SARS

2023 - 1 - 9

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Research suggests people on rheumatoid arthritis drugs show ... (News-Medical.net)

Researchers conducted a comparative study among a cohort of individuals on rheumatoid arthritis (RA) therapies vis-à-vis healthy controls to assess their ...

Strikingly, ceasing the drug treatment reversed the effect of abatacept on the magnitude and transcriptional profile of Tfh cells almost instantaneously. The T cell activator-induced marker (AIM) assay confirmed that MTX-treated RA subjects had a markedly lower magnitude of the SARS-CoV-2 S-specific cluster of differentiation (CD4)+ T cell response to COVID-19 mRNA vaccines. First, they measured antibody responses to the SARS-CoV-2 spike (S) in the patient's serum. Thus, the observed substantially diminished anti-SARS-CoV-2 S antibodies in the abatacept cohort were clinically relevant. Abatacept and MTX both reduce antibody production in response to SARS-CoV-2 mRNA vaccines. Furthermore, they examined the amount, phenotype, and functionality of SARS-CoV-2-specific T cells and B cells. It helped them assess whether serum from SARS-CoV-2 naïve and unvaccinated individuals on RA therapies effectively blocked infection of angiotensin-converting enzyme 2 (ACE-2). The study cohorts comprised 40 subjects, 27 with RA and 13 age and gender-matched healthy controls. The American College of Rheumatology has acknowledged that disease-modifying anti-rheumatic drugs (DMARDs) impair the effective COVID-19 vaccine-induced responses. Of the 27 RA subjects, 11 received MTX, and the other 11 received abatacept treatments. Drugs used to treat RA actively suppress people's immune systems, altering their response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. It also likely inhibits mRNA vaccine-induced neutralizing antibody responses in RA patients.

SARS-CoV-2 viral toxin may make COVID worse (Futurity: Research News)

The SARS-CoV-2 spike protein can damage cell barriers that line the inside of blood vessels within organs of the body, researchers report.

By blocking the activity of integrins, the team was able to reverse the vascular leak in mice. To test the theory that the spike protein might also play a role, Biering and other team members used thin layers of human endothelial and epithelial cells to mimic the linings of blood vessels in the body. The resulting increase in permeability can lead to vascular leak, as is commonly observed in severe COVID-19 cases, and we could recapitulate those disease manifestations in our mouse models,” says coauthor Felix Pahmeier, a graduate student in the Harris lab. In addition, they found that mice that were exposed to the spike protein also exhibited vascular leak, even though mice do not express the human ACE2 receptor and cannot be infected with SARS-CoV-2. They found that exposing these cellular layers to the spike protein increased their permeability, a hallmark of vascular leak. “What’s really interesting is that circulating spike protein correlates with severe COVID-19 cases in the clinic,” Biering says. In addition to causing the lung and heart damage observed in severe COVID-19, vascular leak can also lead to hypovolemic shock, the primary cause of death from “People are aware of the role of bacterial toxins, but the concept of a viral toxin is still a really new idea,” Harris says. In addition to opening new avenues for the treatment of severe COVID-19, understanding how the spike protein contributes to vascular leak could shed light on the pathology behind other emerging infectious diseases. When the pandemic hit, the team wondered if a similar viral toxin in SARS-CoV-2 could also be contributing to the acute respiratory distress syndrome that was killing COVID-19 patients. Instead, their study suggests that the spike protein may work in tandem with the virus and the body’s own immune response to trigger life-threatening symptoms. The idea is that it’s able to aid and abet an ongoing infection.”

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Researchers study the spatial distribution of SARS-CoV-2 Omicron ... (News-Medical.net)

Researchers performed a genomic assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant's BA.1 subvariant transmission in ...

The team estimated 20% and 16% lesser connectivity for every unit increase in weekly COVID-19 cases per 100 individuals at the hub when the home and hub units were located within distances of 50 kilometres and 100 kilometres, respectively. Generalized linear modelling (GLM) was performed for quantitative assessment of the role of epidemiological, mobility-associated, and demographic factors on BA.1 transmission in England and to assess their relationship with Omicron movement in LTLAs. Trips taken between home and hub units during the initial growth period of the epidemic reduced by 12.0% for each unit elevation in weekly COVID-19 cases among every 100 individuals at the hub that week, with a four-day lag. Local viral movements in Greater Manchester and Greater London comprised 60% and 90% of all movements from November to December 2021, respectively. Most (70%) of the Omicron BA.1 genome were imported from outside England (70%), and the most initial importation event was estimated between November 5 and November 18. The UKHSA (UK health security agency) VAM (variant and mutations) line list data were obtained for calculating daily counts of incoming travellers later testing Omicron-positive in Pillar 2 (community-level surveillance) of the UK COVID-19 testing programme. The mean BA.1 subvariant EII weekly from US introductions was 4.0-fold higher than from South Africa during restricted travel. More than 6,455 independent importations of Omicron in England were observed. The swift upsurge in coronavirus disease 2019 (COVID-19) case counts due to Omicron infections in England resulted in the enforcement of COVID-19 prevention measures such as compulsory COVID-19 passes to enter particular indoor settings, facemask use, and remote working with accelerated COVID-19 vaccination for improving booster dose availability to all adult individuals. The team analyzed 48,615 genomes of BA.1 from samples obtained (one percent of confirmed Omicron infections) that represented 313 LTLAs (lower-tier local authorities), with anonymized epidemiological and human mobility data aggregated at a sub-city level. Weighted genome subsampling was performed, considering sequencing differences for COVID-19 cases at the UTLA (upper-tier local authority) level. Statistical modelling was performed to explore the effects of altered COVID-19 prevalence on travel connectivity between main travelling hubs of England.

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Sequence similarity between SARS-CoV-2 nucleocapsid and ... (Nature.com)

The novel coronavirus SARS-CoV-2 continues to cause death and disease throughout the world, underscoring the necessity of understanding the virus and host ...

[https://doi.org/10.21203/rs.3.rs-1015570/v1](https://doi.org/10.21203/rs.3.rs-1015570/v1). [https://doi.org/10.21203/rs.3.rs-33197/v1](https://doi.org/10.21203/rs.3.rs-33197/v1). [https://papers.ssrn.com/abstract=3606763](https://papers.ssrn.com/abstract=3606763)(2020). [http://www.iedb.org/](http://www.iedb.org/)). [38](/articles/s41598-022-27348-8#ref-CR38), [65](/articles/s41598-022-27348-8#ref-CR65). [1](/articles/s41598-022-27348-8#MOESM1)). [3](/articles/s41598-022-27348-8#Fig3)B). [3](/articles/s41598-022-27348-8#ref-CR3), [4](/articles/s41598-022-27348-8#ref-CR4), [30](/articles/s41598-022-27348-8#ref-CR30), [31](/articles/s41598-022-27348-8#ref-CR31). [20](/articles/s41598-022-27348-8#ref-CR20), [38](#ref-CR38), [39](#ref-CR39), [40](/articles/s41598-022-27348-8#ref-CR40). [4](/articles/s41598-022-27348-8#Fig4)C). [3](/articles/s41598-022-27348-8#Fig3)C). [2](/articles/s41598-022-27348-8#Fig2)C).

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Free Spike Antigen ID'd in Post-SARS-CoV-2 mRNA Vaccine ... (Physician's Weekly)

MONDAY, Jan. 9, 2023 (HealthDay News) -- Individuals who develop myocarditis following a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA ...

The researchers found that extensive antibody profiling and T-cell responses were essentially indistinguishable for individuals who developed postvaccine myocarditis and those of vaccinated controls, despite a modest increase in cytokine production. Extensive antibody profiling was performed and results were compared to those from 45 healthy, asymptomatic, age-matched vaccinated controls. Yonker, M.D., from Massachusetts General Hospital in Boston, and colleagues prospectively collected blood from 16 patients who were hospitalized for myocarditis after SARS-CoV-2 mRNA vaccination.

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Deletions in the antigenic regions in SARS-CoV-2 increase ... (News-Medical.net)

A recent study published in the journal Scientific Reports examined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole genome data to ...

These deletions were also found only in the NTD region of the spike protein, suggesting a correlation between NTD-associated deletion mutations and increased transmission of the virus. (b) Heatmap showing the expansion of “deletable” regions in the course of the pandemic, where the rows denote residue positions in the Spike protein and columns denote the time course of the pandemic (in months). The number of surge-associated mutations — those which monotonically increased along with a monotonic increase in positive SARS-CoV-2 tests during three-month intervals — was 92, of which 42 were also found in the CDC-identified variants of interest or concern. (a) Frequency of occurrences of deletion mutations in the N-terminal domain across 2.13 million Spike protein sequences (as of 30 June 2021). The monthly prevalence of mutations and SARS-CoV-2 test positivity rates were assessed across three-month intervals to determine mutations associated with sudden increases in COVID-19 cases. [Scientific Reports](https://www.nature.com/articles/s41598-022-26646-5) examined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole genome data to determine the deletion mutations around the [spike protein](/health/What-are-Spike-Proteins.aspx) region associated with increased transmission of the virus and identified an increase in the deletion-prone spike protein regions indicating an evolution strategy for immune escape. The repertoire of deletions in the Spike protein N-terminal domain is expanding over the course of the pandemic. The researchers also constructed a time series tile plot to examine the temporal expansion of regions with recurrent deletions. [neutralizing antibodies](/health/What-are-Neutralizing-Antibodies.aspx) from COVID-19 patients have identified the spike protein’s receptor binding domain (RBD) and N-terminal domain (NTD) as the main targets of neutralizing antibodies. Additionally, the various mutation types, such as insertions, deletions, and substitutions, were assessed to determine their enrichment in surge-associated mutations. Epidemiological data consisting of SARS-CoV-2 positivity rates were acquired from Our World in Data (OWID) and other databases. Study: [Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants](https://www.nature.com/articles/s41598-022-26646-5).

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The Dual Mechanisms of Engineered hACE-2 Decoy Peptide for ... (Pitt Health Sciences)

This is the first of 12 lectures in the 2023 Senior Vice Chancellor's Research Seminar series. Speaker Lianghui (Lucy) Zhang, MD, PhD Assistant Professor of ...

Using molecular-dynamics simulations, Zhang and colleagues show that three amino acid substitutions in an engineered soluble ACE2 protein markedly augment the affinity for the S protein of the SARS-CoV-2 WA-1/2020 isolate as well as multiple VOC: B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), B.1.1.529 (omicron), among others. Furthermore, Zhang and colleagues found that loss of catalytic activity reduced the decoy’s therapeutic efficacy, which supports the hypothesis of dual mechanisms of action—direct blocking of viral S and turnover of ACE2 substrates associated with lung injury and inflammation. The emergence of SARS-CoV-2 variants of concern (VOC) escaping vaccine-induced immune responses highlight the urgency for novel COVID-19 therapeutics. Engineered ACE2 proteins with augmented binding affinities for SARS-CoV-2 Spike (S) protein may prove to be especially effective against multiple variants. In humanized K18-hACE2 mice inoculated with SARS-CoV-2 VOCs, prophylactic injections of sACE22.v2.4-IgG1 prevented lung vascular injury, and therapeutic injection or inhalation of sACE22.v2.4-IgG1 ameliorated lung vascular injury and improved survival. studies demonstrate the broad efficacy of an engineered ACE2 decoy against SARS-CoV-2 variants and point to its therapeutic potential. [Health & Wellness](/search/events?event_types%5B%5D=117197), [Research](/search/events?event_types%5B%5D=117199) [Undergraduate Students](/search/events?event_types%5B%5D=117190), [Faculty](/search/events?event_types%5B%5D=128155), [Graduate Students](/search/events?event_types%5B%5D=128731), [Postdocs](/search/events?event_types%5B%5D=144324) [Registration](https://pitt.zoom.us/webinar/register/WN_SQ_HCHv7StKn4pSeAajKaQ) for the lecture is required to receive event instructions. The Dual Mechanisms of Engineered hACE-2 Decoy Peptide for SARS-CoV-2 Variants-Induced Acute Lung Injury Assistant Professor of Medicine (Division of Pulmonary, Allergy, and Critical Care Medicine), School of Medicine [13 Jan](https://calendar.pitt.edu/photo/41802681623487) [Health & Wellness](/search/events?event_types%5B%5D=117197), [Research](/search/events?event_types%5B%5D=117199) [Undergraduate Students](/search/events?event_types%5B%5D=117190), [Faculty](/search/events?event_types%5B%5D=128155), [Graduate Students](/search/events?event_types%5B%5D=128731), [Postdocs](/search/events?event_types%5B%5D=144324) This is the first of 12 lectures in the 2023 Senior Vice Chancellor’s Research Seminar series.

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Seroprevalence of anti-SARS-CoV-2 antibodies and factors ... (BMC Public Health)

Brazil was strongly affected by the COVID-19 pandemic and the impact of the pandemic on sexual and gender minorities' youth remains unknown.

The Creative Commons Public Domain Dedication waiver ( [http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. [29](/articles/10.1186/s12889-022-14969-x#ref-CR29)]. [19](/articles/10.1186/s12889-022-14969-x#ref-CR19), [20](/articles/10.1186/s12889-022-14969-x#ref-CR20)]. This study (PrEP1519) was approved by the Research Ethics Committee (ERC) of the World Health Organization (Protocol ID: Fiotec-PrEP Adolescent study), of the Federal University of Bahia (# 3,224,384) and the University of São Paulo (USP) (Protocol ID: #3,082,360). [27](/articles/10.1186/s12889-022-14969-x#ref-CR27)]. Secretaria da Saúde do Estado da Bahia (Sesab). [22](/articles/10.1186/s12889-022-14969-x#ref-CR22)]. A minority lived alone (2.7%) or with siblings (38.8%), and half of the participants lived with more than 3 people in the same household (50.4%). [1](/articles/10.1186/s12889-022-14969-x#ref-CR1)]. household characteristics: number of people in the household (≤ 3 people; > 3 people), living alone (no; yes), living with mother (no; yes), living with siblings (no; yes), number of rooms at home (≤ 3 rooms; > 3 rooms); iii. This study (PrEP1519) was approved by the Research Ethics Review Committee (ERC) of the World Health Organization (Protocol ID: Fiotec-PrEP Adolescent study), the Federal University of Bahia (# 3,224,384), and of the University of São Paulo (USP) (Protocol ID: #3,082,360). The dynamics of the pandemic has varied around the world with populations facing different “waves” [ [5](/articles/10.1186/s12889-022-14969-x#ref-CR5)].

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It looks like SARS is focused on getting non-compliant High-Net ... (Independent Online)

In 2022, SARS demonstrated its increased focus on revenue collection and compliance, specifically pertaining to High-Net-Worth Individuals.

This development has made it near impossible for taxpayers to hold undisclosed offshore interests, where if caught, opens the taxpayer up to a dual audit with the active participation of both SARS and the revenue authority in which the assets / investments are situated. The on-going investigations into South African taxpayers’ offshore interests has long been on the cards with SARS, with foreign asset/income disclosure notices being issued as far back as 2020, entailing a blanket disclosure of offshore assets. Unfortunately, and in light of South Africa’s shrinking tax base, the middle to HNWI classes are taking the largest tax hit. Over and above this, the implementation of a dedicated HNWI Unit at SARS, headed up by Ms Natasha Singh, evidences that this is not just some passing phase for the revenue authority, but rather a long game to be built on in the forthcoming years. In 2022, the South African Revenue Service (SARS) demonstrated its increased focus on revenue collection and compliance, specifically pertaining to High-Net-Worth Individuals (HNWIs). This targeted strategy encompasses lifestyle audits, which were initiated by SARS back in 2007, however actual action earnestly began only a few years ago with the arrival of SARS Commissioner Edward Kieswetter.

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