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2.
J Am Soc Nephrol ; 33(7): 1293-1307, 2022 07.
Article in English | MEDLINE | ID: covidwho-1799028

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) uses full-length angiotensin converting enzyme 2 (ACE2) as a main receptor to enter target cells. The goal of this study was to demonstrate the preclinical efficacy of a novel soluble ACE2 protein with increased duration of action and binding capacity in a lethal mouse model of COVID-19. METHODS: A human soluble ACE2 variant fused with an albumin binding domain (ABD) was linked via a dimerization motif hinge-like 4-cysteine dodecapeptide (DDC) to improve binding capacity to SARS-CoV-2. This novel soluble ACE2 protein (ACE2-1-618-DDC-ABD) was then administered intranasally and intraperitoneally to mice before intranasal inoculation of SARS-CoV-2 and then for two additional days post viral inoculation. RESULTS: Untreated animals became severely ill, and all had to be humanely euthanized by day 6 or 7 and had pulmonary alveolar hemorrhage with mononuclear infiltrates. In contrast, all but one mouse infected with a lethal dose of SARS-CoV-2 that received ACE2-1-618-DDC-ABD survived. In the animals inoculated with SARS-CoV-2 that were untreated, viral titers were high in the lungs and brain, but viral titers were absent in the kidneys. Some untreated animals, however, had variable degrees of kidney proximal tubular injury as shown by attenuation of the proximal tubular brush border and increased NGAL and TUNEL staining. Viral titers in the lung and brain were reduced or nondetectable in mice that received ACE2-1-618-DDC-ABD, and the animals developed only moderate disease as assessed by a near-normal clinical score, minimal weight loss, and improved lung and kidney injury. CONCLUSIONS: This study demonstrates the preclinical efficacy of a novel soluble ACE2 protein, termed ACE2-1-618-DDC-ABD, in a lethal mouse model of SARS-CoV-2 infection that develops severe lung injury and variable degrees of moderate kidney proximal tubular injury.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Angiotensin-Converting Enzyme 2/therapeutic use , Animals , COVID-19/therapy , Kidney/virology , Lung/virology , Mice , SARS-CoV-2
3.
BMJ Open ; 12(4): e059294, 2022 04 15.
Article in English | MEDLINE | ID: covidwho-1794491

ABSTRACT

OBJECTIVES: To describe the need for, and utility of, online community-based exercise (CBE) interventions with adults living with HIV and identify factors to consider in developing and implementing an online CBE intervention with adults living with HIV. DESIGN: Qualitative descriptive study using web-based semistructured interviews. PARTICIPANTS: We recruited adults representing at least one of five stakeholder groups with experience in CBE and/or HIV: (1) adults living with HIV, (2) rehabilitation professionals, (3) fitness personnel, (4) educators with eLearning experience and (5) representatives from HIV community-based organisations (CBOs). DATA COLLECTION: We asked participants to describe their experiences with online CBE, need and utility for online CBE and factors in developing and implementing online CBE interventions. We analysed data using a group-based thematic analytical approach. RESULTS: Among the 11 participants, most had experience working with adults living with HIV (73%) or with telehealth/rehabilitation/coaching in HIV or other chronic conditions (91%). Participants (eight women; two men; one non-binary; median age: 49 years), identified the need and utility for online CBE interventions to increase accessibility and continuity of care with adults living with HIV. Six factors to consider in developing and implementing online CBE included: (1) person-specific considerations (episodic nature of HIV, stigma, HIV disclosure), (2) accessibility of programme (physical space to exercise, reliable internet, access to devices, digital literacy), (3) programme delivery and technology (live vs prerecorded online classes, multiple online platforms for delivery, physical activity tracking, troubleshooting technology), (4) attributes of programme personnel (working with CBOs, relatable instructors, diverse staff), (5) programme content and design (tailored exercise classes, educational sessions) and (6) building community (shared experiences, peer support, social opportunities). CONCLUSIONS: There is a need and utility for online CBE in the context of HIV. Considerations for development and implementation span individual, structural and technical, and community dimensions. Results can inform the future development and implementation of online CBE with adults living with HIV and other chronic episodic conditions.


Subject(s)
HIV Infections , Adult , Exercise , Exercise Therapy , Female , HIV Infections/therapy , Humans , Male , Middle Aged , Qualitative Research , Social Stigma
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