ABSTRACT
Background: The COVID-19 pandemic has negatively impacted the mental health of children, especially child welfare-involved youth, who are at a higher risk for behavioral health issues (Turney, K., & Wildeman, C. 2016). Approximately a quarter of Massachusetts youth who previously received psychotherapy discontinued care at the beginning of social distancing restrictions in 2020 (Massachusetts Health Policy Commission, 2021) and similarly the utilization rate of mental health services like Youth Mobile Crisis Intervention (YMCI) teams declined during the pandemic (Commonwealth of Massachusetts: MCI, 2021). YMCI teams provide urgent mental health evaluation and stabilization services for children in crisis either in the child's home or school, reducing emergency department visits. This project aims to identify and address barriers children in foster care may face when accessing YMCI. The goals are to 1. Characterize the Foster Children Evaluation Services (FaCES) clinic staff's and community organizations' understanding of YMCI use by foster parents 2. Create resources that guide families on when and how to access YMCI. Methods: Strategic exploration discussions were held with community organizations involved with foster youth to identify barriers to accessing YMCI. Additional meetings were organized with members of the FaCES interdisciplinary pediatric and behavioral health team, which ncludes clinicians and foster caregivers, to better understand the clinical team's current experience with utilizing YMCI as well as identifying when clinicians discuss YMCI with caregivers. Clinic workflow was reviewed to identify how educational materials may be provided to patients and foster families. Results: Based on discussions with the FaCES clinic team and community organizations, a lack of knowledge about YMCI among foster caregivers was identified. This included confusion about when to call YMCI and misunderstandings regarding the possible outcomes of a YMCI evaluation. Targeted educational handouts were created to help foster caregivers better understand accessing YMCI when a child is in a mental health crisis. These resources were integrated into the clinic's current workflow as handouts clinicians can e-mail to foster parents and posted on the clinic's website. Conclusion: The COVID-19 pandemic has exacerbated and exposed the mental health needs of children in foster care. Discussions with foster caregivers, clinical providers, and other professionals revealed a need for clear guidelines on accessing resources, such as YMCI, for youth in foster care experiencing mental health crises. The created materials guide families on how to access these resources to help keep youth in their care emotionally and physically safe.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes an extensively glycosylated surface spike (S) protein to mediate host cell entry and the S protein glycosylation is strongly implicated in altering viral binding/function and infectivity. However, the structures and relative abundance of the new O-glycans found on the S protein regional-binding domain (S-RBD) remain cryptic because of the challenges in intact glycoform analysis. Here, we report the complete structural characterization of intact O-glycan proteoforms using native top-down mass spectrometry (MS). By combining trapped ion mobility spectrometry (TIMS), which can separate the protein conformers of S-RBD and analyze their gas phase structural variants, with ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS analysis, the O-glycoforms of the S-RBD are comprehensively characterized, so that seven O-glycoforms and their relative molecular abundance are structurally elucidated for the first time. These findings demonstrate that native top-down MS can provide a high-resolution proteoform-resolved mapping of diverse O-glycoforms of the S glycoprotein, which lays a strong molecular foundation to uncover the functional roles of their O-glycans. This proteoform-resolved approach can be applied to reveal the structural O-glycoform heterogeneity of emergent SARS-CoV-2 S-RBD variants, as well as other O-glycoproteins in general.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.