A Selective SARS-CoV-2 Host-Directed Antiviral Targeting Stress Response to Reactive Oxygen Species.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) catalyzed the development of vaccines and antivirals. Clinically approved drugs against SARS-CoV-2 target the virus directly, which makes them susceptible to viral mutations, which in turn can attenuate their antiviral activity. Here we report a host-directed antiviral (HDA), piperlongumine (PL), which exhibits robust antiviral activity as a result of selective induction of reactive oxygen species in infected cells by GSTP1 inhibition. Using a transgenic K18-hACE2 mouse model, we benchmarked PL against plitidepsin, a HDA undergoing phase III clinical trials. We observed that intranasal administration of PL is superior in delaying disease progression and reducing lung inflammation. Importantly, we showed that PL is effective against several variants of concern (VOCs), making it an ideal pan-variant antiviral. PL may display a critical role as an intranasal treatment or prophylaxis against a range of viruses, expanding the arsenal of tools to fight future outbreaks.

A Multifaceted Evaluation of a COVID-19 Contact Tracing Program in King County, Washington.

CONTEXT: Despite the massive scale of COVID-19 case investigation and contact tracing (CI/CT) programs operating worldwide, the evidence supporting the intervention's public health impact is limited. OBJECTIVE: To evaluate the Public Health-Seattle & King County (PHSKC) CI/CT program, including its reach, timeliness, effect on isolation and quarantine (I&Q) adherence, and potential to mitigate pandemic-related hardships. DESIGN: This program evaluation used descriptive statistics to analyze surveillance records, case and contact interviews, referral records, and survey data provided by a sample of cases who had recently ended isolation. SETTING: The PHSKC is one of the largest governmental local health departments in the United States. It serves more than 2.2 million people who reside in Seattle and 38 other municipalities. PARTICIPANTS: King County residents who were diagnosed with COVID-19 between July 2020 and June 2021. INTERVENTION: The PHSKC integrated COVID-19 CI/CT with prevention education and service provision. RESULTS: The PHSKC CI/CT team interviewed 42 900 cases (82% of cases eligible for CI/CT), a mean of 6.1 days after symptom onset and 3.4 days after SARS-CoV-2 testing. Cases disclosed the names and addresses of 10 817 unique worksites (mean = 0.8/interview) and 11 432 other recently visited locations (mean = 0.5/interview) and provided contact information for 62 987 household members (mean = 2.7/interview) and 14 398 nonhousehold contacts (mean = 0.3/interview). The CI/CT team helped arrange COVID-19 testing for 5650 contacts, facilitated grocery delivery for 7253 households, and referred 9127 households for financial assistance. End of I&Q Survey participants (n = 304, 54% of sampled) reported self-notifying an average of 4 nonhousehold contacts and 69% agreed that the information and referrals provided by the CI/CT team helped them stay in isolation. CONCLUSIONS: In the 12-month evaluation period, CI/CT reached 42 611 households and identified thousands of exposure venues. The timing of CI/CT relative to infectiousness and difficulty eliciting nonhousehold contacts may have attenuated the intervention's effect. Through promotion of I&Q guidance and services, CI/CT can help mitigate pandemic-related hardships.

Survivors' experiences of informal social support in coping and recovering after the 2017 Manchester Arena bombing.

BACKGROUND: Much of the psychosocial care people receive after major incidents and disasters is informal and is provided by families, friends, peer groups and wider social networks. Terrorist attacks have increased in recent years. Therefore, there is a need to better understand and facilitate the informal social support given to survivors. AIMS: We addressed three questions. First, what is the nature of any informal support-seeking and provision for people who experienced the 2017 Manchester Arena terrorist attack? Second, who provided support, and what makes it helpful? Third, to what extent do support groups based on shared experience of the attack operate as springboards to recovery? METHOD: Semi-structured interviews were carried out with a purposive sample of 18 physically non-injured survivors of the Manchester Arena bombing, registered at the NHS Manchester Resilience Hub. Interview transcripts were thematically analysed. RESULTS: Participants often felt constrained from sharing their feelings with friends and families, who were perceived as unable to understand their experiences. They described a variety of forms of helpful informal social support, including social validation, which was a feature of support provided by others based on shared experience. For many participants, accessing groups based on shared experience was an important factor in their coping and recovery, and was a springboard to personal growth. CONCLUSIONS: We recommend that people who respond to survivors' psychosocial and mental healthcare needs after emergencies and major incidents should facilitate interventions for survivors and their social networks that maximise the benefits of shared experience and social validation.

Cross-Sector Monitoring and Evaluation Framework: Social, Economic, and Health Conditions Impacted During the COVID-19 Pandemic.

Public Health 3.0 approaches are critical for monitoring disparities in economic, social, and overall health impacts following the COVID-19 pandemic and its associated policy changes to slow community spread. Timely, cross-sector data as identified using this approach help decisionmakers identify changes, track racial disparities, and address unintended consequences during a pandemic. We applied a monitoring and evaluation framework that combined policy changes with timely, relevant cross-sector data and community review. Indicators covered unemployment, basic needs, family violence, education, childcare, access to health care, and mental, physical, and behavioral health. In response to increasing COVID-19 cases, nonpharmaceutical intervention strategies were implemented in March 2020 in King County, Washington. By December 2020, 554 000 unemployment claims were filed. Social service calls increased 100%, behavioral health crisis calls increased 25%, and domestic violence calls increased 25%, with disproportionate impact on communities of color. This framework can be replicated by local jurisdictions to inform and address racial inequities in ongoing COVID-19 mitigation and recovery. Cross-sector collaboration between public health and sectors addressing the social determinants of health are an essential first step to have an impact on long-standing racial inequities. (Am J Public Health. 2021;111(S3):S215-S223. https://doi.org/10.2105/AJPH.2021.306422).