RESUMO
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, was first reported in Wuhan, China, in December 2019 and has since become a pandemic. The COVID-19 containment measures were comparable to those used with severe acute respiratory syndrome (SARS), although these were stricter and more organized, and were initiated earlier and on a larger scale. Based on the lessons learned from SARS, the Chinese government acted aggressively in response to COVID-19, through a unified and effective commanding system, using law-based and science-driven strategies, and coordinated deployment of medical resources. Additionally, the application of high-tech measures, traditional Chinese medicine, and hierarchical medical systems also played an important role in control measures. Despite the remarkable performance, the initial delay in response suggests that the coordination between public health and medical services, reserve and coordination of emergency materials, and capacity for disease control and prevention need to be strengthened.
Assuntos
COVID-19 , China/epidemiologia , Surtos de Doenças/prevenção & controle , Humanos , Pandemias , SARS-CoV-2RESUMO
Severe fever with thrombocytopenia syndrome (SFTS) caused by a recently identified bunyavirus, SFTSV, is an emerging infectious disease with extensive geographical distribution and high mortality. Progressive viral replication and severe thrombocytopenia are key features of SFTSV infection and fatal outcome, whereas the underlying mechanisms are unknown. We revealed arginine deficiency in SFTS cases by performing metabolomics analysis on two independent patient cohorts, suggesting that arginine metabolism by nitric oxide synthase and arginase is a key pathway in SFTSV infection and consequential death. Arginine deficiency was associated with decreased intraplatelet nitric oxide (Plt-NO) concentration, platelet activation, and thrombocytopenia. An expansion of arginase-expressing granulocytic myeloid-derived suppressor cells was observed, which was related to T cell CD3-ζ chain down-regulation and virus clearance disturbance, implicating a role of arginase activity and arginine depletion in the impaired anti-SFTSV T cell function. Moreover, a comprehensive measurement of arginine bioavailability, global arginine bioavailability ratio, was shown to be a good prognostic marker for fatal prediction in early infection. A randomized controlled trial demonstrated that arginine administration was correlated with enhanced Plt-NO concentration, suppressed platelet activation, and elevated CD3-ζ chain expression and eventually associated with an accelerated virus clearance and thrombocytopenia recovery. Together, our findings revealed the arginine catabolism pathway-associated regulation of platelet homeostasis and T cell dysregulation after SFTSV infection, which not only provided a functional mechanism underlying SFTS pathogenesis but also offered an alternative therapy choice for SFTS.
Assuntos
Arginina/deficiência , Infecções por Bunyaviridae/complicações , Infecções por Bunyaviridae/imunologia , Terapia de Imunossupressão , Phlebovirus/fisiologia , Trombocitopenia/complicações , Trombocitopenia/virologia , Arginina/uso terapêutico , Plaquetas/metabolismo , Infecções por Bunyaviridae/sangue , Infecções por Bunyaviridae/tratamento farmacológico , Complexo CD3/metabolismo , Suplementos Nutricionais , Humanos , Imunidade , Metaboloma , Metabolômica , Células Supressoras Mieloides/metabolismo , Óxido Nítrico/metabolismo , Linfócitos T/imunologia , Trombocitopenia/sangue , Trombocitopenia/tratamento farmacológicoRESUMO
Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.
Assuntos
Infecções por Hantavirus/epidemiologia , Infecções por Hantavirus/veterinária , Selênio/deficiência , Animais , Estudos de Casos e Controles , China , Células Endoteliais/virologia , Feminino , Orthohantavírus/crescimento & desenvolvimento , Humanos , Incidência , Masculino , RoedoresRESUMO
Naphthoquine phosphate and artemisinine are two antimalarials developed in China. Both drugs have proven to be efficacious and well tolerated as monotherapy as well as in combination in patients suffering from malaria. The Co-naphthoquine, a novel antimalarial combination, is an oral fixed combination tablet of the naphthoquine phosphate and artemisinine. Artemisinin is characterised by a rapid onset of schizonticidal action and a short half-life. Parasite clearance is, however, often incomplete when it is employed as a single agent unless high dosages are used over several days, but such a regimen may reduce patient compliance and increase the danger of toxicity. Naphthoquine phosphate, by contrast, has a slower onset of action and a longer half-life, associated with a low recrudescence rate. The two components act synergistically in animal, and clinically provide more rapid relief of symptoms and a higher cure rate than either component alone. The combination tablet was initially developed by the Academy of Military Medical Sciences (AMMS), Beijing, China.