Human anti-ACE2 monoclonal antibodies as pan-sarbecovirus prophylactic agents (preprint)

Human monoclonal antibodies from convalescent individuals that target the SARS-CoV-2 spike protein have been deployed as therapeutics against SARS-CoV-2. However, nearly all of these antibodies have been rendered obsolete by SARS-CoV-2 variants that evolved to resist similar, naturally occurring antibodies. Here, we describe the development of human monoclonal antibodies that bind the ACE2 receptor rather than the viral spike protein. These antibodies block infection by all ACE2 binding sarbecoviruses, including emergent SARS-CoV-2 variants. Structural and biochemical analyses revealed that the antibodies target an ACE2 epitope that engages SARS-CoV-2 spike. Importantly, the antibodies do not inhibit ACE2 enzymatic activity, nor do they induce ACE depletion from cell surfaces. The antibodies exhibit favorable pharmacology and protect human ACE2 knock-in mice against SARS-CoV-2 infection. Such antibodies should be useful prophylactic and treatment agents against any current and future SARS-CoV-2 variants, as well as ACE2-binding sarbecoviruses that might emerge as future pandemic threats

Remote assessment of cognitive aging and mental health in older Black Americans

Introduction Older Black Americans (BAs) are more likely than white Americans to develop depression, anxiety, sleep disturbances, cognitive impairment, and Alzheimer's disease and related dementias (ADRD).1-7 They are also more likely to encounter disparities in ADRD diagnosis and care8-10 and to experience digital divides in mobile health (mHealth) care that may have been amplified by the social-distancing precautions of the COVID-19 pandemic, particularly for individuals who are at risk for cognitive impairment or ADRD.11 To address these disparities, we have designed a study to learn about the preferences of BAs in the effective assessment of COVID-19, cognition, and mental health. Methods In this pilot study, we will conduct satisfaction interviews with BAs who are age 65+, who agree to use mHealth devices (see Table 1 for device list) to monitor potential COVID-19 symptoms, and who participate in three remote modalities (pen-and-paper, telephone, and online) of cognitive and mental health assessments (see Figure 1 for within-person study design and Table 2 for assessment questionnaires). Participants will be randomly assigned modality orders upon enrollment, and each modality will last two weeks and will be followed by a two-week washout period. Participants will complete weekly subjective reports of their experiences using the mHealth devices and completing the mental and cognitive health assessments, and study companions will be asked about the amount of assistance participants need to complete each assessment modality. Results To date, we have screened 16 BAs, but 2 BAs were ineligible due to existing dementia diagnosis, and 1 opted not to participate. We have enrolled 7 participants (M=72, SD=4.95;1 out of 7 female), who have not received clinical diagnosis of dementia but expressed concerns about their memory. These concerns were reflected in an average MOCA score of 22.8 (range=20-25) at enrollment, which is in the range for mild cognitive impairment. For the participants who have included at least two assessment modalities of the study (n=4), all preferred the pen-and-paper modality to the telephone modality due to its faster administration time (i.e., ∼15 minutes vs. ∼45 minutes). Note that no preference data is available for the online modality, as only 1 participant has completed it at this time. Furthermore, all 4 participants expressed surprise at their own willingness and comfort with the mHealth devices, with 2 noting that they have begun using the devices to self-monitor daily vitals, and 2 noting that wearing the actigraphy wristwatch serves as a reminder to increase their physical activity and make health-conscious choices. All 4 participants also reported that they appreciate the focus on social and mental well-being in the weekly questionnaires and look forward to check-in calls from research team members. These qualitative findings are reinforced by the results of the anxiety/depression scales, which show decreased feelings of loneliness, social isolation, and anxiety in participants over the initial 6 weeks. Conclusions Our preliminary findings suggest that older BAs with mild cognitive impairment are able to complete in-home assessments of cognitive and mental health assessments. They have also reported that mHealth devices are easy to use in their everyday lives. We will continue to enroll participants in order to evaluate the feasibility of in-home assessments and to identify statistically significant trends in modality preferences among these vulnerable older adults. This research was funded by Garvey Institute for Brain Health Solutions, University of Washington Department of Psychiatry, School of Medicine

Mild disease course in cognitively impaired oldest old individuals with COVID-19: A description of two cases

Abstract Background The COVID-19 pandemic has swept across the world, causing a staggering number of deaths, particularly among older individuals. The most common symptoms of COVID-19 are fever, dry cough, and shortness of breath, but delirium has been reported in older adults, including those with preexisting neurodegenerative disorders. Some research has suggested that the role of neuropsychiatric sequelae in COVID-19, especially delirium, has been underreported and that the lack of fever and respiratory distress in this population may exacerbate underdiagnosis and subsequent mortality. Here, we discuss the variable course of COVID-19 by detailing the course of illness in two individuals who are age 90+ with mild COVID-19. Method We conducted chart reviews and telephone interviews in two patients who were age 90+. Case 1 had an outpatient follow-up visit via teleconferencing. Due to COVID-19 protocols, in-person research assessments were not completed. Both were on hospice due to underlying terminal medical conditions. Result Both cases are age 90+ patients with dementia who receive hospice care for multiple underlying medical comorbidities. Case 1 presented at home with a low-grade temperature that was below the CDC COVID-19 guidelines for fever at that time;he experienced cough, confusion, and functional decline and was admitted to a COVID-19 unit after testing positive for the disease. His workup also included a COVID-19 laboratory panel, which was mostly abnormal (including extremely elevated brain natriuretic peptide) but had normal WBC. He did not experience further deterioration, and 22 days later, after testing COVID-19 negative, he was discharged to a skilled nursing facility (SNF), followed by discharge to home 15 days later. Case 2 had metastatic carcinoma and a preexisting diagnosis of probable dementia with Lewy bodies. COVID-19 was diagnosed through all-resident screening at his SNF. He did not exhibit respiratory symptoms or fever at that time. While nursing staff reported confusion, agitation, and restlessness, these symptoms could not be differentiated from complications related to his underlying dementia. This patient was isolated within the SNF and was not hospitalized. Conclusion These two cases demonstrate the variability of symptom manifestation in COVID-19 in this high-risk population.