Animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19

Psychological Distress in International University Students: An Australian Study

Australia is a much sort after destination of study for many thousands of international university students. However, tertiary study brings with it many challenges that may potentially precipitate psychological distress in international students. Psychological distress may be experienced in various ways. The aim of this study was to investigate the manner in which psychological distress is manifested in international students and the factors that contribute to their psychological distress. The participants consisted of 86 international students enrolled at a Queensland university who completed a battery of nine self-report questionnaires. Results showed that obsessive-compulsiveness reflected by worry, ruminations and perfectionist tendencies was the most common symptom of psychological distress in international students. Dysfunctional coping was the only factor contributing to psychological distress. These findings have important implications for the international students with reference to the assessment of their mental health issues and the designing of suitable intervention programs

Cardiac Surgery in Nonagenarians: Single-Centre Series and Review

&lt;i&gt;Background:&lt;/i&gt; Cardiac surgery is widely believed to be an excessively high-risk intervention for very elderly patients with coronary artery or valvular disease. However, as life expectancy and the prospect of sustained quality of life into older age increase, this assumption should be challenged so that surgery is not denied to patients who may derive significant symptomatic benefit with acceptable levels of operative risk. &lt;i&gt;Objective:&lt;/i&gt; To evaluate outcomes from cardiac surgery in nonagenarian patients. &lt;i&gt;Design:&lt;/i&gt; Analysis of prospectively collected single-centre data and review of outcomes reported in the literature. &lt;i&gt;Results:&lt;/i&gt; Twenty-three patients (13 males) aged 90 years or more underwent open cardiac surgery between 1998 and 2007. Four patients died within 30 days of surgery (surgical mortality 17.4%) and all-cause in-hospital morbidity was 74%. Actuarial survival at 1 and 5 years was estimated at 72 and 54%, respectively. Comparison of patients’ survival against age-matched life tables for the English population found a standardised mortality ratio of 0.57 (95% CI: 0.24–0.99; one-sample log-rank test χ&lt;sup&gt;2&lt;/sup&gt; = 3.93; p &lt; 0.05) representing a significant survival benefit associated with surgery. The majority of patients reported symptomatic improvement reflected by significant decreases in angina and dyspnoea scores. Six single-centre series of nonagenarians and 3 reviews from national databases in the US and UK were identified in the literature. Pooled surgical mortality was 12.7% (95% CI: 8.7–17.3%) with no significant heterogeneity (χ&lt;sup&gt;2&lt;/sup&gt; = 4.12; p = 0.77; I&lt;sup&gt;2&lt;/sup&gt; = 0). &lt;i&gt;Conclusion:&lt;/i&gt; Cardiac surgery in the elderly carries higher operative risk than in younger patients. However, in selected nonagenarians, surgery can be performed with acceptable morbidity and early mortality, and patients gain significant symptomatic relief and survival benefit.</jats:p

Cross-protective immune responses induced by sequential influenza virus infection and by sequential vaccination with inactivated influenza vaccines

AbstractSequential infection with antigenically distinct influenza viruses induces cross-protective immune responses against heterologous virus strains in animal models. Here we investigated whether sequential immunization with antigenically distinct influenza vaccines can also provide cross-protection. To this end, we compared immune responses and protective potential against challenge with A(H1N1)pdm09 in mice infected sequentially with seasonal A(H1N1) virus followed by A(H3N2) virus or immunized sequentially with whole inactivated virus (WIV) or subunit (SU) vaccine derived from these viruses. Sequential infection provided solid cross-protection against A(H1N1)pdm09 infection while sequential vaccination with WIV, though not capable of preventing weight loss upon infection completely, protected the mice from reaching the humane endpoint. In contrast, sequential SU vaccination did not prevent rapid and extensive weight loss. Protection correlated with levels of cross-reactive but non-neutralizing antibodies of the IgG2a subclass, general increase of memory T cells and induction of influenza-specific CD4+ and CD8+ T cells. Adoptive serum transfer experiments revealed that despite lacking neutralizing activity, serum antibodies induced by sequential infection protected mice from weight loss and vigorous virus growth in the lungs upon A(H1N1)pdm09 virus challenge. Antibodies induced by WIV vaccination alleviated symptoms but could not control virus growth in the lung. Depletion of T cells prior to challenge revealed that CD8+ T cells, but not CD4+ T cells, contributed to cross-protection. These results imply that sequential immunization with WIV but not SU derived from antigenically distinct viruses could alleviate the severity of infection caused by a pandemic and may improve protection to unpredictable seasonal infection.ImportanceNew influenza virus strains entering the human population may have large impact and therefore their emergence requires immediate action. Yet, since these strains are unpredictable, vaccines cannot be prepared in advance, at least not as long as there is no universal or broadly protective influenza vaccine available. It is therefore important to elucidate in how far immunization strategies based on currently available seasonal vaccines can provide at least some protection against newly emerging virus strains. Moreover, insight in the possible mechanisms of protection can guide the further development of pre-pandemic immunization strategies. Our study presents a vaccination strategy based on sequential administration of readily available seasonal whole inactivated virus vaccines which could be easily applied in case of a new pandemic. In addition, our study identifies immune mechanisms, in particular cross-reactive non-neutralizing antibodies and CD8+ T cells, which should be targeted by broadly protective influenza vaccines.</jats:sec

Human milk: From complex tailored nutrition to bioactive impact on child cognition and behavior

Human milk is a highly complex liquid food tailor-made to match an infant's needs. Beyond documented positive effects of breastfeeding on infant and maternal health, there is increasing evidence that milk constituents also impact child neurodevelopment. Non-nutrient milk bioactives would contribute to the (long-term) development of child cognition and behavior, a process termed 'Lactocrine Programming'. In this review we discuss the current state of the field on human milk composition and its links with child cognitive and behavioral development. To promote state-of-the-art methodologies and designs that facilitate data pooling and meta-analytic endeavors, we present detailed recommendations and best practices for future studies. Finally, we determine important scientific gaps that need to be filled to advance the field, and discuss innovative directions for future research. Unveiling the mechanisms underlying the links between human milk and child cognition and behavior will deepen our understanding of the broad functions of this complex liquid food, as well as provide necessary information for designing future interventions