The Role of Inflammasomes in COVID-19: Potential Therapeutic Targets.

The coronavirus 2019 disease (COVID-19) pandemic has caused massive morbidity and mortality worldwide. In severe cases, it is mainly associated with acute pneumonia, cytokine storm, and multi-organ dysfunction. Inflammasomes play a primary role in various pathological processes such as infection, injury, and cancer. However, their role in COVID-19-related complications has not been explored. In addition, the role of underlying medical conditions on COVID-19 disease severity remains unclear. Therefore, this review expounds on the mechanisms of inflammasomes following COVID-19 infection and provides recent evidence on the potential double-edged sword effect of inflammasomes during COVID-19 pathogenesis. The assembly and activation of inflammasomes are critical for inducing effective antiviral immune responses and disease resolution. However, uncontrolled activation of inflammasomes causes excessive production of proinflammatory cytokines (cytokine storm), increased risk of acute respiratory distress syndrome, and death. Therefore, discoveries in the role of the inflammasome in mediating organ injury are key to identifying therapeutic targets and treatment modifications to prevent or reduce COVID-19-related complications.

The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes a number of strategies to modulate viral and host mRNA translation. Here, we used ribosome profiling in SARS-CoV-2-infected model cell lines and primary airway cells grown at an air-liquid interface to gain a deeper understanding of the translationally regulated events in response to virus replication. We found that SARS-CoV-2 mRNAs dominate the cellular mRNA pool but are not more efficiently translated than cellular mRNAs. SARS-CoV-2 utilized a highly efficient ribosomal frameshifting strategy despite notable accumulation of ribosomes within the slippery sequence on the frameshifting element. In a highly permissive cell line model, although SARS-CoV-2 infection induced the transcriptional upregulation of numerous chemokine, cytokine, and interferon-stimulated genes, many of these mRNAs were not translated efficiently. The impact of SARS-CoV-2 on host mRNA translation was more subtle in primary cells, with marked transcriptional and translational upregulation of inflammatory and innate immune responses and downregulation of processes involved in ciliated cell function. Together, these data reveal the key role of mRNA translation in SARS-CoV-2 replication and highlight unique mechanisms for therapeutic development. IMPORTANCE SARS-CoV-2 utilizes a number of strategies to modulate host responses to ensure efficient propagation. Here, we used ribosome profiling in SARS-CoV-2-infected cells to gain a deeper understanding of the translationally regulated events in infected cells. We found that although viral mRNAs are abundantly expressed, they are not more efficiently translated than cellular mRNAs. SARS-CoV-2 utilized a highly efficient ribosomal frameshifting strategy and alternative translation initiation sites that help increase the coding potential of its RNAs. In permissive cells, SARS-CoV-2 infection induced the translational repression of numerous innate immune mediators. Though the impact of SARS-CoV-2 on host mRNA translation was more subtle in primary airway cell cultures, we noted marked transcriptional and translational upregulation of inflammatory and innate immune responses and downregulation of processes involved in ciliated cell function. Together, these data provide new insight into how SARS-CoV-2 modulates innate host responses and highlight unique mechanisms for therapeutic intervention.

The Effect of the Online and Offline Blended Teaching Mode on English as a Foreign Language Learners' Listening Performance in a Chinese Context.

With the rapid development of digitalisation, multimedia and network-based communication technology, all walks of life are undergoing change and development driven by the application of the internet to conventional industries. Especially because of the outbreak of coronavirus disease of 2019 (COVID-19), English teaching and learning modes are undergoing revolutionary changes worldwide (Wong et al., 2020). Online courses and materials have become the norm for students, and combined with offline English learning activities, an online and offline blended learning mode has ultimately emerged (Graham, 2006; Whittaker, 2013). Whereas blended learning has been considered in several contexts, it has been less investigated in the field of blended English learning mode for the listening comprehension ability and emotional experiences of young learners of Chinese English as a foreign language (EFL) while doing the tasks. Thus, this study focussed on the achievement and experience of Chinese EFL junior high school students during blended learning using Quizlet software as the online learning tool. This study aimed to explore the following: (1) the effect of the online and offline blended mode on the learning outcomes of students and (2) the experience of students while engaging with blended tasks in terms of their learning interest, attitude, and strategy use in English listening learning. A 4-month teaching intervention involving the online and offline blended mode was conducted in English listening classes. Adopting mixed-methods qualitative and quantitative research, this study examined the engagement process of two classes of students and analysed data from their English listening tests and follow-up in-depth interviews. The results suggested that the blended activity was conducive to enhancing the listening performance of students. Moreover, the attitudes of students toward English listening learning shifted from a relatively negative engagement to a more positive one. Meanwhile, the interest of students grew and their learning strategies became more diversified. These findings have implications for English teaching and learning activity design for young learners.

Association of Healthcare Access With Intensive Care Unit Utilization and Mortality in Patients of Hispanic Ethnicity Hospitalized With COVID-19.

BACKGROUND: Racial and ethnic minority groups in the United States experience a disproportionate burden of COVID-19 deaths. OBJECTIVE: To evaluate whether outcome differences between Hispanic and non-Hispanic COVID-19 hospitalized patients exist and, if so, to identify the main malleable contributing factors. DESIGN, SETTING, PARTICIPANTS: Retrospective, cross-sectional, observational study of 6097 adult COVID-19 patients hospitalized within a single large healthcare system from March to November 2020. EXPOSURES: Self-reported ethnicity and primary language. MAIN OUTCOMES AND MEASURES: Clinical outcomes included intensive care unit (ICU) utilization and in-hospital death. We used age-adjusted odds ratios (OR) and multivariable analysis to evaluate the associations between ethnicity/language groups and outcomes. RESULTS: 32.1% of patients were Hispanic, 38.6% of whom reported a non-English primary language. Hispanic patients were less likely to be insured, have a primary care provider, and have accessed the healthcare system prior to the COVID-19 admission. After adjusting for age, Hispanic inpatients experienced higher ICU utilization (non-English-speaking: OR, 1.75; 95% CI, 1.47-2.08; English-speaking: OR, 1.13; 95% CI, 0.95-1.33) and higher mortality (non-English-speaking: OR, 1.43; 95% CI, 1.10-1.86; English-speaking: OR, 1.53; 95% CI, 1.19-1.98) compared to non-Hispanic inpatients. There were no observed treatment disparities among ethnic groups. After adjusting for age, Hispanic inpatients had elevated disease severity at admission (non-English-speaking: OR, 2.27; 95% CI, 1.89-2.72; English-speaking: OR, 1.33; 95% CI, 1.10- 1.61). In multivariable analysis, the associations between ethnicity/language and clinical outcomes decreased after considering baseline disease severity (P < .001). CONCLUSION: The associations between ethnicity and clinical outcomes can be explained by elevated disease severity at admission and limited access to healthcare for Hispanic patients, especially non-English-speaking Hispanics.

Family Care, Economic Stress, and Depressive Symptoms Among Chinese Adults During the COVID-19 Outbreak: Difference by Urban and Rural Areas.

Background: Although several studies have shown an association of family care with a high level of depressive symptoms, the relationship between them remains indistinguishable. Objective: This study aims to examine the associations between family care, economic stress, and depressive symptoms among Chinese adults in urban and rural areas during the COVID-19 outbreak. Methods: Based on cross-sectional data collected through online surveys from February 1st to 10th 2020 in China the present study recruited 2,858 adults. It used multiple linear regression to examine the association between family care and depressive symptoms, while economic stress was examined as moderators on the above relationship. Results: The results showed that caring for both the elderly and children was significantly associated with higher depressive symptoms compared with non-caregivers (B = 2.584, 95%CI: 1.254, 3.915), and a similar result was also found in urban areas. Also, caring for the elderly only was also had a higher level of depressive symptoms than non-caregivers in rural areas (B = 3.135, 95%CI: 0.745, 5.525). Meeting the care needs was significantly associated with lower depressive symptoms compared with unmet care needs, while for rural caregivers, the results were not significant. Besides, economic stress strengthened the effect of family care needs on depressive symptoms for sandwich-generation caregivers who provide care to both the elderly and children (B = 0.605, 95%CI: 0.077, 1.134). While in rural areas, the moderation effects of economic stress were only found for elderly caregivers (B = 1.106, 95%CI: 0.178, 2.035). Conclusion: These findings suggest that we should pay more attention to the family caregiver's mental health during the COVID-19 outbreak. In addition, more effective policies should be developed to provide financial support for family caregivers, especially for sandwich-generation caregivers and rural elderly caregivers.

Media Exposure Related to the PTSS During COVID-19 Pandemic: The Mediating Role of Risk Perception.

Objectives: The objectives of this study are to assess the relationship between media exposure and post-traumatic stress symptoms (PTSS) and to highlight the underlying mechanisms mediated by risk perception. Methods: This survey was conducted online in China from February 1st to February 10th, 2020. A total of 2,858 Chinese citizens aged ≥18 years from 31 provinces and autonomous regions were recruited to participate in a cross-sectional study. Self-report questionnaires were used to assess media exposure, PTSS, and risk perception. Results: The prevalence of respondents with heightened PTSS scores was 22.2%. After controlling for covariates, media exposure (more than five times a day) was significantly and positively associated with a high level of PTSS (B = 4.11, p < 0.001), and risk perception (worry and severity) significantly mediated the relationship between media exposure and PTSS (all 95% CIs did not include 0). Conclusions: Based on these findings, the frequency of media exposure was associated with PTSS. Risk perception (worry and severity) mediated the relationship between media exposure and PTSS. The mental health, particularly PTSS, of the general population should be closely monitored and "infodemics" should be combatted while addressing the COVID-19 outbreak; cognitive interventions may be promising.

The Combined Impact of Gender and Age on Post-traumatic Stress Symptoms, Depression, and Insomnia During COVID-19 Outbreak in China.

The mental health problems might have been increased owing to the COVID-19 pandemic with the commencement of the year 2020, therefore, an epidemiological survey appraising the burden of mental health issues among the general population is imperative. This cross-sectional study attempts to reveal the underlying mental health conditions, such as Post-Traumatic Stress Symptoms (PTSS), depression, and insomnia, relating to the pandemic situation, and to further examine the combined effects of gender and age on the COVID-19 related mental health consequences. An online survey was conducted among 2,992 adults in China from February 1st 2020 to February 10th 2020. The study uses binary logistic regression to analyze the potential factors associated with PTSD, depression, and insomnia. The results indicate that the prevalence of PTSS, depression, and insomnia are 19.5, 26.9, and 19.6% respectively during the COVID-19. Men and women show different rates of PTSS and depression, whereas no insomnia is found in both males and females. The females above 50 years of age have a lower level of depressive symptoms (OR = 0.448, 95%CI: 0.220-0.911, Cohen's d = -0.443) as compared with females aged 18-25; while the highest effect sizes for PTSS (OR = 2.846, 95%CI: 1.725-4.695, Cohen's d = 0.537) and the depression (OR = 2.024, 95%CI: 1.317-3.111, Cohen's d = 0.314) are seen in males aged 26 to 30. Besides gender, education, living conditions, direct exposure to COVID-19, the post mental and the physical health condition is related to PTSS, depression, and insomnia. Our study suggests that high-risk groups, especially those having two or more related factors and young men, should be the focus of mental health intervention.