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1.
Virologie (Montrouge) ; 24(3): 142-146, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32648549

RESUMO

The emerging coronavirus called SARS-CoV-2 has spread rapidly around the world. Responsible for severe pneumonitis (Covid-19), there are also doubts concerning a possible mother-to-fetal transmission of this virus. Current data are patchy and obtained from small groups of patients. They tend to support the idea that the mother-to-fetal transmission of SARS-CoV-2 is very rare, but the period between infection and childbirth was often very short and may not allow sufficient replication to consider transplacental passage. Here, we reviewed the existing virological data and those remaining to explore. Thus, the natural history of SARS-CoV-2 infection in pregnant women and the risk of transmission in utero is not yet fully understood and defined. Four months from the emergence of this virus, it is therefore reasonable to wait for the results of specific studies on larger cohorts which, to be conclusive, must meet the best scientific criteria.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Transmissão Vertical de Doença Infecciosa , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez , Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Feminino , Doenças Fetais/virologia , Humanos , Recém-Nascido , Pandemias , Placenta/virologia , Pneumonia Viral/virologia , Gravidez , Carga Viral , Tropismo Viral
3.
BMC Res Notes ; 13(1): 336, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660556

RESUMO

OBJECTIVE: To explore and compare the age, source and future risk of COVID-19 infection in Hong Kong SAR China and Singapore as of March 5, 2020. RESULTS: We find significant difference in age patterns of confirmed cases in these 2 localities early in the pandemic. CONCLUSION: We highlight the potential importance of population age structure in confirmed cases, which should be considered in evaluation of the effectiveness of control effort in different localities.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Distribuição por Idade , Fatores Etários , Betacoronavirus/fisiologia , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Hong Kong/epidemiologia , Humanos , Pneumonia Viral/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Singapura/epidemiologia , Viagem/estatística & dados numéricos
4.
J Genet ; 992020.
Artigo em Inglês | MEDLINE | ID: mdl-32661206

RESUMO

At present, more than 200 countries and territories are directly affected by the coronavirus disease-19 (COVID-19) pandemic. Incidence and case fatality rate are significantly higher among elderly individuals (age>60 years), type 2 diabetes and hypertension patients. Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection. We hypothesised that common variants from TMPRSS2 and CD26 may play critical role in infection susceptibility of predisposed population or group of individuals. Coding (missense) and regulatory variants from TMPRSS2 and CD26 were studied across 26 global populations. Two missense and five regulatory SNPs were identified to have differential allelic frequency. Significant linkage disequilibrium (LD) signature was observed in different populations. Modelled protein-protein interaction (PPI) predicted strong molecular interaction between these two receptors and SARS-CoV-2 spike protein (S1 domain). However, two missense SNPs, rs12329760 (TMPRSS2) and rs1129599 (CD26), were not found to be involved physically in the said interaction. Four regulatory variants (rs112657409, rs11910678, rs77675406 and rs713400) from TMPRSS2 were found to influence the expression of TMPRSS2 and pathologically relevant MX1. rs13015258 a 50 UTR variant from CD26 have significant role in regulation of expression of key regulatory genes that could be involved in SARS-CoV-2 internalization. Overexpression of CD26 through epigenetic modification at rs13015258-C allele was found critical and could explain the higher SARS-CoV-2 infected fatality rate among type 2 diabetes.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/genética , Dipeptidil Peptidase 4/genética , Pneumonia Viral/genética , Serina Endopeptidases/genética , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Dipeptidil Peptidase 4/metabolismo , Epigenômica , Predisposição Genética para Doença , Variação Genética , Humanos , Desequilíbrio de Ligação , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Polimorfismo de Nucleotídeo Único , Domínios e Motivos de Interação entre Proteínas , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus
5.
Physiol Res ; 69(3): 511-514, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32682363

RESUMO

Knowledge of genomic interindividual variability could help us to explain why different manifestation of clinical severity of Covid-19 infection as well as modified pharmacogenetic relations can be expected during this pandemic condition.


Assuntos
Infecções por Coronavirus/genética , Pneumonia Viral/genética , Betacoronavirus/fisiologia , Predisposição Genética para Doença , Interações Hospedeiro-Patógeno/genética , Humanos , Pandemias , Peptidil Dipeptidase A/genética
6.
Infect Dis Poverty ; 9(1): 104, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703281

RESUMO

From December 25, 2019 to January 31, 2020, 33 cases of the coronavirus disease 2019 (COVID-19) were identified in the Department of Respiratory and Critical Care Medicine of Zhongnan Hospital of Wuhan University, China, yet none of the affiliated HCWs was infected. Here we analyzed the infection control measures used in three different departments in the Zhongnan Hospital of Wuhan University and correlated the measures with the corresponding infection data of HCWs affiliated with these departments. We found that three infection control measures, namely the isolation of the presumed positive patients, the use of facemasks and intensified hand hygiene play important roles in preventing nosocomial transmission of COVID-19.


Assuntos
Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/prevenção & controle , Higiene das Mãos/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos , Máscaras/estatística & dados numéricos , Pandemias/prevenção & controle , Isolamento de Pacientes/estatística & dados numéricos , Pneumonia Viral/prevenção & controle , Adulto , Idoso , Betacoronavirus/fisiologia , China , Infecções por Coronavirus/transmissão , Infecção Hospitalar/transmissão , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/transmissão , Adulto Jovem
7.
Appl Clin Inform ; 11(3): 452-459, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32610350

RESUMO

BACKGROUND: Relaxation of laws and regulations around privacy and billing during the COVID-19 pandemic provide expanded opportunities to use telehealth to provide patient care at a distance. Many health systems have transitioned to providing outpatient care via telehealth; however, there is an opportunity to utilize telehealth for inpatients to promote physical distancing. OBJECTIVE: This article evaluates the use of a rapidly implemented, secure inpatient telehealth program. METHODS: We assembled a multidisciplinary team to rapidly design, implement, and iteratively improve an inpatient telehealth quality improvement initiative using an existing videoconferencing system at our academic medical center. We assigned each hospital bed space a unique meeting link and updated the meeting password for each new patient. Patients and families were encouraged to use their own mobile devices to join meetings when possible. RESULTS: Within 7 weeks of go-live, we hosted 1,820 inpatient telehealth sessions (13.3 sessions per 100 bedded days). We logged 104,647 minutes of inpatient telehealth time with a median session duration of 22 minutes (range 1-1,961). There were 5,288 participant devices used with a mean of 3 devices per telehealth session (range 2-22). Clinicians found they were able to build rapport and perform a reasonable physical exam. CONCLUSION: We successfully implemented and scaled a secure inpatient telehealth program using an existing videoconferencing system in less than 1 week. Our implementation provided an intuitive naming convention for providers and capitalized on the broad availability of smartphones and tablets. Initial comments from clinicians suggest the system was useful; however, further work is needed to streamline initial setup for patients and families as well as care coordination to support clinician communication and workflows. Numerous use cases identified suggest a role for inpatient telehealth will remain after the COVID-19 crisis underscoring the importance of lasting regulatory reform.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Implementação de Plano de Saúde , Pacientes Internados , Pandemias , Pneumonia Viral/epidemiologia , Telemedicina , Retroalimentação , Hospitais , Humanos
8.
PLoS Comput Biol ; 16(7): e1008031, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32614817

RESUMO

The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries.


Assuntos
Busca de Comunicante/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Previsões/métodos , Modelos Estatísticos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Fatores Etários , Infecções Assintomáticas/epidemiologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , China/epidemiologia , Biologia Computacional/métodos , Surtos de Doenças/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Replicação Viral/fisiologia
9.
Epidemiol Infect ; 148: e120, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32600479

RESUMO

Since the beginning of the COVID-19 epidemic, there is an ongoing debate and research regarding the possible ways of virus transmission. We conducted an epidemiological investigation which revealed a cluster of five COVID-19 cases, linked to playing squash at a sports venue in Maribor, Slovenia. Acquired data raises possibility that the transmission occurred indirectly through contaminated objects in changing room or squash hall or via aerosolisation in squash hall.


Assuntos
Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Betacoronavirus/fisiologia , Infecções por Coronavirus/diagnóstico , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Esportes com Raquete , Eslovênia/epidemiologia , Instalações Esportivas e Recreacionais , Ventilação
10.
PLoS Comput Biol ; 16(7): e1007990, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32609732

RESUMO

The effective reproduction number, Rt, is a key time-varying prognostic for the growth rate of any infectious disease epidemic. Significant changes in Rt can forewarn about new transmissions within a population or predict the efficacy of interventions. Inferring Rt reliably and in real-time from observed time-series of infected (demographic) data is an important problem in population dynamics. The renewal or branching process model is a popular solution that has been applied to Ebola and Zika virus disease outbreaks, among others, and is currently being used to investigate the ongoing COVID-19 pandemic. This model estimates Rt using a heuristically chosen piecewise function. While this facilitates real-time detection of statistically significant Rt changes, inference is highly sensitive to the function choice. Improperly chosen piecewise models might ignore meaningful changes or over-interpret noise-induced ones, yet produce visually reasonable estimates. No principled piecewise selection scheme exists. We develop a practical yet rigorous scheme using the accumulated prediction error (APE) metric from information theory, which deems the model capable of describing the observed data using the fewest bits as most justified. We derive exact posterior prediction distributions for infected population size and integrate these within an APE framework to obtain an exact and reliable method for identifying the piecewise function best supported by available epidemic data. We find that this choice optimises short-term prediction accuracy and can rapidly detect salient fluctuations in Rt, and hence the infected population growth rate, in real-time over the course of an unfolding epidemic. Moreover, we emphasise the need for formal selection by exposing how common heuristic choices, which seem sensible, can be misleading. Our APE-based method is easily computed and broadly applicable to statistically similar models found in phylogenetics and macroevolution, for example. Our results explore the relationships among estimate precision, forecast reliability and model complexity.


Assuntos
Biologia Computacional/métodos , Infecções por Coronavirus/epidemiologia , Previsões/métodos , Modelos Estatísticos , Pneumonia Viral/epidemiologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Surtos de Doenças/prevenção & controle , Humanos , Teoria da Informação , Pandemias , Pneumonia Viral/virologia , Reprodutibilidade dos Testes , Replicação Viral/fisiologia
11.
Nat Commun ; 11(1): 3618, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681106

RESUMO

Global emergencies caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle-East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 significantly endanger human health. The spike (S) glycoprotein is the key antigen and its conserved S2 subunit contributes to viral entry by mediating host-viral membrane fusion. However, structural information of the post-fusion S2 from these highly pathogenic human-infecting coronaviruses is still lacking. We used single-particle cryo-electron microscopy to show that the post-fusion SARS-CoV S2 forms a further rotated HR1-HR2 six-helix bundle and a tightly bound linker region upstream of the HR2 motif. The structures of pre- and post-fusion SARS-CoV S glycoprotein dramatically differ, resembling that of the Mouse hepatitis virus (MHV) and other class I viral fusion proteins. This structure suggests potential targets for the development of vaccines and therapies against a wide range of SARS-like coronaviruses.


Assuntos
Betacoronavirus/química , Betacoronavirus/fisiologia , Glicoproteína da Espícula de Coronavírus/química , Motivos de Aminoácidos , Coronavirus/química , Coronavirus/classificação , Infecções por Coronavirus/virologia , Microscopia Crioeletrônica , Humanos , Fusão de Membrana , Modelos Moleculares , Pandemias , Pneumonia Viral/virologia , Conformação Proteica , Multimerização Proteica , Internalização do Vírus
12.
Infect Dis Poverty ; 9(1): 99, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690096

RESUMO

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused a public catastrophe and global concern. The main symptoms of COVID-19 are fever, cough, myalgia, fatigue and lower respiratory tract infection signs. Almost all populations are susceptible to the virus, and the basic reproduction number (R0) is 2.8-3.9. The fight against COVID-19 should have two aspects: one is the treatment of infected patients, and the other is the mobilization of the society to avoid the spread of the virus. The treatment of patients includes supportive treatment, antiviral treatment, and oxygen therapy. For patients with severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) and circulatory support are recommended. Plasma therapy and traditional Chinese medicine have also achieved good outcomes. This review is intended to summarize the research on this new coronavirus, to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and to provide guidance regarding new methods of prevention, diagnosis and clinical treatment based on autodock simulations. METHODS: This review compares the multifaceted characteristics of the three coronaviruses including COVID-19, SARS and MERS. Our researchers take the COVID-19, SARS, and MERS as key words and search literatures in the Pubmed database. We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses. RESULTS: We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S. We also found that the types and severity of clinical symptoms vary, which means that the diagnosis and nursing measures also require differentiation. In addition to the common route of transmission including airborne transmission, these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19. CONCLUSIONS: In evolutionary history, these three coronaviruses have some similar biological features as well as some different mutational characteristics. Their receptors and routes of transmission are not all the same, which makes them different in clinical features and treatments. We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19.


Assuntos
Antivirais/química , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A/química , Pneumonia Viral , Receptores Virais/química , Síndrome Respiratória Aguda Grave , Animais , Antivirais/metabolismo , Betacoronavirus/genética , Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Técnicas de Laboratório Clínico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Reservatórios de Doenças , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/ultraestrutura , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Receptores Virais/metabolismo , Vírus da SARS/genética , Vírus da SARS/fisiologia , Vírus da SARS/ultraestrutura , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão
14.
Rev Int Androl ; 18(3): 117-123, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32660697

RESUMO

OBJECTIVE: The main objective of this revision is to summarize the current existing evidence of the potential adverse effects of SARS-CoV-2 on the male reproductive system and provide the recommendations of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) concerning the implications of COVID-19 infection in the management of male infertilty patients and testicular endocrine dysfunction. METHODS: A comprehensive systematic literature search of the databases of PubMed, Web of Science, Embase, Medline, Cochrane and MedRxiv, was carried out. RESULTS: The presence of orchitis as a potential complication of the infection by SARS-CoV-2 has not yet been confirmed. One study reported that 19% of males with COVID-19 infection had scrotal symptoms suggestive of viral orchitis which could not be confirmed. It is possible that the virus, rather than infecting the testes directly, may induce a secondary autoimmune response leading to autoimmune orchitis. COVID-19 has been associated with coagulation disorders and thus the orchitis could be the result of segmental vasculitis. Existing data concerning the presence of the virus in semen are contradictory. Only one study reported the presence of RNA in 15.8% of patients with COVID-19. However, the presence of nucleic acid or antigen in semen is not synonyms of viral replication capacity and infectivity. It has been reported an increase in serum levels of LH in males with COVID-19 and a significant reduction in the T/LH and FSH/LH ratios, consistent with subclinical hypogonadism. CONCLUSIONS: The findings of recent reports related to the potential effects of COVID-19 infection on the male reproductive system are based on poorly designed, small sample size studies that provide inconclusive, contradictory results. Since there still exists a theoretical possibility of testicular damage and male infertilty as a result of the infection by COVID-19, males of reproductive age should be evaluated for gonadal function and semen analysis. With regard to the sexual transmission of the virus, there is not sufficient evidence to recommend asymptomatic couples to abstein from having sex in order to protect themselves from being infected by the virus. Additional studies are needed to understand the long-term effects of SARS-CoV-2 on male reproductive function, including male fertility potential and endocrine testicular function.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Saúde Reprodutiva , Saúde Sexual , Adulto , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Hormônio Foliculoestimulante/sangue , Humanos , Hipogonadismo/sangue , Hipogonadismo/etiologia , Imunoglobulina G/análise , Leucócitos , Hormônio Luteinizante/sangue , Masculino , Orquite/etiologia , Orquite/virologia , Próstata/virologia , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sêmen/virologia , Preservação do Sêmen , Espanha , Testículo/imunologia , Testículo/patologia , Testículo/virologia , Testosterona/sangue , Vasculite/etiologia , Adulto Jovem
15.
Int J Mol Sci ; 21(14)2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32664543

RESUMO

Recently, the world has been dealing with a devastating global pandemic coronavirus infection, with more than 12 million infected worldwide and over 300,000 deaths as of May 15th 2020, related to a novel coronavirus (2019-nCoV), characterized by a spherical morphology and identified through next-generation sequencing. Although the respiratory tract is the primary portal of entry of SARS-CoV-2, gastrointestinal involvement associated with nausea, vomiting and diarrhoea may also occur. No drug or vaccine has been approved due to the absence of evidence deriving from rigorous clinical trials. Increasing interest has been highlighted on the possible preventative role and adjunct treatment of lactoferrin, glycoprotein of human secretions part of a non-specific defensive system, known to play a crucial role against microbial and viral infections and exerting anti-inflammatory effects on different mucosal surfaces and able to regulate iron metabolism. In this review, analysing lactoferrin properties, we propose designing a clinical trial to evaluate and verify its effect using a dual combination treatment with local, solubilized intranasal spray formulation and oral administration. Lactoferrin could counteract the coronavirus infection and inflammation, acting either as natural barrier of both respiratory and intestinal mucosa or reverting the iron disorders related to the viral colonization.


Assuntos
Infecções por Coronavirus/prevenção & controle , Lactoferrina/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Inflamação , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/virologia , Ferro/metabolismo , Lactoferrina/farmacologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/virologia , Internalização do Vírus/efeitos dos fármacos
16.
Int J Mol Sci ; 21(14)2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32668803

RESUMO

In line with SARS and MERS, the SARS-CoV-2/COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide. SARS-CoV-2 infection/COVID-19 provides numerous therapeutic targets, each of them promising, but not leading to the success of therapy to date. Neither an antiviral nor an immunomodulatory therapy in patients with SARS-CoV-2 infection/COVID-19 or pre-exposure prophylaxis against SARS-CoV-2 has proved to be effective. In this review, we try to close the gap and point out the likely relationships among lysosomotropism, increasing lysosomal pH, SARS-CoV-2 infection, and disease process, and we deduce an approach for the treatment and prophylaxis of COVID-19, and cytokine release syndrome (CRS)/cytokine storm triggered by bacteria or viruses. Lysosomotropic compounds affect prominent inflammatory messengers (e.g., IL-1B, CCL4, CCL20, and IL-6), cathepsin-L-dependent viral entry of host cells, and products of lysosomal enzymes that promote endothelial stress response in systemic inflammation. As supported by recent clinical data, patients who have already taken lysosomotropic drugs for other pre-existing conditions likely benefit from this treatment in the COVID-19 pandemic. The early administration of a combination of antivirals such as remdesivir and lysosomotropic drugs, such as the antibiotics teicoplanin or dalbavancin, seems to be able to prevent SARS-CoV-2 infection and transition to COVID-19.


Assuntos
Infecções por Coronavirus/patologia , Lisossomos/metabolismo , Pneumonia Viral/patologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/patologia , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismo , Internalização do Vírus/efeitos dos fármacos
17.
J Transl Med ; 18(1): 261, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600410

RESUMO

Amino-bisphosphonates such as zoledronic acid (ZA) can possibly ameliorate or prevent severe COVID-19 disease by at least three distinct mechanisms: (1) as immunostimulants which could boost γδ T cell expansion, important in the acute response in the lung; (2) as DC modulators, limiting their ability to only partially activate T cells; and (3) as prenylation inhibitors of small GTPases in the endosomal pathway of the DC to prevent expulsion of lysosomes containing SARS-CoV-2 virions. Use of ZA or other amino-bisphosphonates as modulators of COVID-19 disease should be considered.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Células Dendríticas/virologia , Difosfonatos/uso terapêutico , Endossomos/metabolismo , Fatores Imunológicos/farmacologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Animais , Células Dendríticas/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Humanos , Pandemias
18.
J Transl Med ; 18(1): 270, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620125

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) broke out globally. Early prediction of the clinical progression was essential but still unclear. We aimed to evaluate the timeline of COVID-19 development and analyze risk factors of disease progression. METHODS: In this retrospective study, we included 333 patients with laboratory-confirmed COVID-19 infection hospitalized in the Third People's Hospital of Shenzhen from 10 January to 10 February 2020. Epidemiological feature, clinical records, laboratory and radiology manifestations were collected and analyzed. 323 patients with mild-moderate symptoms on admission were observed to determine whether they exacerbated to severe-critically ill conditions (progressive group) or not (stable group). We used logistic regression to identify the risk factors associated with clinical progression. RESULTS: Of all the 333 patients, 70 (21.0%) patients progressed into severe-critically ill conditions during hospitalization and assigned to the progressive group, 253 (76.0%) patients belonged to the stable group, another 10 patients were severe before admission. we found that the clinical features of aged over 40 (3.80 [1.72, 8.52]), males (2.21 [1.20, 4.07]), with comorbidities (1.78 [1.13, 2.81]) certain exposure history (0.38 [0.20, 0.71]), abnormal radiology manifestations (3.56 [1.13, 11.40]), low level of T lymphocytes (0.99 [0.997, 0.999]), high level of NLR (0.99 [0.97, 1.01]), IL-6 (1.05 [1.03, 1.07]) and CRP (1.67 [1.12, 2.47]) were the risk factors of disease progression by logistic regression. CONCLUSIONS: The potential risk factors of males, older age, with comorbidities, low T lymphocyte level and high level of NLR, CRP, IL-6 can help to predict clinical progression of COVID-19 at an early stage.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Progressão da Doença , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Feminino , Hospitalização , Humanos , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Curva ROC , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Int J Mol Sci ; 21(13)2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32629817

RESUMO

By attaching to the angiotensin converting enzyme 2 (ACE2) protein on lung and intestinal cells, Sudden Acute Respiratory Syndrome (SARS-CoV-2) can cause respiratory and homeostatic difficulties leading to sepsis. The progression from acute respiratory failure to sepsis has been correlated with the release of high-mobility group box 1 protein (HMGB1). Lack of effective conventional treatment of this septic state has spiked an interest in alternative medicine. This review of herbal extracts has identified multiple candidates which can target the release of HMGB1 and potentially reduce mortality by preventing progression from respiratory distress to sepsis. Some of the identified mixtures have also been shown to interfere with viral attachment. Due to the wide variability in chemical superstructure of the components of assorted herbal extracts, common motifs have been identified. Looking at the most active compounds in each extract it becomes evident that as a group, phenolic compounds have a broad enzyme inhibiting function. They have been shown to act against the priming of SARS-CoV-2 attachment proteins by host and viral enzymes, and the release of HMGB1 by host immune cells. An argument for the value in a nonspecific inhibitory action has been drawn. Hopefully these findings can drive future drug development and clinical procedures.


Assuntos
Betacoronavirus/fisiologia , Proteína HMGB1/metabolismo , Insuficiência Respiratória/patologia , Sepse/patologia , Proteína HMGB1/antagonistas & inibidores , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Macrófagos/virologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Exsudatos de Plantas/química , Exsudatos de Plantas/farmacologia , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Insuficiência Respiratória/metabolismo , Insuficiência Respiratória/prevenção & controle , Sepse/metabolismo , Sepse/prevenção & controle , Internalização do Vírus/efeitos dos fármacos
20.
J Transl Med ; 18(1): 274, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631442

RESUMO

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.


Assuntos
Betacoronavirus/fisiologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Humanos , Estudos Observacionais como Assunto , Pandemias , Viés de Publicação , Risco , Resultado do Tratamento
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