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1.
IUBMB Life ; 73(8): 1005-1015, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34118117

RESUMO

The kidney is one of the main targets attacked by viruses in patients with a coronavirus infection. Until now, SARS-CoV-2 has been identified as the seventh member of the coronavirus family capable of infecting humans. In the past two decades, humankind has experienced outbreaks triggered by two other extremely infective members of the coronavirus family; the MERS-CoV and the SARS-CoV. According to several investigations, SARS-CoV causes proteinuria and renal impairment or failure. The SARS-CoV was identified in the distal convoluted tubules of the kidney of infected patients. Also, renal dysfunction was observed in numerous cases of MERS-CoV infection. And recently, during the 2019-nCoV pandemic, it was found that the novel coronavirus not only induces acute respiratory distress syndrome (ARDS) but also can induce damages in various organs including the liver, heart, and kidney. The kidney tissue and its cells are targeted massively by the coronaviruses due to the abundant presence of ACE2 and Dpp4 receptors on kidney cells. These receptors are characterized as the main route of coronavirus entry to the victim cells. Renal failure due to massive viral invasion can lead to undesirable complications and enhanced mortality rate, thus more attention should be paid to the pathology of coronaviruses in the kidney. Here, we have provided the most recent knowledge on the coronaviruses (SARS, MERS, and COVID19) pathology and the mechanisms of their impact on the kidney tissue and functions.


Assuntos
COVID-19/mortalidade , Infecções por Coronavirus/mortalidade , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/mortalidade , Tropismo Viral/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/genética , COVID-19/patologia , COVID-19/virologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Regulação da Expressão Gênica , Humanos , Rim/metabolismo , Rim/patologia , Rim/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Ligação Proteica , Receptores Virais/genética , Receptores Virais/metabolismo , Vírus da SARS/genética , Vírus da SARS/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Análise de Sobrevida
2.
Nat Biomed Eng ; 5(7): 666-677, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34031558

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid and sensitive protein detection and quantification in simple and robust formats for widespread point-of-care applications. Here, we report on nanobody-functionalized organic electrochemical transistors with a modular architecture for the rapid quantification of single-molecule-to-nanomolar levels of specific antigens in complex bodily fluids. The sensors combine a solution-processable conjugated polymer in the transistor channel and high-density and orientation-controlled bioconjugation of nanobody-SpyCatcher fusion proteins on disposable gate electrodes. The devices provide results after 10 min of exposure to 5 µl of unprocessed samples, maintain high specificity and single-molecule sensitivity in human saliva and serum, and can be reprogrammed to detect any protein antigen if a corresponding specific nanobody is available. We used the sensors to detect green fluorescent protein, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV) spike proteins, and for the COVID-19 screening of unprocessed clinical nasopharyngeal swab and saliva samples with a wide range of viral loads.


Assuntos
Técnicas Biossensoriais/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Nanotecnologia/métodos , Vírus da SARS/patogenicidade , COVID-19/virologia , Humanos , Anticorpos de Domínio Único/imunologia
3.
NPJ Syst Biol Appl ; 7(1): 21, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031419

RESUMO

COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV, and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA, and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that has therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.


Assuntos
COVID-19/genética , Epigênese Genética/genética , SARS-CoV-2/genética , Transcriptoma/genética , COVID-19/virologia , Perfilação da Expressão Gênica , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/genética , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Transdução de Sinais/genética
4.
Nature ; 594(7862): 246-252, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33845483

RESUMO

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


Assuntos
COVID-19/metabolismo , Interações Hospedeiro-Patógeno , Proteoma/metabolismo , Proteômica , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/metabolismo , Animais , Antivirais/farmacologia , Autofagia/efeitos dos fármacos , COVID-19/imunologia , COVID-19/virologia , Linhagem Celular , Conjuntos de Dados como Assunto , Avaliação Pré-Clínica de Medicamentos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inibidores de Metaloproteinases de Matriz/farmacologia , Fosforilação , Mapas de Interação de Proteínas , Inibidores de Proteínas Quinases/farmacologia , Processamento de Proteína Pós-Traducional , Proteoma/química , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Fator de Crescimento Transformador beta/metabolismo , Ubiquitinação , Proteínas Virais/química , Proteínas Virais/metabolismo , Proteínas Viroporinas/metabolismo
5.
Epidemiol Infect ; 149: e96, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33849679

RESUMO

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


Assuntos
COVID-19/transmissão , SARS-CoV-2/patogenicidade , Carga Viral , Adenoviridae/patogenicidade , Animais , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Chlorocebus aethiops , Controle de Doenças Transmissíveis , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Cricetinae , Enterovirus/patogenicidade , Furões , Humanos , Macaca mulatta , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Orthomyxoviridae/patogenicidade , Vírus Sinciciais Respiratórios/patogenicidade , Rhinovirus/patogenicidade , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Viroses/epidemiologia , Viroses/transmissão , Viroses/virologia
7.
Pharm. pract. (Granada, Internet) ; 19(1): 0-0, ene.-mar. 2021. tab, graf
Artigo em Inglês | IBECS | ID: ibc-201720

RESUMO

BACKGROUND: COVID-19 vaccine development is proceeding at an unprecedented pace. Once COVID-19 vaccines become widely available, it will be necessary to maximize public vaccine acceptance and coverage. OBJECTIVE: This research aimed to analyze the predictors of COVID-19 vaccine acceptance in Russia. METHODS: A cross-sectional online survey was conducted among Russian adults from September 26th to November 9th, 2020. Predictors of the intent to take up COVID-19 vaccination were explored using logistic regression. RESULTS: Out of 876 participants, 365 (41.7%) would be willing to receive the vaccine if it became available. Acceptance increased for a vaccine with verified safety and effectiveness (63.2%). Intention to receive the COVID-19 vaccine was relatively higher among males (aOR=2.37, 95% CI 1.41-4.00), people with lower monthly income (aOR=2.94, 95%CI 1.32-6.57), and with positive trust in the healthcare system (aOR=2.73, 95% CI 1.76-4.24). The Russian people were more likely to accept the COVID-19 vaccine if they believed that the vaccine reduces the risk of virus infection (aOR=8.80, 95%CI 5.21-14.87) or relieves the complications of the disease (aOR=10.46, 95%CI 6.09-17.96). Other barriers such as being unconcerned about side-effects (aOR=1.65, 95%CI 1.03-2.65) and the effectiveness and safety of the vaccination (aOR=2.55, 95%CI 1.60-4.08), also affected acceptance. CONCLUSIONS: The study showed the usefulness of the health belief model constructs in understanding the COVID-19 vaccination acceptance rate in the Russian population. This rate was influenced by sociodemographic and health-related characteristics, and health beliefs. These findings might help guide future efforts for policymakers and stakeholders to improve vaccination rates by enhancing trust in the healthcare system


No disponible


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Infecções por Coronavirus/prevenção & controle , Programas de Imunização/estatística & dados numéricos , Vacinação em Massa/estatística & dados numéricos , Federação Russa/epidemiologia , Vírus da SARS/patogenicidade , Vacinas/administração & dosagem , Programas de Imunização/organização & administração , Pandemias/prevenção & controle , Estudos Transversais , Inquéritos e Questionários/estatística & dados numéricos
8.
Pharm. pract. (Granada, Internet) ; 19(1): 0-0, ene.-mar. 2021. tab, graf
Artigo em Inglês | IBECS | ID: ibc-201721

RESUMO

BACKGROUND: The pandemic is at a paradoxical stage, with vaccine roll out initiated but a significantly elevated level of infection and death. Hope for recovery lies in high equitable vaccine uptake. OBJECTIVE: The study aimed to: i) explore attitudes and factors influencing attitudes, towards the COVID-19 vaccine amongst people living in Malta, ii) identify the reasons as to why individuals are unsure or unwilling to take the vaccine. METHODS: Two consecutive, short, anonymous online surveys using social media platforms were used to gather data from adult individuals. The first study was open to residents in Malta, while the second study invited international participation. Study 1 consisted of 17 questions inspired by the Theories of Planned Behaviour and Reasoned Action. Study 2 asked participates whether they were willing, unwilling or unsure of taking the vaccine and their reasons for being unsure or unwilling. RESULTS: A total of 2,529 individuals participated in Study 1 and 834 in Study 2. In both studies respondents were predominantly female having a tertiary education. Over 50% declared that they were willing to take the vaccine, with males being more willing (t=5.83, df=1164.2, p < 0.00005). Opinions of significant others- family and friends (r=0.22, p < 0.005) and health professionals (r=0.74, p < 0.005) were associated with willingness to take the vaccine. Vaccine hesitancy was present in the study population with 32.6% being unsure and 15.6% declaring that they were not willing to take the vaccine. Females were more likely to be unsure (Chi-squared=14.63, df=4, p = 0.006). Lack of vaccine safety was the main reason cited for unwillingness to take the vaccine. Predictors for willingness to take the vaccine were: i) The belief that the COVID-19 vaccine will protect the health of the people who take it; ii) Valuing the advice of health professionals regarding the effectiveness of COVID-19 vaccine; iii) Having taken the influenza vaccine last year and; iv) Encouraging their elderly parents to take the vaccine. CONCLUSIONS: COVID-19 vaccination information campaigns should promote group strategies, focusing on emphasising the safety of the vaccine and offer reassurance, especially to women


No disponible


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Infecções por Coronavirus/prevenção & controle , Programas de Imunização/estatística & dados numéricos , Vacinação em Massa/estatística & dados numéricos , Atitude , Intenção , Vírus da SARS/patogenicidade , Vacinas/administração & dosagem , Programas de Imunização/organização & administração , Pandemias/prevenção & controle , Estudos Transversais , Inquéritos e Questionários/estatística & dados numéricos , Movimento contra Vacinação/estatística & dados numéricos , Malta/epidemiologia
9.
Fisioterapia (Madr., Ed. impr.) ; 43(1): 58-62, ene.-feb. 2021. tab
Artigo em Espanhol | IBECS | ID: ibc-202431

RESUMO

ANTECEDENTES Y OBJETIVO: La pandemia actual por el Coronavirus SARS-Cov-2 está generando un elevado número de pacientes que necesitan ingreso hospitalario por neumonía y que, tras su alta hospitalaria, precisan de un control evolutivo por persistencia de sintomatología. Dada la poca evidencia existente sobre el abordaje fisioterápico de estos pacientes, y las restricciones de acceso al centro de salud, el objetivo es comprobar si una intervención de fisioterapia en atención primaria, realizada a un paciente a través de consulta no presencial (CNP), es eficaz. MATERIAL Y MÉTODOS: Se realizó la intervención fisioterápica: mediante CNP por vía telefónica a un paciente varón de 47 años, a los 7 días tras ser dado de alta de neumonía por Coronavirus. Se efectuó seguimiento de la disnea a través de escala de Borg modificada y la escala del Medical Research Council, pruebas de función física a través del Short Physical Performance Battery (SPPB) y de la calidad de vida relacionada con la salud mediante la encuesta EuroQol-5D, así como del control evolutivo de constantes fisiológicas (temperatura, frecuencia cardiaca y saturación de oxígeno) durante 28 días de seguimiento. La intervención consistió en un programa de educación para la salud y ejercicio terapéutico. RESULTADOS Y CONCLUSIONES: El programa de atención fisioterápica telefónica ha permitido el tratamiento y el seguimiento del paciente (variables fisiológicas, Short Physical Performance Battery, calidad de visa relacionada con la salud, en las que se ha objetivado mejoría), por lo que este tipo de intervenciones mediante CNP, para pacientes dados de alta de neumonía por Coronavirus, merecen ser estudiados en profundidad en futuros estudios


BACKGROUND AND OBJECTIVE: The current SARS-Cov-2 Coronavirus pandemic is resulting in a high number of patients who need hospital admission for pneumonia and in many cases subsequent follow-up due to persistent symptoms after discharge. Since there is little existing evidence on the physiotherapy treatment approach, and there are restrictions to usual consultation, the aim is to check whether Physical Therapy Primary Care (PTPC) intervention through remote consultation is effective. MATERIAL AND METHODS: A 47-year-old male patient with Coronavirus pneumonia underwent a physiotherapy intervention through remote consultation (RC) over the phone 7 days after being discharged. On the one hand, dyspnoea was followed up by employing the modified Borg scale and modified Medical Research Council scale (mMRC), where physical function is assessed through the Short Physical Performance Battery (SPPB). On the other hand, the Health Related Quality of Life (HRQL) was assessed through the EuroQol-5D questionnaire, and vital signs (temperature, heart rate and oxygen pressure) were monitored for 28 days. The intervention consisted of an educational programme for health and exercise therapy. RESULTS AND CONCLUSIONS: The physiotherapy phone consultation programme allowed the treatment and follow up of this patient (physiological variables, SPPB and HRQL) which resulted in improvement. Therefore, we suggest future trials are worth undertaking to study in-depth interventions based on remote consultation directed at these patients with Coronavirus pneumonia after discharge


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Infecções por Coronavirus/complicações , Síndrome Respiratória Aguda Grave/complicações , Pneumonia Viral/complicações , Atenção Primária à Saúde/métodos , Vírus da SARS/patogenicidade , Telemedicina/métodos , Consulta Remota/métodos , Pandemias/estatística & dados numéricos , Continuidade da Assistência ao Paciente , Monitorização Ambulatorial/métodos
10.
Med. intensiva (Madr., Ed. impr.) ; 45(1): 14-26, ene.-feb. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-202577

RESUMO

OBJETIVO: Describir las características demográficas y de comorbilidad de los pacientes con COVID-19 fallecidos en hospitales españoles durante el brote pandémico de 2020 y compararlas según si ingresaron o no en una Unidad de Cuidados Intensivos (UCI) antes del fallecimiento. MÉTODOS: Análisis secundario de los pacientes de la cohorte SIESTA (formada por pacientes COVID de 62 hospitales españoles) fallecidos durante la hospitalización. Se recogieron sus características demográficas y comorbilidades, individuales y globalmente, estimadas mediante el índice de comorbilidad de Charlson (ICC). Se identificaron los factores independientes relacionados con ingreso en UCI, y se realizaron diversos análisis de sensibilidad para contrastar la consistencia de los hallazgos del análisis principal. RESULTADOS: Se incluyeron los 338 pacientes de la cohorte SIESTA fallecidos; de ellos, 77 (22,8%) accedieron a una UCI previamente al fallecimiento. En el análisis multivariable, tres de las 20 características basales analizadas se asociaron independientemente con ingreso en UCI de los pacientes fallecidos: demencia (no hubo pacientes fallecidos con demencia que ingresasen en UCI; OR = 0, IC 95% = no calculable), cáncer activo (OR = 0,07, IC 95% = 0,02-0,21) y edad (< 70 años: OR = 1, referencia; 70-74 años: OR = 0,21, IC 95% = 0,08-0,54; 75-79 años: OR = 0,21, IC 95% = 0,08-0,54; ≥ 80 años: OR = 0,02, IC 95% = 0,01-0,05). La probabilidad de ingreso en UCI de los pacientes que fallecieron disminuyó significativamente al aumentar el ICC, incluso tras ajustarla por edad (ICC 0 puntos: OR = 1, referencia; ICC 1 punto: OR = 0,36, IC 95% = 0,16-0,83; ICC 2 puntos: OR = 0,36, IC 95% = 0,16-0,83; ICC > 2 puntos: OR = 0,09, IC 95% = 0,04-0,23). Los análisis de sensibilidad no mostraron diferencias destacables respecto al análisis principal. CONCLUSIONES: El perfil de los pacientes COVID fallecidos sin ingresar en UCI se ajustó a lo observado en la práctica médica habitual antes de la pandemia, y las características basales que limitaron su ingreso fueron la edad y la carga de comorbilidad global, especialmente la demencia y el cáncer activo


OBJECTIVE: To describe and compare the demographic characteristics and comorbidities of patients with COVID-19 who died in Spanish hospitals during the 2020 pandemic based on whether they were or were not admitted to an intensive care unit (ICU) prior to death. METHODS: We performed a secondary analysis of COVID-19 patients who died during hospitalization included by 62 Spanish emergency departments in the SIESTA cohort. We collected the demographic characteristics and comorbidities, determined both individually and estimated globally by the Charlson index (ChI). Independent factors related to ICU admission were identified and different analyses of sensitivity were performed to contrast the consistency of the findings of the principal analysis. RESULTS: We included the 338 patients from the SIESTA cohort that died during hospitalization. Of these, 77 (22.8%) were admitted to an ICU before dying. After multivariate adjustment, 3 out of the 20 basal characteristics analyzed in the present study were independently associated with ICU admission: dementia (no patients with dementia who died were admitted to the ICU: OR = 0, 95%CI = not calculable), active cancer (OR = 0.07; 95%CI = 0.02-0.21) and age (< 70 years: OR = 1, reference; 70-74 years: OR = 0.21; 95%CI = 0.08-0.54; 75-79 years: OR = 0.21; 95%CI = 0.08-0.54; ≥ 80 years: OR = 0.02; 95%CI = 0.01-0.05). The probability of ICU admission significantly increased in parallel to the ChI, even after adjustment for age (ChI 0 points: OR = 0, reference; ChI 1 point: OR = 0.36; 95%CI = 0.16-0.83; ChI 2 points: OR = 0.36; 95%CI = 0.16-0.83; ChI >2 points: OR = 0.09; 95%CI = 0.04-0.23). The sensitivity analyses showed no gross differences compared to the principal analysis. CONCLUSIONS: The profile of COVID-19 patients who died without ICU admission is similar to that observed in the usual medical practice before the pandemic. The basal characteristics limiting their admission were age and global burden due to comorbidity, especially dementia and active cancer


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/mortalidade , Síndrome Respiratória Aguda Grave/mortalidade , Vírus da SARS/patogenicidade , Resultados de Cuidados Críticos , Unidades de Terapia Intensiva/estatística & dados numéricos , Indicadores de Morbimortalidade , Registros de Doenças/estatística & dados numéricos , Fatores Etários , Fatores de Risco , Espanha/epidemiologia
11.
Comunidad (Barc., Internet) ; 22(3): 0-0, nov.-feb. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-195072

RESUMO

INTRODUCCIÓN: La pandemia ocasionada por el SARS-CoV-2 ha supuesto una reestructuración sin precedentes de la asistencia sanitaria y también de los centros de salud. OBJETIVO: Conocer las percepciones del personal médico del Centro de Salud Albaycín sobre la respuesta del equipo de Atención Primaria ante la pandemia de la COVID-19 en los meses de marzo y abril de 2020. MÉTODOS: Estudio cualitativo, observacional de orientación fenomenológica mediante entrevistas individuales. El ámbito de estudio es el Centro de Salud Albaycín. La saturación teórica determinó el tamaño de la muestra (la totalidad de la plantilla médica). Se llevó a cabo un análisis narrativo del contenido. RESULTADOS: Los discursos muestran seis categorías de análisis: organización de la toma de decisiones, características de la respuesta dada, mantenimiento de los pilares de la Atención Primaria, cualidades del equipo potenciadas, rol de la docencia y nuevas dinámicas generadas. Los resultados describen una respuesta adecuada, coordinada con la comunidad y anticipada a las directrices institucionales. La toma de decisiones ha sido consensuada y horizontal, potenciándose las cualidades del equipo. A pesar de las limitaciones, se ha mantenido la accesibilidad y la longitudinalidad. Durante la pandemia se ha visto afectada la calidad asistencial y la actividad docente. DISCUSIÓN: Un liderazgo transformacional, que refuerza el vínculo entre profesionales y fomenta la participación activa también de los residentes, permite una respuesta satisfactoria ante una situación emergente. Contar con la participación de la comunidad puede generar confianza en la organización y mejorar los resultados en salud


INTRODUCTION: The SARS-CoV-2 pandemic has brought about an unprecedented restructuring of healthcare and health centers. OBJECTIVES: Learn the perceptions of medical staff from Albayzín Health Centre regarding the Primary Care team's response to the COVID-19 pandemic in March and April 2020. METHODS: Qualitative, observational study with a phenomenological approach conducted by means of individual interviews. The scope of the study is Albaycín Health Centre. The theoretical saturation determined sample size (the entire medical staff). Content was analysed in narrative terms. RESULTS: Conversations revealed six categories of analysis: organization of the decision-making process, characteristics of the response provided, maintaining the cornerstones of Primary Care, enhanced team qualities, role of teaching and new dynamics generated. The results report an adequate response, which was coordinated with the community and anticipated institutional guidelines. Decision-making was consensual and horizontal, which enhanced the team's qualities. Despite the limitations, accessibility and longitudinal configuration have been maintained. Both the quality of care and teaching have been affected during the pandemic. DISCUSSION: Transformational leadership, which strengthens the bond between professionals and encourages residents to participate actively, facilitates a satisfactory response to an emerging situation. Having the community participate can build trust in the organization and improve health outcomes


Assuntos
Humanos , Infecções por Coronavirus/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Vírus da SARS/patogenicidade , Planejamento de Instituições de Saúde/organização & administração , Pessoal de Saúde/organização & administração , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Técnicas de Apoio para a Decisão
12.
Emerg Microbes Infect ; 10(1): 196-205, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33399028

RESUMO

ABSTRACT Following outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2002 and 2012, respectively, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third highly pathogenic emerging human coronavirus (hCoV). SARS-CoV-2 is currently causing the global coronavirus disease 2019 (COVID-19) pandemic. CoV infections in target cells may stimulate the formation of numerous double-membrane autophagosomes and induce autophagy. Several studies provided evidence that hCoV infections are closely related to various cellular aspects associated with autophagy. Autophagy may even promote hCoV infection and replication. However, so far it is unclear how hCoV infections induce autophagy and whether the autophagic machinery is necessary for viral propagation. Here, we summarize the most recent advances concerning the mutual interplay between the autophagic machinery and the three emerging hCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 and the model system mouse hepatitis virus. We also discuss the applicability of approved and well-tolerated drugs targeting autophagy as a potential treatment against COVID-19.


Assuntos
Autofagossomos/virologia , Autofagia , COVID-19/fisiopatologia , SARS-CoV-2/patogenicidade , Animais , COVID-19/tratamento farmacológico , Ensaios Clínicos como Assunto , Genoma Viral , Humanos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da Hepatite Murina/patogenicidade , Vírus da SARS/genética , Vírus da SARS/patogenicidade , SARS-CoV-2/genética , Internalização do Vírus/efeitos dos fármacos
13.
Infect Genet Evol ; 88: 104708, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33421654

RESUMO

The pandemic due to novel coronavirus, SARS-CoV-2 is a serious global concern now. More than thousand new COVID-19 infections are getting reported daily for this virus across the globe. Thus, the medical research communities are trying to find the remedy to restrict the spreading of this virus, while the vaccine development work is still under research in parallel. In such critical situation, not only the medical research community, but also the scientists in different fields like microbiology, pharmacy, bioinformatics and data science are also sharing effort to accelerate the process of vaccine development, virus prediction, forecasting the transmissible probability and reproduction cases of virus for social awareness. With the similar context, in this article, we have studied sequence variability of the virus primarily focusing on three aspects: (a) sequence variability among SARS-CoV-1, MERS-CoV and SARS-CoV-2 in human host, which are in the same coronavirus family, (b) sequence variability of SARS-CoV-2 in human host for 54 different countries and (c) sequence variability between coronavirus family and country specific SARS-CoV-2 sequences in human host. For this purpose, as a case study, we have performed topological analysis of 2391 global genomic sequences of SARS-CoV-2 in association with SARS-CoV-1 and MERS-CoV using an integrated semi-alignment based computational technique. The results of the semi-alignment based technique are experimentally and statistically found similar to alignment based technique and computationally faster. Moreover, the outcome of this analysis can help to identify the nations with homogeneous SARS-CoV-2 sequences, so that same vaccine can be applied to their heterogeneous human population.


Assuntos
COVID-19/epidemiologia , Infecções por Coronavirus/epidemiologia , Variação Genética , Genoma Viral , Pandemias , SARS-CoV-2/genética , Síndrome Respiratória Aguda Grave/epidemiologia , África/epidemiologia , América/epidemiologia , Ásia/epidemiologia , Austrália/epidemiologia , Sequência de Bases , COVID-19/transmissão , COVID-19/virologia , Biologia Computacional/métodos , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Europa (Continente)/epidemiologia , Interações Hospedeiro-Patógeno/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/genética , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Alinhamento de Sequência , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia
14.
Int Rev Immunol ; 40(1-2): 5-53, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32744465

RESUMO

Coronavirus infections are responsible for mild, moderate, and severe infections in birds and mammals. These were first isolated in humans as causal microorganisms responsible for common cold. The 2002-2003 SARS epidemic caused by SARS-CoV and 2012 MERS epidemic (64 countries affected) caused by MERS-CoV showed their acute and fatal side. These two CoV infections killed thousands of patients infected worldwide. However, WHO has still reported the MERS case in December 2019 in middle-eastern country (Saudi Arabia), indicating the MERS epidemic has not ended completely yet. Although we have not yet understood completely these two CoV epidemics, a third most dangerous and severe CoV infection has been originated in the Wuhan city, Hubei district of China in December 2019. This CoV infection called COVID-19 or SARS-CoV2 infection has now spread to 210 countries and territories around the world. COVID-19 has now been declared a pandemic by the World Health Organization (WHO). It has infected more than 16.69 million people with more than 663,540 deaths across the world. Thus the current manuscript aims to describe all three (SARS, MERS, and COVID-19) in terms of their causal organisms (SARS-CoV, MERS-CoV, and SARS-CoV2), similarities and differences in their clinical symptoms, outcomes, immunology, and immunopathogenesis, and possible future therapeutic approaches.


Assuntos
COVID-19/patologia , Coronaviridae/ultraestrutura , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/patologia , Animais , COVID-19/diagnóstico , COVID-19/mortalidade , Camelus/virologia , Quirópteros/virologia , Coronaviridae/classificação , Reservatórios de Doenças/virologia , Suscetibilidade a Doenças/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/mortalidade , Replicação Viral/fisiologia
15.
Brief Bioinform ; 22(2): 1175-1196, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-32778874

RESUMO

The novel coronavirus (2019-nCoV) has recently emerged, causing COVID-19 outbreaks and significant societal/global disruption. Importantly, COVID-19 infection resembles SARS-like complications. However, the lack of knowledge about the underlying genetic mechanisms of COVID-19 warrants the development of prospective control measures. In this study, we employed whole-genome alignment and digital DNA-DNA hybridization analyses to assess genomic linkage between 2019-nCoV and other coronaviruses. To understand the pathogenetic behavior of 2019-nCoV, we compared gene expression datasets of viral infections closest to 2019-nCoV with four COVID-19 clinical presentations followed by functional enrichment of shared dysregulated genes. Potential chemical antagonists were also identified using protein-chemical interaction analysis. Based on phylogram analysis, the 2019-nCoV was found genetically closest to SARS-CoVs. In addition, we identified 562 upregulated and 738 downregulated genes (adj. P ≤ 0.05) with SARS-CoV infection. Among the dysregulated genes, SARS-CoV shared ≤19 upregulated and ≤22 downregulated genes with each of different COVID-19 complications. Notably, upregulation of BCL6 and PFKFB3 genes was common to SARS-CoV, pneumonia and severe acute respiratory syndrome, while they shared CRIP2, NSG1 and TNFRSF21 genes in downregulation. Besides, 14 genes were common to different SARS-CoV comorbidities that might influence COVID-19 disease. We also observed similarities in pathways that can lead to COVID-19 and SARS-CoV diseases. Finally, protein-chemical interactions suggest cyclosporine, resveratrol and quercetin as promising drug candidates against COVID-19 as well as other SARS-like viral infections. The pathogenetic analyses, along with identified biomarkers, signaling pathways and chemical antagonists, could prove useful for novel drug development in the fight against the current global 2019-nCoV pandemic.


Assuntos
COVID-19/virologia , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/tratamento farmacológico , Estudos de Casos e Controles , Comorbidade , Genoma Viral , Humanos , MicroRNAs/metabolismo , Vírus da SARS/genética , Fatores de Transcrição/metabolismo
16.
Mol Biol Evol ; 38(2): 702-715, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-32941612

RESUMO

Despite SARS-CoV and SARS-CoV-2 being equipped with highly similar protein arsenals, the corresponding zoonoses have spread among humans at extremely different rates. The specific characteristics of these viruses that led to such distinct outcomes remain unclear. Here, we apply proteome-wide comparative structural analysis aiming to identify the unique molecular elements in the SARS-CoV-2 proteome that may explain the differing consequences. By combining protein modeling and molecular dynamics simulations, we suggest nonconservative substitutions in functional regions of the spike glycoprotein (S), nsp1, and nsp3 that are contributing to differences in virulence. Particularly, we explain why the substitutions at the receptor-binding domain of S affect the structure-dynamics behavior in complexes with putative host receptors. Conservation of functional protein regions within the two taxa is also noteworthy. We suggest that the highly conserved main protease, nsp5, of SARS-CoV and SARS-CoV-2 is part of their mechanism of circumventing the host interferon antiviral response. Overall, most substitutions occur on the protein surfaces and may be modulating their antigenic properties and interactions with other macromolecules. Our results imply that the striking difference in the pervasiveness of SARS-CoV-2 and SARS-CoV among humans seems to significantly derive from molecular features that modulate the efficiency of viral particles in entering the host cells and blocking the host immune response.


Assuntos
Simulação de Dinâmica Molecular , Proteômica , Vírus da SARS/química , Vírus da SARS/patogenicidade , SARS-CoV-2/química , SARS-CoV-2/patogenicidade , Proteínas Virais/química , Animais , Humanos , Domínios Proteicos , Vírus da SARS/metabolismo , SARS-CoV-2/metabolismo , Especificidade da Espécie , Proteínas Virais/metabolismo
17.
Cell Mol Gastroenterol Hepatol ; 11(3): 771-781, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33010495

RESUMO

BACKGROUND AND AIMS: Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile. METHODS: Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines. RESULTS: SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues. CONCLUSION: Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Imunidade Inata/imunologia , Mucosa Intestinal/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Vírus da SARS/patogenicidade , Replicação Viral/imunologia , Replicação Viral/fisiologia
18.
Rev Med Virol ; 31(2): e2171, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33350025

RESUMO

From 2002 to 2019, three deadly human coronaviruses (hCoVs), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged to produce outbreaks of SARS, MERS and coronavirus disease 2019 (Covid-19), respectively. All three hCoVs are members of the Betacoronavirus genus in the subfamily Orthocoronavirinae and share many similarities in virology and epidemiology. However, the pattern and scale of Covid-19 global spread is similar to 2009 pandemic H1N1 influenza (H1N1pdm09), rather than SARS or MERS. Covid-19 exhibits high viral shedding in the upper respiratory tract at an early stage of infection, and has a high proportion of transmission competent individuals that are pre-symptomatic, asymptomatic and mildly symptomatic, characteristics seen in H1N1pdm09 but not in SARS or MERS. These two traits of Covid-19 and H1N1pdm09 result in reduced efficiency in identification of transmission sources by symptomatic screening and play important roles in their ability to spread unchecked to cause pandemics. To overcome these attributes of Covid-19 in community transmission, identifying the transmission source by testing for virus shedding and interrupting chains of transmission by social distancing and public masking are required.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , Influenza Humana/epidemiologia , Pandemias/prevenção & controle , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Animais , COVID-19/virologia , Surtos de Doenças/prevenção & controle , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/transmissão , Influenza Humana/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/patogenicidade , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/virologia
19.
ACS Infect Dis ; 6(12): 3174-3189, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33263384

RESUMO

Human coronaviruses (hCoVs) have become a threat to global health and society, as evident from the SARS outbreak in 2002 caused by SARS-CoV-1 and the most recent COVID-19 pandemic caused by SARS-CoV-2. Despite a high sequence similarity between SARS-CoV-1 and -2, each strain has a distinctive virulence. A better understanding of the basic molecular mechanisms mediating changes in virulence is needed. Here, we profile the virus-host protein-protein interactions of two hCoV nonstructural proteins (nsps) that are critical for virus replication. We use tandem mass tag-multiplexed quantitative proteomics to sensitively compare and contrast the interactomes of nsp2 and nsp4 from three betacoronavirus strains: SARS-CoV-1, SARS-CoV-2, and hCoV-OC43-an endemic strain associated with the common cold. This approach enables the identification of both unique and shared host cell protein binding partners and the ability to further compare the enrichment of common interactions across homologues from related strains. We identify common nsp2 interactors involved in endoplasmic reticulum (ER) Ca2+ signaling and mitochondria biogenesis. We also identify nsp4 interactors unique to each strain, such as E3 ubiquitin ligase complexes for SARS-CoV-1 and ER homeostasis factors for SARS-CoV-2. Common nsp4 interactors include N-linked glycosylation machinery, unfolded protein response associated proteins, and antiviral innate immune signaling factors. Both nsp2 and nsp4 interactors are strongly enriched in proteins localized at mitochondria-associated ER membranes suggesting a new functional role for modulating host processes, such as calcium homeostasis, at these organelle contact sites. Our results shed light on the role these hCoV proteins play in the infection cycle, as well as host factors that may mediate the divergent pathogenesis of OC43 from SARS strains. Our mass spectrometry workflow enables rapid and robust comparisons of multiple bait proteins, which can be applied to additional viral proteins. Furthermore, the identified common interactions may present new targets for exploration by host-directed antiviral therapeutics.


Assuntos
COVID-19/metabolismo , Interações Hospedeiro-Patógeno/genética , SARS-CoV-2/patogenicidade , Proteínas não Estruturais Virais/metabolismo , COVID-19/virologia , Coronavirus Humano OC43/patogenicidade , Retículo Endoplasmático/metabolismo , Células HEK293 , Humanos , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Ligação Proteica , Mapas de Interação de Proteínas/genética , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/virologia , Transfecção , Proteínas não Estruturais Virais/genética , Virulência/genética , Replicação Viral/genética
20.
Med Sci Monit ; 26: e928572, 2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33311429

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the third (following SARS-CoV and Middle East Respiratory Syndrome-CoV) zoonotic coronavirus that has crossed the species barrier in the 21st century, resulting in the development of serious human infection. The punishing effect of the recent outbreak of pandemic disease termed COVID-19 (coronavirus disease-19) caused by SARS-CoV-2 impelled us to gather the facts about the nature of coronaviruses. First, we introduce the basic information about coronavirus taxonomy, structure, and replication process to create the basis for more advanced consideration. In the following part of this review, we focused on interactions between the virus and the receptor on the host cell, as this stage is the critical process determining the species and tissue tropism, as well as clinical course of infection. We also illuminate the molecular basis of the strategy used by coronaviruses to cross the species barrier. We give special attention to the cellular receptor's interaction with S protein of different CoVs (dipeptidyl peptidase IV and angiotensin-converting enzyme 2), as well as the cellular proteases involved in proteolysis of this protein. These factors determine the virus entry and replication; thus, even fine quantitative or qualitative differences in their expression may crucially affect outcomes of infection. Understanding virus biology and characterization of the host factors involved in coronavirus transmission and pathogenesis may offer novel options for development of efficient therapeutic and preventive strategies.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Infecções por Coronavirus/virologia , Dipeptidil Peptidase 4/metabolismo , Interações Hospedeiro-Patógeno , Glicoproteína da Espícula de Coronavírus/metabolismo , Zoonoses/virologia , Animais , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias/prevenção & controle , Vírus da SARS/metabolismo , Vírus da SARS/patogenicidade , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Especificidade da Espécie , Internalização do Vírus , Replicação Viral , Zoonoses/epidemiologia , Zoonoses/patologia
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