Values and well-being change amidst the COVID-19 pandemic in Poland -

COVID-19 caused a global change in the lifestyles of people around the world. It provided a unique opportunity to examine how external circumstances impact two crucial aspects of functioning relating to “who I am” (values) and “how I feel” (well-being). Participants (N = 150) reported their values, subjective and eduaimonic well-being nine months before lockdown in Poland, two weeks and four weeks into lockdown. We observed significant changes in values: an increase in self-direction, achievement, security, conformity, humility, benevolence and universalism, and a decrease in hedonism. All well-being indices showed a decrease in well-being with one specific difference between men and women: women experienced a more significant increase of negative affect compared to men. Finally, we showed that Openness to change values predict lower negative affect and higher eudaimonic well-being two weeks into lockdown. This study is unique in that it shows, that well-being and individually held values are flexible and adaptive systems that react to external circumstances, such as global critical events.

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The Social and Psychological Changes of the First Months of COVID-19 -

The initial wave of the COVID-19 pandemic disrupted the lives of people across the globe. The current research sought to understand how the pandemic affected people’s social and psychological states during the first three months after the first U.S. death was reported. How did people’s emotions, thought patterns, and social lives change as the pandemic unfolded? The Reddit language of 200,000+ people across 18 cities in the U.S. was analyzed along with surveys from 11,000+ people in the U.S. and Canada. Overall, large psychological shifts were found that reflected three distinct phases. As the first COVID warnings emerged but prior to the shelter-in-place directives, people’s attentional focus switched to the impending threat. Anxiety levels surged, and positive emotion and anger dropped. In parallel, people’s thinking became more immediate and intuitive rather than analytic. When cities began lockdowns, anxiety levels spiked and sadness increased, and language shifted in ways that revealed people’s attempts to make sense of the situation. Six weeks after the onset, people’s psychological states stabilized but the COVID-produced changes had not abated. Converging evidence from survey responses and natural language analysis indicated that people’s ties with family strengthened but that social ties to broader groups (friends, city, and country) weakened. The psychological shifts were amplified on days when the country’s and cities’ COVID infection growth rates were higher, marking the link between the pandemic and the observed psychological patterns. Together, the study underscores the large psychological impacts across the country during the first three months of the crisis.

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Imagination, anxiety, and loneliness during the COVID-19 pandemic. -

Imagination is relevant in many aspects of our lives, and has been associated with creativity and overall cognitive development, yet imagination may also have a dark side. In two studies we examined the link between imagination, anxiety, and loneliness during the COVID-19 pandemic. US college students (N = 101, Study 1) and participants from an international community sample (N = 61, Study 2) were tested around the time that rates of COVID-19 cases were escalating. Across both samples, we found that spending more time in one’s imagination was associated with elevated levels of anxiety. Furthermore, frequency of imagination interacted with loneliness in predicting changes in anxiety during, compared to before the pandemic. Specifically, lonely people who spent more time imagining experienced the largest increases in anxiety during, compared to before the pandemic. In Study 1 valence of imagination and changes in anxiety were also moderated by feelings of loneliness, although this effect was not replicated in Study 2. Results indicate that at least some features of imagination, particularly how much time people spend in imaginative states, may be associated with negative mood states, such as feelings of anxiety. Implications and future directions are discussed.

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Fluvastatin mitigates SARS-CoV-2 infection in human lung cells -

Clinical data of patients suffering from COVID-19 have indicated that statin therapy, used to treat hypercholesterolemia, is associated with a better clinical outcome. We therefore investigated the effect of statins on SARS-CoV-2 infection in human lung cells and found that fluvastatin inhibited coronavirus infection, while other tested statins did not. Fluvastatin inhibited high and low pathogenic coronaviruses in vitro and ex vivo in a dose-dependent manner. Proteomic analyses of infected versus uninfected lung epithelial cells treated with fluvastatin, simvastatin, or rosuvastatin revealed that all tested statins modulated the cholesterol synthesis pathways without compromising the innate antiviral immune response. Strikingly, fluvastatin treatment uniquely affected the proteome of SARS CoV 2 infected cells, specifically downregulating proteins that modulate protein translation and viral replication. These results suggest that statin therapy poses no additional risk to individuals exposed to SARS-CoV-2 and that fluvastatin may have a moderate beneficial effect on SARS CoV-2 infection by modulating protein translation.

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The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children -

Background: Children are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed. Methods: We tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS). Findings: Children have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.

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Cohort Profile: A national prospective cohort study of SARS-CoV-2 pandemic outcomes in the U.S. - The CHASING COVID Cohort Study -

Purpose: The CHASING COVID Cohort study is a U.S.-based prospective cohort study launched during the upswing of the U.S. COVID-19 epidemic. The objectives are to: 1) estimate and evaluate determinants of the cumulative incidence of SARS-CoV-2 infection, disease, and deaths; 2) assess the impact of the pandemic on psychosocial and economic outcomes; and 3) assess the uptake of pandemic mitigation strategies. Participants: We began enrolling participants March 28, 2020 using internet-based strategies. Adults >=18 years residing anywhere in the U.S. or U.S. territories were eligible. 6,753 people are enrolled in the cohort, including participants from all 50 U.S. states, the District of Columbia, Puerto Rico, and Guam. Participants are contacted regularly to complete study assessments, including interviews and specimen collection. Findings to date: Of 4,247 participants who provided a specimen for baseline serologic testing, 135 were seropositive by screening antibody testing (3.2%, 95% CI 2.7%-3.5%) and 90 were seropositive by confirmatory antibody testing (2.1%, 95% CI 1.7%-2.6%). Cohort data have been used to assess the role of household crowding and the presence of children in the household as potential risk factors for severe COVID-19 early in the U.S. pandemic; to describe the prevalence of anxiety symptoms and its relationship to COVID-19 outcomes and other potential stressors; and to identify preferences for SARS-CoV-2 diagnostic testing when community transmission is on the rise via a discrete choice experiment. Future plans: The CHASING COVID Cohort Study has outlined a research agenda that involves ongoing monitoring of the cumulative incidence and determinants of SARS-CoV-2 outcomes, mental health outcomes and economic outcomes. Additional priorities include COVID-19 vaccine hesitancy, uptake and effectiveness; incidence, prevalence and correlates of long-haul COVID-19; and the extent and duration of the protective effect of SARS-CoV-2 antibodies.

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The ancient cardioprotective mechanisms of ACE2 bestow SARS-CoV-2 with a wide host range -

SARS-CoV-2 infects a broader range of mammalian species than previously anticipated, suggesting there may be additional unknown hosts wherein the virus can evolve and potentially circumvent effective vaccines. We find that SARS-CoV-2 gains a wide host range by binding ACE2 sites essential for ACE2 carboxypeptidase activity. Six mutations found only in rodent species immune to SARS-CoV-2 are sufficient to abolish viral binding to human and dog ACE2. This is achieved through context-dependent mutational effects (intramolecular epistasis) conserved despite ACE2 sequence divergence between species. Across mammals, this epistasis generates sequence-function diversity, but through structures all bound by SARS-CoV-2. Mutational trajectories to the mouse conformation not bound by SARS-CoV-2 are blocked, by single mutations functionally deleterious in isolation, but compensatory in combination, explaining why human polymorphisms at these sites are virtually non-existent. Closed to humans, this path was opened to rodents via permissive cardiovascular phenotypes and ancient increases to ACE2 activity, serendipitously granting SARS-CoV-2 immunity. This reveals how ancient evolutionary trajectories are linked with unprecedented phenotypes such as COVID-19 and suggests extreme caution should be taken to monitor and prevent emerging animal reservoirs of SARS-CoV-2.

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Spike protein disulfide disruption as a potential treatment for SARS-CoV-2 -

The coronaviral pandemic is exerting a tremendously detrimental impact on global health, quality of life and the world economy, emphasizing the need for effective medications for current and future coronaviral outbreaks as a complementary approach to vaccines. The Spike protein, responsible for cell receptor binding and viral internalization, possesses multiple disulfide bonds raising the possibility that disulfide-reducing agents might disrupt Spike function, prevent viral entry and serve as effective drugs against SARS-CoV-2. Here we show the first experimental evidence that reagents capable of reducing disulfide bonds can inhibit viral infection in cell-based assays. Molecular dynamics simulations of the Spike receptor-binding domain (RBD) predict increased domain flexibility when the four disulfide bonds of the domain are reduced. This flexibility is particularly prominent for the surface loop, comprised of residues 456-490, which interacts with the Spike cell receptor ACE2. Consistent with this finding, the addition of exogenous disulfide bond reducing agents affects the RBD secondary structure, lowers its melting temperature from 52 to 36-39 degrees Celsius and decreases its binding affinity to ACE2 by two orders of magnitude at 37C. Finally, the reducing agents dithiothreitol (DTT) and tris(2-carboxyethyl)phosphine (TCEP) inhibit viral replication at high microM - low milliM levels with a negligible effect on cell viability at these concentrations. The antiviral effect of monothiol-based reductants N-Acetyl-L-cysteine (NAC) and reduced glutathione (GSH) was not observed due to decreases in cell viability. Our research demonstrates the clear potential for medications that disrupt Spike disulfides as broad-spectrum anticoronaviral agents and as a first-line defense against current and future outbreaks.

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Structure-function investigation of a new VUI-202012/01 SARS-CoV-2 variant -

The SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus) has accumulated multiple mutations during its global circulation. Recently, a new strain of SARS-CoV-2 (VUI 202012/01) had been identified leading to sudden spike in COVID-19 cases in South-East England. The strain has accumulated 23 mutations which have been linked to its immune evasion and higher transmission capabilities. Here, we have highlighted structural-function impact of crucial mutations occurring in spike (S), ORF8 and nucleocapsid (N) protein of SARS-CoV-2. Some of these mutations might confer higher fitness to SARS-CoV-2.

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Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck -

The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems.

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Remdesivir and Lopinavir/Ritonavir as Potential Drugs to Treat Corona Virus Disease 2019 -

Drugs that are efficacious against SARS-CoV-2 have yet to be established. Remdesivir and Lopinavir/ritonavir have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Remdesivir not only in vivo but also in vitro testing shows the inhibition of human coronavirus replication, including SARS-CoV as well as Lopinavir/ritonavir that shows promising antiviral drug against SARS-CoV-2.

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Do Chloroquine and Hydroxychloroquine Treat COVID-19? -

Chloroquine is an anti-malarial and autoimmune disease drug, which has an anti- viral activity. In vitro, the Chloroquine and Hydroxychloroquine are potent at inhibiting SARS-CoV. Therefore, Chloroquine and Hydroxychloroquine are being studied for their potential treatment of coronavirus disease 2019. Those drugs are now recommended by the FDA, and multiple health organizations. This aims of this review is to explore the efficacy of the chloroquine and hydrochloroquine in the treatment of the novel COVID-19.

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Evidence for a Connection Between COVID-19 and Exposure to Radiofrequency Radiation from Wireless Telecommunications Including Microwaves and Millimeter Waves -

COVID-19 public health policy has focused on the SARS-CoV-2 virus and its effects on human health while environmental factors have been largely ignored. In considering the epidemiological triad (agent-host-environment) applicable to all disease, we investigated a possible environmental factor in the COVID-19 pandemic: ambient radiofrequency radiation from wireless communication systems including microwaves and millimeter waves. COVID-19 surfaced in Wuhan, China shortly after the implementation of city-wide 5G (fifth generation of wireless radiation), and spread globally, demonstrating a statistical correlation to international communities with 5G antennas installed. In this study, we examined the peer-reviewed scientific literature on the detrimental bioeffects of radiofrequency radiation (RFR) and identified several ways in which RFR may be contributing to COVID-19 as a toxic environmental cofactor. We conclude that RFR and, in particular, 5G, which involves 4G infrastructure densification, has exacerbated COVID-19 prevalence and severity by weakening host immunity and increasing SARS-CoV-2 virulence by (1) causing morphologic changes in erythrocytes including echinocyte and rouleaux formation that may be contributing to hypercoagulation; (2) impairing microcirculation and reducing erythrocyte and hemoglobin levels exacerbating hypoxia; (3) amplifying immune system dysfunction, including immunosuppression, autoimmunity, and hyperinflammation; (4) increasing cellular oxidative stress and the production of free radicals exacerbating vascular injury and organ damage; (5) augmenting intracellular Ca2+ essential for viral entry, replication, and release, in addition to promoting pro-inflammatory pathways; and (6) worsening heart arrhythmias and cardiac disorders. In short, RFR is a ubiquitous environmental stressor that contributes to adverse health outcomes of COVID-19. We invoke the Precautionary Principle and strongly recommend a moratorium on 5G wireless infrastructure at this crucial time to help mitigate the pandemic, and to preserve public health until governmental safety standards for RFR exposure based on current and future research are defined and employed.

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Brazilian model estimation for SARS-CoV-2 peak contagion (BMESPC): first and second wave -

With newer data for SARS-CoV-2 and entering the second wave of contagion required the improvement of the forecasting model, structuring its model to forecast the peak of the first and second contagion wave in Brazil. The Brazilian model estimation for SARS-CoV-2 peak contagion (BMESPC) was structured, capable of estimating the peak of contagion for SARS-CoV-2 in the first and second waves, as the main objective of this work. Using the BMESPC model, it was possible to estimate, with a certain reliability degree, the peak of contagion for the first and second waves in Brazil, with one day difference from the real to the forecast. While at the state level, the calculated confidence interval proved to be more accurate. In this way, it is possible to use BMESPC to forecast the peak of contagion for several regions, provided that the necessary structure and calibration are respected.

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Oxygen saturation instability in suspected covid-19 patients; contrasting effects of reduced VA/Q and shunt. -

Patients in the UK at risk of Covid-19 pneumonia, but not needing immediate hospital attention, are to be given pulse oximeters to identify a fall in oxygen saturation (SaO2 or SpO2) at home. A recent finding in Covid-19 pneumonia is a dominant reduction in ventilation to perfused alveoli (VA/Q). A mathematical model of gas exchange was used to predict the effect of shunt or reduced VA/Q on SaO2 stability inferred from the slope of the PIO2 vs SaO2 curve as it intersected the line representing ambient PIO2. A ±1 kPa variation in PIO2 predicted a 1.5% and 8% change in SpO2 with 15% shunt and 0.4 VA/Q respectively. As a consistency check, two patients with pre-existing lung disease and 12 hour continuous SpO2 monitoring breathing air had gas exchange impairment analysed in terms of shunt and reduced VA/Q. The patient with 16% shunt and normal VA/Q had a stable but reduced SpO2 (circa 93±1%) throughout the 12 hr period. The patient with a VA/Q reduced to 0.48 had SpO2 ranging from 75-95% during the same period. SpO2 monitoring in suspected covid-19 patients should focus on SpO2 varying >5% in 30 minutes. Such instability in at risk patients is not diagnostic of Covid -19 pneumonia but this may be suspected from a dominant reduction in VA/Q if episodic hypoxaemia has progressed from a stable SpO2. Key words. Covid-19, Respiratory Measurement, Pneumonia, ARDS, VA/Q, Shunt, Oxygen Saturation.

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Covid-19 Sentry

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