Summary SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2 1 , and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro , the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.

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Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.

The 2020 COVID-19 pandemic and resulting stay at home orders halted face-to-face in-home therapy for youth at risk of out-ofhome placement in Pennsylvania and Delaware. Three family therapy training centers collaborated with state officials managed care organizations, and supervisors to create a two-step process for orchestrating an abrupt, unwanted shift to technology-assisted intensive in-home family therapy. The first step encouraged supervisors to set the stage for this change through an ethics-based lens. The central tenet was to tenaciously advance the wellbeing of the child and their family. The second step encouraged supervisors to remain grounded in the basic principles of treatment and supervision that they followed before telehealth, but with a few adaptations. Three principles are emphasized. Principle one focused on securing clinician commitment to a adapting a family therapy model to a telehealth format. Principle two focused on an unremitting adherence to a preferred family therapy model by using a checklist adapted for technology-based challenges. Finally, principle three focused on fostering professional competence through attending to case conceptualization, supervision-based practice, person-of-the-self challenges, and family-cliniciansupervisor isomorphic patterns. Two case examples illustrate the beginning and ending phases of technology-assisted intensive in-home family therapy. Based on feedback from in-home agencies, implementation of these two-steps helped supervisors effectively lead pandemic-induced, practice-based change to a telehealth format with intentionality, conviction, and selfefficacy. KEYWORDS Pandemic-induced; practicebased change; technologyassisted intensive in-home family therapy; family systems approach; clinical supervision Hardship, tragedy, and trauma are ruthlessly rearing their ugly heads through a new conduit, COVID-19, and relying on an ancient forum, worldwide pandemic, to afflict, once again, their menacing presence in the lives of children and their families. This disease's ultimate impact on child development, family life, and our social world is yet to be determined. Mental health professionals using intensive in-home family therapy to thwart out-of-home placement of children at risk from neglect and abuse very recently experienced CONTACT

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