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1.
Genes (Basel) ; 12(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209818

RESUMO

This study builds a coronavirus knowledge graph (KG) by merging two information sources. The first source is Analytical Graph (AG), which integrates more than 20 different public datasets related to drug discovery. The second source is CORD-19, a collection of published scientific articles related to COVID-19. We combined both chemo genomic entities in AG with entities extracted from CORD-19 to expand knowledge in the COVID-19 domain. Before populating KG with those entities, we perform entity disambiguation on CORD-19 collections using Wikidata. Our newly built KG contains at least 21,700 genes, 2500 diseases, 94,000 phenotypes, and other biological entities (e.g., compound, species, and cell lines). We define 27 relationship types and use them to label each edge in our KG. This research presents two cases to evaluate the KG's usability: analyzing a subgraph (ego-centered network) from the angiotensin-converting enzyme (ACE) and revealing paths between biological entities (hydroxychloroquine and IL-6 receptor; chloroquine and STAT1). The ego-centered network captured information related to COVID-19. We also found significant COVID-19-related information in top-ranked paths with a depth of three based on our path evaluation.


Assuntos
COVID-19 , Bases de Conhecimento , COVID-19/epidemiologia , COVID-19/etiologia , Cloroquina/farmacologia , Gráficos por Computador , Bases de Dados Factuais , Doença pelo Vírus Ebola/tratamento farmacológico , Humanos , Hidroxicloroquina/farmacologia , Reconhecimento Automatizado de Padrão , Peptidil Dipeptidase A/genética , PubMed , Receptores de Interleucina-6/sangue , SARS-CoV-2 , Fator de Transcrição STAT1
2.
Pak J Pharm Sci ; 34(1(Supplementary)): 275-281, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275851

RESUMO

This study investigated the significance of difference between presence and absence of different neurological findings in COVID-19, in relation with the biochemistry. Various significant correlations in connection with the disease severity and clinical factors were also identified. 351 COVID-19 patients were included. Different laboratory/ clinical findings were investigated. Correlations Kendall's tau and Pearson Chi-Square were applied to find the correlations between severity and clinical findings. The Mann-Whitney Test was applied for a comparison between two types of neurological groups for each biochemistry parameter. Headache was reported in 28% and dizziness in 13% patients. The impaired smell and impaired taste were reported in 28.5% and 36.2% patients, respectively. The muscle pain was present in 39% patients. 80% patients had low lymphocytes & 70% had high neutrophils. 54.5% were found with high ALP. LDH was elevated in 73%. Severity was found significantly correlated with decreased oxygen saturation, age and raised levels of urea, creatinine and LDH. The groups (with/without CNS involvement) were statistically different in ALP, groups (with/without PNS involvement) in WBC, lymphocytes, neutrophils, ALP, urea, creatinine, CK, CKMB and LDH and groups (with/without MSK involvement) in WBC. Oxygen saturation, age, urea, creatinine and LDH are significant indicators of disease severity in COVID-19. The altered levels of different biochemistry can impact the neurological states of COVID-19 patients.


Assuntos
COVID-19/sangue , COVID-19/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Análise Química do Sangue , COVID-19/diagnóstico por imagem , COVID-19/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Paquistão , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
3.
Pak J Pharm Sci ; 34(1(Supplementary)): 321-325, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275857

RESUMO

The study was aimed to mention the epidemiology of smoking in Pakistani COVID-19 infected patients along with the disease severity, oxygen dependency and fatality rate. A cross sectional epidemiological study was carried out on 555 confirmed cases of COVID-19 infection. The median age was 47±16 years. 59% were male and 41% were female. Most of the patients (97.5%) survived, while only 2.5% expired. 25.6% patients required the oxygen. Total 17 (3%) COVID-19 patients with age 20-75 years were identified as smokers. No mortality was observed in smokers. The 1.4% smokers presented with mild disease, 1.2% with moderate disease and 0.4% had severe disease. According to Chi-Square test, there existed an insignificant difference (p-value: 0.38649) between smokers and non-smokers in disease severity levels. Smoking is a precursor for countless diseases, but it behaved differently in COVID-19 infected patients, as its prevalence was significantly low. We found no significant variation of the disease severity among the smokers and non-smokers. Profound experiments should be conducted to recommend whether nicotine can be used as a protective agent to negate COVID-19 infection.


Assuntos
COVID-19/epidemiologia , COVID-19/etiologia , Fumar/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Índice de Gravidade de Doença , Distribuição por Sexo , Fumar Tabaco/epidemiologia , Adulto Jovem
4.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281262

RESUMO

Thousands of drugs and nutraceuticals along with their combinations can be used to select candidate therapeutics for targeting the transmission, proliferation and the fatal or severe symptoms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to reduce the unacceptably high mortality rate observed in the coronavirus disease 2019 (COVID-19) pandemic and its associated negative effects on daily life worldwide [...].


Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/etiologia , Aprovação de Drogas , Quimioterapia Combinada , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Fatores de Tempo
5.
Genes (Basel) ; 12(6)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201032

RESUMO

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.


Assuntos
Receptor do Fator Ativador de Células B/genética , COVID-19/etiologia , COVID-19/genética , Feminino , Frequência do Gene , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Índice de Gravidade de Doença
6.
BMC Infect Dis ; 21(1): 635, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215210

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has changed our lives. The scientific community has been investigating re-purposed treatments to prevent disease progression in coronavirus disease (COVID-19) patients. OBJECTIVE: To determine whether ivermectin treatment can prevent hospitalization in individuals with early COVID-19. DESIGN, SETTING AND PARTICIPANTS: A randomized, double-blind, placebo-controlled study was conducted in non-hospitalized individuals with COVID-19 in Corrientes, Argentina. Patients with SARS-CoV-2 positive nasal swabs were contacted within 48 h by telephone to invite them to participate. The trial randomized 501 patients between August 19th 2020 and February 22nd 2021. INTERVENTION: Patients were randomized to ivermectin (N = 250) or placebo (N = 251) arms in a staggered dose, according to the patient's weight, for 2 days. MAIN OUTCOMES AND MEASURES: The efficacy of ivermectin to prevent hospitalizations was evaluated as primary outcome. We evaluated secondary outcomes in relationship to safety and other efficacy end points. RESULTS: The mean age was 42 years (SD ± 15.5) and the median time since symptom onset to the inclusion was 4 days [interquartile range 3-6]. The primary outcome of hospitalization was met in 14/250 (5.6%) individuals in ivermectin group and 21/251 (8.4%) in placebo group (odds ratio 0.65; 95% confidence interval, 0.32-1.31; p = 0.227). Time to hospitalization was not statistically different between groups. The mean time from study enrollment to invasive mechanical ventilatory support (MVS) was 5.25 days (SD ± 1.71) in ivermectin group and 10 days (SD ± 2) in placebo group, (p = 0.019). There were no statistically significant differences in the other secondary outcomes including polymerase chain reaction test negativity and safety outcomes. LIMITATIONS: Low percentage of hospitalization events, dose of ivermectin and not including only high-risk population. CONCLUSION: Ivermectin had no significant effect on preventing hospitalization of patients with COVID-19. Patients who received ivermectin required invasive MVS earlier in their treatment. No significant differences were observed in any of the other secondary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04529525 .


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Ivermectina/uso terapêutico , Adulto , Antivirais/efeitos adversos , COVID-19/etiologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Método Duplo-Cego , Feminino , Hospitalização , Humanos , Ivermectina/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Placebos , Resultado do Tratamento
7.
Front Endocrinol (Lausanne) ; 12: 649525, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220706

RESUMO

The relationship between COVID-19 and diabetes mellitus is complicated and bidirectional. On the one hand, diabetes mellitus is considered one of the most important risk factors for a severe course of COVID-19. Several factors that are often present in diabetes mellitus are likely to contribute to this risk, such as older age, a proinflammatory and hypercoagulable state, hyperglycemia and underlying comorbidities (hypertension, cardiovascular disease, chronic kidney disease and obesity). On the other hand, a severe COVID-19 infection, and its treatment with steroids, can have a specific negative impact on diabetes itself, leading to worsening of hyperglycemia through increased insulin resistance and reduced ß-cell secretory function. Worsening hyperglycemia can, in turn, adversely affect the course of COVID-19. Although more knowledge gradually surfaces as the pandemic progresses, challenges in understanding the interrelationship between COVID-19 and diabetes remain.


Assuntos
COVID-19/etiologia , COVID-19/patologia , Diabetes Mellitus , COVID-19/diagnóstico , COVID-19/epidemiologia , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/patologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Progressão da Doença , Humanos , Pandemias , Prognóstico , Fatores de Risco , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença
8.
Eur Rev Med Pharmacol Sci ; 25(12): 4422-4425, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34227079

RESUMO

The huge concern raised by SARS-CoV2 pandemic about public health management and social impact is still under debate, particularly because COVID-19 may affect infected people much longer than expected from a typical air-borne viral disease. The scientific community is actually wondering about the etiopathogenesis and clinical development of this "post-COVID" complex symptomatology, very close to symptoms typically observed in chronic fatigue syndrome, so recently named as "post-acute sequelae of COVID-19 (PASC)". This commentary tries to focus on the most recent news about this issue.


Assuntos
COVID-19/complicações , COVID-19/epidemiologia , COVID-19/etiologia , COVID-19/terapia , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/etiologia , Síndrome de Fadiga Crônica/terapia , Humanos , SARS-CoV-2/isolamento & purificação , Síndrome
9.
Front Endocrinol (Lausanne) ; 12: 649525, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1295632

RESUMO

The relationship between COVID-19 and diabetes mellitus is complicated and bidirectional. On the one hand, diabetes mellitus is considered one of the most important risk factors for a severe course of COVID-19. Several factors that are often present in diabetes mellitus are likely to contribute to this risk, such as older age, a proinflammatory and hypercoagulable state, hyperglycemia and underlying comorbidities (hypertension, cardiovascular disease, chronic kidney disease and obesity). On the other hand, a severe COVID-19 infection, and its treatment with steroids, can have a specific negative impact on diabetes itself, leading to worsening of hyperglycemia through increased insulin resistance and reduced ß-cell secretory function. Worsening hyperglycemia can, in turn, adversely affect the course of COVID-19. Although more knowledge gradually surfaces as the pandemic progresses, challenges in understanding the interrelationship between COVID-19 and diabetes remain.


Assuntos
COVID-19/etiologia , COVID-19/patologia , Diabetes Mellitus , COVID-19/diagnóstico , COVID-19/epidemiologia , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/patologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Progressão da Doença , Humanos , Pandemias , Prognóstico , Fatores de Risco , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença
10.
BMC Infect Dis ; 21(1): 635, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: covidwho-1295445

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has changed our lives. The scientific community has been investigating re-purposed treatments to prevent disease progression in coronavirus disease (COVID-19) patients. OBJECTIVE: To determine whether ivermectin treatment can prevent hospitalization in individuals with early COVID-19. DESIGN, SETTING AND PARTICIPANTS: A randomized, double-blind, placebo-controlled study was conducted in non-hospitalized individuals with COVID-19 in Corrientes, Argentina. Patients with SARS-CoV-2 positive nasal swabs were contacted within 48 h by telephone to invite them to participate. The trial randomized 501 patients between August 19th 2020 and February 22nd 2021. INTERVENTION: Patients were randomized to ivermectin (N = 250) or placebo (N = 251) arms in a staggered dose, according to the patient's weight, for 2 days. MAIN OUTCOMES AND MEASURES: The efficacy of ivermectin to prevent hospitalizations was evaluated as primary outcome. We evaluated secondary outcomes in relationship to safety and other efficacy end points. RESULTS: The mean age was 42 years (SD ± 15.5) and the median time since symptom onset to the inclusion was 4 days [interquartile range 3-6]. The primary outcome of hospitalization was met in 14/250 (5.6%) individuals in ivermectin group and 21/251 (8.4%) in placebo group (odds ratio 0.65; 95% confidence interval, 0.32-1.31; p = 0.227). Time to hospitalization was not statistically different between groups. The mean time from study enrollment to invasive mechanical ventilatory support (MVS) was 5.25 days (SD ± 1.71) in ivermectin group and 10 days (SD ± 2) in placebo group, (p = 0.019). There were no statistically significant differences in the other secondary outcomes including polymerase chain reaction test negativity and safety outcomes. LIMITATIONS: Low percentage of hospitalization events, dose of ivermectin and not including only high-risk population. CONCLUSION: Ivermectin had no significant effect on preventing hospitalization of patients with COVID-19. Patients who received ivermectin required invasive MVS earlier in their treatment. No significant differences were observed in any of the other secondary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04529525 .


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Ivermectina/uso terapêutico , Adulto , Antivirais/efeitos adversos , COVID-19/etiologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Método Duplo-Cego , Feminino , Hospitalização , Humanos , Ivermectina/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Placebos , Resultado do Tratamento
11.
Front Immunol ; 12: 680891, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194434

RESUMO

The network of tunneling nanotubes (TNTs) represents the filamentous (F)-actin rich tubular structure which is connected to the cytoplasm of the adjacent and or distant cells to mediate efficient cell-to-cell communication. They are long cytoplasmic bridges with an extraordinary ability to perform diverse array of function ranging from maintaining cellular physiology and cell survival to promoting immune surveillance. Ironically, TNTs are now widely documented to promote the spread of various pathogens including viruses either during early or late phase of their lifecycle. In addition, TNTs have also been associated with multiple pathologies in a complex multicellular environment. While the recent work from multiple laboratories has elucidated the role of TNTs in cellular communication and maintenance of homeostasis, this review focuses on their exploitation by the diverse group of viruses such as retroviruses, herpesviruses, influenza A, human metapneumovirus and SARS CoV-2 to promote viral entry, virus trafficking and cell-to-cell spread. The later process may aggravate disease severity and the associated complications due to widespread dissemination of the viruses to multiple organ system as observed in current coronavirus disease 2019 (COVID-19) patients. In addition, the TNT-mediated intracellular spread can be protective to the viruses from the circulating immune surveillance and possible neutralization activity present in the extracellular matrix. This review further highlights the relevance of TNTs in ocular and cardiac tissues including neurodegenerative diseases, chemotherapeutic resistance, and cancer pathogenesis. Taken together, we suggest that effective therapies should consider precise targeting of TNTs in several diseases including virus infections.


Assuntos
COVID-19/etiologia , Citoplasma/ultraestrutura , Citoplasma/virologia , Nanotubos/virologia , Doenças Neurodegenerativas/etiologia , Viroses/etiologia , Animais , COVID-19/virologia , Comunicação Celular , Humanos
12.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200325

RESUMO

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).


Assuntos
Envelhecimento/genética , COVID-19/genética , COVID-19/fisiopatologia , Ilhas de CpG , Encurtamento do Telômero , Telômero/metabolismo , Adulto , Idoso , Enzima de Conversão de Angiotensina 2/sangue , Biomarcadores , COVID-19/complicações , COVID-19/etiologia , Metilação de DNA , Dipeptidil Peptidase 4/sangue , Epigenômica , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Interações entre Hospedeiro e Microrganismos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sobreviventes
13.
Int J Med Sci ; 18(13): 2789-2798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220307

RESUMO

Coronavirus disease 2019 (COVID-19) has spread widely in the communities in many countries. Although most of the mild patients could be cured by their body's ability to self-heal, many patients quickly progressed to severe disease and had to undergo treatment in the intensive care unit (ICU). Thus, it is very important to effectively predict which patients with mild disease are more likely to progress to severe disease. A total of 72 patients hospitalized with COVID-19 in Shandong Provincial Public Health Clinical Center and 1141 patients included in the published papers were enrolled in this study. We determined that the combination of interleukin-6 (IL-6), Neutrophil (NEUT), and Natural Killer (NK) cells had the highest prediction accuracy (with 75% sensitivity and 95% specificity) for progression of COVID-19 infection. A binomial regression equation that accounted for a multiple risk score for the combination of IL-6, NEUT, and NK was also established. The multiple risk score is a good indicator for early stratification of mild patients into risk categories, which is very important for adjusting the treatment plan and preventing death.


Assuntos
Biomarcadores/análise , COVID-19/etiologia , Idoso , Biomarcadores/sangue , Contagem de Células Sanguíneas , COVID-19/epidemiologia , Comorbidade , Progressão da Doença , Humanos , Interleucina-6/sangue , Células Matadoras Naturais , Pessoa de Meia-Idade , Neutrófilos , Estudos Retrospectivos
14.
Genes (Basel) ; 12(7)2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202464

RESUMO

ABO blood system is an inborn trait determined by the ABO gene. The genetic-phenotypic mechanism underneath the four mutually exclusive and collectively exhaustive types of O, A, B and AB could theoretically be elucidated. However, genetic polymorphisms in the human populations render the link elusive, and importantly, past studies using genetically determined rather than biochemically determined ABO types were not and could not be evaluated for the inference errors. Upon both blood-typing and genotyping a cohort of 1008 people of the Han Chinese population, we conducted a genome-wide association study in parallel with both binomial and multinomial log-linear models. Significant genetic variants are all mapped to the ABO gene, and are quantitatively evaluated for binary and multi-class classification performances. Three single nucleotide polymorphisms of rs8176719, rs635634 and rs7030248 would together be sufficient to establish a multinomial predictive model that achieves high accuracy (0.98) and F1 scores (micro 0.99 and macro 0.97). Using the set of identified ABO-associated genetic variants as instrumental variables, we demonstrate the application in causal analysis by Mendelian randomization (MR) studies on blood pressures (one-sample MR) and severe COVID-19 with respiratory failure (two-sample MR).


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Sistema ABO de Grupos Sanguíneos/genética , COVID-19/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Pressão Sanguínea/genética , COVID-19/etiologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Modelos Estatísticos , Testes Sorológicos
15.
Bioengineered ; 12(1): 2836-2850, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34227905

RESUMO

Angiotensin I-converting enzyme 2 (ACE2), type II transmembrane serine protease 2 and 4 (TMPRSS2 and TMPRSS4) are important receptors for SARS-CoV-2 infection. In this study, the full-length tree shrewACE2 gene was cloned and sequenced, and its biological information was analyzed. The expression levels of ACE2, TMPRSS2 and TMPRSS4 in various tissues or organs of the tree shrew were detected. The results showed that the full-length ACE2 gene in tree shrews was 2,786 bp, and its CDS was 2,418 bp, encoding 805 amino acids. Phylogenetic analysis based on the CDS of ACE2 revealed that tree shrews were more similar to rabbits (85.93%) and humans (85.47%) but far from mice (82.81%) and rats (82.58%). In silico analysis according to the binding site of SARS-CoV-2 with the ACE2 receptor of different species predicted that tree shrews had potential SARS-CoV-2 infection possibility, which was similar to that of rabbits, cats and dogs but significantly higher than that of mice and rats. In addition, various tissues or organs of tree shrews expressed ACE2, TMPRSS2 and TMPRSS4. Among them, the kidney most highly expressed ACE2, followed by the lung and liver. The esophagus, lung, liver, intestine and kidney had relatively high expression levels of TMPRSS2 and TMPRSS4. In general, we reported for the first time the expression of ACE2, TMPRSS2 and TMPRSS4 in various tissues or organs in tree shrews. Our results revealed that tree shrews could be used as a potential animal model to study the mechanism underlying SARS-CoV-2 infection.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/etiologia , Proteínas de Membrana/genética , SARS-CoV-2 , Serina Endopeptidases/genética , Tupaiidae/genética , Tupaiidae/metabolismo , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Bioengenharia , COVID-19/enzimologia , COVID-19/genética , Biologia Computacional , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Modelos Moleculares , Filogenia , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos , Serina Endopeptidases/química , Serina Endopeptidases/metabolismo , Homologia Estrutural de Proteína , Distribuição Tecidual , Tupaiidae/virologia
16.
J Clin Invest ; 131(14)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263736

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.


Assuntos
COVID-19/etiologia , Pneumonia Viral/etiologia , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/fisiologia , Autopsia , COVID-19/epidemiologia , COVID-19/patologia , Citocinas/biossíntese , Humanos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/virologia , Modelos Biológicos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Receptores Virais/fisiologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/patologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença
17.
Nutrients ; 13(6)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203027

RESUMO

BACKGROUND: Nutritional status influences immunity but its specific association with susceptibility to COVID-19 remains unclear. We examined the association of specific dietary data and incident COVID-19 in the UK Biobank (UKB). METHODS: We considered UKB participants in England with self-reported baseline (2006-2010) data and linked them to Public Health England COVID-19 test results-performed on samples from combined nose/throat swabs, using real time polymerase chain reaction (RT-PCR)-between March and November 2020. Baseline diet factors included breastfed as baby and specific consumption of coffee, tea, oily fish, processed meat, red meat, fruit, and vegetables. Individual COVID-19 exposure was estimated using the UK's average monthly positive case rate per specific geo-populations. Logistic regression estimated the odds of COVID-19 positivity by diet status adjusting for baseline socio-demographic factors, medical history, and other lifestyle factors. Another model was further adjusted for COVID-19 exposure. RESULTS: Eligible UKB participants (n = 37,988) were 40 to 70 years of age at baseline; 17% tested positive for COVID-19 by SAR-CoV-2 PCR. After multivariable adjustment, the odds (95% CI) of COVID-19 positivity was 0.90 (0.83, 0.96) when consuming 2-3 cups of coffee/day (vs. <1 cup/day), 0.88 (0.80, 0.98) when consuming vegetables in the third quartile of servings/day (vs. lowest quartile), 1.14 (1.01, 1.29) when consuming fourth quartile servings of processed meats (vs. lowest quartile), and 0.91 (0.85, 0.98) when having been breastfed (vs. not breastfed). Associations were attenuated when further adjusted for COVID-19 exposure, but patterns of associations remained. CONCLUSIONS: In the UK Biobank, consumption of coffee, vegetables, and being breastfed as a baby were favorably associated with incident COVID-19; intake of processed meat was adversely associated. Although these findings warrant independent confirmation, adherence to certain dietary behaviors may be an additional tool to existing COVID-19 protection guidelines to limit the spread of this virus.


Assuntos
COVID-19/etiologia , Café , Dieta , Comportamento Alimentar , Carne , Estado Nutricional , Verduras , Idoso , Bancos de Espécimes Biológicos , Aleitamento Materno , COVID-19/virologia , Inglaterra , Feminino , Manipulação de Alimentos , Humanos , Incidência , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Saúde Pública , Fatores de Risco , SARS-CoV-2 , Reino Unido
18.
PLoS Med ; 18(6): e1003605, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34061844

RESUMO

BACKGROUND: Increased vitamin D levels, as reflected by 25-hydroxy vitamin D (25OHD) measurements, have been proposed to protect against COVID-19 based on in vitro, observational, and ecological studies. However, vitamin D levels are associated with many confounding variables, and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used 2-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity. METHODS AND FINDINGS: Genetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and up to 1,284,876 without COVID-19, from up to 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by 1 standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (odds ratio [OR] = 0.95; 95% CI 0.84, 1.08; p = 0.44), hospitalization (OR = 1.09; 95% CI: 0.89, 1.33; p = 0.41), and severe disease (OR = 0.97; 95% CI: 0.77, 1.22; p = 0.77). We used an additional 6 meta-analytic methods, as well as conducting sensitivity analyses after removal of variants at risk of horizontal pleiotropy, and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency. CONCLUSIONS: In this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.


Assuntos
COVID-19/sangue , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , COVID-19/etiologia , Estudos de Casos e Controles , Causalidade , Suplementos Nutricionais , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hospitalização , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , SARS-CoV-2 , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/genética
19.
JAMA Netw Open ; 4(6): e2112852, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34100936

RESUMO

Importance: Food insecurity is prevalent among racial/ethnic minority populations in the US. To date, few studies have examined the association between pre-COVID-19 experiences of food insecurity and COVID-19 infection rates through a race/ethnicity lens. Objective: To examine the associations of race/ethnicity and past experiences of food insecurity with COVID-19 infection rates and the interactions of race/ethnicity and food insecurity, while controlling for demographic, socioeconomic, risk exposure, and geographic confounders. Design, Setting, and Participants: This cross-sectional study examined the associations of race/ethnicity and food insecurity with cumulative COVID-19 infection rates in 3133 US counties, as of July 21 and December 14, 2020. Data were analyzed from November 2020 through March 2021. Exposures: Racial/ethnic minority groups who experienced food insecurity. Main Outcomes and Measures: The dependent variable was COVID-19 infections per 1000 residents. The independent variables of interest were race/ethnicity, food insecurity, and their interactions. Results: Among 3133 US counties, the mean (SD) racial/ethnic composition was 9.0% (14.3%) Black residents, 9.6% (13.8%) Hispanic residents, 2.3% (7.3%) American Indian or Alaska Native residents, 1.7% (3.2%) Asian American or Pacific Islander residents, and 76.1% (20.1%) White residents. The mean (SD) proportion of women was 49.9% (2.3%), and the mean (SD) proportion of individuals aged 65 years or older was 19.3% (4.7%). In these counties, large Black and Hispanic populations were associated with increased COVID-19 infection rates in July 2020. An increase of 1 SD in the percentage of Black and Hispanic residents in a county was associated with an increase in infection rates per 1000 residents of 2.99 (95% CI, 2.04 to 3.94; P < .001) and 2.91 (95% CI, 0.39 to 5.43; P = .02), respectively. By December, a large Black population was no longer associated with increased COVID-19 infection rates. However, a 1-SD increase in the percentage of Black residents in counties with high prevalence of food insecurity was associated with an increase in infections per 1000 residents of 0.90 (95% CI, 0.33 to 1.47; P = .003). Similarly, a 1-SD increase in the percentage of American Indian or Alaska Native residents in counties with high levels of food insecurity was associated with an increase in COVID-19 infections per 1000 residents of 0.57 (95% CI, 0.06 to 1.08; P = .03). By contrast, a 1-SD increase in Hispanic populations in a county remained independently associated with a 5.64 (95% CI, 3.54 to 7.75; P < .001) increase in infection rates per 1000 residents in December 2020 vs 2.91 in July 2020. Furthermore, while a 1-SD increase in the proportion of Asian American or Pacific Islander residents was associated with a decrease in infection rates per 1000 residents of -1.39 (95% CI, -2.29 to 0.49; P = .003), the interaction with food insecurity revealed a similar association (interaction coefficient, -1.48; 95% CI, -2.26 to -0.70; P < .001). Conclusions and Relevance: This study sheds light on the association of race/ethnicity and past experiences of food insecurity with COVID-19 infection rates in the United States. These findings suggest that the channels through which various racial/ethnic minority population concentrations were associated with COVID-19 infection rates were markedly different during the pandemic.


Assuntos
COVID-19/etiologia , Grupos de Populações Continentais , Grupos Étnicos , Insegurança Alimentar , Disparidades nos Níveis de Saúde , Grupos Minoritários , Adulto , Afro-Americanos , Idoso , Nativos Estadunidenses , Americanos Asiáticos , COVID-19/etnologia , Estudos Transversais , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Humanos , Masculino , Pessoa de Meia-Idade , Grupo com Ancestrais Oceânicos , Pandemias , Prevalência , SARS-CoV-2 , Estados Unidos
20.
Sci Rep ; 11(1): 11898, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099828

RESUMO

Here we document 47,381 individuals from 38 species, including 31 protected species sold between May 2017 and November 2019 in Wuhan's markets. We note that no pangolins (or bats) were traded, supporting reformed opinion that pangolins were not likely the spillover host at the source of the current coronavirus (COVID-19) pandemic. While we caution against the misattribution of COVID-19's origins, the wild animals on sale in Wuhan suffered poor welfare and hygiene conditions and we detail a range of other zoonotic infections they can potentially vector. Nevertheless, in a precautionary response to COVID-19, China's Ministries temporarily banned all wildlife trade on 26th Jan 2020 until the COVID-19 pandemic concludes, and permanently banned eating and trading terrestrial wild (non-livestock) animals for food on 24th Feb 2020. These interventions, intended to protect human health, redress previous trading and enforcement inconsistencies, and will have collateral benefits for global biodiversity conservation and animal welfare.


Assuntos
Animais Selvagens/virologia , COVID-19/etiologia , SARS-CoV-2/patogenicidade , Zoonoses/epidemiologia , Animais , COVID-19/virologia , China , Quirópteros/virologia , Comércio , Inocuidade dos Alimentos , Humanos , Pangolins/microbiologia
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