Project description:The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing (a) reduces the peak incidence of infections, (b) delays the occurrence of this peak, and (c) reduces the total number of infections during epidemics. In view of the extraordinary efforts underway to identify existing medications that are active against SARS-CoV-2 and to develop new antiviral drugs, vaccines and antibody therapies, any of which may have community-level effects, we also describe how pharmaceutical interventions affect transmission.
Project description:Testing for COVID-19 is a key intervention that supports tracking and isolation to prevent further infections. However, diagnostic tests are a scarce and finite resource, so abundance in one country can quickly lead to shortages in others, creating a competitive landscape. Countries experience peaks in infections at different times, meaning that the need for diagnostic tests also peaks at different moments. This phase lag implies opportunities for a more collaborative approach, although countries might also worry about the risks of future shortages if they help others by reallocating their excess inventory of diagnostic tests. This article features a simulation model that connects three subsystems: COVID-19 transmission, the diagnostic test supply chain, and public policy interventions aimed at flattening the infection curve. This integrated system approach clarifies that, for public policies, there is a time to be risk-averse and a time for risk-taking, reflecting the different phases of the pandemic (contagion vs. recovery) and the dominant dynamic behavior that occurs in these phases (reinforcing vs. balancing). In the contagion phase, policymakers cannot afford to reject extra diagnostic tests and should take what they can get, in line with a competitive mindset. In the recovery phase, policymakers can afford to give away excess inventory to other countries in need (one-sided collaboration). When a country switches between taking and giving, in a form of two-sided collaboration, it can flatten the curve, not only for itself but also for others.
Project description:Natural Killer (NK) cells are innate immune responders critical for viral clearance and immunomodulation. Despite their vital role in viral infection, the contribution of NK cells in fighting SARS-CoV-2 has not yet been directly investigated. Insights into pathophysiology and therapeutic opportunities can therefore be inferred from studies assessing NK cell phenotype and function during SARS, MERS, and COVID-19. These studies suggest a reduction in circulating NK cell numbers and/or an exhausted phenotype following infection and hint toward the dampening of NK cell responses by coronaviruses. Reduced circulating NK cell levels and exhaustion may be directly responsible for the progression and severity of COVID-19. Conversely, in light of data linking inflammation with coronavirus disease severity, it is necessary to examine NK cell potential in mediating immunopathology. A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. In this review, we summarize the current understanding of how NK cells respond in both early and late coronavirus infections, and the implication for ongoing COVID-19 clinical trials. Using this immunological lens, we outline recommendations for therapeutic strategies against COVID-19 in clearing the virus while preventing the harm of immunopathological responses.
Project description:The immune system is one of the most important adaptations that has evolved to protect animals from a wide range of pathogens they encounter from early life onwards. During the early developmental period this is particularly true for the innate immunity, as other components of the immune system are, as yet, poorly developed. But innate immunity may not only be crucial for early life survival, but may also have long-lasting effects, for example if early life immunity reflects the functioning of the immune system as a whole. For this reason, we investigated the importance of four constitutive innate immune parameters (natural antibodies, complement activity, concentrations of haptoglobin, and concentrations of nitric oxide) for recruitment in free-living great tits. We compared nestling immunity of recruits with nestling immunity of their nonrecruited siblings. We also investigated within individual consistency of these innate immune parameters for those individuals that recruited, which may be taken as a measure of immune capacity. In accordance with previous studies, we found a clear effect of tarsus length and a trend for body mass on the likelihood to recruit. Nevertheless, we found no evidence that higher levels of constitutive innate immunity as a nestling facilitated local recruitment. Furthermore, individual innate immunity was not consistent across life stages, that is to say, nestling immune parameters did not determine, or respectively, reflect adult innate immune parameters. This plasticity in innate immune components may explain why we did not find long-lasting survival benefits.
Project description:PurposeWe examined multidimensional, heterogeneous reactions to the COVID-19 pandemic and associated measures to provide further insights into the developmental processes of risk and adaptation.MethodWe used three-wave questionnaire data from 8156 individuals participating in the Norwegian County Public Health Survey assessed 1-5 months before and three (June 2020) and nine (December 2020) months after the outbreak. Latent profile and latent transition analyses were used to identify latent quality of life (QoL) classes and multiform changes, their probabilities, and predictors.ResultsWe identified five distinct QoL classes of varying proportions, namely Flourishing (i.e. 24-40%), Content (31-46%), Content-Symptomatic (8-10%), Languishing (14-20%), and Troubled (2-5%). Despite higher levels of negative affect and lower levels of life satisfaction and positive emotions, most individuals remained in their pre-pandemic QoL profiles. Yet, changes occurred for a meaningful proportion, with transition to a less favourable class more common than to a favourable. Between time 1 and 3, the flourishing and troubled groups decreased by 40% and 60%, while the content and languishing groups increased by 48% and 43%, respectively. Favourable pre-pandemic relational (marital status, support, interpersonal trust, and belonging), health, and economy-related status predicted significantly lower odds of belonging to the high-risk groups both pre-pandemic and during the pandemic.ConclusionsOverall, this study shows lower levels of QoL amid the COVID-19 pandemic, but substantial stability in the QoL distribution, and an overall levelling of the QoL distribution. Our findings also underscore the importance of financial, health-related, and social capital to QoL.
Project description:IntroductionAcross four countries (Canada, USA, UK, and Italy), we explored the effects of persuasive messages on intended and actual preventive actions related to COVID-19, and the role of emotions as a potential mechanism for explaining these effects.MethodsOne thousand seventy-eight participants first reported their level of concern and emotions about COVID-19 and then received a positive persuasive text, negative persuasive text, or no text. After reading, participants reported their emotions about the pandemic and their willingness to take preventive action. One week following, the same participants reported the frequency with which they engaged in preventive action and behaviors that increased the risk of contracting COVID-19.ResultsResults revealed that the positive persuasive text significantly increased individuals' willingness to and actual engagement in preventive action and reduced risky behaviors 1 week following the intervention compared to the control condition. Moreover, significant differences were found between the positive persuasive text condition and negative persuasive text condition whereby individuals who read the positive text were more willing and actually engaged in more preventive action compared to those who read the negative text. No differences were found, however, at the 1-week follow-up for social distancing and isolation behaviors. Results also revealed that specific discrete emotions mediated relations between the effects of the texts and preventive action (both willing and actual).DiscussionThis research highlights the power of educational interventions to prompt behavioral change and has implications for pandemic-related interventions, government policy on health promotion messages, and future research.
Project description:Mitochondria are cellular organelles involved in host-cell metabolic processes and the control of programmed cell death. A direct link between mitochondria and innate immune signalling was first highlighted with the identification of MAVS-a crucial adaptor for RIGI-like receptor signalling-as a mitochondria-anchored protein. Recently, other innate immune molecules, such as NLRX1, TRAF6, NLRP3 and IRGM have been functionally associated with mitochondria. Furthermore, mitochondrial alarmins-such as mitochondrial DNA and formyl peptides-can be released by damaged mitochondria and trigger inflammation. Therefore, mitochondria emerge as a fundamental hub for innate immune signalling.
Project description:Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease.