ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection

Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchioalveolar lavage fluid from critically ill COVID-19 patients was associated with reduced ICU and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.

Gut microbiome dysbiosis during COVID-19 is associated with increased risk for bacteremia and microbial translocation.

The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate in a mouse model that SARS-CoV-2 infection can induce gut microbiome dysbiosis, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Comparison with stool samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.

Estudio sobre la reducción de eventos adversos en pacientes y problemas de bioseguridad de los profesionales derivados de la aplicación de catéteres vasculares en urgencias / Peripheral venous catheter use in the emergency department: reducing adverse events in patients and biosafety problems for staff

Objetivo: Reducir la tasa de eventos adversos (EA) derivados de catéteres vasculares periféricos (CVP) en pacientes atendidos en servicios de urgencias (SU), así como accidentes de bioseguridad en profesionales, mediante una estrategia que combine formación, protocolización de la indicación y catéteres de bioseguridad. Método: Estudio prospectivo, multicéntrico, observacional no postautorización en pacientes atendidos en el SU que precisen de CVP. El estudio tiene dos fases: en la primera se procede a formación, protocolización y monitorización mediante ua lista de comprobación, utilizando CVP convencionales. En la segunda fase se introducen CVP de bioseguridad. Se comparan ambas fases y sus resultados en la reducción de EA y bioseguridad. Resultados: Se incluyeron un total de 520 pacientes: 180 en fase I y 340 en fase II. Se evidencian deficiencias en la técnica relacionadas con la desinfección, mantenimiento del campo estéril y manejo de equipo y apósitos; algunos mejoran significativamente con la progresión del estudio en fase II. Se observaron 86 EA, 34 en Fase I (18,8%) y 52 en fase II (15,4%) (p = ns). Destaca una reducción del 50% de flebitis en fase II. Sobre bioseguridad se detectaron 8 casos (7 salpicaduras, 1 pinchazo accidental) con CVP convencionales (fase I) y 2 salpicaduras con CVP de bioseguridad (fase II), equivalente a una reducción del 36% de accidentes (p = 0,04), especialmente con catéteres de corta duración (p = 0,02). Conclusiones: La combinación de formación, protocolización de la indicación y empleo de CVP de bioseguridad se muestra como una intervención más efectiva para mejorar la seguridad del paciente y del profesional (AU)

Objectives: To test a strategy to reduce the rate of adverse events in patients and safety problems for emergency department staff who insert peripheral venous catheters (PVCs). The strategy consisted of training, implementing a protocol, and introducing safety-engineered PVCs. Methods: Prospective, multicenter, observational, preauthorization study in patients requiring PVC placement in an emergency department. The study had 2 phases. The first consisted of training, implementing a protocol for using conventional PVCs, and monitoring practice. The second phase introduced safety-engineered PVC sets. The number of adverse events in patients and threats to safety for staff were compared between the 2 phases. Results: A total of 520 patients were included, 180 in the first phase and 340 in the second. We detected breaches in aseptic technique, failure to maintain a sterile field, and improper management of safety equipment and devices. Some practices improved significantly during the second phase. Eighty-six adverse events occurred in the first phase and 52 (15.4%) in the second; the between-phase difference was not statistically significant. The incidence of postinfusion phlebitis was 50% lower in the second phase. Seven splash injuries and 1 accidental puncture occurred with conventional PVCs in the first phase; 2 splash injuries occurred with the safety-engineered PVCs in the second phase (36% decrease, P = .04). Differences were particularly noticeable for short-term PVC placements (P = .02). Conclusion: Combining training, a protocol, and the use of safety-engineered PVC sets offers an effective strategy for improving patient and staff safety (AU)

[Peripheral venous catheter use in the emergency department: reducing adverse events in patients and biosafety problems for staff]. / Estudio sobre la reducción de eventos adversos en pacientes y problemas de bioseguridad de los profesionales derivados de la aplicación de catéteres vasculares en urgencias.

OBJECTIVES: To test a strategy to reduce the rate of adverse events in patients and safety problems for emergency department staff who insert peripheral venous catheters (PVCs). The strategy consisted of training, implementing a protocol, and introducing safety-engineered PVCs. MATERIAL AND METHODS: Prospective, multicenter, observational, preauthorization study in patients requiring PVC placement in an emergency department. The study had 2 phases. The first consisted of training, implementing a protocol for using conventional PVCs, and monitoring practice. The second phase introduced safety-engineered PVC sets. The number of adverse events in patients and threats to safety for staff were compared between the 2 phases. RESULTS: A total of 520 patients were included, 180 in the first phase and 340 in the second. We detected breaches in aseptic technique, failure to maintain a sterile field, and improper management of safety equipment and devices. Some practices improved significantly during the second phase. Eighty-six adverse events occurred in the first phase and 52 (15.4%) in the second; the between-phase difference was not statistically significant. The incidence of postinfusion phlebitis was 50% lower in the second phase. Seven splash injuries and 1 accidental puncture occurred with conventional PVCs in the first phase; 2 splash injuries occurred with the safety-engineered PVCs in the second phase (36% decrease, P = .04). Differences were particularly noticeable for short-term PVC placements (P = .02). CONCLUSION: Combining training, a protocol, and the use of safety-engineered PVC sets offers an effective strategy for improving patient and staff safety.

OBJETIVO: Reducir la tasa de eventos adversos (EA) derivados de catéteres vasculares periféricos (CVP) en pacientes atendidos en servicios de urgencias (SU), así como accidentes de bioseguridad en profesionales, mediante una estrategia que combine formación, protocolización de la indicación y catéteres de bioseguridad. METODO: Estudio prospectivo, multicéntrico, observacional no postautorización en pacientes atendidos en el SU que precisen de CVP. El estudio tiene dos fases: en la primera se procede a formación, protocolización y monitorización mediante ua lista de comprobación, utilizando CVP convencionales. En la segunda fase se introducen CVP de bioseguridad. Se comparan ambas fases y sus resultados en la reducción de EA y bioseguridad. RESULTADOS: Se incluyeron un total de 520 pacientes: 180 en fase I y 340 en fase II. Se evidencian deficiencias en la técnica relacionadas con la desinfección, mantenimiento del campo estéril y manejo de equipo y apósitos; algunos mejoran significativamente con la progresión del estudio en fase II. Se observaron 86 EA, 34 en Fase I (18,8%) y 52 en fase II (15,4%) (p = ns). Destaca una reducción del 50% de flebitis en fase II. Sobre bioseguridad se detectaron 8 casos (7 salpicaduras, 1 pinchazo accidental) con CVP convencionales (fase I) y 2 salpicaduras con CVP de bioseguridad (fase II), equivalente a una reducción del 36% de accidentes (p = 0,04), especialmente con catéteres de corta duración (p = 0,02). CONCLUSIONES: La combinación de formación, protocolización de la indicación y empleo de CVP de bioseguridad se muestra como una intervención más efectiva para mejorar la seguridad del paciente y del profesional.