Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model.

Molnupiravir (EIDD-2801) is a prodrug of a ribonucleoside analogue that is currently being used under a US FDA emergency use authorization for the treatment of mild to moderate COVID-19. We evaluated molnupiravir for efficacy as an oral treatment in the rhesus macaque model of SARS-CoV-2 infection. Twenty non-human primates (NHPs) were challenged with SARS-CoV-2 and treated with 75 mg/kg (n = 8) or 250 mg/kg (n = 8) of molnupiravir twice daily by oral gavage for 7 days. The NHPs were observed for 14 days post-challenge and monitored for clinical signs of disease. After challenge, all groups showed a trend toward increased respiration rates. Treatment with molnupiravir significantly reduced viral RNA levels in bronchoalveolar lavage (BAL) samples at Days 7 and 10. Considering the mild to moderate nature of SARS-CoV-2 infection in the rhesus macaque model, this study highlights the importance of monitoring the viral load in the lung as an indicator of pharmaceutical efficacy for COVID-19 treatments. Additionally, this study provides evidence of the efficacy of molnupiravir which supplements the current ongoing clinical trials of this drug.

Latent Classes of Adverse and Benevolent Childhood Experiences in a Multinational Sample of Parents and Their Relation to Parent, Child, and Family Functioning during the COVID-19 Pandemic.

Adverse Childhood Experiences (ACEs) are known to contribute to later mental health. Conversely, Benevolent Childhood Experiences (BCEs) may buffer against mental health difficulties. The importance of ACEs and BCEs for mental health of both parents and children may be most obvious during periods of stress, with potential consequences for functioning of the family. Subgroups of ACEs and BCEs in parents during the COVID-19 pandemic were investigated and validated in relation to indices of parent, child, and family well-being. In May 2020, ACEs/BCEs were assessed in 547 parents of 5-18-year-old children from the U.K., U.S., Canada, and Australia. Subgroups of parents with varying levels of ACEs and BCEs were identified via latent class analysis. The subgroups were validated by examining associations between class membership and indices of parent and child mental health and family well-being. Four latent classes were identified: low-ACEs/high-BCEs, moderate-ACEs/high-BCEs, moderate-ACEs/low-BCEs, and high-ACEs/moderate-BCEs. Regardless of the extent of BCEs, there was an increased risk of parent and child mental health difficulties and family dysfunction among those reporting moderate-to-high levels of ACEs. Parents' history of adversity may influence the mental health of their family. These findings highlight the importance of public health interventions for preventing early-life adversity.

The disparate impact of COVID-19 on the mental health of female and male caregivers.

Caregiver mental health is crucial to the wellbeing of children. This is most apparent when caregivers face high levels of stress or life adversity. To study this phenomenon in the current global context, this study examined the relation between stress/disruption from the COVID-19 pandemic and the mental health of female and male caregivers. Pre-pandemic childhood adversity was considered as a moderator of this association. A multi-national sample (United Kingdom, 76%; United States, 19%; Canada, 4%, and Australia, 1%) was recruited in May 2020, of whom 348 female and 143 male caregivers of 5-18 year-old children provided data on the constructs of interest. At this time, caregivers reported on their history of adverse childhood experiences (ACEs) and COVID stress/disruption. About two months later (July 2020) caregiver mental health was evaluated. We examined differences between female and male caregivers on ACEs, COVID stress/disruption, and mental health (distress, anxiety, substance use, and posttraumatic stress). Main and interactive effects of ACEs and COVID stress/disruption on each mental health outcome were examined. Female caregivers reported higher COVID stress/disruption, more ACEs, and greater distress, anxiety, and posttraumatic stress symptoms compared to male caregivers. Among female caregivers, higher COVID stress/disruption and more adverse childhood experiences (ACEs) independently predicted all mental health outcomes, consistent with a stress accumulation model. Among male caregivers, a pattern of interactions between COVID stress/disruption and ACEs suggested that the effects of COVID stress/disruption on mental health was stronger for those with higher ACEs, especially for substance use, consistent with a stress sensitization model. Higher levels of stress and mental health difficulties among female caregivers suggests a disproportionate burden due to pandemic-related disruption compared to male caregivers. Findings speak to the disparate effects of COVID-19 on the mental health of female compared to male caregivers, and the role of pre-existing vulnerabilities in shaping current adaptation.