Establishment of an Inactivation Method for Ebola Virus and SARS-CoV-2 Suitable for Downstream Sequencing of Low Cell Numbers.

Technologies that facilitate the bulk sequencing of small numbers of cells as well as single-cell RNA sequencing (scRNA-seq) have aided greatly in the study of viruses as these analyses can be used to differentiate responses from infected versus bystander cells in complex systems, including in organoid or animal studies. While protocols for these analyses are typically developed with biosafety level 2 (BSL-2) considerations in mind, such analyses are equally useful for the study of viruses that require higher biosafety containment levels. Many of these workstreams, however, are not directly compatible with the more stringent biosafety regulations of BSL-3 and BSL-4 laboratories ensuring virus inactivation and must therefore be modified. Here we show that TCL buffer (Qiagen), which was developed for bulk sequencing of small numbers of cells and also facilitates scRNA-seq, inactivates both Ebola virus (EBOV) and SARS-CoV-2, BSL-4 and BSL-3 viruses, respectively. We show that additional heat treatment, necessary for the more stringent biosafety concerns for BSL-4-derived samples, was additionally sufficient to inactivate EBOV-containing samples. Critically, this heat treatment had minimal effects on extracted RNA quality and downstream sequencing results.

Feasibility and Acceptability of a Remote Stepped Care Mental Health Programme for Adolescents during the COVID-19 Pandemic in India.

Remote mental health services were rapidly deployed during the COVID-19 pandemic, yet there is relatively little contemporaneous evidence on their feasibility and acceptability. This study assessed the feasibility and acceptability of a stepped care mental health programme delivered remotely by lay counsellors to adolescents in New Delhi, India, during a period of 'lockdown'. The programme consisted of a brief problem-solving intervention ("Step 1") followed by a tailored behavioural module ("Step 2") for non-responders. We enrolled 34 participants (M age = 16.4 years) with a self-identified need for psychological support. Feasibility and acceptability were assessed through quantitative process indicators and qualitative interviews (n = 17 adolescents; n = 5 counsellors). Thirty-one (91%) adolescents started Step 1 and 16 (52%) completed the planned Step 1 protocol. Twelve (75%) of the Step 1 completers were non-responsive. Eight (67%) non-responsive cases started Step 2, all of whom met response criteria when reassessed at 12 weeks post-enrolment. Adolescents favoured voice-only sessions over video-calls due to privacy concerns and difficulties accessing suitable devices. Counsellors noted challenges of completing remote sessions within the allotted time while recognising the importance of supervision for developing competence in new ways of working. Both adolescents and counsellors discussed the importance of working collaboratively and flexibly to fit around individual preferences and circumstances. Disentangling pandemic-specific barriers from more routine challenges to remote delivery should be a focus of future research.

'She didn't know how to go back': School attendance problems in the context of the COVID-19 pandemic-A multiple stakeholder qualitative study with parents and professionals.

BACKGROUND: The COVID-19 pandemic resulted in school closures worldwide and unexcused absences have increased since schools reopened. AIMS: Drawing on multiple stakeholders' perspectives, we aimed to (i) develop a detailed understanding of how school attendance problems (SAPs) have manifested for primary school-aged children in the context of COVID-19; and (ii) identify promising community-based intervention strategies. METHODS: We used a qualitative design with two sequential phases of data collection. Phase 1 involved insight generation using qualitative surveys with parents and professionals working in primary education settings. These results were used to guide in-depth stakeholder interviews in Phase 2. SAMPLE: Phase 1 included 29 parents of primary-school children experiencing SAPs and 19 professionals. Phase 2 included 10 parents and 12 professionals. Parents were recruited through social media; professionals were identified through schools and associated networks in Southern England. RESULTS: Attendance was particularly challenging for children with special educational needs and pre-existing anxiety problems. Compounding factors included COVID-related anxiety, difficulties adapting to new school routines, poor home-school communication and collaboration, and concerns about academic catch-up. Effective support was characterized by schools and families working closely together. Recommendations for practice improvements centred on early intervention, re-building parent-school relationships, peer support for parents, and improving special educational provision. CONCLUSION: New interventions for SAPs must be sensitive to the ongoing COVID-19 context. Help should be easily accessible in the community and address modifiable risk and protective factors for individual children, in family systems, and at the home-school interface.

Pilot randomised controlled trial of a remotely delivered online intervention for adolescent mental health problems in India: lessons learned about low acceptability and feasibility during the COVID-19 pandemic.

BACKGROUND: 'POD Adventures' is a gamified problem-solving intervention delivered via smartphone app, and supported by non-specialist counsellors for a target population of secondary school students in India during the COVID-19 pandemic. AIMS: To evaluate the feasibility and acceptability of undertaking a randomised controlled trial of POD Adventures when delivered online with telephone support from counsellors. METHOD: We conducted a parallel, two-arm, individually randomised pilot-controlled trial with 11 secondary schools in Goa, India. Participants received either the POD Adventures intervention delivered over 4 weeks or usual care comprising information about local mental health services and national helplines. Outcomes were assessed at two timepoints: baseline and 6 weeks post-randomisation. RESULTS: Seventy-nine classroom sensitisation sessions reaching a total of 1575 students were conducted. Ninety-two self-initiated study referrals (5.8%) were received, but only 11 participants enrolled in the study. No intervention arm participants completed the intervention. Outcomes at 6 weeks were not available for intervention arm participants (n = 5), and only four control arm participants completed outcomes. No qualitative interviews or participant satisfaction measures were completed because participants could not be reached by the study team. CONCLUSIONS: Despite modifications to address barriers arising from COVID-19 restrictions, online delivery was not feasible in the study context. Low recruitment and missing feasibility and acceptability data make it difficult to draw conclusions about intervention engagement and indicative clinical outcomes. Prior findings showing high uptake, adherence and engagement with POD Adventures when delivered in a school-based context suggest that an online study and delivery posed the biggest barriers to study participation and engagement.

Barbershops as a setting for supporting men's mental health during the COVID-19 pandemic: a qualitative study from the UK.

BACKGROUND: Previous research has highlighted the need to promote help-seeking by men with mental health problems. AIMS: To investigate barbers' views about offering mental health support for men in barbershops, with a specific focus on the psychosocial impacts of the COVID-19 pandemic. METHOD: We used a sequential mixed-methods qualitative design with online data collection. In Phase 1, 30 barbers in Southern England completed surveys exploring perceptions of their clients' mental health during the COVID-19 pandemic, experiences of informal supportive roles and scope for providing formal mental health support in barbershops. Phase 2 involved member validation interviews and explored practice implications with three Phase 1 respondents. RESULTS: Thematic analysis identified three overarching themes: 'more than a haircut' (describing how the physical and relational contexts of barbershops can offer a supportive environment for clients); 'impacts of COVID-19' (describing stressors related to the pandemic and implications for clients' mental health and barber-client relationships); and 'formal mental health strategies' (describing opportunities for, and potential barriers to, formalising mental health support in barbershops). CONCLUSIONS: Barbers were aware of their clients' worsening mental health during the COVID-19 pandemic. Barbershops were generally considered to be a suitable setting in which to promote good mental health, monitor for signs of mental ill health and provide information about local mental health services. Future work is needed to co-produce and evaluate formal mental health promotion and prevention strategies in barbershops. Particular attention should be given to service innovations that preserve the credibility and trust that are fundamental to the barbershop experience for many males.

A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune-epithelial interface.

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled, by in vitro coculture, the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV-2-specific inflammatory gene cluster distinct from that seen in influenza A or Ebola virus-infected cocultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV-2 proteins (Spike and some nonstructural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV-2 induces in epithelia.

A Guided Internet-Based Problem-Solving Intervention Delivered Through Smartphones for Secondary School Pupils During the COVID-19 Pandemic in India: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: "POD Adventures" is a gamified mental health intervention delivered via a smartphone app and supported by counsellors for a target population of secondary school students in India. This paper describes the protocol for a pilot randomized controlled trial of a remotely delivered version of the intervention in the context of COVID-19 restrictions. OBJECTIVE: Our objectives are to assess the feasibility of research procedures and intervention delivery and to generate preliminary estimates of the effectiveness of the intervention to inform the sample size calculation of a full-scale trial. METHODS: We will conduct a parallel, 2-arm, individually randomized pilot controlled trial in 11 secondary schools in Goa, India. This pilot trial aims to recruit 70 participants with a felt need for psychological support. Participants will receive either the POD Adventures intervention delivered over 4 weeks or usual care comprising information about local mental health services and national helplines. Outcomes will be assessed at two timepoints: baseline and 6 weeks post randomization. RESULTS: The first participant was enrolled on January 28, 2021, and 6-week assessment completed on April 4, 2021. Owing to a second wave of the COVID-19 pandemic in India, schools in Goa were closed on April 22, 2021. Trial participants are currently receiving the intervention or completing follow-up assessments. CONCLUSIONS: This pilot trial will help understand the feasibility of implementing and evaluating a remotely delivered digital mental health intervention in a low-resource setting. Our findings will be used to design future trials that can address difficulties of accessing psychosocial support in-person and support wider efforts to scale up evidence-based mental health interventions for young people. TRIAL REGISTRATION: ClinicalTrials.gov NCT04672486; https://clinicaltrials.gov/ct2/show/NCT04672486. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30339.

Profound Treg perturbations correlate with COVID-19 severity.

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19-linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role.

Scaling Up Parenting Interventions is Critical for Attaining the Sustainable Development Goals.

Of all the potentially modifiable influences affecting children's development and mental health across the life course, none is more important than the quality of parenting and family life. In this position paper, we argue that parenting is fundamentally linked to the development of life skills that children need in order to achieve the United Nations Sustainable Development Goals. We discuss key principles that should inform the development of a global research and implementation agenda related to scaling up evidence-based parenting support programs. Research over the past 50 years has shown that parenting support programs of varied intensity and delivery modality can improve a wide range of developmental, emotional, behavioral and health outcomes for parents and their children. Such findings have been replicated across culturally and socioeconomically diverse samples, albeit primarily in studies from Western countries. We highlight the evidence for the relevance of parenting interventions for attaining the SDGs globally, and identify the barriers to and strategies for achieving their scale-up. The implications of the global COVID-19 pandemic for the delivery of evidence-based parenting support are also discussed.