10 March, 2021

Transparent Communication About COVID-19 Vaccines Is Not Sufficient for Acceptance but It is Necessary for Trust -

During the rapid development and rolling-out of vaccines against SARS-CoV-2, researchers have called for an approach of “radical transparency”, where vaccine information is transparently disclosed to the public, even if negative information can decrease vaccine uptake. Consistent with theories about the psychology of conspiracy beliefs, these calls predict that a lack of transparency may reduce trust in health authorities and facilitate the spread of conspiracy theories, which may limit the long-term capabilities of health authorities during and after the pandemic. On the basis of pre-registered experiments conducted on large, representative samples of Americans and Danes (N > 13,000), the present study contrasts the effects of vague vaccine communication with transparent communication, which discloses either positive or negative vaccine features. The evidence demonstrates that transparent negative communication may indeed harm vaccine acceptance here and now but that it increases trust in health authorities. Furthermore, the alternative of vague, reassuring communication does not increase vaccine acceptance either and leads to both lower trust and higher endorsements of conspiracy theories.

🖺 Full Text HTML: Transparent Communication About COVID-19 Vaccines Is Not Sufficient for Acceptance but It is Necessary for Trust

Gender and Racial/Ethnic Disparities in Undergraduate and Graduate Students’ Mental Health and Treatment Use amid the COVID-19 Pandemic -

Objective: To investigate gender and racial/ethnic disparities in mental health and treatment use in college and graduate students amid the COVID-19 pandemic. Method: Based on a large-scale online survey (N = 1,415) administered during the weeks following a pandemic-related university-wide campus closure in March 2020, we examined gender and racial disparities in current internalizing severity and treatment use with t-tests and logistic regression models. Results: Specifically, we found that students with marginalized gender (e.g., woman [p < .001], non-binary gender [p < .001]) or Hispanic/Latinx identity (p = .002) reported higher levels of internalizing problem severity compared to their privileged counterparts (e.g., man, non- Hispanic/Latinx White). Regarding treatment use, Asian (p < .001) and multiracial students (p = .002) reported lower treatment use after controlling for internalizing problem severity. Internalizing severity was generally associated with higher treatment use (logit = 0.53, p = .001), indicating a match of objective needs with service use. However, this relationship was offset by a negative interaction between internalizing problem severity and Asian (logit = -0.49, p < .001) or Black identity (logit = -0.57, p = .03) in predicting treatment use. Conclusion: The findings revealed unique mental health challenges faced by different demographic groups and served as a call that specific actions to enhance mental health equity, such as continued mental health support for students with marginalized gender identities, additional COVID-related mental and practical support for Hispanic/Latinx students, and promotion of mental health awareness and trust in Asian/Black students, are desperately needed.

🖺 Full Text HTML: Gender and Racial/Ethnic Disparities in Undergraduate and Graduate Students’ Mental Health and Treatment Use amid the COVID-19 Pandemic

Site-specific steric control of SARS-CoV-2 spike glycosylation -

A central tenet in the design of recombinant vaccines is the display of native-like antigens in the elicitation of protective immunity. However, the diversity of global vaccine strategies against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses challenges to benchmark antigens across global vaccine programs. Here, we investigate the glycosylation of a variety of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against the glycan shield of an infectious virus. The site-specific stalling of glycan maturation is a highly sensitive reporter of local protein structure and we find there is remarkable conservation of this feature across all samples. Analysis of molecular dynamics simulations of a fully glycosylated spike supports a model of steric restrictions that shape enzymatic processing of the glycans. Furthermore, we show that there is a conserved glycosylation pattern across the monomeric receptor binding domain (RBD) protein and the complete trimeric spike (S) protein. This is in contrast to RBD glycosylation in Middle East respiratory syndrome coronavirus (MERS-CoV) where quaternary architecture limits glycan processing when in the context of full-length MERS-CoV S protein. These results suggest that spike-based immunogen glycosylation reproducibly recapitulates viral glycosylation.

🖺 Full Text HTML: Site-specific steric control of SARS-CoV-2 spike glycosylation

The FDA-approved drug cobicistat synergizes with remdesivir to inhibit SARS-CoV-2 replication -

Combinations of direct-acting antivirals are needed to minimize drug-resistance mutations and stably suppress replication of RNA viruses. Currently, there are limited therapeutic options against the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) and testing of a number of drug regimens has led to conflicting results. Here we show that cobicistat, which is an-FDA approved drug-booster that blocks the activity of the drug metabolizing proteins Cytochrome P450-3As (CYP3As) and P-glycoprotein (P-gp), inhibits SARS-CoV-2 replication. Cell-to-cell membrane fusion assays indicated that the antiviral effect of cobicistat is exerted through inhibition of spike protein-mediated membrane fusion. In line with this, incubation with low micromolar concentrations of cobicistat decreased viral replication in three different cell lines including cells of lung and gut origin. When cobicistat was used in combination with the putative CYP3A target and nucleoside analog remdesivir, a synergistic effect on the inhibition of viral replication was observed in cell lines and in a primary human colon organoid. The cobicistat/remdesivir combination was able to potently abate viral replication to levels comparable to mock-infected cells leading to an almost complete rescue of infected cell viability. These data highlight cobicistat as a therapeutic candidate for treating SARS-CoV-2 infection and as a potential building block of combination therapies for COVID-19.

🖺 Full Text HTML: The FDA-approved drug cobicistat synergizes with remdesivir to inhibit SARS-CoV-2 replication

In vitro rapid inactivation of SARS-CoV-2 by visible light photocatalysis using boron-doped bismuth oxybromide -

Inactivation of SARS-CoV-2 in wastewater and on surfaces is critical to prevent the fecal-oral and fomite transmission, respectively. We hypothesized that visible light active photocatalysts could dramatically enhance the rate or extent of virus inactivation and enable the use of visible light rather than shorter wavelength ultraviolet light. A novel visible light active photocatalyst, boron-doped bismuth oxybromide (B-BiOBr), was synthesized and tested for its SARS-CoV-2 inactivation towards Vero E6 cell lines in dark and under irradiation at 426 nm by a light emitting diode (LED) in water. SARS-CoV-2 inactivation in the presence of B-BiOBr (0.8 g/L) under LED irradiation reached 5.32-log in 5 min, which was 400 to 10,000 times higher than those achieved with conventional photocatalysts of tungsten or titanium oxide nanomaterials, respectively. Even without LED irradiation, B-BiOBr inactivated 3.32-log of SARS-CoV-2 in the dark due to the ability of bismuth ions interfering with the SARS-CoV-2 helicase function. LED irradiation at 426 nm alone, without the photocatalyst, contributed to 10% of the observed inactivation and was attributed to production of reactive oxygen species due to blue-light photoexcitation of molecules in the culture media, which opens further modes of action to engineer disinfection strategies. The visible light active B-BiOBr photocatalyst, with its rapid SARS-CoV-2 inactivation in the presence and absence of light, holds tremendous opportunities to build a healthy environment by preventing the fecal-oral and fomite transmission of emerging pathogens.

🖺 Full Text HTML: In vitro rapid inactivation of SARS-CoV-2 by visible light photocatalysis using boron-doped bismuth oxybromide

A recombinant ACE2 Triple Decoy that traps and neutralizes SARS-CoV-2 shows enhanced affinity for highly transmissible SARS-CoV-2 variants -

The highly-transmissible SARS-CoV-2 variants now replacing the first wave strain pose an increased threat to human health by their ability, in some instances, to escape existing humoral protection conferred by previous infection, neutralizing antibodies, and possibly vaccination. Thus, other therapeutic options are necessary. One such therapeutic option that leverages SARS-CoV-2 initiation of infection by binding of its spike receptor binding domain (S RBD) to surface-expressed host cell angiotensin-converting enzyme 2 (ACE2) is an ACE2 decoy that would trap the virus by competitive binding and thus inhibit propagation of infection. Here, we used Molecular Dynamic (MD) simulations to predict ACE2 mutations that might increase its affinity for S RBD and screened these candidates for binding affinity in vitro. A double mutant ACE2(T27Y/H34A)-IgG1FC fusion protein was found to have very high affinity for S RBD and to show greater neutralization of SARS-CoV-2 in a live virus assay as compared to wild type ACE2. We further modified the double mutant ACE2 decoy by addition of an H374N mutation to inhibit ACE2 enzymatic activity while maintaining high S RBD affinity. We then confirmed the potential efficacy of our ACE2(T27Y/H34A/H374N)-IgG1FC Triple Decoy against S RBD expressing variant-associated E484K, K417N, N501Y, and L452R mutations and found that our ACE2 Triple Decoy not only maintains its high affinity for S RBD expressing these mutations, but shows enhanced affinity for S RBD expressing the N501Y or L452R mutations and the highest affinity for S RBD expressing both the E484K and N501Y mutations. The ACE2 Triple Decoy also demonstrates the ability to compete with wild type ACE2 in the cPass surrogate virus neutralization in the presence of S RBD with these mutations. Additional MD simulation of ACE2 WT and decoy interactions with S RBD WT or B.1.351 variant sequence S RBD provides insight into the enhanced affinity of the ACE2 decoy for S RBD and reveals its potential as a tool to predict affinity and inform therapeutic design. The ACE2 Triple Decoy is now undergoing continued assessment, including expression by a human adenovirus serotype 5 (hAd5) construct to facilitate delivery in vivo.

🖺 Full Text HTML: A recombinant ACE2 Triple Decoy that traps and neutralizes SARS-CoV-2 shows enhanced affinity for highly transmissible SARS-CoV-2 variants

COVIDrugNet: a network-based web tool to investigate the drugs currently in clinical trial to contrast COVID-19 -

The COVID-19 pandemic poses a huge problem of public health that requires the implementation of all available means to contrast it, and drugs are one of them. In this context, we observed an unmet need of depicting the continuously evolving scenario of the ongoing drug clinical trials through an easy-to-use, freely accessible online tool. Starting from this consideration, we developed COVIDrugNet (http://compmedchem.unibo.it/covidrugnet), a web application that allows users to capture a holistic view and keep up to date on how the clinical drug research is responding to the SARS-CoV-2 infection. Here, we describe the web app and show through some examples how one can explore the whole landscape of medicines in clinical trial for the treatment of COVID-19 and try to probe the consistency of the current approaches with the available biological and pharmacological evidence. We conclude that careful analyses of the COVID-19 drug-target system based on COVIDrugNet can help to understand the biological implications of the proposed drug options, and eventually improve the search for more effective therapies.

🖺 Full Text HTML: COVIDrugNet: a network-based web tool to investigate the drugs currently in clinical trial to contrast COVID-19

Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps -

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses.

🖺 Full Text HTML: Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps

The N501Y spike substitution enhances SARS-CoV-2 transmission -

Beginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom (UK). This B.1.1.7 variant increased rapidly in prevalence among sequenced strains, attributed to an increase in infection and/or transmission efficiency. The UK variant has 19 nonsynonymous mutations across its viral genome including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 UK spike mutations, suggesting it is a major determinant responsible for increased transmission of this variant. Mechanistically, the N501Y substitution improved the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil and South Africa, our results indicate that N501Y substitution is a major adaptive spike mutation of major concern.

🖺 Full Text HTML: The N501Y spike substitution enhances SARS-CoV-2 transmission

Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host-factors having implication in the disease pathogenesis and severity -

Syrian golden hamsters (Mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests lung pathology that resembles human COVID-19 patients. In this study, efforts were made to check the infectivity of a local SARS-CoV-2 isolate in hamster model and evaluate the differential expression of lung proteins during acute infection and convalescence. The findings of this study confirm the infectivity of this isolate in vivo. Analysis of clinical parameters and tissue samples shows a similar type of pathophysiological manifestation of SARS-CoV-2 infection as reported earlier in COVID-19 patients and hamsters infected with other isolates. The lung-associated pathological changes were very prominent on the 4th day post-infection (dpi), mostly resolved by 14dpi. Here, we carried out quantitative proteomic analysis of the lung tissues from SARS-CoV-2-infected hamsters at day 4 and day 14 post infection. This resulted in the identification of 1,585 differentially expressed proteins of which 68 proteins were significantly altered among both the infected groups. Pathway analysis revealed complement and coagulation cascade, platelet activation, ferroptosis and focal adhesion as the top enriched pathways. In addition, we also identified altered expression of two pulmonary surfactant-associated proteins (Sftpd and Sftpb), known for their protective role in lung function. Together, these findings will aid in the identification of candidate biomarkers and understanding the mechanism(s) involved in SARS-CoV-2 pathogenesis.

🖺 Full Text HTML: Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host-factors having implication in the disease pathogenesis and severity

Spike mutations in SARS-CoV-2 variants confer resistance to antibody neutralization -

New SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS CoV 2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS CoV 2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N E484K N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

🖺 Full Text HTML: Spike mutations in SARS-CoV-2 variants confer resistance to antibody neutralization

Serological surveys to estimate cumulative incidence of SARS-CoV-2 infection in adults (Sero-MAss study), Massachusetts, July-August 2020- a mail-based cross-sectional study -

Background The SARS-CoV-2 pandemic is an unprecedented global health crisis. The state of Massachusetts was especially impacted during the initial stages; however, the extent of asymptomatic transmission remains poorly understood due to limited asymptomatic testing in the “first wave.” To address this gap, a geographically representative and contact-free seroprevalence survey was conducted in July-August 2020, to estimate prior undetected SARS-CoV-2 infections. Methods Students, faculty, librarians and staff members at the University of Massachusetts, Amherst without a previous COVID-19 diagnosis were invited to participate in this study along with one member of their household in June 2020. Two separate sampling frames were generated from administrative lists: all undergraduates and their household members (primary sampling group) were randomly selected with probability proportional to population size. All staff, faculty, graduate students and librarians (secondary sampling group) were selected as a simple random sample. After informed consent and a socio-behavioral survey, participants were mailed test kits and asked to return self-collected dried blood spot (DBS) samples. Samples were analyzed via ELISA for anti-SARS-CoV-2 IgG antibodies, and then IgM antibodies if IgG-positive. Seroprevalence estimates were adjusted for survey non-response. Binomial models were used to assess factors associated with seropositivity in both sample groups separately. Results Approximately 27,000 persons were invited via email to assess eligibility. Of the 1,001 individuals invited to participate in the study, 762 (76%) returned blood samples for analysis. In the primary sampling group 548 returned samples, of which 230 enrolled a household member. Within the secondary sampling group of 214 individuals, 79 enrolled a household member. In the primary sample group, 36 (4.6%) had IgG antibodies detected for an estimated weighed prevalence for this population of 5.3% (95% CI: 3.5 to 8.0). In the secondary sampling group, 10 (3.4%) of 292 individuals had IgG antibodies detected for an estimated adjusted prevalence of 4.0% (95% CI: 2.2 to 7.4). No samples were IgM positive. No association was found in either sample group between seropositivity and self-reported work duties or customer-facing hours. In the primary sampling group, self-reported febrile illness since Feb 2020, male sex, and minority race (Black or American Indian/Alaskan Native) were associated with seropositivity. No factors except geographic regions within the state were associated with evidence of prior SARS-CoV-2 infection in the secondary sampling group. Interpretation This study provides insight into the seroprevalence of university-related populations and their household members across the state of Massachusetts during the summer of 2020 of the pandemic and helps to fill a critical gap in estimating the levels of sub-clinical and asymptomatic infection. Estimates like these can be used to calibrate models that estimate levels of population immunity over time to inform public health interventions and policy.

🖺 Full Text HTML: Serological surveys to estimate cumulative incidence of SARS-CoV-2 infection in adults (Sero-MAss study), Massachusetts, July-August 2020- a mail-based cross-sectional study

Covid-19 and Human Resource Management: a study on Moldavia, Romania -

Dramatic changes due to the current COVID-19 coronavirus have unparalleled effects on businesses across the globe and have deeply affected human resources management. HRM has taken the lead in handling employees to deal with pressures and continue to work remotely to continue its activities in a vague current and unforeseen future. However, the HRM had to contend with the pandemic lock-down dismissal and staff reduction. The paper is focused on the analysis approach used by qualitative experts. It addresses the problems faced by HRM in Romania, identifies the human resources ramifications of the situation and identifies solutions. It addresses the problems HRM has been facing in Romania, ascertains the effects the crisis has on human resources, points out the strategies companies implemented, and make s suggestions for addressing the crisis from the point of view of HRM. Based on the results, this study recommend the following: giving more consideration for worker mental wellbeing, performing medical tests during the selection process, and encouraging the sick employees to remain at home and developing crisis management plans.

🖺 Full Text HTML: Covid-19 and Human Resource Management: a study on Moldavia, Romania

Categorizing the Status of COVID-19 Outbreaks Around the World -

Although the SARS-CoV-19 virus spread rapidly around in world in early 2020, disease epidemics in different places evolved differently as the year progressed - and the state of the COVID-19 pandemic now varies significantly across different countries and territories. We have created a taxonomy of possible categories of disease dynamics, and used the evolution of reported COVID-19 cases relative to changes in disease control measures, together with total reported cases and deaths, to allocate most countries and territories among the possible categories. As of 31 January 2021, we find that the disease was (1) kept out or suppressed quickly through quarantines and testing & tracing in 39 countries with 29 million people, (2) suppressed on one or more occasions through control measures in 74 countries with 2.49 billion people, (3) spread slowly but not suppressed, with cases still increasing or just past a peak, in 31 countries with 1.45 billion people, (4) spread through the population, but slowed a result of control measures, leading to a “flattened curve” and fewer infections than if the epidemic were unmitigated, in 32 countries with 2.24 billion people, and (5) spread through the population with some but limited mitigation in 5 countries with 168 million people. In addition, several countries have experienced increases in cases after disease appeared to have finished spreading due to declining numbers of susceptible people. For some of these countries - for example Kenya, Pakistan and Afghanistan - the resurgences can be explained by the relaxation of control measures (and may have been enhanced by disease spread in population segments that experienced lower infection levels during the first waves). For other countries, the resurgences point to the effects of new virus variants with higher-transmissibility or immunity resistance - including most countries in Southern Africa (where the B.1.351 variant has been identified) and several countries in West Africa (maybe due to the B.1.351 or a different variant). These findings are consistent with mounting evidence of high infection rates in several low- and middle-income countries, both from seroprevalence studies and estimates of actual deaths from COVID-19 combined with estimates of expected mortality rates. We estimate that 1.3-3.0 billion people, or 17-39% of the global population, have been infected by SARS-CoV-2 to date, and that at least 5 million people have died from COVID-19 - much higher than reported cases and deaths. Disease control policies and vaccination strategies should be designed based on the state of the COVID-19 epidemic in the population - and consequently may need to be different in different countries.

🖺 Full Text HTML: Categorizing the Status of COVID-19 Outbreaks Around the World

Beliefs about Mask Efficacy and the Effect of Social Norms on Mask Wearing Intentions for COVID-19 Risk Reduction -

In the absence of widespread vaccination for COVID-19, governments and public health officials have advocated for the public to wear masks during the pandemic. The decision to wear a mask in public is likely affected by both beliefs about its efficacy and the prevalence of the behavior. Greater mask use in the community may encourage others to follow this norm, but it also creates an incentive for individuals to free ride on the protection afforded to them by others. We report the results of two vignette-based experiments conducted in the United States and Italy to examine the causal relationship between beliefs, social norms, and reported intentions to engage in mask promoting behavior. We find that providing factual information about how masks protect others increases the likelihood that someone would wear a mask or encourage others to do so in the United States, but not in Italy. There is no effect of providing information about how masks protect the wearer in either country. Additionally, greater mask use increases intentions to wear a mask and encourage someone else to wear theirs properly in both the United States and Italy. Thus, community mask use may be self-reinforcing.

🖺 Full Text HTML: Beliefs about Mask Efficacy and the Effect of Social Norms on Mask Wearing Intentions for COVID-19 Risk Reduction

Covid-19 Sentry

Contents

From Preprints

From Clinical Trials

From PubMed

From Patent Search