Changes in Relationship Satisfaction in the Early Stages of the COVID-19 Pandemic: A Cross-National Examination of Situational, Dispositional, and Relationship Factors -

The outbreak of the COVID-19 pandemic has had a large impact on various aspects of life, but questions about its effect on close relationships remain largely unanswered. In the present study, we examined changes in relationship satisfaction at the beginning of the COVID-19 pandemic by using a sample of 3,243 individuals from 68 different countries. Participants responded to an online survey that included questions about relationship aspects (e.g., shared time, housework division), special circumstances (e.g., exit restrictions), and enduring dispositions (e.g., insecure attachment). A decline in time shared with one’s partner was the strongest predictor of decreases in relationship satisfaction, resulting in a different pattern of findings for cohabiting and non-cohabiting individuals. Among the most influential moderators were lockdown policies and insecure attachment. Differential involvement of men and women in household duties remained largely unchanged. The findings offer insights into aggravating and/or protecting factors in couples’ responses to pandemic-related stressors.

🖺 Full Text HTML: Changes in Relationship Satisfaction in the Early Stages of the COVID-19 Pandemic: A Cross-National Examination of Situational, Dispositional, and Relationship Factors

The angiotensin type 2 receptor agonist C21 restores respiratory function in COVID19 - a double-blind, randomized, placebo-controlled Phase 2 trial -

Background: Although several therapies have been evaluated for treatment of COVID-19, the morbidity and mortality in COVID-19 are still significant, and the need for safe and effective drugs remains high even after launch of vaccine programs. Methods: We conducted a double-blind, randomized, placebo-controlled trial with the novel oral angiotensin II type 2 receptor agonist C21 in hospitalized COVID-19 patients with C-reactive protein 50-150 mg/L but not needing mechanical ventilation. Patients were randomly assigned to oral C21 (100 mg twice daily) or placebo for 7 days in addition to standard of care, including glucocorticoids and remdesivir. Results: 106 patients underwent randomization (51 in the C21 group and 55 in the placebo group). At day 14 after start of treatment, the proportion of patients still requiring supplemental oxygen was significantly reduced by 90% in the C21 group compared to the placebo group (p=0.003). Moreover, fewer patients required mechanical ventilation (one C21 patient and four placebo patients), and C21 was associated with a numerical reduction in the mortality rate (one and three deaths in the C21 and placebo group, respectively). Treatment with C21 was safe and well tolerated. Conclusions: As studied in hospitalized COVID-19 patients, C21 on top of standard of care led to a clinically beneficial improvement in respiratory function compared to placebo, paving the way for a pivotal randomised controlled trial.

🖺 Full Text HTML: The angiotensin type 2 receptor agonist C21 restores respiratory function in COVID19 - a double-blind, randomized, placebo-controlled Phase 2 trial

Immune response to SARS-CoV-2 in the nasal mucosa in children and adults -

Rationale: Despite similar viral load and infectivity rates between children and adults infected with SARS-CoV-2, children rarely develop severe illness. Differences in the host response to the virus at the primary infection site are among the proposed mechanisms. Objectives: To investigate the host response to SARS-CoV-2, respiratory syncytial virus (RSV), and influenza virus (IV) in the nasal mucosa in children and adults. Methods: Clinical outcomes and gene expression in the nasal mucosa were analyzed in 36 children hospitalized with SARS-CoV-2 infection, 24 children with RSV infection, 9 children with IV infection, 16 adults with mild to moderate SARS-CoV-2 infection, and 7 healthy pediatric and 13 healthy adult controls. Results: In both children and adults, infection with SARS-CoV-2 leads to an interferon response in the nasal mucosa. The magnitude of the interferon response correlated with the abundance of viral reads and was comparable between symptomatic children and adults infected with SARS-CoV-2 and symptomatic children infected with RSV and IV. Cell type deconvolution identified an increased abundance of immune cells in the samples from children and adults with a viral infection. Expression of ACE2 and TMPRSS2 - key entry factors for SARS-CoV-2 - did not correlate with age or presence or absence of viral infection. Conclusions: Our findings support the hypothesis that differences in the immune response to SARS-CoV-2 determine disease severity, independent of viral load and interferon response at the primary infection primary site. Keywords: COVID-19, pneumonia, viral infections, interferons

🖺 Full Text HTML: Immune response to SARS-CoV-2 in the nasal mucosa in children and adults

Individual factors underlie temperature variation in sickness and in health: influence of age, BMI and genetic factors in a multi-cohort study -

Introduction: Ageing affects immune function resulting in aberrant fever response to infection. We assess the effects of biological variables on basal temperature and temperature in COVID-19 infection, proposing an updated temperature threshold for older adults. Methods: Participants: a) Unaffected twin volunteers: 1089 adult TwinsUK participants. b) London hospitalised COVID-19+: 520 adults with emergency admission. c) Birmingham hospitalised COVID-19+: 757 adults with emergency admission. d) Community-based COVID-19+: 3972 adults self-reporting a positive test using the COVID Symptom Study mobile application. Analysis: Heritability assessed using saturated and univariate ACE models: Linear mixed-effect and multivariable linear regression analysing associations between temperature, age, sex and BMI; multivariable logistic regression analysing associations between fever (>=37.8degC) and age; receiver operating characteristic (ROC) analysis to identify temperature threshold for adults >=65 years. Results: Among unaffected volunteers, lower BMI (p=0.001), and older age (p<0.001) associated with lower basal temperature. Basal temperature showed a heritability of 47% (95% Confidence Interval 18-57%). In COVID-19+ participants, increasing age associated with lower temperatures in cohorts (c) and (d) (p<0.001). For each additional year of age, participants were 1% less likely to demonstrate a fever (OR 0.99; p<0.001). Combining healthy and COVID-19+ participants, a temperature of 37.4degC in adults >=65 years had similar sensitivity and specificity to 37.8degC in adults <65 years for discriminating fever in COVID-19. Conclusions: Ageing affects temperature in health and acute infection. Significant heritability indicates biological factors contribute to temperature regulation. Our observations indicate a lower threshold (37.4degC) should be considered for assessing fever in older adults.

🖺 Full Text HTML: Individual factors underlie temperature variation in sickness and in health: influence of age, BMI and genetic factors in a multi-cohort study

Trajectories of Hypoxemia & Respiratory System Mechanics of COVID-19 ARDS in the NorthCARDS dataset -

Rationale: The preliminary reports of COVID Acute Respiratory Distress Syndrome (COVIDARDS) suggest the existence of a subset of patients with higher lung compliance despite profound hypoxemia. Understanding heterogeneity seen in patients with COVIDARDS and comparing to non-COVIDARDS may inform tailored treatments. Objectives: To describe the trajectories of hypoxemia and respiratory compliance in COVIDARDS and associations with outcomes. Methods: A multidisciplinary team of frontline clinicians and data scientists created the Northwell COVIDARDS dataset (NorthCARDS) leveraging over 11,542 COVID-19 hospital admissions. Data was summarized to describe differences based on clinically meaningful categories of lung compliance, and compared to non-COVIDARDS reports. A sophisticated method of extrapolating PaO2 from SpO2, as well estimating FiO2 from non invasive oxygen delivery devices were utilized to create meaningful trends of derived PaO2 to FiO2 (P/F). Measurements and Main Results: Of the 1595 COVIDARDS patients in the NorthCARDS dataset, there were 538 (34.6%) who had very low lung compliance (<20ml/cmH2O), 982 (63.2%) with low-normal compliance (20-50ml/cmH2O), and 34 (2.2%) with high lung compliance (>50ml/cmH2O). The very low compliance group had double the median time to intubation compared to the low-normal group (107 hours(IQR 26.3, 238.3) vs. 37.9 hours(IQR 4.8, 90.7)). Oxygenation trends have improved in all groups after a nadir immediately post intubation. The P/F ratio improved from a mean of 109 to 155, with the very low compliance group showing a smaller improvement compared to low compliance group. The derived P/F trends closely correlated with blood gas analysis driven P/F trends, except immediately post intubation were the trends diverge as illustrated in the image. Overall, 67.5% (n=1049) of the patients died during the hospitalization. In comparison to non-COVIDARDS reports, there were less patients in the high compliance category (2.2%vs 12%, compliance equal or over 50mL/cmH20), and more patients with P/F less than 150 ( 57.8% vs. 45.6%). No correlation was apparent between lung compliance and P/F ratio. The Oxygenation Index was similar, (11.12(SD 5.67)vs 12.8(SD 10.8)). Conclusions: Heterogeneity in lung compliance is seen in COVIDARDS, without apparent correlation to degree of hypoxemia. Notably, time to intubation was greater in the very low lung compliance category. Understanding ARDS patient heterogeneity must include consideration of treatment patterns in addition to trajectories of change in patient-level data and demographics.

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Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19 -

Although T cells are likely players in SARS-CoV-2 immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe COVID-19. We analyzed T cells from longitudinal specimens of 34 COVID-19 patients with severities ranging from mild (outpatient) to critical culminating in death. Relative to patients that succumbed, individuals that recovered from severe COVID-19 harbored elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 displayed elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of severe COVID-19 patients, these results support a model whereby lung-homing T cells activated through bystander effects contribute to immunopathology, while a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.

🖺 Full Text HTML: Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19

Effect of COVID-19 response policies on walking behavior in US cities -

The COVID-19 pandemic has caused mass disruption to our daily lives. Mobility restrictions implemented to reduce the spread of COVID-19 have impacted walking behavior, but the magnitude and spatio-temporal aspects of these changes have yet to be explored. Walking is the most common form of physical activity and non-motorized transport, and so has an important role in our health and economy. Understanding how COVID-19 response measures have affected walking behavior of populations and distinct subgroups is paramount to help devise strategies to prevent the potential health and societal impacts of declining walking levels. In this study, we integrated mobility data from mobile devices and area-level data to study the walking patterns of 1.62 million anonymous users in 10 metropolitan areas in the United States (US). The data covers the period from mid-February 2020 (pre-lockdown) to late June 2020 (easing of lockdown restrictions). We detected when users were walking, measured distance walked and time of the walk, and classified each walk as recreational or utilitarian. Our results revealed dramatic declines in walking, especially utilitarian walking, while recreational walking has recovered and even surpassed the levels before the pandemic. However, our findings demonstrated important social patterns, widening existing inequalities in walking behavior across socio-demographic groups. COVID-19 response measures had a larger impact on walking behavior for those from low-income areas, of low education, and high use of public transportation. Provision of equal opportunities to support walking could be key to opening up our society and the economy.

🖺 Full Text HTML: Effect of COVID-19 response policies on walking behavior in US cities

Retrospective Analysis of Interventions to Epidemics using Dynamic Simulation of Population Behavior -

Retrospective analyses of interventions to epidemics, in which the effectiveness of strategies implemented are compared to hypothetical alternatives, are valuable for performing the cost-benefit calculations necessary to optimize infection countermeasures. SIR (susceptible-infected-removed) models are useful in this regard but are limited by the challenge of deciding how and when to update the numerous parameters as the epidemic changes in response to population behaviors. We present a method that uses a 9dynamic spread function9 to systematically capture the continuous variation in the population behavior, and the gradual change in infection dynamics, resulting from interventions. No parameter updates are made by the user. We use the tool to quantify the reduction in infection rate realizable from the population of New York City adopting different facemask strategies during COVID-19. Assuming a baseline facemask of 67% filtration efficiency, calculations show that increasing the efficiency to 75% could reduce the roughly 5000 new infections per day occurring at the peak of the epidemic to 3000. Mitigation strategies that may not be varied as part of the retrospective analysis, such as social distancing, are automatically captured as part of the calibration of the dynamic spread function.

🖺 Full Text HTML: Retrospective Analysis of Interventions to Epidemics using Dynamic Simulation of Population Behavior

COVID-19 Susceptibility and Severity Risks in a Survey of Over 500,000 Individuals -

The enormous toll of the COVID-19 pandemic has heightened the urgency of collecting and analyzing population-scale datasets in real time to monitor and better understand the evolving pandemic. The AncestryDNA COVID-19 Study collected self-reported survey data on symptoms, outcomes, risk factors, and exposures for over 563,000 adult individuals in the U.S. in just under four months, including over 4,700 COVID-19 cases as measured by a self-reported positive test. We replicated previously reported associations between several risk factors and COVID-19 susceptibility and severity outcomes, and additionally found that differences in known exposures accounted for many of the susceptibility associations. A notable exception was elevated susceptibility for males even after adjusting for known exposures and age (adjusted odds ratio [aOR]=1.36, 95% confidence interval [CI] = (1.19, 1.55)). We also demonstrated that self-reported data can be used to build accurate risk models to predict individualized COVID-19 susceptibility (area under the curve [AUC]=0.84) and severity outcomes including hospitalization and critical illness (AUC=0.87 and 0.90, respectively). The risk models achieved robust discriminative performance across different age, sex, and genetic ancestry groups within the study. The results highlight the value of self-reported epidemiological data to rapidly provide public health insights into the evolving COVID-19 pandemic.

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Honesty-Humility, beliefs, and prosocial behaviour: A test on stockpiling during the COVID-19 pandemic -

Increasing evidence links personality to prosocial behaviour. HEXACO Honesty-Humility, in particular, has been linked to prosocial behaviour when it comes with a personal cost. Yet, evidence for such a link is mostly limited to the laboratory, although social dilemmas abound in daily life. Emergencies such as the COVID-19 pandemic pose salient conflicts of interests between individual and societal welfare. One example is the run on many basic goods in the anticipation of lockdowns. Such social dilemmas afford the expression of personality traits associated with individual differences in prosocial behaviour. Indeed, across two studies (N = 601), Honesty-Humility was positively, albeit weakly associated with refraining from stockpiling in the past and intentions to do so in the future. Causal mediation analysis shows that this was not due to differences in beliefs that others would refrain from stockpiling. Instead, results suggest that faced with a social dilemma, individuals high in Honesty-Humility may have been willing to forego individual benefit. This provides rare evidence on the relationship between Honesty-Humility and prosocial behaviour in a field setting.

🖺 Full Text HTML: Honesty-Humility, beliefs, and prosocial behaviour: A test on stockpiling during the COVID-19 pandemic

E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil -

The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people since its beginning in 2019. The propagation of new lineages and the discovery of key mechanisms adopted by the virus to overlap the immune system are central topics for the entire public health policies, research and disease management. Since the second semester 2020, the mutation E484K has been progressively found in the Brazilian territory, composing different lineages over time. It brought multiple concerns related to the risk of reinfection and the effectiveness of new preventive and treatment strategies due to the possibility of escaping from neutralizing antibodies. To better characterize the current scenario we performed genomic and phylogenetic analyses of the E484K mutated genomes sequenced from brazilian samples in 2020. From October, 2020, 43.9% of the sequenced genomes present the E484K mutation, which was identified in three different lineages (P1, P2 and B.1.1.33) in four Brazilian regions. We also evaluated the presence of E484K associated mutations and identified selective pressures acting on the spike protein, leading us to some insights about adaptive and purifying selection driving the virus evolution.

🖺 Full Text HTML: E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil

Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro. -

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a vast number of infections and fatalities worldwide. As the development and safety validation of effective vaccines are ongoing, drug repurposing is most efficient approach to search FDA approved agents against coronavirus disease 2019 (COVID-19). In the present study, we found that endogenous ACE2 expressions could be detected in H322M and Calu-3 cell lines, as well as their ACE2 mRNA and protein expressions were suppressed by pyrrolidine dithiocarbamate (PDTC), a NF-kappa B inhibitor, in dose- and time-dependent manners. Moreover, N-acetyl-cysteine (NAC) pretreatment reversed PDTC-induced ACE2 suppression, as well as the combined treatment of hydrogen peroxide and knockdown of p50 subunit of NF-kappa B by siRNA reduced ACE2 expression in H322M cells. In addition, anthelmintic drug triclabendazole and antiprotozoal drug emetine, repurposed drugs of NF-kappa B inhibitor, also inhibited ACE2 mRNA and protein expressions in H322M cells. Moreover, zinc supplement augmented the suppressive effects of triclabendazole and emetine on ACE2 suppression in H322M and Calu-3 cells. Taken together, these results indicate that ACE2 expression is modulated by reactive oxygen species (ROS) and NF-kappa B signal in human lung cell lines, and zinc combination with triclabendazole or emetine has the clinical potential for the prevention and treatment of COVID-19.

🖺 Full Text HTML: Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro.

Lysosomal-Immune Axis Is Associated with COVID 19 Disease Severity: Insights from Patient Single Cell Data -

SARS-COV-2 has become a leading cause of illness, hospitalizations, and deaths worldwide yet heterogeneity in disease morbidity remains a conundrum. In this study, we analyzed publicly available single-cell RNA-seq data from 75076 cells sequenced from clinically staged COVID-19 patients using a network approach and identified lysosomal-immune axis as a factor significantly associated with disease severity. Our results suggest modulation of lysosomal-immune pathways may present a novel drug-targeting strategy to attenuate SARS-Cov-2 infections.

🖺 Full Text HTML: Lysosomal-Immune Axis Is Associated with COVID 19 Disease Severity: Insights from Patient Single Cell Data

Computational Analysis of Protein Stability and Allosteric Interaction Networks in Distinct Conformational Forms of the SARS-CoV-2 Spike D614G Mutant: Reconciling Functional Mechanisms through Allosteric Model of Spike Regulation -

Structural and biochemical studies SARS-CoV-2 spike mutants with the enhanced infectivity have attracted significant attention and offered several mechanisms to explain the experimental data. The development of a unified view and a working model which is consistent with the diverse experimental data is an important focal point of the current work. In this study, we used an integrative computational approach to examine molecular mechanisms underlying functional effects of the D614G mutation by exploring atomistic modeling of the SARS-CoV-2 spike proteins as allosteric regulatory machines. We combined coarse-grained simulations, protein stability and dynamic fluctuation communication analysis along with network-based community analysis to simulate structures of the native and mutant SARS-CoV-2 spike proteins in different functional states. The results demonstrated that the D614 position anchors a key regulatory cluster that dictates functional transitions between open and closed states. Using molecular simulations and mutational sensitivity analysis of the SARS-CoV-2 spike proteins we showed that the D614G mutation can improve stability of the spike protein in both closed and open forms, but shifting thermodynamic preferences towards the open mutant form. The results offer support to the reduced shedding mechanism of S1 domain as a driver of the increased infectivity triggered by the D614G mutation. Through distance fluctuations communication analysis, we probed stability and allosteric communication propensities of protein residues in the native and mutant SARS-CoV-2 spike proteins, providing evidence that the D614G mutation can enhance long-range signaling of the allosteric spike engine. By employing network community analysis of the SARS-CoV-2 spike proteins, our results revealed that the D614G mutation can promote the increased number of stable communities and allosteric hub centers in the open form by reorganizing and enhancing the stability of the S1-S2 inter-domain interactions and restricting mobility of the S1 regions. This study provides atomistic-based view of the allosteric interactions and communications in the SARS-CoV-2 spike proteins, suggesting that the D614G mutation can exert its primary effect through allosterically induced changes on stability and communications in the residue interaction networks.

🖺 Full Text HTML: Computational Analysis of Protein Stability and Allosteric Interaction Networks in Distinct Conformational Forms of the SARS-CoV-2 Spike D614G Mutant: Reconciling Functional Mechanisms through Allosteric Model of Spike Regulation

An Updated Investigation Prior To COVID-19 Vaccination Program In Indonesia: Full-Length Genome Mutation Analysis Of SARS-CoV-2 -

Indonesia kick-started the big project of COVID-19 vaccination program in January 2021 by employed vaccine to the president of Indonesia. The outbreak and rapid transmission of COVID-19 have endangered the global health and economy. This study aimed to investigate the full-length genome mutation analysis of 166 Indonesian SARS-CoV-2 isolates as 12 January 2021. All data of isolates was extracted from the Global Initiative on Sharing All Influenza Data (GISAID) EpiCoV database. CoVsurver was employed to investigate the full-length genome mutation analysis of all isolates. Furthermore, this study also focused on the unlocking of mutation in Indonesian SARS-CoV-2 isolates S protein. WIV04 isolate that was originated from Wuhan, China was used as a virus reference according to CoVsurver default. All data was visualized using GraphPad Prism software, PyMOL, and BioRender. This study result showed that a full-length genome mutation analysis of 166 Indonesian SARS-CoV-2 isolates was successfully discovered. Every single mutation in S protein was described and then visualised by employing BioRender. Furthermore, it also found that D614G mutation appeared in 103 Indonesian SARS-CoV-2 isolates. To sum up, this study helps to observe the spread of the COVID-19 transmission. However, it would like to propose that the epidemiological surveillance and genomics studies might be improved on COVID-19 pandemic in Indonesia.

🖺 Full Text HTML: An Updated Investigation Prior To COVID-19 Vaccination Program In Indonesia: Full-Length Genome Mutation Analysis Of SARS-CoV-2

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