(1): 197-204, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427922

RESUMO

Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID-19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID-19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.


Assuntos
Vacinas contra COVID-19 , COVID-19/epidemiologia , SARS-CoV-2/genética , Ásia/epidemiologia , COVID-19/mortalidade , COVID-19/transmissão , COVID-19/virologia , Europa (Continente)/epidemiologia , Saúde Global , Humanos , Mutação , Índice de Gravidade de Doença , América do Sul/epidemiologia , Estados Unidos/epidemiologia
10.
J Med Virol ; 94(1): 222-228, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449894

RESUMO

The current study aimed at characterizing the dynamics of SARS-CoV-2 nucleocapsid (N) antigenemia in a cohort of critically ill adult COVID-19 patients and assessing its potential association with plasma levels of biomarkers of clinical severity and mortality. Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial plasma (n = 340) specimens were collected. A lateral flow immunochromatography assay and reverse-transcription polymerase chain reaction (RT-PCR) were used for SARS-CoV-2 N protein detection and RNA quantitation and in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were measured. SARS-CoV-RNA N-antigenemia and viral RNAemia were documented in 40.1% and 35.6% of patients, respectively at a median of 9 days since symptoms onset. The level of agreement between the qualitative results returned by the N-antigenemia assay and plasma RT-PCR was moderate (k = 0.57; p < 0.0001). A trend towards higher SARS-CoV-2 RNA loads was seen in plasma specimens testing positive for N-antigenemia assay than in those yielding negative results (p = 0.083). SARS-CoV-2 RNA load in tracheal aspirates was significantly higher (p < 0.001) in the presence of concomitant N-antigenemia than in its absence. Significantly higher serum levels of ferritin, lactose dehydrogenase, C-reactive protein, and D-dimer were quantified in paired plasma SARS-CoV-2 N-positive specimens than in those testing negative. Occurrence of SARS-CoV-2 N-antigenemia was not associated with increased mortality in univariate logistic regression analysis (odds ratio, 1.29; 95% confidence interval, 0.49-3.34; p = 0.59). In conclusion, SARS-CoV-2 N-antigenemia detection is relatively common in ICU patients and appears to associate with increased serum levels of inflammation and tissue-damage markers. Whether this virological parameter may behave as a biomarker of poor clinical outcome awaits further investigations.


Assuntos
COVID-19/virologia , Proteínas do Nucleocapsídeo de Coronavírus/sangue , Estado Terminal , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/sangue , Biomarcadores/análise , Biomarcadores/sangue , COVID-19/mortalidade , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/sangue , Fosfoproteínas/imunologia , Estudos Prospectivos , RNA Viral/análise , RNA Viral/sangue , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Traqueia/virologia , Adulto Jovem
14.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34543404

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to exert a significant impact on global health care systems, causing devastating mortality and morbidity. As time passes and our understanding of this novel respiratory virus deepens, it is increasingly clear that its effects extend beyond that of the respiratory system. The coronavirus responsible for COVID-19, severe acute respiratory syndrome coronavirus 2, obtains cellular access through the angiotensin-converting enzyme 2 (ACE2) receptor in a process requiring the transmembrane serine protease 2 (TMPRSS2) protein. Both ACE2 and TMPRSS2 are widely expressed in many endocrine glands. This, along with several case reports of thyroid and pituitary disruption in patients with COVID-19, has resulted in significant interest in its impact on the endocrine system. Indeed, as mortality is abated by the increasing availability of effective vaccines, there is increasing focus on the long-term effects on health in COVID-19 survivors. This review summarizes data investigating the effects of COVID-19 on each of the endocrine axes to guide appropriate investigations and optimal management.


Assuntos
COVID-19/metabolismo , Sistema Endócrino/metabolismo , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/virologia , Humanos , Pandemias , SARS-CoV-2/genética , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo
18.
Int J Mol Med ; 49(2)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34935057

RESUMO

The pathophysiology of coronavirus disease 2019 (COVID­19) is mainly dependent on the underlying mechanisms that mediate the entry of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) into the host cells of the various human tissues/organs. Recent studies have indicated a higher order of complexity of the mechanisms of infectivity, given that there is a wide­repertoire of possible cell entry mediators that appear to co­localise in a cell­ and tissue­specific manner. The present study provides an overview of the 'canonical' SARS­CoV­2 mediators, namely angiotensin converting enzyme 2, transmembrane protease serine 2 and 4, and neuropilin­1, expanding on the involvement of novel candidates, including glucose­regulated protein 78, basigin, kidney injury molecule­1, metabotropic glutamate receptor subtype 2, ADAM metallopeptidase domain 17 (also termed tumour necrosis factor­α convertase) and Toll­like receptor 4. Furthermore, emerging data indicate that changes in microRNA (miRNA/miR) expression levels in patients with COVID­19 are suggestive of further complexity in the regulation of these viral mediators. An in silico analysis revealed 160 candidate miRNAs with potential strong binding capacity in the aforementioned genes. Future studies should concentrate on elucidating the association between the cellular tropism of the SARS­CoV­2 cell entry mediators and the mechanisms through which they might affect the clinical outcome. Finally, the clinical utility as a biomarker or therapeutic target of miRNAs in the context of COVID­19 warrants further investigation.


Assuntos
COVID-19/metabolismo , MicroRNAs/metabolismo , Receptores Virais/metabolismo , SARS-CoV-2/metabolismo , Internalização do Vírus , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/genética , COVID-19/virologia , /metabolismo , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , Neuropilina-1/genética , Neuropilina-1/metabolismo , Receptores Virais/genética , SARS-CoV-2/fisiologia , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Tropismo Viral
19.
J Virol Methods ; 300: 114422, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34915086

RESUMO

Vaccination and the emergence of SARS-CoV-2 variants mark the second year of the pandemic. Variants have amino acid mutations at the spike region, a viral protein central in the understanding of COVID-19 pathogenesis and vaccine response. Variants may dominate local epidemics, as Gamma (P.1) in Brazil, emerging in 2020 and prevailing until mid-2021. Different obstacles hinder a wider use of Next-Generation Sequencing for genomic surveillance. We describe Sanger based sequencing protocols: i) Semi-nested RT-PCR covering up to 3.684 kb (>96 %) spike gene; ii) One-Step RT-PCR for key Receptor Binding Domain (RBD) mutations (codons 417-501); iii) One-Step RT-PCR of partial N region to improve genomic capability. Protocols use leftovers of RNA extracted from nasopharyngeal swabs for quantitative RT-PCR diagnosis; with retro-transcribed DNA sequenced at ABI 3500 using dye termination chemistry. Analyses of sequences from 95 individuals (late 2020/early 2021) identified extensive amino acid variation, 57 % with at least one key mutation at the Receptor Binding Domain, with B.1.1.28 lineage most prevalent, followed by Gamma and Zeta variants, with no Delta variant observed. The relatively low cost and simplicity may provide an accessible tool to improve surveillance of SARS-CoV-2 evolution, monitor new variants and vaccinated breakthroughs.


Assuntos
COVID-19 , Evolução Molecular , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , COVID-19/virologia , Humanos , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
20.
J Med Virol ; 94(1): 240-245, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34460115

RESUMO

Many countries in the world are experiencing a recent surge in COVID-19 cases. This is mainly attributed to the emergence of new SARS-CoV-2 variants. Genome sequencing is the only means to detect the evolving virus mutants and emerging variants. Cycle threshold values have an inverse relationship with viral load and lower Ct values are also found to be associated with increased infectivity. In this study, we propose to use Ct values as an early indicator for upcoming COVID-19 waves. A retrospective cross-sectional study was carried out to analyze the Ct values of positive samples reported during the first wave and second wave (April 2020-May 2021). Median Ct values of confirmatory genes were taken into consideration for comparison. Ct values below 25, >25-30, and >30 were categorized as high, moderate, and low viral load respectively. Our study found a significantly higher proportion of positive samples with a low Ct value (<25) across age groups and gender during the second wave of the COVID-19 pandemic. A higher proportion of positive samples with a low Ct value (high viral load) may act as an early indicator of an upcoming surge.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , Adolescente , Adulto , Infecções Assintomáticas/epidemiologia , COVID-19/virologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/fisiologia , Carga Viral , Adulto Jovem
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