Healthcare Workers and COVID-19-Related Moral Injury: An Interpersonally-Focused Approach Informed by PTSD.

The COVID-19 pandemic has resulted in a still-unfolding series of novel, potentially traumatic moral and ethical challenges that place many healthcare workers at risk of developing moral injury. Moral injury is a type of psychological response that may arise when one transgresses or witnesses another transgress deeply held moral values, or when one feels that an individual or institution that has a duty to provide care has failed to do so. Despite knowledge of this widespread exposure, to date, empirical data are scarce as to how to prevent and, where necessary, treat COVID-19-related moral injury in healthcare workers. Given the relation between moral injury and post-traumatic stress disorder (PTSD), we point here to social and interpersonal factors as critical moderators of PTSD symptomology and consider how this knowledge may translate to interventions for COVID-19-related moral injury. Specifically, we first review alterations in social cognitive functioning observed among individuals with PTSD that may give rise to interpersonal difficulties. Drawing on Nietlisbach and Maercker's 2009 work on interpersonal factors relevant to survivors of trauma with PTSD, we then review the role of perceived social support, social acknowledgment and social exclusion in relation to potential areas of targeted intervention for COVID-19-related moral injury in healthcare workers. Finally, building on existing literature (e.g., Phoenix Australia-Centre for Posttraumatic Mental Health and the Canadian Centre of Excellence-PTSD, 2020) we conclude with individual and organizational considerations to bolster against the development of moral injury in healthcare workers during the pandemic.

Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV-2.

To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.

Eviction, post-traumatic stress, and emergency department use among low-income individuals in New Haven, CT.

We sought to examine whether and how landlord-related forced moves (inclusive of, but not limited to, legal eviction) were associated with emergency department (ED) use over time. We used survey data collected between 2017 and 2019 among 283 low-income participants in New Haven, CT to examine whether experiencing a legal eviction or other landlord-related forced move (T0) was associated with increased odds of ED use 6 months (T1) and 12 months (T2) later. We conducted bootstrapped mediation analyses to examine indirect effects of post-traumatic stress symptoms. One-fifth of participants (n = 61) reported a recent forced move at baseline (T0); half of these were legally evicted. Landlord-related forced moves were associated with ED use at T1 (AOR = 2.06, 95 % CI: 1.04-4.06) and T2 (AOR = 3.05, 95 % CI: 1.59-5.88). After adjustment for sociodemographic factors and other health-related confounders, legal eviction was not significantly associated with ED use at T1 (AOR = 1.61, 95 % CI: 0.68-3.81), but was significantly associated with ED use at T2 (AOR = 3.58, 95 % CI: 1.58-8.10). Post-traumatic stress symptoms accounted for 15.1% of forced moves' association with ED use (p <.05). Landlord-related forced moves are positively associated with subsequent ED use, and post-traumatic stress symptoms are one factor that may help explain this association. Structural interventions that promote housing stability are needed to advance health equity, and they may also help to reduce preventable ED use. Such interventions are imperative in the context of the COVID-19 pandemic, which has strained health system capacity and exacerbated housing instability for many low-income renters. Results underscore the relevance of trauma-informed care and integrated care management to clinical practice in emergency settings.

Healthcare Workers and COVID-19-Related Moral Injury: An Interpersonally-Focused Approach Informed by PTSD

The COVID-19 pandemic has resulted in a still-unfolding series of novel, potentially traumatic moral and ethical challenges that place many healthcare workers at risk of developing moral injury. Moral injury is a type of psychological response that may arise when one transgresses or witnesses another transgress deeply held moral values, or when one feels that an individual or institution that has a duty to provide care has failed to do so. Despite knowledge of this widespread exposure, to date, empirical data are scarce as to how to prevent and, where necessary, treat COVID-19-related moral injury in healthcare workers. Given the relation between moral injury and post-traumatic stress disorder (PTSD), we point here to social and interpersonal factors as critical moderators of PTSD symptomology and consider how this knowledge may translate to interventions for COVID-19-related moral injury. Specifically, we first review alterations in social cognitive functioning observed among individuals with PTSD that may give rise to interpersonal difficulties. Drawing on Nietlisbach and Maercker's 2009 work on interpersonal factors relevant to survivors of trauma with PTSD, we then review the role of perceived social support, social acknowledgment and social exclusion in relation to potential areas of targeted intervention for COVID-19-related moral injury in healthcare workers. Finally, building on existing literature (e.g., Phoenix Australia—Centre for Posttraumatic Mental Health and the Canadian Centre of Excellence—PTSD, 2020) we conclude with individual and organizational considerations to bolster against the development of moral injury in healthcare workers during the pandemic.

Well-being of Canadian Veterans during the COVID-19 pandemic: cross-sectional results from the COVID-19 Veteran well-being study Bienestar de los veteranos canadienses durante la pandemia de COVID-19: Resultados transversales del estudio de bienestar de veteranos de COVID-19 COVID-19 疫情期间加拿大退伍军人的幸福感: 来自 COVID-19 退伍军人幸福感研究的横断面结果

Background The impacts of the COVID-19 pandemic have disproportionally affected different population groups. Veterans are more likely to have pre-existing mental health conditions compared to the general Canadian population, experience compounded stressors resulting from disruptions to familial, social, and occupational domains, and were faced with changes in health-care delivery (e.g. telehealth). The objectives of this study are to assess (a) the mental health impact of COVID-19 and related life changes on the well-being of Veterans and (b) perceptions of and satisfaction with changes in health-care treatments and delivery during the pandemic. Methods A total of 1136 Canadian Veterans participated in an online survey. Participants completed questions pertaining to their mental health and well-being, lifestyle changes, and concerns relating to the COVID-19 pandemic, as well as experiences and satisfaction with health-care treatments during the pandemic. Results Results showed that 55.9% of respondents reported worse mental health functioning compared to before the pandemic. The frequency of probable posttraumatic stress disorder, major depressive disorder, generalized anxiety disorder, alcohol use disorder, and suicidal ideation were 34.2%, 35.3%, 26.8%, 13.0%, and 22.0%, respectively. Between 38.6% and 53.1% of respondents attributed their symptoms as either directly related to or exacerbated by the pandemic. Approximately 18% of respondents reported using telehealth for mental health services during the pandemic, and among those, 72.8% indicated a choice to use telehealth even after the pandemic. Conclusions This study found that Veterans experienced worsening mental health as a result of the COVID-19 pandemic. The use of telehealth services was widely endorsed by mental health treatment-seeking Veterans who transitioned to virtual care during the pandemic. Our findings have important clinical and programmeadministrator implications, emphasizing the need to reach out to support veterans, especially those with pre-existing mental health conditions and to enhance and maintain virtual care even post-pandemic. HIGHLIGHTS Over 50% of Veterans reported worse mental health compared to before the pandemic. Probable mental health conditions based on self-reports ranged from 13% to 35%. Nearly 1 in 5 Veterans surveyed reported using telehealth for mental health services during the pandemic.

Well-being of Canadian Veterans during the COVID-19 pandemic: cross-sectional results from the COVID-19 Veteran well-being study.

Background: The impacts of the COVID-19 pandemic have disproportionally affected different population groups. Veterans are more likely to have pre-existing mental health conditions compared to the general Canadian population, experience compounded stressors resulting from disruptions to familial, social, and occupational domains, and were faced with changes in health-care delivery (e.g. telehealth). The objectives of this study are to assess (a) the mental health impact of COVID-19 and related life changes on the well-being of Veterans and (b) perceptions of and satisfaction with changes in health-care treatments and delivery during the pandemic. Methods: A total of 1136 Canadian Veterans participated in an online survey. Participants completed questions pertaining to their mental health and well-being, lifestyle changes, and concerns relating to the COVID-19 pandemic, as well as experiences and satisfaction with health-care treatments during the pandemic. Results: Results showed that 55.9% of respondents reported worse mental health functioning compared to before the pandemic. The frequency of probable posttraumatic stress disorder, major depressive disorder, generalized anxiety disorder, alcohol use disorder, and suicidal ideation were 34.2%, 35.3%, 26.8%, 13.0%, and 22.0%, respectively. Between 38.6% and 53.1% of respondents attributed their symptoms as either directly related to or exacerbated by the pandemic. Approximately 18% of respondents reported using telehealth for mental health services during the pandemic, and among those, 72.8% indicated a choice to use telehealth even after the pandemic. Conclusions: This study found that Veterans experienced worsening mental health as a result of the COVID-19 pandemic. The use of telehealth services was widely endorsed by mental health treatment-seeking Veterans who transitioned to virtual care during the pandemic. Our findings have important clinical and programmeadministrator implications, emphasizing the need to reach out to support veterans, especially those with pre-existing mental health conditions and to enhance and maintain virtual care even post-pandemic.

Antecedentes: Los impactos de la pandemia del COVID-19 han afectado de manera desproporcionada a diferentes grupos de la población. Los veteranos tienen más probabilidades de tener afecciones de salud mental preexistentes en comparación con la población canadiense en general, experimentar factores estresantes agravados como resultado de las interrupciones en los dominios familiares, sociales, y ocupacionales, y se enfrentan a cambios en la prestación de la atención médica (por ejemplo, telesalud). Los objetivos de este estudio son evaluar (a) el impacto en la salud mental del COVID-19 y los cambios de vida relacionados en el bienestar de los Veteranos y (b) las percepciones y la satisfacción con los cambios en los tratamientos y la entrega de la atención médica durante la pandemia.Métodos: Un total de 1136 veteranos canadienses participaron en una encuesta en línea. Los participantes completaron preguntas relacionadas con su salud mental y bienestar, cambios en el estilo de vida, e inquietudes relacionadas con la pandemia del COVID-19, así como experiencias y satisfacción con los tratamientos de atención médica durante la pandemia.Resultados: Los resultados mostraron que el 55,9% de los encuestados informaron un peor funcionamiento de la salud mental en comparación con antes de la pandemia. La frecuencia de probable trastorno de estrés postraumático, trastorno depresivo mayor, trastorno de ansiedad generalizada, trastorno por consumo de alcohol, e ideación suicida fue del 34,2%, 35,3%, 26,8%, 13,0% y 22,0%, respectivamente. Entre el 38,6% y el 53,1% de los encuestados atribuyeron sus síntomas como directamente relacionados con la pandemia o agravados por ella. Aproximadamente el 18% de los encuestados informó haber utilizado la telesalud para los servicios de salud mental durante la pandemia, y entre ellos, el 72,8% indicó que había optado por utilizar la telesalud incluso después de la pandemia.Conclusiones: Este estudio encontró que los Veteranos experimentaron un empeoramiento de la salud mental como resultado de la pandemia del COVID-19. El uso de los servicios de telesalud fue ampliamente respaldado por los Veteranos en busca de tratamiento de salud mental que hicieron la transición a la atención virtual durante la pandemia. Nuestros hallazgos tienen importantes implicaciones clínicas y para los administradores de programas, enfatizando la necesidad de ayudar a los veteranos, especialmente a aquellos con condiciones de salud mental preexistentes, y de mejorar y mantener la atención virtual incluso después de una pandemia.

Advancing Equity in Academic Medicine Through Holistic Review for Faculty Recruitment and Retention.

The Association of American Medical Colleges (AAMC) in 2007 developed the Holistic Review Framework for medical school admissions to increase mission-aligned student diversity. This approach balances an applicant's experiences, attributes, and metrics during the screening, interview, and selection processes. Faculty recruitment provides its own set of challenges, and there is persistent underrepresentation of certain racial and ethnic minority groups and women in faculty and leadership positions in U.S. academic health centers (AHCs). In 2019, the AAMC initiated a pilot program to adapt and implement the framework for use in faculty recruitment at AHCs. In this Invited Commentary, the authors describe the pilot implementation of the Holistic Review Framework for Faculty Recruitment and Retention and share lessons learned to date. Although the pilot proceeded during 2020, institutional implementation was impacted by the COVID-19 pandemic and racial justice movement. Pilot institutions encountered hiring freezes, reductions in funding, and restrictions on in-person meetings due to COVID-19 that resulted in both barriers and opportunities in implementing the framework. Renewed commitment to racial justice was associated with increased momentum and urgency for the implementation of faculty holistic review at the majority of pilot institutions. Common themes from the pilot leads' experiences included the importance of achieving "buy in," having a dedicated implementation team, and being explicit about core values. Other themes included the importance of adaptability and flexibility to meet the needs of different institutions and mission areas. The faculty holistic review framework has shown promise as an approach to advancing faculty diversity goals. The pilot institutions will continue to share best practices, track outcomes, implement quality improvement, and disseminate findings to assist other institutions and health care communities with their endeavors to recruit and retain diverse faculty.

Well-being of Canadian Armed Forces Veterans and Spouses of Veterans During the COVID-19 Pandemic: Protocol for a Prospective Longitudinal Survey.

BACKGROUND: The COVID-19 pandemic has resulted in significant changes to everyday life, including social distancing mandates, changes to health care, and a heightened risk of infection. Previous research has shown that Canadian Armed Forces (CAF) veterans are at higher risk of developing mental and physical health conditions. Veterans and their families may face unique social challenges that can compound with pandemic-related disruptions to negatively impact well-being. OBJECTIVE: This study aims to longitudinally characterize the mental health of CAF veterans and spouses of CAF veterans throughout the pandemic and to understand the dynamic influences of pandemic-related stressors on psychological health over time. METHODS: We employed a prospective longitudinal panel design using an online data collection platform. Study participation was open to all CAF veterans and spouses of CAF veterans residing in Canada. Participants were asked to complete a comprehensive battery of assessments representing psychological well-being, chronic pain, health care access patterns, physical environment, employment, social integration, and adjustment to pandemic-related lifestyle changes. Follow-up assessments were conducted every 3 months over an 18-month period. This study was approved by the Western University Health Sciences and Lawson Health Research Institute Research Ethics Boards. RESULTS: Baseline data were collected between July 2020 and February 2021. There were 3 population segments that participated in the study: 1047 veterans, 366 spouses of veterans, and 125 veterans who are also spouses of veterans completed baseline data collection. As of November 2021, data collection is ongoing, with participants completing the 9- or 12-month follow-up surveys depending on their date of self-enrollment. Data collection across all time points will be complete in September 2022. CONCLUSIONS: This longitudinal survey is unique in its comprehensive assessment of domains relevant to veterans and spouses of veterans during the COVID-19 pandemic, ranging from occupational, demographic, social, mental, and physical domains, to perceptions and experiences with health care treatments and access. The results of this study will be used to inform policy for veteran and veteran family support, and to best prepare for similar emergencies should they occur in the future. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34984.

Impacts of morally distressing experiences on the mental health of Canadian health care workers during the COVID-19 pandemic.

Background: Research is urgently needed to understand health care workers' (HCWs') experiences of moral-ethical dilemmas encountered throughout the COVID-19 pandemic, and their associations with organizational perceptions and personal well-being. This research is important to prevent long-term moral and psychological distress and to ensure that workers can optimally provide health services. Objective: Evaluate associations between workplace experiences during COVID-19, moral distress, and the psychological well-being of Canadian HCWs. Method: A total of 1362 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in an online survey. Participants completed measures reflecting moral distress, perceptions of organizational response to the pandemic, burnout, and symptoms of psychological disorders, including depression, anxiety, and posttraumatic stress disorder (PTSD). Results: Structural equation modelling showed that when organizational predictors were considered together, resource adequacy, positive work life impact, and ethical work environment negatively predicted severity of moral distress, whereas COVID-19 risk perception positively predicted severity of moral distress. Moral distress also significantly and positively predicted symptoms of depression, anxiety, PTSD, and burnout. Conclusions: Our findings highlight an urgent need for HCW organizations to implement strategies designed to prevent long-term moral and psychological distress within the workplace. Ensuring availability of adequate resources, reducing HCW risk of contracting COVID-19, providing organizational support regarding individual priorities, and upholding ethical considerations are crucial to reducing severity of moral distress in HCWs.

Antecedentes: Se necesita con urgencia investigaciones para comprender las experiencias de los dilemas éticos y morales que los trabajadores de la salud encontraron durante la pandemia de la COVID-19 y su asociación con las percepciones de la organización y el bienestar personal. Esta investigación es importante para prevenir la angustia moral y psicológica a largo plazo y para asegurar que los trabajadores de la salud puedan proveer de manera óptima los servicios de salud.Objetivo: Evaluar la asociación entre las experiencias en el lugar de trabajo durante la COVID-19, la angustia moral y el bienestar psicológico de los trabajadores de salud canadienses.Métodos: Se reclutó a un total de 1362 trabajadores de salud canadienses, que hablaban francés e inglés y que fueron contratados durante la pandemia de la COVID-19, para participar en un cuestionario en línea. Los participantes completaron mediciones que reflejaban la angustia moral, la percepción de la respuesta de la organización a la pandemia, el burnout y los síntomas de trastornos psicológicos, que incluían a la depresión, a la ansiedad y al trastorno de estrés postraumático (TEPT).Resultados: El modelo de ecuaciones estructurales mostró que cuando los predictores de la organización se consideraban en conjunto ­ los recursos adecuados, el impacto positivo en la vida laboral y un ambiente de trabajo ético ­, predijeron negativamente la gravedad de la angustia moral, mientras que la percepción del riesgo de contraer la COVID-19 predijo positivamente la gravedad de la angustia moral. La angustia moral también predijo de manera significativa y positiva los síntomas de la depresión, la ansiedad, el TEPT y el burnout.Conclusiones: Nuestros hallazgos resaltan la urgente necesidad de que las organizaciones de trabajadores de salud implementen estrategias diseñadas para prevenir la angustia moral y psicológica a largo plazo en el lugar de trabajo. El asegurar la disponibilidad de los recursos adecuados, el reducir el riesgo de que los trabajadores de salud contraigan la COVID-19, el proveer un soporte organizacional adecuado según las prioridades individuales y el respetar las consideraciones éticas son fundamentales para reducir la gravedad de la angustia moral en los trabajadores de salud.

Using in silico viral kinetic models to guide therapeutic strategies during a pandemic: An example in SARS-CoV-2.

AIMS: We propose the use of in silico mathematical models to provide insights that optimize therapeutic interventions designed to effectively treat respiratory infection during a pandemic. A modelling and simulation framework is provided using SARS-CoV-2 as an example, considering applications for both treatment and prophylaxis. METHODS: A target cell-limited model was used to quantify the viral infection dynamics of SARS-CoV-2 in a pooled population of 105 infected patients. Parameter estimates from the resulting model were used to simulate and compare the impact of various interventions against meaningful viral load endpoints. RESULTS: Robust parameter estimates were obtained for the basic reproduction number, viral release rate and infected-cell mortality from the infection model. These estimates were informed by the largest dataset currently available for SARS-CoV-2 viral time course. The utility of this model was demonstrated using simulations, which hypothetically introduced inhibitory or stimulatory drug mechanisms at various target sites within the viral life-cycle. We show that early intervention is crucial to achieving therapeutic benefit when monotherapy is administered. In contrast, combination regimens of two or three drugs may provide improved outcomes if treatment is initiated late. The latter is relevant to SARS-CoV-2, where the period between infection and symptom onset is relatively long. CONCLUSIONS: The use of in silico models can provide viral load predictions that can rationalize therapeutic strategies against an emerging viral pathogen.

Exploring the Well-being of Health Care Workers During the COVID-19 Pandemic: Protocol for a Prospective Longitudinal Study.

BACKGROUND: Health care workers (HCWs) have experienced several stressors associated with the COVID-19 pandemic. Structural stressors, including extended work hours, redeployment, and changes in organizational mandates, often intersect with interpersonal and personal stressors, such as caring for those with COVID-19 infections; worrying about infection of self, family, and loved ones; working despite shortages of personal protective equipment; and encountering various difficult moral-ethical dilemmas. OBJECTIVE: The paper describes the protocol for a longitudinal study seeking to capture the unique experiences, challenges, and changes faced by HCWs during the COVID-19 pandemic. The study seeks to explore the impact of COVID-19 on the mental well-being of HCWs with a particular focus on moral distress, perceptions of and satisfaction with delivery of care, and how changes in work structure are tolerated among HCWs providing clinical services. METHODS: A prospective longitudinal design is employed to assess HCWs' experiences across domains of mental health (depression, anxiety, posttraumatic stress, and well-being), moral distress and moral reasoning, work-related changes and telehealth, organizational responses to COVID-19 concerns, and experiences with COVID-19 infections to self and to others. We recruited HCWs from across Canada through convenience snowball sampling to participate in either a short-form or long-form web-based survey at baseline. Respondents to the baseline survey are invited to complete a follow-up survey every 3 months, for a total of 18 months. RESULTS: A total of 1926 participants completed baseline surveys between June 26 and December 31, 2020, and 1859 participants provided their emails to contact them to participate in follow-up surveys. As of July 2021, data collection is ongoing, with participants nearing the 6- or 9-month follow-up periods depending on their initial time of self-enrollment. CONCLUSIONS: This protocol describes a study that will provide unique insights into the immediate and longitudinal impact of the COVID-19 pandemic on the dimensions of mental health, moral distress, health care delivery, and workplace environment of HCWs. The feasibility and acceptability of implementing a short-form and long-form survey on participant engagement and data retention will also be discussed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32663.

End of the Field? Hacking Online and Hybrid Environments for Field-Based Learning in Geography Education

Increased liability, limited resources, and global pandemics reduce opportunities for field-based learning and accelerate transition to online education across grade levels and geographic contexts. Conventional expectations about teaching through fieldwork (i.e., in-person, led by the instructor) no longer encompass geography as a field discipline. Prospects for field-based learning diversify as technologies make "out there" available "right here" and as online courses grant students agency to engage with and redefine the field. This essay presents those possibilities and describes online modes of deploying and assessing field-based learning.

Blueprint for pandemic response: Focus on translational medicine, clinical pharmacology and pharmacometrics.

Perhaps the most important lesson learned from the COVID-19 pandemic is that of preparedness. Enhanced surveillance systems for early threat detection will be crucial to maximizing response time for implementation of public health measures and mobilization of resources in containing an emerging pandemic. Recent outbreaks have been dominated by viral pathogens, with RNA respiratory viruses being the most likely to have pandemic potential. These should therefore be a preparedness priority. Tools in the areas of virology, drug discovery, clinical pharmacology, translational medicine and pharmacometrics should be considered key components in the rapid identification and development of existing and novel interventions for a pandemic response. Prioritization of therapeutics should be based on in vitro activity, likelihood of achieving effective drug concentrations at the site of action, and safety profile at the doses that will be required for clinical efficacy. Deployment strategies must be tailored to the epidemiology of the disease, and the adequacy of the response should be re-evaluated in view of evolving epidemiological factors. An interdisciplinary framework integrating drug pharmacology, viral kinetics, epidemiology and health economics could help optimize the deployment strategy by improving decision-making around who to treat, when to treat, and with what type of intervention for optimal outcomes. Lastly, while an effective vaccine will ultimately end a pandemic, antiviral drug intervention guided by clinical pharmacology principles will continue to play a critical role in any pandemic response.

Accelerating Clinical Evaluation of Repurposed Combination Therapies for COVID-19.

As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development is the evaluation of drug combinations in the absence of prior monotherapy data. This approach is appealing for a number of reasons. First, combining two or more drugs with related or complementary therapeutic effects permits a multipronged approach addressing the variable pathways of the disease. Second, if an individual component of a combination offers a therapeutic effect, then in the absence of antagonism, a trial of combination therapy should still detect individual efficacy. Third, this strategy is time saving. Rather than taking a stepwise approach to evaluating monotherapies, this strategy begins with testing all relevant therapeutic options. Finally, given the severity of the current pandemic and the absence of treatment options, the likelihood of detecting a treatment effect with combination therapy maintains scientific enthusiasm for evaluating repurposed treatments. Antiviral combination selection can be facilitated by insights regarding SARS-CoV-2 pathophysiology and cell cycle dynamics, supported by infectious disease and clinical pharmacology expert advice. We describe a clinical evaluation strategy using adaptive combination platform trials to rapidly test combination therapies to treat COVID-19.

Debate: Recognising and responding to the mental health needs of young people in the era of COVID-19.

The COVID-19 pandemic is a 'perfect storm' for the mental health of young people, because of exposure to known risk factors for psychopathology and lack of support from the infrastructures that are normally in place to ensure safety and provide support. However, it is yet unclear if this 'perfect storm' will flood the Child & Adolescent Mental Health Services. The early, normative emotional responses observed may not lead to enduring psychopathology in most young people. Nevertheless, a minority of young people may show complex presentations, particularly in relation to bereavement. As epidemiology and clinical practice will reveal the actual needs of young people, the hope is that we will find the focus and determination to build new solutions to promote young people's mental health.

Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load.

We modeled the viral dynamics of 13 untreated patients infected with severe acute respiratory syndrome-coronavirus 2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than two logs, drug efficacy needs to be > 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severely ill patients.