ABSTRACT
Background. AZD7442-a combination of 2 human, extended-half-life, SARS-CoV-2-neutralizing monoclonal antibodies (mAbs) (tixagevimab/cilgavimab)-has received US Food and Drug Administration emergency use authorization for COVID-19 prevention in immunocompromised individuals. We evaluated the effect of AZD7442 in prevention and treatment settings in Syrian hamsters challenged with SARS-CoV-2. Methods. Hamsters received intraperitoneal isotype control mAb (2 mg) or AZD7442 (0.002-2 mg) 1 day before intranasal (IN) SARS-CoV-2 challenge (USA-WA1/2020;1x105 plaque-forming units) in prevention;OR control mAb (5 mg) or AZD7442 (0.5-5 mg) 1 day after IN SARS-CoV-2 challenge in treatment. The impact of AZD7442 on lung viral RNA and pathology and AZD7442 serum levels was assessed on Days 3 and 7 post infection. Body weight was recorded daily through Day 7. Results. With AZD7442 prevention, lower lung viral loads were observed compared to controls;at Day 3 post infection, lowest infectious virus titer and viral subgenomic mRNA (sgmRNA) levels were seen with doses >=0.2 mg AZD7442. Concomitantly, increased serum levels of AZD7442 were observed. By Day 7, infectious virus titer and sgmRNA fell below the level of detection (LOD) at all doses tested. Moreover, AZD7442 at doses >=0.2 mg protected hamsters from weight loss versus controls. Lung pathology scores (scale: 0 [normal] to 25 [most severe]) were generally dose dependent, with mean scores of < 2 for AZD7442 versus 10 for controls, indicating less SARS-CoV-2-induced inflammation and alveolar damage in hamsters given AZD7442. Lower AZD7442 doses were associated with mean pathology scores similar to controls. With AZD7442 treatment, infectious virus titers were below the LOD at Day 3 post infection and at Day 7 for sgmRNA, for all doses tested. Mean lung pathology score was <2 for AZD7442 versus 12 for controls. AZD7442 doses >=0.5 mg protected against weight loss relative to controls. Conclusion. In a SARS-CoV-2 challenge model, AZD7442 administered as prevention or treatment led to significantly lower lung viral loads and improved lung pathology, without weight loss. There was also no evidence that AZD7442 mediated antibody-dependent enhancement of disease or infection.
ABSTRACT
Study Objectives: COVID-19 dramatically changed weekly academic conferences with virtual presentations replacing in-person didactics. Through group chat functions, modern communication platforms provide the opportunity for synchronous online discussions to occur in parallel with didactic presentations. We sought to qualitatively characterize the content, nature, and educational uses of synchronous online discussions occurring during weekly academic conferences and to assess the attitudes of lecturers and audience members towards these discussions. Methods: Transcripts of synchronous online discussions occurring from 7/1/20 to 12/31/20 were qualitatively analyzed using a grounded theory approach. Initial themes were identified by the primary author. Following a preliminary coding by the study authors, the themes were iteratively refined to arrive at a final coding strategy. Each month’s transcripts were coded by 2 study authors. When there was disagreement between coders, the primary author made a final coding determination. Following the study period, a survey distributed to residents and faculty assessed attitudes towards the synchronous online discussions. Results: The qualitative analysis of the transcripts identified 2352 coded messages. The final coding schema can be seen in Figure 1. Of 1720 identified content codes, the most commonly identified themes were cultural communications (40.8%) and knowledge sharing (39.0%). Within the broader theme of knowledge sharing, participants were most likely to share individual practice experience (366/671 codes). Statements with uncited data/evidence (113 codes) occurred in similar frequency to sharing of academic resources (137 codes). Questions directed towards other members of the audience (48.8% of questions) were only slightly less common than questions directed to the lecturer (51.2% of questions). There were 56 respondents to the survey (30 residents, 25 faculty, 1 fellow). Of the 44 respondents that had presented didactics, 54.5% (24/44) identified that it was challenging to keep up with the synchronous online discussion. From the perspective of the audience, 82.1% (46/56) felt it was easy to keep up with the discussion. Presenters of didactics felt identifying a member of the audience as a surrogate was the easiest means to keep up with the discussion (75%, 33/44 presenters). Audience members agreed that they were much more likely to ask a question in a synchronous online discussion as opposed to speaking out loud (71.4%, 40/56). Conclusions: Weekly academic conferences are a critical component of residency education, enabling not only the acquisition of knowledge but also the social sharing of knowledge/experiences developing of robust communities of practice. Our qualitative analysis found that cultural communication occurred with near equal frequency to knowledge sharing and that sharing of individual practice experiences was more common than sharing of academic resources. These synchronous online discussions may make it more likely for audience members to ask questions of each other or the lecturer but keeping up with the discussion was challenging for lecturers. [Formula presented]
ABSTRACT
PURPOSE: Evaluation of CT sarcopenia as a predictor of intensive care hospitalization during SARS-COV2 infection. MATERIALS AND METHODS: Single-center retrospective study of patients admitted to hospital with SARS-COV2 infection. The estimation of muscle mass (skeletal muscle index (SMI)) for sarcopenia, measurement of muscle density for muscle quality and body adiposity, were based on CT views on the T4 and L3 levels measured at admission. Demographic data, percentage of pulmonary parenchymal involvement as well as the orientation of patients during hospitalization and the risk of hospitalization in intensive care were collected. RESULTS: A total of 162 patients hospitalized for SARS-COV2 infection were included (92 men and 70 women, with an average age of 64.6 years and an average BMI of 27.4). The muscle area measured at the level of L3 was significantly associated with the patient's unfavorable evolution (124.4cm2 [97; 147] vs 141.5 cm2 [108; 173]) (p = 0.007), as was a lowered SMI (p < 0.001) and the muscle area measured in T4 (OR = 0.98 [0.97; 0.99]), (p = 0.026). Finally, an abdominal visceral fat area measured at the level of L3 was also associated with a risk of hospitalization in intensive care (249.4cm2 [173; 313] vs 147.5cm2 [93.1; 228] (p < 0.001). CONCLUSION: This study demonstrates that thoracic and abdominal sarcopenia are independently associated with an increased risk of hospitalization in an intensive care unit, suggesting the need to assess sarcopenia on admission during SARS-COV2 infection.