The challenge of asymptomatic carriers of COVID-19: A rapid review of literature.

OBJECTIVES: To describe the epidemiological and sociodemographic characteristics of asymptomatic carriers reported in the literature, and to review the strategies used for diagnosis and control. METHODS: Systematic literature review approach. As inclusion criteria, all studies published between January 1 and June 26, 2020, conducted in humans, that reported people who remained asymptomatic of COVID-19. Descriptors were adapted to the interfaces of eight bibliographic databases were configured: PubMed, Ovid, SciELO, Ebsco, Scopus, LILACS, Epistemonikos and Embase. RESULTS: About 45% of the articles reported adult population, thirteen reported mixed population (adult and pediatric). 3 525 asymptomatic people were reported, with an average of 37,1 years [0.5-82 years]. Although the effectiveness of the control and prevention measures was not reported, the identification, isolation and follow-up of contacts stands out as a potential effective mechanism to prevent the transmission. CONCLUSIONS: The use of this information could be relevant to guide evidence-based public health policies and the protection of populations and the improvement of health care that contributes to stopping this pandemic.

In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist.

3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d][1,2,4]triazine (MRK-016) is a pyrazolotriazine with an affinity of between 0.8 and 1.5 nM for the benzodiazepine binding site of native rat brain and recombinant human alpha1-, alpha2-, alpha3-, and alpha5-containing GABA(A) receptors. It has inverse agonist efficacy selective for the alpha5 subtype, and this alpha5 inverse agonism is greater than that of the prototypic alpha5-selective compound 3-(5-methylisoxazol-3-yl)-6-[(1-methyl-1,2,3-triazol-4-hdyl)methyloxy]-1,2,4-triazolo[3,4-a]phthalazine (alpha5IA). Consistent with its greater alpha5 inverse agonism, MRK-016 increased long-term potentiation in mouse hippocampal slices to a greater extent than alpha5IA. MRK-016 gave good receptor occupancy after oral dosing in rats, with the dose required to produce 50% occupancy being 0.39 mg/kg and a corresponding rat plasma EC(50) value of 15 ng/ml that was similar to the rhesus monkey plasma EC(50) value of 21 ng/ml obtained using [(11)C]flumazenil positron emission tomography. In normal rats, MRK-016 enhanced cognitive performance in the delayed matching-to-position version of the Morris water maze but was not anxiogenic, and in mice it was not proconvulsant and did not produce kindling. MRK-016 had a short half-life in rat, dog, and rhesus monkey (0.3-0.5 h) but had a much lower rate of turnover in human compared with rat, dog, or rhesus monkey hepatocytes. Accordingly, in human, MRK-016 had a longer half-life than in preclinical species ( approximately 3.5 h). Although it was well tolerated in young males, with a maximal tolerated single dose of 5 mg corresponding to an estimated occupancy in the region of 75%, MRK-016 was poorly tolerated in elderly subjects, even at a dose of 0.5 mg, which, along with its variable human pharmacokinetics, precluded its further development.

The challenge of asymptomatic carriers of COVID-19: A rapid review of literature / El desafío de los portadores asintomáticos de COVID-19: una revisión rápida de la literatura

ABSTRACT Objectives To describe the epidemiological and sociodemographic characteristics of asymptomatic carriers reported in the literature, and to review the strategies used for diagnosis and control. Methods Systematic literature review approach. As inclusion criteria, all studies published between January 1 and June 26, 2020, conducted in humans, that reported people who remained asymptomatic of COVID-19. Descriptors were adapted to the interfaces of eight bibliographic databases were configured: PubMed, Ovid, SciELO, Ebsco, Scopus, LILACS, Epistemonikos and Embase. Results About 45% of the articles reported adult population, thirteen reported mixed population (adult and pediatric). 3 525 asymptomatic people were reported, with an average of 37,1 years [0.5-82 years]. Although the effectiveness of the control and prevention measures was not reported, the identification, isolation and follow-up of contacts stands out as a potential effective mechanism to prevent the transmission. Conclusions The use of this information could be relevant to guide evidence-based public health policies and the protection of populations and the improvement of health care that contributes to stopping this pandemic.

RESUMEN Objetivos Describir las características epidemiológicas y sociodemográficas de los portadores asintomáticos reportadas en la literatura y revisar las estrategias utilizadas para el diagnóstico y control. Métodos Se realizó una revisión sistemática de la literatura. Se incluyeron todos los estudios publicados entre el 1.° de enero y el 26 de junio de 2020 realizados en humanos que informaron personas que permanecieron asintomáticas por COVID-19. Se adaptaron descriptores a las interfaces de ocho bases de datos bibliográficas: Pub-Med, Ovid, SciELO, Ebsco, Scopus, LILACS, Epistemonikos y Embase. Resultados Aproximadamente el 45% de los artículos reportaron población adulta, trece estudios informaron población mixta (adultos y pediátricos). Se identificaron 3 525 personas asintomáticas, con un promedio de 37,1 años [0,5-82 años]. Si bien no se reportó efectividad de medidas de control y prevención, la identificación, aislamiento y seguimiento de los contactos se destaca como un potencial mecanismo efectivo para prevenir la transmisión. Conclusiones El uso de esta información podría ser relevante para orientar las políticas de salud pública basadas en la evidencia y la protección de las poblaciones y la mejora de la atención médica que contribuya a detener esta pandemia.

The challenge of asymptomatic carriers of COVID-19: A rapid review of literature / El desafío de los portadores asintomáticos de COVID-19: una revisión rápida de la literatura

ABSTRACT Objectives To describe the epidemiological and sociodemographic characteristics of asymptomatic carriers reported in the literature, and to review the strategies used for diagnosis and control. Methods Systematic literature review approach. As inclusion criteria, all studies published between January 1 and June 26, 2020, conducted in humans, that reported people who remained asymptomatic of COVID-19. Descriptors were adapted to the interfaces of eight bibliographic databases were configured: PubMed, Ovid, SciELO, Ebsco, Scopus, LILACS, Epistemonikos and Embase. Results About 45% of the articles reported adult population, thirteen reported mixed population (adult and pediatric). 3 525 asymptomatic people were reported, with an average of 37,1 years [0.5-82 years]. Although the effectiveness of the control and prevention measures was not reported, the identification, isolation and follow-up of contacts stands out as a potential effective mechanism to prevent the transmission. Conclusions The use of this information could be relevant to guide evidence-based public health policies and the protection of populations and the improvement of health care that contributes to stopping this pandemic.

RESUMEN Objetivos Describir las características epidemiológicas y sociodemográficas de los portadores asintomáticos reportadas en la literatura y revisar las estrategias utilizadas para el diagnóstico y control. Métodos Se realizó una revisión sistemática de la literatura. Se incluyeron todos los estudios publicados entre el 1.° de enero y el 26 de junio de 2020 realizados en humanos que informaron personas que permanecieron asintomáticas por COVID-19. Se adaptaron descriptores a las interfaces de ocho bases de datos bibliográficas: Pub-Med, Ovid, SciELO, Ebsco, Scopus, LILACS, Epistemonikos y Embase. Resultados Aproximadamente el 45% de los artículos reportaron población adulta, trece estudios informaron población mixta (adultos y pediátricos). Se identificaron 3 525 personas asintomáticas, con un promedio de 37,1 años [0,5-82 años]. Si bien no se reportó efectividad de medidas de control y prevención, la identificación, aislamiento y seguimiento de los contactos se destaca como un potencial mecanismo efectivo para prevenir la transmisión. Conclusiones El uso de esta información podría ser relevante para orientar las políticas de salud pública basadas en la evidencia y la protección de las poblaciones y la mejora de la atención médica que contribuya a detener esta pandemia.

PET imaging of neurokinin-1 receptors with [(18)F]SPA-RQ in human subjects: assessment of reference tissue models and their test-retest reproducibility.

[(18)F]SPA-RQ (substance P antagonist receptor quantifier) labels the substance P-preferring (NK(1)) receptor in human brain. A prior study showed that [(18)F]SPA-RQ brain uptake can be quantified with a reference tissue method and thereby avoid invasive blood sampling. The purposes of this study were to compare three different reference tissue methods and to assess test-retest reproducibility. Eight healthy subjects underwent two [(18)F]SPA-RQ scans. We calculated the binding potential (BP), which is proportional to receptor density, from both regional volume of interest and voxel-wise data. We compared three reference tissue methods: simplified reference tissue model, multilinear reference tissue model (MRTM), and its two-parameter version (MRTM2). The three methods generated equivalent values of regional BP, but MRTM2 was the most resistant to noise. Temporally stable values of BP were obtained with 240 min of imaging data. MRTM2 had excellent test-retest reproducibility, with high reliability (intraclass correlation > 0.9) and low variability (< 10%). In addition to regional volume of interest analysis, we also created parametric images of BP, variability, and reliability based on voxel-wise time-activity data. The reproducibility of parametric BP was also good, with variability < 20% and reliability > 0.7 in gray matter regions. In conclusion, a two-parameter reference tissue method (MRTM2) provided reproducible and reliable measurements of [(18)F]SPA-RQ brain uptake using 240 min of both regional and voxel-wise data.