18 March, 2021

How do Good and Bad News Impact Mood During the Covid-19 Pandemic? The Role of Similarity -

How do media reports about the Covid-19 pandemic influence our mood? Building on the social comparison theory, we predicted that reading negative news affecting a similar group would result in an impaired mood. In contrast, reading negative news about a dissimilar group should lead to improved mood. To test this, 150 undergraduate students read positive or negative news about the well-being of a similar or dissimilar group during the pandemic. As predicted, a mood assimilation effect occurred for similar groups, whilst a contrast effect occurred for a dissimilar group. This pattern went so far that undergraduates reported the best mood after learning that the elder generation suffered from Covid-19. This finding seems worrying and calls for future research.

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Social network factors in university student well-being and resilience during a large-scale stressor -

The transition to college is a challenging time during which many students suffer declines in well-being. Social connections play a key role in supporting mental health, but only tell part of the story of social life on campus. For instance, the personalities of one’s friends and neighbors on campus contribute to a “social microclimate.” Here, we quantify the collective impact of individual, social network, and community factors in the well-being of a first-year college cohort during (i) their first academic term and (ii) a stressor (the COVID-19 pandemic). Students who maintained supportive connections and belonged to emotionally stable and tight-knit microclimates reported greater well-being in their first academic term, and less anxiety when exposed to stress during the COVID-19 pandemic, highlighting the importance of both personal relationships and community factors in supporting mental health.

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Anti-Asian Discrimination and Antiracist Bystander Behaviors amid the COVID-19 Outbreak -

Anti-Asian racism is a public health concern, and it has escalated during the coronavirus disease 2019 (COVID-19) outbreak. Bystanders—individuals who witness acts of racism—can help by discouraging perpetrations of discrimination (and other forms of interpersonal violence), offering help and support to victims, and reinforcing (antiracist) prosocial norms. Yet, little is known about who engages in antiracist bystander intervention behaviors in response to discriminatory events, and who engages in proactive bystander behaviors in general. In the current study, 456 US community adults of diverse ethnic backgrounds (18-85 years, Mage = 48.8, 52.0% women, 212 Asian Americans) reported on their experiences with discrimination, attitudes about the acceptability of discrimination, and engagement in proactive and reactive bystander behaviors. About 40% of the Asian American participants experienced COVID-related discrimination during a one-week period. Among individuals who witnessed anti-Asian discrimination during the COVID-19 outbreak, 45% of them engaged in any antiracist reactive bystander interventions. More frequent everyday discrimination experiences predicted greater odds of reactive bystander behaviors, over and above ethnicity, gender, and attitudes about the acceptability of discrimination. Initial evidence supported the utility of a new measure assessing bystander behaviors in response to racial discrimination. Prior exposure to discrimination may contribute to individuals’ active engagement in antiracist bystander behaviors. Future research directions on antiracist bystander actions and allyship are discussed.

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Pneumolysis: a fundamental concept in COVID-19 lung disease -

Background COVID-19 severe lung compromise often evolves to life-threatening hypoxia. The experience led to the implementation of standardized protocols assuming similarity to SARS-CoV. Impulsive use of ventilators ended in up to 88% fatality. Methods COVID-19 pathophysiology and histopathological lung biopsy photomicrographs are analyzed. Results Pneumolysis is defined as progressive alveolar-capillary destruction resulting from the CoV-2 attack on pneumocytes. The histopathological results show the presence of Masson bodies, alveolar coating cells with nuclear atypia, reactive pneumocytes, reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates, microabscesses, microthrombus, hyaline membrane remnants, and emphysema. The three theoretical pathophysiological stages of progressive hypoxemia (silent hypoxemia, gasping, and death zone) are depicted. Conclusion Silent hypoxemia suddenly evolves to critical hypoxemia. This, as a consequence of progressive pneumolysis + inflammation + overexpressed immunity + autoimmunity + HAPE-type edema resulting in acute pulmonary insufficiency. The proposed treatment (based on Tolerance to Hypoxia and the Hemoglobin factor) includes: prompt oxygen administration, inflammation and immunity reaction control, antibiotics, rehydration & anticoagulation.

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Epigallocatechin Gallate from Green Tea Effectively Blocks Infection of SARS-CoV-2 and New Variants by Inhibiting Spike Binding to ACE2 Receptor -

As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Here, we demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

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SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway -

Pathogenesis of COVID-19 is associated with a hyperinflammatory response; however, the precise mechanism of SARS-CoV-2-induced inflammation is poorly understood. Here we investigated direct inflammatory functions of major structural proteins of SARS-CoV-2. We observed that spike (S) protein potently induces inflammatory cytokines and chemokines including IL-6, IL-1b, TNFa, CXCL1, CXCL2, and CCL2, but not IFNs in human and mouse macrophages. No such inflammatory response was observed in response to membrane (M), envelope (E), and neucleocapsid (N) proteins. When stimulated with extracellular S protein, human lung epithelial cells A549 also produce inflammatory cytokines and chemokines. Interestingly, epithelial cells expressing S protein intracellularly are non-inflammatory, but elicit an inflammatory response in macrophages when co-cultured. Biochemical studies revealed that S protein triggers inflammation via activation of the NF-kB pathway in a MyD88-dependent manner. Further, such an activation of the NF-kB pathway is abrogated in Tlr2-deficient macrophages. Consistently, administration of S protein induces IL-6, TNF-a, and IL-1b in wild-type, but not Tlr2-deficient mice. Together these data reveal a mechanism for the cytokine storm during SARS-CoV-2 infection and suggest that TLR2 could be a potential therapeutic target for COVID-19.

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Longitudinal characterization of humoral and cellular immunity in hospitalized COVID-19 patients reveal immune persistence up to 9 months after infection -

Background: Insights into early, specific humoral and cellular responses to infection with SARS-CoV-2, as well as the persistence and magnitude of resulting immune memory is important amidst the ongoing pandemic. The combination of humoral and cellular immunity will most likely contribute to protection from reinfection or severe disease. Methods: Here, we conducted a longitudinal study on hospitalized moderate and severe COVID-19 patients from the acute phase of disease into convalescence at five- and nine-months post symptom onset. Utilizing flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune memory during and after human SARS-CoV-2 infection. Findings: During acute COVID-19, we observed an increase in germinal center activity, a substantial expansion of antibody-secreting cells, and the generation of SARS-CoV-2-neutralizing antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralizing antibody titers as well as robust specific memory B cell responses and polyfunctional T cell responses at five- and nine-months after symptom onset in both moderate and severe COVID-19 patients. Long-term SARS-CoV-2 specific responses were marked by preferential targeting of spike over nucleocapsid protein. Conclusions: Our findings describe the initiation and, importantly, persistence of cellular and humoral SARS-CoV-2 specific immunological memory in hospitalized COVID-19 patients long after recovery, likely contributing towards protection against reinfection.

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Identification of ACE2 mutations that modulate SARS-CoV-2 spike binding across multiple mammalian species -

Understanding how SARS-CoV-2 interacts with different mammalian angiotensin-converting enzyme II (ACE2) cell entry receptors will help elucidate determinants of intra- and cross-species virus transmission, facilitate development of effective new vaccines for both humans and livestock animals, and guide livestock farming and coronavirus screening procedures to ensure food supply security. In this work we applied laboratory directed evolution to several mammalian ACE2s with the goal of identifying conserved ACE2 mutations that increase spike binding affinity across multiple species. We found the Gln42Leu mutation increased ACE2-spike binding for human as well as four of four other mammalian ACE2s, while the Leu79Ile mutation had a similar effect for human and three of three mammalian ACE2 orthologs. These results are especially notable given the residues’ high levels of representation, i.e., 83% for Gln42 and 56% for Leu79, among annotated mammalian ACE2s. We also found that substitutions at ACE2 position 34, which is relatively variable across mammalian ACE2s, increased binding for multiple ACE2 orthologs. Taken together, these results speak strongly to the plausibility of SARS-CoV-2 strains with increased ability to cross species transmission barriers. Our results can guide further computational and experimental studies to develop biomedical technologies and animal husbandry practices that help protect both humans and livestock from existing and future SARS-CoV-2 variants.

🖺 Full Text HTML: Identification of ACE2 mutations that modulate SARS-CoV-2 spike binding across multiple mammalian species

Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein -

SARS-CoV-2 is the coronavirus causing the catastrophic pandemic which already led to >120 millions of infections and >2.6 millions of deaths. Hydroxychloroquine (HCQ) has been shown to own promising potential in clinically combating SARS-CoV-2 but the underlying mechanisms still remain almost unknown. So far, all action sites are proposed on the host cells, and in particular no specific viral target protein has been experimentally identified. In this study, by use of DIC microscopy and NMR spectroscopy, for the first time we have decoded that HCQ specifically binds to both N-terminal domain (NTD) and C-terminal domain (CTD) of SARS-CoV-2 nucleocapsid (N) protein to inhibit their interactions with nucleic acids (NAs), as well as to disrupt its NA-induced liquid- liquid phase separation (LLPS) essential for the viral life cycle including the package of gRNA and N protein into new virions. These results suggest that HCQ may achieve its anti-SARS-CoV-2 activity by interfering in several key steps of the viral life cycle. The study not only provides a structural basis for the anti-SARS-CoV-2 activity of HCQ, but also indicates that SARS-CoV-2 N protein and its LLPS represent key targets for further optimization and development of anti-SARS-CoV-2 drugs.

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Characterisation of a novel ACE2-based therapeutic with enhanced rather than reduced activity against SARS-CoV2 variants -

The human angiotensin-converting enzyme 2 acts as the host cell receptor for SARS-CoV-2 and the other members of the Coronaviridae family SARS-CoV-1 and HCoV-NL63. Here we report the biophysical properties of the SARS-CoV-2 spike variants D614G, B.1.1.7 and B.1.351 with affinities to the ACE2 receptor and infectivity capacity, revealing weaknesses in the developed neutralising antibody approaches. Furthermore, we report a pre-clinical characterisation package for a soluble receptor decoy engineered to be catalytically inactive and immunologically inert, with broad neutralisation capacity, that represents an attractive therapeutic alternative in light of the mutational landscape of COVID-19. This construct efficiently neutralised four SARS-CoV-2 variants of concern. The decoy also displays antibody-like biophysical properties and manufacturability, strengthening its suitability as a first-line treatment option in prophylaxis or therapeutic regimens for COVID-19 and related viral infections.

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ACE2 polymorphisms interplay with the apelinergic peptide system: potential tools for COVID-19 diagnosis and treatment -

ACE2 polymorphisms have been previously linked to increased susceptibility to multiple diseases and are currently linked to SARS CoV-2 susceptibility and complications. Notably, ACE2 transcribed or regulated proteins include the activity of metaloproteinsase-2 and apelin-13 and 36, might be linked to abnormal immune responses and complications. Furthermore, potential genetic or serological tests might be developed to detect the higher vulnerable groups to SARS CoV-2 complications and/or mortality. Furthermore, we hypothesize that diabetic and obese patients suffer from exhausted and/or abnormally functioning apelinergic peptides that predispose them to a higher severe COVID-19 risk. Moreover, infusion of apelin-13 to treat selected critical cases of COVID-19, especially those complaining of refractory advanced heart failure not responding to other drugs, might be considered for clinical trials.

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Examining face-mask usage as an effective strategy to control COVID-19 spread -

The COVID-19 global crisis is facilitated by high virus transmission rates and high percentages of asymptomatic and presymptomatic infected individuals. Containing the pandemic hinged on combinations of social distancing and face mask use. Here we examine the efficacy of these measures, using an agent-based modeling approach that evaluates face masks and social distancing in realistic confined spaces scenarios. We find face masks are more effective than social distancing. Importantly, combining face masks with even moderate social distancing provides optimal protection. The finding that widespread usage of face masks limits COVID-19 outbreaks can inform policies to reopening of social functions.

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Discovery of TMPRSS2 inhibitors from virtual screening -

The SARS-CoV-2 pandemic has prompted researchers to pivot their efforts to finding anti-viral compounds and vaccines. In this study, we focused on the human host cell transmembrane protease serine 2 (TMPRSS2), which plays an important role in the viral life cycle by cleaving the spike protein to initiate membrane fusion. TMPRSS2 is an attractive target and has received attention for the development of drugs against SARS and MERS. Starting with comparative structural modeling and binding model analysis, we developed an efficient pharmacophore-based approach and applied a large-scale in silico database screening for small molecule inhibitors against TMPRSS2. The hits were evaluated in the TMPRSS2 biochemical assay and the SARS-CoV-2 pseudotyped particle (PP) entry assay. A number of novel inhibitors were identified, providing starting points for further development of drug candidates for the treatment of COVID-19.

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Identification of a High-frequency Intra-host SARS-CoV-2 spike Variant with Enhanced Cytopathic and Fusogenic Effect -

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that is continuously evolving. Although its RNA-dependent RNA polymerase exhibits some exonuclease proofreading activity, viral sequence diversity can be produced by replication errors and host factors. A diversity of genetic variants can be observed in the intra-host viral population structure of infected individuals. Most mutations will follow a neutral molecular evolution and won’t make significant contributions to variations within and between infected hosts. Herein, we profiled the intra-sample genetic diversity of SARS-CoV-2 variants using high-throughput sequencing datasets from 15,289 infected individuals and infected cell lines. Most of the genetic variations observed, including C->U and G->U, were consistent with errors due to heat-induced DNA damage during sample processing and/or sequencing protocols. Despite high mutational background, we identified recurrent intra-variable positions in the samples analyzed, including several positions at the end of the gene encoding the viral Spike (S) protein. Strikingly, we observed a high-frequency C->A missense mutations resulting in the S protein lacking the last 20 amino acids (S{Delta}20). We found that this truncated S protein undergoes increased processing and increased syncytia formation, presumably due to escaping M protein retention in intracellular compartments. Our findings suggest the emergence of a high-frequency viral sublineage that is not horizontally transmitted but potentially involved in intra-host disease cytopathic effects.

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Show us the Data: Global COVID-19 Wastewater Monitoring Efforts, Equity, and Gaps -

A year since the declaration of the global coronavirus disease 2019 (COVID-19) pandemic there have been over 110 million cases and 2.5 million deaths. Using methods to track community spread of other viruses such as poliovirus, environmental virologists and those in the wastewater based epidemiology (WBE) field quickly adapted their existing methods to detect SARS-CoV-2 RNA in wastewater. Unlike COVID-19 case and mortality data, there was not a global dashboard to track wastewater monitoring of SARS-CoV-2 RNA worldwide. This study describes the development of the COVIDPoops19 dashboard to disseminate information regarding sites, universities, research institutions and private laboratories in countries that are involved in WBE for SARS-CoV-2. Methods to assemble the dashboard combined standard literature review, direct submissions, and daily, social media keyword searches. Over 200 universities, 1,000 sites, and 50 countries with 59 dashboards monitor wastewater for SARS-CoV-2 RNA. However, monitoring is inequitably distributed in high-income countries and data are not widely shared publicly or accessible to researchers to inform public health actions, meta-analysis, better coordinate, and determine equitable distribution of monitoring sites. For WBE to be used to its full potential during COVID-19 and beyond, show us the data.

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