14 May, 2022

BEHAVIOURS IN THE STOCK MARKET - AN EMPIRICAL STUDY -

This study has two main purposes. Its first purpose is to analyse the influence of sociodemographic characteristics and investment experience of individual and institutional investors on their investment behaviours in the stock market. The second purpose of the present paper is to study the impact of the investment behaviours on the investment decisions following the market selloff in March 2020 that preceded the emergence of COVID 19. Additionally, this study seeks to analyse the potential impact of the social distancing measures on the herd mentality influencing the investment decision.

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Psychological Issues on Family Caregivers of Stroke Patients in Brunei Darussalam: In the Era of Pandemic Covid-19 -

Family caregivers play an important role in providing main support for family members with a disability in order for them to function normally in their everyday life. The main goal of this research study is to promote psychological health awareness of stroke family caregivers in Brunei Darussalam, especially during the pandemic of Covid-19. This study concentrated particularly on long-term family caregivers who provide care to stroke family members who were severely affected by the disease that caused them to heavily depended on their family caretakers. This qualitative research involves interviewing 8 locals participants using snowballing sampling and a thematic analysis approach that investigate thoroughly the challenges and identifies the needs required by family caregivers in Brunei. The findings of the study discovered that all family caregivers experience psychological issues such as ‘Depression’ and ‘Stress’ and are in need of family support and self-care to reduce challenges they experience such as emotional exhaustion, physical problem, sleep deprivation, financial issues, and accessibility to basic needs in caregiving.

🖺 Full Text HTML: Psychological Issues on Family Caregivers of Stroke Patients in Brunei Darussalam: In the Era of Pandemic Covid-19

Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody -

The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 - 0.05 ug/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.

🖺 Full Text HTML: Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody

Three-doses of BNT162b2 COVID-19 mRNA vaccine establishes long-lasting CD8+ T cell immunity in CLL and MDS patients -

Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk for severe SARS-CoV-2 infection related disease and mortality. To understand T cell immunity, its long-term persistence, and correlation with antibody response, we evaluated the BNT162b2 COVID 19 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8+ T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 Spike-protein (415 peptides) showed vaccine- specific T cell activation and persistence of memory T cells up to six months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8+ T cell was observed in the patient group compared to a healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8+ T cells as well as the total number of T cell specificities. Altogether 59 BNT162b2 vaccine-derived immunogenic epitopes were identified, of which 23 established long-term CD8+ T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. In summary, we mapped the vaccine-induced antigen-specific CD8+ T cells and showed a booster-specific activation and enrichment of memory T cells that could be important for long-term disease protection in this patient group.

🖺 Full Text HTML: Three-doses of BNT162b2 COVID-19 mRNA vaccine establishes long-lasting CD8+ T cell immunity in CLL and MDS patients

Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens -

The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID-19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2.S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS- CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2.S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.

🖺 Full Text HTML: Humoral immunity to SARS- CoV-2 elicited by combination COVID-19 vaccination regimens

In situ architecture and membrane fusion of SARS-CoV-2 Delta variant -

Among the current five Variants of Concern, infections caused by the SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, architecture of intact Delta virions remains veiled. Moreover, the detailed mechanism of S-mediated membrane fusion remains elusive. Here we report the molecular assembly and fusion snapshots of the authentic Delta variant. Envelope invagination and fusion events were frequently observed. Native structures of pre- and postfusion S were determined up to 4.1-A resolution. Site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S over that of the Wuhan-Hu-1 S. Based on these findings, we proposed a model for S-mediated membrane fusion and a model for the invagination formation.

🖺 Full Text HTML: In situ architecture and membrane fusion of SARS-CoV-2 Delta variant

Optimality of Maximal-Effort Vaccination -

It is widely acknowledged that vaccinating at maximal effort in the face of an ongoing epidemic is the best strategy to minimise infections and deaths from the disease. Despite this, no one has proved that this is guaranteed to be true if the disease follows multi-group SIR (Susceptible-Infected-Recovered) dynamics. This paper provides a novel proof of this principle for the existing SIR framework, showing that the total number of deaths or infections from an epidemic is decreasing in vaccination effort. Furthermore, it presents a novel model for vaccination which assumes that vaccines are distributed randomly to the unvaccinated population and suggests, using COVID-19 data, that this more accurately captures vaccination dynamics than the model commonly found in the literature. However, as the novel model provides a strictly larger set of possible vaccination policies, the results presented in this paper hold for both models.

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Higher contact among vaccinated can be a mechanism for negative vaccine effectiveness -

Evidence from early observational studies suggested negative vaccine effectiveness for the SARS-CoV-2 Omicron variant. Using transmission modeling, we illustrated how increased contact between vaccinated individuals, vaccinated contact heterogeneity, paired with lower vaccine efficacies could produce negative measurements and how we can identify this mechanism via a key temporal signature.

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Multiple Introductions of SARS-CoV-2 Alpha and Delta Variants into White-Tailed Deer in Pennsylvania -

The SARS-CoV-2 pandemic likely began by viral spillover from animals to humans1-3; today multiple animal species are known to be susceptible to infection4-8. White-tailed deer, Odocoileus virginianus are infected in North America at substantial levels9-11, and genomic data suggests that a variant in deer may have spilled back to humans12,13. Here we characterize SARS-CoV-2 in deer from Pennsylvania (PA) sampled during fall and winter 2021. Of 123 nasal swab samples analyzed by RT-qPCR, 20 (16.3%) were positive for SARS-CoV-2. Seven whole-genome sequences were obtained, together with six more partial spike sequences. These annotated as alpha and delta variants, the first reported observations of these lineages in deer, documenting multiple new jumps from humans to deer. The alpha lineage persisted in deer after its displacement by delta in humans, and deer-derived alpha variants diverged significantly from those in humans, consistent with a distinctive evolutionary trajectory in deer.

🖺 Full Text HTML: Multiple Introductions of SARS-CoV-2 Alpha and Delta Variants into White-Tailed Deer in Pennsylvania

The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein -

The SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, the Omicron/BA.2 lineage in early 2022. Here, we describe how Omicron BA.1 and BA.2 show a lower severity phenotype in a hamster model of pathogenicity which maps specifically to the spike gene. We further show that Omicron is attenuated in a lung cell line but replicates more rapidly, albeit to lower peak titres, in human primary nasal cells. This replication phenotype also maps to the spike gene. Omicron spike (including the emerging Omicron lineage BA.4) shows attenuated fusogenicity and a preference for cell entry via the endosomal route. We map the altered Omicron spike entry route and partially map the lower fusogenicity to the S2 domain, particularly the substitution N969K. Finally, we show that pseudovirus with Omicron spike, engineered in the S2 domain to confer a more Delta-like cell entry route retains the antigenic properties of Omicron. This shows a distinct separation between the genetic determinants of these two key Omicron phenotypes, raising the concerning possibility that future variants with large antigenic distance from currently circulating and vaccine strains will not necessarily display the lower intrinsic severity seen during Omicron infection.

🖺 Full Text HTML: The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

Using CATA and Machine Learning to Operationalize Old Constructs in New Ways: An Illustration Using U.S. Governors’ COVID-19 Press Briefings -

Increased computing power and greater access to online data have led to rapid growth in the use of computer-aided text analysis (CATA) and machine learning methods. Using “big data”, researchers have not only advanced new streams of research, but also new research methodologies. Noting this trend and simultaneously recognizing the value of traditional research methods, we lay out a methodology that bridges the gap between old and new approaches to operationalize old constructs in new ways. With a combination of web scraping, CATA, and supervised machine learning, using labeled ground truth data (i.e., data with known inputs and outputs), we train a model to predict CIP (Charismatic-Ideological- Pragmatic) leadership styles from running text. To illustrate this method, we apply the model to classify U.S. state governors’ COVID-19 press briefings according to their CIP leadership style. In addition, we demonstrate content and convergent validity of the method.

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Pregnancies and contraceptive use in four African countries during the COVID-19 pandemic -

The COVID-19 pandemic and the public health measures adopted in response to it have triggered plenty of speculation about the potential impact on fertility in different regions of the globe. This study provides evidence on the fertility response in four sub-Saharan African countries during the first year of the pandemic. Using harmonized data on women of childbearing age from the Performance Monitoring for Action (PMA) data series, this study compares pregnancy rates by the turn of the year 2020/21 to a pre-pandemic baseline. There is no indication of a general increase in pregnancy rates since the beginning of the pandemic. In some of the sample countries, pregnancy rates during COVID-19 have instead fallen significantly among the youngest and the least educated women of childbearing age, respectively. In parallel, rates of modern contraceptive usage have risen significantly among the surveyed female populations in several sample countries.

🖺 Full Text HTML: Pregnancies and contraceptive use in four African countries during the COVID-19 pandemic

The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling -

Objectives: The coronavirus disease-19 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the molecular and cellular levels, the SARS-Cov-2 uses its envelope glycoprotein, the spike S protein, to infect the target cells in the lungs via binding with their transmembrane receptor, the angiotensin- converting enzyme 2 (ACE2). Here, we wanted to invesitgate if other molecular targets and pathways may be used by SARS- Cov-2. Methods: We investigated the possibility for the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation was examined upon cell treatment with the recombinant full spike 1 S protein or RBD. Results: We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical ERK1/2 and AKT kinases and an increase of survivin expression controlling the survival pathway. Conclusions: Our study suggests the putative implication of EGFR and its related signaling pathways in SARS-CoV-2 infectivity and Covid-19 pathology. This may open new perspectives in the treatment of Covid-19 patients by targeting EGFR.

🖺 Full Text HTML: The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling

Biochemical Characterization of Emerging SARS-CoV-2 Nsp15 Endoribonuclease Variants -

Global sequencing efforts from the ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, continue to provide insight into the evolution of the viral genome. Coronaviruses encode 16 nonstructural proteins, within the first two-thirds of their genome, that facilitate viral replication and transcription as well as evasion of the host immune response. However, many of these viral proteins remain understudied. Nsp15 is a uridine-specific endoribonuclease conserved across all coronaviruses. The nuclease activity of Nsp15 helps the virus evade triggering an innate immune response. Understanding how Nsp15 has changed over the course of the pandemic, and how mutations affect its RNA processing function, will provide insight into the evolution of an oligomerization-dependent endoribonuclease and inform drug design. In combination with previous structural data, bioinformatics analyses of 1.9+ million SARS-CoV-2 sequences revealed mutations across Nsp15’s three structured domains (N-terminal, Middle, EndoU). Selected Nsp15 variants were characterized biochemically and compared to wild type Nsp15. We found that mutations to important catalytic residues decreased cleavage activity but increased the hexamer/monomer ratio of the recombinant protein. Many of the highly prevalent variants we analyzed led to decreased nuclease activity as well as an increase in the inactive, monomeric form. Overall, our work establishes how Nsp15 variants seen in patient samples affect nuclease activity and oligomerization, providing insight into the effect of these variants in vivo.

🖺 Full Text HTML: Biochemical Characterization of Emerging SARS-CoV-2 Nsp15 Endoribonuclease Variants

Low immune response after 1.5 years of primary SARS-CoV-2 infection and Covishield vaccination lead to SARS-CoV-2 reinfection -

We have investigated six COVID recovered cases with two doses of Covishield vaccination followed by reinfection. The primary SARS-CoV-2 infection found to occur with B.1 and reinfection with Omicron BA.1 and BA.2 variants. The genomic characterization and duration between two infections confirms these cases as SARS-CoV-2 reinfection. The mutation analysis of the reinfection cases correlated with immune evasion potential of BA.1 and BA.2 sub lineages. The immune response determined at different time intervals demonstrated boost post two dose vaccination, decline in pre- reinfection sera post 7 months and rise post reinfection. Apparently, these cases suffered from SARS-CoV-2 reinfection with the declined hybrid immunity acquired from primary infection and two dose covishield vaccination. This suggests the need for booster dose of vaccination. Besides this, multiple non-pharmaceutical interventions should be used to cope up with SARS-CoV-2 infection.

🖺 Full Text HTML: Low immune response after 1.5 years of primary SARS-CoV-2 infection and Covishield vaccination lead to SARS-CoV-2 reinfection

Covid-19 Sentry

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