Exosomal miR-145-5p derived from orthohantavirus-infected endothelial cells inhibits HTNV infection.

Human infection of orthohantavirus can cause potentially fatal diseases, such as hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) in Eurasia. Exosomes are new carriers for information exchange between cells. Cumulative findings suggest that exosomes released from parental infected cells can block or promote viral infection in recipient cells, but the role of exosomes in hantavirus infection is poorly understood. In our study, we identified the exosomes derived from HTNV-infected human vascular endothelial cells (HUVECs) (Exo-HV) and found the antiviral properties of Exo-HV in the uninfected recipient cells. High-throughput sequencing revealed the distinctly expressed miRNAs transcriptomes in Exo-HV. MiR-145-5p, one of the abundant miRNAs packaged into Exo-HV, was found to be able to transferred to recipient cells and functioned by directly targeting M RNA of HTNV 76-118 and inducing type I interferon (IFN-I) response, thus, blocking the viral replication. Concluding, this study indicated that exosomes released by HTNV-infected HUVECs were able to transfer active molecules, miR-145-5p as a proving sample, to mediate novel anti-HTNV activity in the neighboring uninfected cells, which will help us to explore new strategies for the treatment of infectious disease utilizing exosomes with miRNA.

Association of diabetes with severity and mortality in hospitalized patients with COVID-19 in Wuhan, China: a single-centered, retrospective study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. The aim this study was to investigate the association of diabetes with severity and mortality among hospitalized patients with COVID-19 in Wuhan, China. METHODS: This retrospective, single-center case study enrolled a total of 564 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, between January 20 and March 15, 2020. RESULTS: Among the 564 patients with confirmed COVID-19, 509 (85.1%) were discharged and 55 (9.8%) died. The median age was 59 years (range, 10-93 years). A total of 85 (15.1%) patients were diagnosed with diabetes on admission (median age, 65.0 [range, 34-91] years). Patients with diabetes had significantly higher proportions of critical cases (24 [28.2%] vs. 66 [13.8%]) and in-hospital mortality (17 [20%] vs. 38 [7.9%]). Moreover, patients with diabetes presented abnormal levels of multiple indicators concerning lymphopenia, inflammation, heart, liver, kidney, and lung function on admission, while diabetic patient group still display higher troponin T (TnT) levels when approaching discharge. The Kaplan-Meier survival curve indicated a trend toward poorer survival in diabetic patients compared to non-diabetic patients, also evidenced by abnormal laboratory biomarker changes regarding multiple system impairments among COVID-19 patients with diabetes with in-hospital death. CONCLUSION: The detailed clinical investigation of 564 hospitalized patients with COVID-19 indicated a considerable association between diabetes and COVID-19 severity or mortality. Thus, more intensive treatment may be considered for COVID-19 patients with diabetes, especially regarding to cardiac injury.

Association of Hypertension with Severity and Mortality in Hospitalized Patients with COVID-19 in Wuhan, China: A Single-centered, Retrospective Study. / Associação da Hipertensão com a Gravidade e a Mortalidade de Pacientes Hospitalizados com COVID-19 em Wuhan, China: Estudo Unicêntrico e Retrospectivo.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. OBJECTIVE: To investigate the association between hypertension and severity/mortality in hospitalized patients with COVID-19 in Wuhan, China. METHODS: A total of 337 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, from January 20 to February 25, 2020, were enrolled and analyzed in a retrospective, single-center case study. The significance level adopted in the statistical analysis was 0.05. RESULTS: Of the 337 patients with confirmed diagnosis of COVID-19, 297 (87.8%) were discharged from the hospital and 40 patients (22.9%) died. The median age was 58 years (range, 18-91 years). There were 112 (33.2%) patients diagnosed with hypertension at admission (median age, 65.0 years [range, 38-91 years]; 67 [59.8%, 95%CI: 50.6%-69.0%] men, p=0.0209). Patients with hypertension presented a significantly higher portion of severe cases (69 [61.6%, 95%CI:52.5%-70.8%] vs. 117 [52.0%, 95%CI: 45.4%-58.6%] in severe patients and 23 [19.3%, 95%CI:12.9%-28.1%] vs. 27 [12.0%, 95%CI: 7.7%-16.3%] in critical patients, p=0.0014) and higher mortality rates (20 [17.9%, 95%CI: 10.7%-25.1%] vs. 20 [8.9%, 95%CI: 5.1%-12.6%, p=0.0202). Moreover, hypertensive patients presented abnormal levels of multiple indicators, such as lymphopenia, inflammation, heart, liver, kidney, and lung function at admission. The hypertension group still displayed higher levels of TnT and creatinine at approaching discharge. CONCLUSION: Hypertension is strongly associated with severity or mortality of COVID-19. Aggressive treatment may be considered for COVID-19 patients with hypertension, especially regarding cardiac and kidney injury.

FUNDAMENTO: A doença Coronavírus 2019 (COVID-19), causada pela síndrome respiratória aguda grave Coronavírus 2 (SARS-CoV-2), espalhou-se pelo mundo. OBJETIVO: Investigar a associação entre a hipertensão e a gravidade/mortalidade de pacientes hospitalizados com COVID-19 em Wuhan, China. MÉTODOS: Um total de 337 pacientes diagnosticados com COVID-19 no Sétimo Hospital da cidade de Wuhan, de 20 de janeiro a 25 de fevereiro de 2020, foram inseridos e analisados em um estudo de caso unicêntrico e retrospectivo. O nível de significância adotado para a análise estatística foi 0,05. RESULTADOS: Dos 337 pacientes com diagnóstico confirmado de COVID-19, 297 (87.8%) tiveram alta do hospital e 40 pacientes (22,9%) morreram. A idade média foi de 58 anos (variando de 18 a 91 anos). Havia 112 (33,2%) pacientes diagnosticados com hipertensão no momento da internação (idade média, 65,0 anos [variação, 38-91 anos]; sendo 67 homens [59,8%, IC95%: 50,6%-69,0%], p=0,0209). Pacientes com hipertensão apresentaram uma porção significativamente maior de casos graves (69 [61,6%, IC95%: 52,5%-70,8%] vs. 117 [52,0%, IC95%: 45,4%-58,6%] em pacientes graves e 23 [19,3%, IC95%: 12,9%-28,1%] vs. 27 [12,0%, IC95%: 7,7%-16,3%] em pacientes críticos, p=0,0014) e maiores taxas de mortalidade (20 [17,9%, IC95%: 10,7%-25,1%] vs. 20 [8,9%, IC95%: 5,1%-12,6%, p=0,0202). Além disso, pacientes hipertensos apresentaram níveis anormais de vários indicadores, como linfopenia e inflamação, e nas funções cardíacas, hepáticas, renais e pulmonares no momento da internação. O grupo de pacientes com hipertensão também demonstrou níveis maiores de TNT e creatinina próximo da alta. CONCLUSÃO: A hipertensão está altamente associada à gravidade ou mortalidade da COVID-19. Um tratamento agressivo deve ser considerado para pacientes hipertensos com COVID-19, principalmente com relação a lesões cardíacas e dos rins.

HTNV Sensitizes Host Toward TRAIL-Mediated Apoptosis-A Pivotal Anti-hantaviral Role of TRAIL.

Hantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and have led to public health threat in China. The pathogenesis of HFRS is complex and involves capillary leakage due to the infection of vascular endothelial cells. Accumulating evidence has demonstrated that hantavirus can induce apoptosis in many cells, but the mechanism remains unclear. Our studies showed that Hantaan virus (HTNV) infection could induce TNF-related apoptosis-inducing ligand (TRAIL) expression in primary human umbilical vein endothelial cells (HUVECs) and sensitize host cells toward TRAIL-mediated apoptosis. Furthermore, TRAIL interference could inhibit apoptosis and enhance the production of HTNV as well as reduce IFN-ß production, while exogenous TRAIL treatment showed reverse outcome: enhanced apoptosis and IFN-ß production as well as a lower level of viral replication. We also observed that nucleocapsid protein (NP) and glycoprotein (GP) of HTNV could promote the transcriptions of TRAIL and its receptors. Thus, TRAIL was upregulated by HTNV infection and then exhibited significant antiviral activities in vitro, and it was further confirmed in the HTNV-infected suckling mice model that TRAIL treatment significantly reduced viral load, alleviated virus-induced tissue lesions, increased apoptotic cells, and decreased the mortality. In conclusion, these results demonstrate that TRAIL-dependent apoptosis and IFN-ß production could suppress HTNV replication and TRAIL treatment might be a novel therapeutic target for HTNV infection.

Association of diabetes with severity and mortality in hospitalized patients with COVID-19 in Wuhan, China: a single-centered, retrospective study

ABSTRACT Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. The aim this study was to investigate the association of diabetes with severity and mortality among hospitalized patients with COVID-19 in Wuhan, China. Subjects and methods: This retrospective, single-center case study enrolled a total of 564 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, between January 20 and March 15, 2020. Results: Among the 564 patients with confirmed COVID-19, 509 (85.1%) were discharged and 55 (9.8%) died. The median age was 59 years (range, 10-93 years). A total of 85 (15.1%) patients were diagnosed with diabetes on admission (median age, 65.0 [range, 34-91] years). Patients with diabetes had significantly higher proportions of critical cases (24 [28.2%] vs. 66 [13.8%]) and in-hospital mortality (17 [20%] vs. 38 [7.9%]). Moreover, patients with diabetes presented abnormal levels of multiple indicators concerning lymphopenia, inflammation, heart, liver, kidney, and lung function on admission, while diabetic patient group still display higher troponin T (TnT) levels when approaching discharge. The Kaplan-Meier survival curve indicated a trend toward poorer survival in diabetic patients compared to non-diabetic patients, also evidenced by abnormal laboratory biomarker changes regarding multiple system impairments among COVID-19 patients with diabetes with in-hospital death. Conclusion: The detailed clinical investigation of 564 hospitalized patients with COVID-19 indicated a considerable association between diabetes and COVID-19 severity or mortality. Thus, more intensive treatment may be considered for COVID-19 patients with diabetes, especially regarding to cardiac injury.

Associação da hipertensão com a gravidade e a mortalidade de pacientes hospitalizados com COVID-19 em Wuhan, China: Estudo unicêntrico e retrospectivo / Association of hypertension with severity and mortality in hospitalized patients with COVID-19 in wuhan, China: A single-centered, retrospective study

Resumo Fundamento A doença Coronavírus 2019 (COVID-19), causada pela síndrome respiratória aguda grave Coronavírus 2 (SARS-CoV-2), espalhou-se pelo mundo. Objetivo Investigar a associação entre a hipertensão e a gravidade/mortalidade de pacientes hospitalizados com COVID-19 em Wuhan, China. Métodos Um total de 337 pacientes diagnosticados com COVID-19 no Sétimo Hospital da cidade de Wuhan, de 20 de janeiro a 25 de fevereiro de 2020, foram inseridos e analisados em um estudo de caso unicêntrico e retrospectivo. O nível de significância adotado para a análise estatística foi 0,05. Resultados Dos 337 pacientes com diagnóstico confirmado de COVID-19, 297 (87.8%) tiveram alta do hospital e 40 pacientes (22,9%) morreram. A idade média foi de 58 anos (variando de 18 a 91 anos). Havia 112 (33,2%) pacientes diagnosticados com hipertensão no momento da internação (idade média, 65,0 anos [variação, 38-91 anos]; sendo 67 homens [59,8%, IC95%: 50,6%-69,0%], p=0,0209). Pacientes com hipertensão apresentaram uma porção significativamente maior de casos graves (69 [61,6%, IC95%: 52,5%-70,8%] vs. 117 [52,0%, IC95%: 45,4%-58,6%] em pacientes graves e 23 [19,3%, IC95%: 12,9%-28,1%] vs. 27 [12,0%, IC95%: 7,7%-16,3%] em pacientes críticos, p=0,0014) e maiores taxas de mortalidade (20 [17,9%, IC95%: 10,7%-25,1%] vs. 20 [8,9%, IC95%: 5,1%-12,6%, p=0,0202). Além disso, pacientes hipertensos apresentaram níveis anormais de vários indicadores, como linfopenia e inflamação, e nas funções cardíacas, hepáticas, renais e pulmonares no momento da internação. O grupo de pacientes com hipertensão também demonstrou níveis maiores de TNT e creatinina próximo da alta. Conclusão A hipertensão está altamente associada à gravidade ou mortalidade da COVID-19. Um tratamento agressivo deve ser considerado para pacientes hipertensos com COVID-19, principalmente com relação a lesões cardíacas e dos rins.

Abstract Background Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Objective To investigate the association between hypertension and severity/mortality in hospitalized patients with COVID-19 in Wuhan, China. Methods A total of 337 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, from January 20 to February 25, 2020, were enrolled and analyzed in a retrospective, single-center case study. The significance level adopted in the statistical analysis was 0.05. Results Of the 337 patients with confirmed diagnosis of COVID-19, 297 (87.8%) were discharged from the hospital and 40 patients (22.9%) died. The median age was 58 years (range, 18-91 years). There were 112 (33.2%) patients diagnosed with hypertension at admission (median age, 65.0 years [range, 38-91 years]; 67 [59.8%, 95%CI: 50.6%-69.0%] men, p=0.0209). Patients with hypertension presented a significantly higher portion of severe cases (69 [61.6%, 95%CI:52.5%-70.8%] vs. 117 [52.0%, 95%CI: 45.4%-58.6%] in severe patients and 23 [19.3%, 95%CI:12.9%-28.1%] vs. 27 [12.0%, 95%CI: 7.7%-16.3%] in critical patients, p=0.0014) and higher mortality rates (20 [17.9%, 95%CI: 10.7%-25.1%] vs. 20 [8.9%, 95%CI: 5.1%-12.6%, p=0.0202). Moreover, hypertensive patients presented abnormal levels of multiple indicators, such as lymphopenia, inflammation, heart, liver, kidney, and lung function at admission. The hypertension group still displayed higher levels of TnT and creatinine at approaching discharge. Conclusion Hypertension is strongly associated with severity or mortality of COVID-19. Aggressive treatment may be considered for COVID-19 patients with hypertension, especially regarding cardiac and kidney injury.