COVID-19 Worries and Insomnia: A Follow-Up Study

The COVID-19 pandemic was associated with significant increases in sleep disorder symptoms and chronic worry. We previously demonstrated that worry about the pandemic was more strongly associated with subsequent insomnia than the converse during the acute (first 6 months) phase of the pandemic. In this report, we evaluated whether that association held over one year of the pandemic. Participants (n = 3560) completed self-reported surveys of worries about the pandemic, exposure to virus risk factors, and the Insomnia Severity Index on five occasions throughout the course of one year. In cross-sectional analyses, insomnia was more consistently associated with worries about the pandemic than exposure to COVID-19 risk factors. In mixed-effects models, changes in worries predicted changes in insomnia and vice versa. This bidirectional relationship was further confirmed in cross-lagged panel models. Clinically, these findings suggest that during a global disaster, patients who report elevations in either worry or insomnia should be considered for evidence-based treatments for these symptoms to prevent secondary symptoms in the future. Future research should evaluate the extent to which dissemination of evidence-based practices for chronic worry (a core feature of generalized anxiety disorder or illness anxiety disorder) or insomnia reduces the development of co-occurring symptoms during a global disaster.

COVID-19 Worries and Insomnia: A Follow-Up Study.

The COVID-19 pandemic was associated with significant increases in sleep disorder symptoms and chronic worry. We previously demonstrated that worry about the pandemic was more strongly associated with subsequent insomnia than the converse during the acute (first 6 months) phase of the pandemic. In this report, we evaluated whether that association held over one year of the pandemic. Participants (n = 3560) completed self-reported surveys of worries about the pandemic, exposure to virus risk factors, and the Insomnia Severity Index on five occasions throughout the course of one year. In cross-sectional analyses, insomnia was more consistently associated with worries about the pandemic than exposure to COVID-19 risk factors. In mixed-effects models, changes in worries predicted changes in insomnia and vice versa. This bidirectional relationship was further confirmed in cross-lagged panel models. Clinically, these findings suggest that during a global disaster, patients who report elevations in either worry or insomnia should be considered for evidence-based treatments for these symptoms to prevent secondary symptoms in the future. Future research should evaluate the extent to which dissemination of evidence-based practices for chronic worry (a core feature of generalized anxiety disorder or illness anxiety disorder) or insomnia reduces the development of co-occurring symptoms during a global disaster.

The unique contribution of depression to cognitive impairment in Post-Acute Sequelae of SARS-CoV-2 infection.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with significant cognitive impairment and increased risk for mental health comorbidities. This study aimed to identify specific associations between cognitive impairment, self-reported disruptions in memory, and psychiatric symptoms including depression, anxiety, posttraumatic stress disorder (PTSD), and perceived sleep concerns. Methods: Data collected from all consecutive patients with Post-Acute Sequelae of SARS-CoV-2 infection (PASC) who presented to a dedicated Post-COVID Clinic were used to evaluate whether certain psychiatric symptoms were more strongly associated with cognitive impairment and self-reported memory disturbances. Results: Univariate and multivariable analyses revealed that depression symptom severity was significantly associated with the severity of cognitive impairment among patients with PASC. This association was driven primarily by lower performance on verbal fluency, attention, and delayed recall tasks among patients with higher depression symptoms severity. Perceived sleep concerns were an important predictor of self-reported memory disturbances. Conversely, neither PTSD symptom severity nor anxiety symptom severity were significant predictors of cognitive impairment or self-reported memory disturbances. Conclusions: These findings have important clinical implications for justifying the need for screening patients with PASC for both depression and cognitive impairment.

Worry about COVID-19 as a predictor of future insomnia.

The coronavirus disease 2019 (COVID-19) pandemic resulted in significant increases in insomnia, with up to 60% of people reporting increased insomnia. However, it is unclear whether exposure to risk factors for the virus or worries about COVID-19 are more strongly associated with insomnia. Using a three-part survey over the course of the first 6 months of the pandemic, we evaluated associations between COVID-19 exposures, COVID-19 worries, and insomnia. We hypothesised that COVID-19-related worries and exposure to risk of COVID-19 would predict increases in insomnia. Participants (N = 3,560) completed a survey at three time-points indicating their exposures to COVID-19 risk factors, COVID-19-related worries, and insomnia. COVID-19 worry variables were consistently associated with greater insomnia severity, whereas COVID-19 exposure variables were not. COVID-19 worries decreased significantly over time, and there were significant interactions between change in COVID-19 worries and change in insomnia severity over time. Individuals who experienced increases in COVID-19 worries also experienced increases in insomnia severity. Changes in worry during the COVID-19 pandemic were associated with changes in insomnia; worries about COVID-19 were a more consistent predictor of insomnia than COVID-19 exposures. Evidence-based treatments targeting virus-related worries may improve insomnia during this and future calamities.

Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a second-generation antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and Ad-ACE2-transduced mice. Tmprss2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cells, however, such antiviral efficacy was lacking in human lung cells and organoids. Accordingly, enzalutamide showed no antiviral activity due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 regulatory locus in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19 through reducing TMPRSS2 expression in lung cells.