22 March, 2021

Tools for Public Health Policy: Nudges and Boosts as Active Support of the Law in Special Situations such as the COVID-19 Pandemic -

In recent years, “nudging” has become a standard behavioral intervention at the individual level and for the design of social policies. Although nudges are effective, such interventions seem to be limited to a given space and time, and there is only scant evidence to support the contrary view. On the other hand, choice architects may utilize another type of intervention called “boosting,” which shows the promise of generalized and lasting behavioral change. The government can use these tools to shape public policy. Behavioral interventions such as policy-making tools have their boundaries, as does the law. We argue that nudging and boosting may serve as active aids in support of the legal system under certain circumstances. Nudging and boosting can also support the legal system especially in relation to emerging social issues or events that are unprecedented, such as the recent COVID-19 pandemic, where certain behavioral patterns are expected, but it would be hard or impossible to enforce them through the law alone.

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The potential impact of co-residence structures on socio-demographic inequalities in COVID-19 mortality -

During the COVID-19 pandemic, confinement measures were adopted across the world to limit the spread of the virus. In France, these measures were applied between March 17 and May 10. Using high-quality population census data and focusing on co-residence structures on French territory, this article analyses how co-residence patterns unevenly put different socio-demographic groups at risk of being infected and dying from COVID-19. The research ambition is to quantify the possible impact of co-residence structures heterogeneity on socioeconomic inequalities in mortality stemming from within-household transmission of the virus. Using a simulation approach, the article highlights the existence of theoretical pronounced inequalities of vulnerability to COVID-19 related to cohabitation structures as well as a reversal of the social gradient of vulnerability when the age of the infected person increases. Among young age categories, infection is simulated to lead to more deaths in the less educated or foreign-born populations. Among the older ones, the inverse holds with infections having a greater potential to provoke deaths through the transmission of the virus within households headed by a highly educated or a native-born person. Demographic patterns such as the cohabitation of multiple generations and the survival of both partners of a couple help to explain these results. Even though inter-generational co-residence and large households are more common among the lower educated and foreign born in general, the higher educated are more likely to still live with their partner at higher ages.

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Moral decision-making and mental health during the COVID-19 pandemic -

The COVID-19 pandemic entails challenging psychological conditions for the population, requiring them to make many decisions under stress. In this study, 641 participants were presented with different moral decision-making tasks, and completed a survey on mental health status and experiences, concerns, behaviors and beliefs related to the COVID-19. Results showed that the pandemic is placing a great psychological burden on the population. Also, that decision-making processes are being affected during the crisis, in a dichotomous way. Altruistic behaviors are promoted when people are suffering with high levels of psychological impact, and when they are concerned about others contracting the disease. However, egoistic behaviors are facilitated when concerns affect the self. Similarly, psychological impact, concerns about the self, and worsened physical health predict more automatic responses to framing problems and moral dilemmas. Nevertheless, when concerns relate to the others, or when people are more informed and/or carefree, more controlled responses emerge.

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COVID-19 through the One Health lens: adding a missing perspective -

The One Health concept offers an integrative approach to disease and health at the human-animal-environment interface. It has often been suggested to view the COVID-19 outbreak within this framework to better understand and mitigate this global crisis. Here, we discuss how the evolutionary ecology of host-pathogen systems can add a valuable additional perspective to the debate around SARS-CoV-2 and its implications for public health awareness and policy-making. In this context, it is especially important to highlight that changes in nature, such as zoonotic spillover events, are often irreversible, and that humans, while deeply embedded in ecosystems, are intricate ecosystems themselves. A better recognition of the complex biology and evolution of human-parasite interactions will assist our understanding of such zoonoses.

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The potential crucial role of COX-1 inhibition and/or Aspirin triggered lipoxins and resolvins in amelioration of COVID-19 mortality -

Low dose aspirin use was recently shown to be associated with significantly lower rate of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality after controlling for confounding variables. However, the interpretation of the published studies included some important flaws and the author provides a rapid response to provide an insight that aims at designing double bind clinical trials that use non-steroidal anti-inflammatory drugs for management of COVID-19. Notably, since April 2020, we have published previously published three pioneering articles to encourage adoption of NSAIDs/nitazoxanide/azithromycin claiming a curative COVID-19 potential and our updated molecular mechanistic basis as well as our observational prospective case series are preprinted and one of them is, finally, under review at a reputable journal.

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Mindfulness Buffers the Impact of COVID-19 Outbreak Information on Sleep Duration -

We examine whether mindfulness can neutralize the negative impact of COVID-19 stressors on employees’ sleep duration and work engagement. In Study 1, we conducted a field experiment in Wuhan, China during the lockdown between February 20, 2020, and March 2, 2020, in which we induced state mindfulness by randomly assigning participants to either a daily mindfulness practice or a daily mind-wandering practice. Results showed that the sleep duration of participants in the mindfulness condition, compared with the control condition, was less impacted by COVID-19 stressors (i.e., the increase of infections in the community). In Study 2, in a 10-day daily diary study in the United Kingdom between June 8, 2020, and June 19, 2020, we replicate our results from Study 1 using a subjective measure of COVID-19 stressors and a daily measure of state mindfulness. In addition, we find that mindfulness buffers the negative effect of COVID-19 stressors on work engagement mediated by sleep duration. As the COVID-19 pandemic is ongoing and the number of reported cases continues to rise globally, our findings suggest that mindfulness is an evidence-based practice that can effectively neutralize the negative effect of COVID-19 stressors on sleep and work outcomes. The findings of the present study contribute to the employee stress and well-being literature as well as the emerging organizational research on mindfulness.

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Acriflavine, a clinically aproved drug, inhibits SARS-CoV-2 and other betacoronaviruses -

The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identified acriflavine as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.

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Structural and energetic profiling of SARS-CoV-2 antibody recognition and the impact of circulating variants -

The SARS-CoV-2 pandemic highlights the need for a detailed molecular understanding of protective antibody responses. This is underscored by the emergence and spread of SARS-CoV-2 variants, including B.1.1.7, P1, and B.1.351, some of which appear to be less effectively targeted by current monoclonal antibodies and vaccines. Here we report a high resolution and comprehensive map of antibody recognition of the SARS-CoV-2 spike receptor binding domain (RBD), which is the target of most neutralizing antibodies, using computational structural analysis. With a dataset of nonredundant experimentally determined antibody-RBD structures, we classified antibodies by RBD residue binding determinants using unsupervised clustering. We also identified the energetic and conservation features of epitope residues and assessed the capacity of viral variant mutations to disrupt antibody recognition, revealing sets of antibodies predicted to effectively target recently described viral variants. This detailed structure-based reference of antibody RBD recognition signatures can inform therapeutic and vaccine design strategies.

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Critical interactions for SARS-CoV-2 spike protein binding to ACE2 identified by machine learning -

Both SARS-CoV and SARS-CoV-2 bind to the human ACE2 receptor. Based on high-resolution structures, the two viruses bind in practically identical conformations, although several residues of the receptor-binding domain (RBD) differ between them. Here we have used molecular dynamics (MD) simulations, machine learning (ML), and free energy perturbation (FEP) calculations to elucidate the differences in RBD binding by the two viruses. Although only subtle differences were observed from the initial MD simulations of the two RBD-ACE2 complexes, ML identified the individual residues with the most distinctive ACE2 interactions, many of which have been highlighted in previous experimental studies. FEP calculations quantified the corresponding differences in binding free energies to ACE2, and examination of MD trajectories provided structural explanations for these differences. Lastly, the energetics of emerging SARS-CoV-2 mutations were studied, showing that the affinity of the RBD for ACE2 is increased by N501Y and E484K mutations but is slightly decreased by K417N.

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Circadian regulation of SARS-CoV-2 infection in lung epithelial cells -

The COVID-19 pandemic, caused by SARS-CoV-2 coronavirus, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via binding human angiotensin-converting enzyme (ACE2), and infection can result in pneumonia and acute respiratory distress syndrome. Circadian rhythms coordinate an organisms response to its environment and recent studies report a role for the circadian clock to regulate host susceptibility to virus infection. Influenza A infection of arhythmic mice, lacking the circadian component BMAL1, results in higher viral replication and elevated inflammatory responses leading to more severe bronchitis, highlighting the impact of circadian pathways in respiratory function. We demonstrate circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with the synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry and RNA replication. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Our study suggests new approaches to understand and improve therapeutic targeting of COVID-19.

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Interferon Resistance of Emerging SARS-CoV-2 Variants -

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity may drive the emergence of these novel variants, studies documenting a critical a role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against 5 viral lineages sampled during the course of the global outbreak that included ancestral and emerging variants. Our data revealed increased interferon resistance in emerging SARS-CoV-2 variants, indicating that evasion of innate immunity is a significant driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

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A bispecific monomeric nanobody induces SARS-COV-2 spike trimer dimers -

Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. Thus, there is a need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we isolated a nanobody that potently neutralizes SARS-CoV-2, including the B.1.351 variant, and cross-neutralizes SARS-CoV. We demonstrate the therapeutic potential of the nanobody in a human ACE2 transgenic mouse model. Using biochemistry and electron cryomicroscopy we show that this nanobody simultaneously interacts with two RBDs from different spike trimers, rapidly inducing the formation of spike trimer-dimers. This naturally elicited bispecific monomeric nanobody establishes a novel strategy for potent immobilization of viral antigens.

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Seeing like a State, Enacting like an Algorithm: (Re)assembling Contact Tracing and Risk Assessment during the Covid-19 Pandemic -

As states increasingly use algorithms to improve the legibility of society, particularly during the Covid-19 pandemic, it is common for concerns of the expanding power of the algorithm or the state to be raised in a deterministic manner. However, little is known about how the algorithms for states’ legibility projects are deployed, experienced, contested, and reconfigured. Drawing on interviews and media data, this study fills this gap by examining Health Code (jiankangma), the Chinese contact tracing and risk assessment algorithmic system. I first explore the intensive and invisible work and infrastructures that enact and stabilize Health Code’s sociotechnical assemblage. I then show how this assemblage is frequently challenged and destabilized by errors, breakdowns, and exclusions. Facing unintended engagements from heterogeneous social actors, local networks, and power hierarchies, Health Code reassembles into multiple and contradictory assemblages at different periods and social localities. Finally, I examine how people game and bypass the algorithm’s surveillance with their agencies. Recognizing this messiness and heterogeneity contributes to a more nuanced and realistic understanding of states’ use of algorithms, including the risks. Doing so also urges us to rethink how technologies have reshaped the relationship between the state and its citizens in the digital age.

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A Queuing Model for Ventilator Capacity Management during the COVID-19 Pandemic -

We present a queue model to inform ventilator capacity management under different COVID-19 pandemic scenarios. Our model was used to support ventilator capacity planning during the first wave of the COVID-19 epidemic in British Columbia (BC), Canada. The core of our framework is an extended Erlang loss model, which incorporates COVID-19 case projections, along with the proportion of cases requiring a ventilator, the delay from symptom onset to ventilation, non-COVID-19 ventilator demand, and ventilation time. We implemented our model using discrete event simulation to forecast ventilator utilization. The results predict when capacity would be reached and the rate at which patients would be unable to access a ventilator. We further determined the number of ventilators required to meet a performance indicator target for ventilator access. We applied our model to BC by calibrating to the BC Intensive Care Unit Database and by using local epidemic projections. Epidemic scenarios with and without reduced transmission, due to social distancing and other behavioral changes, were used to link public health interventions to operational impacts on ventilator utilization. The results predict that reduced transmission could potentially avert up to 50 deaths per day by ensuring that ventilator capacity would likely not be reached. Without reduced transmission, an additional 181 ventilators would be required to meet our performance indicator target that 95% of patients can access a ventilator immediately. Our model provides a tool for policy makers to quantify the interplay between public health interventions, necessary critical care resources, and performance indicators for patient access.

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Effect of vaccination on transmission of COVID-19: an observational study in healthcare workers and their households -

Background: The effect of vaccination for COVID-19 on onward transmission is unknown. Methods: A national record linkage study determined documented COVID-19 cases and hospitalizations in unvaccinated household members of vaccinated and unvaccinated healthcare workers from 8th December 2020 to 3rd March 2021. The primary endpoint was COVID-19 >= 14 days following the first dose. Results: The cohort comprised of 194,362 household members (mean age 31.1 years) and 144,525 healthcare workers (mean age 44.4 years). 113,253 (78.3%) of healthcare workers received at least one dose of the BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccine and 36,227 (25.1%) received a second dose. Household members of vaccinated healthcare workers had a lower risk of COVID-19 case compared to household members of unvaccinated healthcare worker (rate per 100 person-years 9.40 versus 5.93; HR 0.70, 95% confidence interval [CI] 0.63-0.78). The effect size for COVID-19 hospitalization was similar, with the confidence interval crossing the null (HR 0.77 [0.53-1.10]). The rate per 100 person years was lower in vaccinated compared to unvaccinated healthcare workers for documented (20.13 versus 8.51; HR 0.45 [0.42-0.49]) and hospitalized COVID-19 (0.97 versus 0.14; HR 0.16 [0.09-0.27]). Compared to the period before the first dose, the risk of documented COVID-19 case was lower at >= 14 days after the second dose for household members (HR 0.46 [0.30-0.70]) and healthcare workers (HR 0.08 [0.04-0.17]). Conclusion: Vaccination of health care workers was associated with a substantial reduction in COVID-19 cases in household contacts consistent with an effect of vaccination on transmission.

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Covid-19 Sentry

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