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1.
Vaccine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1977891

ABSTRACT

Vaccine development is a complex process, starting with selection of a promising immunogen in the discovery phase, followed by process development in the preclinical phase, and later by clinical trials in tandem with process improvements and scale up. A large suite of analytical techniques is required to gain understanding of the vaccine candidate so that a relevant immunogen is selected and subsequently manufactured consistently throughout the lifespan of the product. For viral vaccines, successful immunogen production is contingent on its maintained antigenicity and/or infectivity, as well as the ability to characterize these qualities within the context of the process, formulation, and clinical performance. In this report we show the utility of flow virometry during preclinical development of a Covid 19 vaccine candidate based on SARS-CoV-2 spike (S) protein expressed on vesicular stomatitis virus (VSV). Using a panel of monoclonal antibodies, we were able to detect the S protein on the surface of the recombinant VSV virus, monitor the expression levels, detect differences in the antigen based on S protein sequence and after virus inactivation, and monitor S protein stability. Collectively, flow virometry provided important data that helped to guide preclinical development of this vaccine candidate.

2.
Nat Genet ; 54(8): 1078-1089, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1960394

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2-host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism.


Subject(s)
COVID-19 , Animals , COVID-19/genetics , Clustered Regularly Interspaced Short Palindromic Repeats , Epigenesis, Genetic , Humans , Mice , Mucins/genetics , SARS-CoV-2
4.
Int J Environ Res Public Health ; 19(11)2022 05 24.
Article in English | MEDLINE | ID: covidwho-1924223

ABSTRACT

Sedentary behavior negatively impacts mental health, which can decrease employee productivity. Employee mental well-being and work performance may improve with sedentary reduction interventions, especially strategies that include environmental workplace modifications and behavior-changing strategies. However, such interventions have not been examined among employees working remotely during the COVID-19 pandemic. As part of the Stand Up Kansas program, 95 sedentary university employees working from home were randomized into one of four intervention arms: height-adjustable desk provision (Desk Only), online sedentary behavior modification program (Program Only), Desk + Program, or Control. The outcomes were measured at a baseline (November 2020) and following the 12-week intervention (February 2021). Employees reported mood (positive and negative affect), stress, fatigue (duration, interference with activities and severity) and work performance (irritability, focus, work satisfaction, non-work satisfaction and productivity) were measured using established self-report instruments. The effect sizes, by comparing the Control arm to the Desk + Program arm, revealed large improvements in mood (positive affect, d = 1.106). Moderate improvements were also seen in fatigue (duration, d = -0.533, and interference with activities, d = -0.648) and several aspects of work performance (focus, d = 0.702, work satisfaction, d = 0.751, and productivity, d = 0.572). Moderate effect sizes were also seen for positive affect (d = 0.566) and fatigue severity (d = 0.577) among the Program Only arm, whereas no noteworthy effect sizes were observed among the Desk Only arm. Combining an online sedentary behavior modification program with height-adjustable desk provisions appeared to positively affect mental well-being and work performance among remote employees.


Subject(s)
COVID-19 , Occupational Health , Work Performance , COVID-19/epidemiology , Fatigue/epidemiology , Humans , Mental Health , Pandemics , Pilot Projects , Sedentary Behavior , Workplace
5.
Textbook of Zoonoses ; n/a(n/a):192-197, 2022.
Article in English | Wiley | ID: covidwho-1913744

ABSTRACT

Summary Coronaviruses (CoVs) are important pathogens for humans and vertebrate animals. These viruses can infect the respiratory, gastrointestinal, hepatic and central nervous system of humans, livestock, birds, bats and other wild animals. The CoVs have frequently crossed species barriers and some have emerged as important human pathogens. Bats are well adapted anatomically and physiologically to CoVs. During the twenty-first century, the world has witnessed two pandemics of coronaviruses (SARSCoV and SARS-CoV-2) and fatal sporadic outbreaks due to the emerging Middle East respiratory syndrome-CoV. Most of the coronaviruses are transmitted through respiratory droplets during coughing or sneezing. Transmission through the ocular surface is also possible. Animal CoVs have been known since the late 1930s. Various diagnostic tests are available for the detection of coronaviruses infection which is mainly based on antigen detection or specific antibody detection. During the development of a SARS-CoV-2 vaccine candidate, at the height of the COVID-19 pandemic, raw materials shortages, including chromatography resins, necessitated the determination of a cleaning in place (CIP) strategy for a multimodal core-shell resin both rapidly and efficiently. Here, we describe the deployment of high throughput (HT) techniques to screen CIP conditions for cleaning Capto? Core 700 resin exposed to clarified cell culture harvest of a SARS-CoV-2 vaccine candidate produced in Vero adherent cell culture. The best performing conditions, comprised of 30% n-propanol and ≥0.75 N NaOH, were deployed in cycling experiments, completed with miniature chromatography columns, to demonstrate their effectiveness. The success of the CIP strategy was ultimately verified at the laboratory scale. Here, its impact was assessed across the entire purification process which also included an ultrafiltration/diafiltration step. It is shown that the implementation of the CIP strategy enabled the re-use of the Capto Core 700 resin for up to ten cycles without any negative impact on the purified product. Hence, the strategic combination of HT and laboratory-scale experiments can lead rapidly to robust CIP procedures, even for a challenging to clean resin, and thus help to overcome supply shortages. This article is protected by copyright. All rights reserved

6.
Adv Ther ; 39(7): 3061-3071, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1906545

ABSTRACT

The COVID-19 pandemic has drawn considerable attention to viral pneumonia from clinicians, public health authorities, and the general public. With dozens of viruses able to cause pneumonia in humans, differentiating viral from bacterial pneumonia can be very challenging in clinical practice using traditional diagnostic methods. Precision medicine is a medical model in which decisions, practices, interventions, and therapies are adapted to the individual patient on the basis of their predicted response or risk of disease. Precision medicine approaches hold promise as a way to improve outcomes for patients with viral pneumonia. This review describes the latest advances in the use of precision medicine for diagnosing and treating viral pneumonia in adults and discusses areas where further research is warranted.


Subject(s)
COVID-19 , Pneumonia, Bacterial , Pneumonia, Viral , Humans , Pandemics , Pneumonia, Bacterial/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Precision Medicine/methods
7.
Biotechnol J ; : e2200191, 2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1905797

ABSTRACT

During the development of a SARS-CoV-2 vaccine candidate, at the height of the COVID-19 pandemic, raw materials shortages, including chromatography resins, necessitated the determination of a cleaning in place (CIP) strategy for a multimodal core-shell resin both rapidly and efficiently. Here, the deployment of high throughput (HT) techniques to screen CIP conditions for cleaning Capto Core 700 resin exposed to clarified cell culture harvest (CCCH) of a SARS-CoV-2 vaccine candidate produced in Vero adherent cell culture are described. The best performing conditions, comprised of 30% n-propanol and ≥0.75 N NaOH, were deployed in cycling experiments, completed with miniature chromatography columns, to demonstrate their effectiveness. The success of the CIP strategy was ultimately verified at the laboratory scale. Here, its impact was assessed across the entire purification process which also included an ultrafiltration/diafiltration step. It is shown that the implementation of the CIP strategy enabled the re-use of the Capto Core 700 resin for up to 10 cycles without any negative impact on the purified product. Hence, the strategic combination of HT and laboratory-scale experiments can lead rapidly to robust CIP procedures, even for a challenging to clean resin, and thus help to overcome supply shortages.

8.
JAC Antimicrob Resist ; 4(3): dlac066, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1901193

ABSTRACT

Antimicrobial resistance (AMR) continues to spread at an alarming rate worldwide. Novel approaches are needed to mitigate its deleterious impact on antibiotic efficacy. Antibiotic stewardship aims to promote the appropriate use of antibiotics through evidence-based interventions. One paradigm is precision medicine, a medical model in which decisions, practices, interventions, and therapies are adapted to the individual patient based on their predicted response or risk of disease. Precision medicine approaches hold promise as a way to improve outcomes for patients with myriad illnesses, including infections such as bacteraemia and pneumonia. This review describes the latest advances in precision medicine as they pertain to antibiotic stewardship, with an emphasis on hospital-based antibiotic stewardship programmes. The impact of the COVID-19 pandemic on AMR and antibiotic stewardship, gaps in the scientific evidence, and areas for further research are also discussed.

9.
Infectious Disease Alert ; 41(10), 2022.
Article in English | ProQuest Central | ID: covidwho-1898323

ABSTRACT

The ARR was 4.5% (95% CI, 2.6% to 6.4%;P < 0.001) with an NNT of 23 patients (95% CI, 16-39 patients) to prevent one cardiovascular event. [...]76 of the 4,510 patients (1.7%) who received the influenza vaccine died as a result of cardiovascular causes compared with 111 of the 4,491 patients (2.5%) who received placebo or control within one year of follow-up (RR, 0.74;95% CI, 0.42-1.30), although this result was not statistically significant (P = 0.29). [...]presumably none of the patients with influenza were co-infected with COVID-19, since only one study was conducted during the pandemic (2021). Unfortunately, the vaccine has to be reformulated before each influenza season because of mutations in viral surface proteins. [...]having a universally effective influenza vaccine would be a major advancement.

10.
Glob Health Epidemiol Genom ; 2022: 6499217, 2022.
Article in English | MEDLINE | ID: covidwho-1891960

ABSTRACT

The 2019 coronavirus disease (COVID-19) pandemic has demonstrated the importance of predicting, identifying, and tracking mutations throughout a pandemic event. As the COVID-19 global pandemic surpassed one year, several variants had emerged resulting in increased severity and transmissibility. Here, we used PCR as a surrogate for viral load and consequent severity to evaluate the real-world capabilities of a genome-based clinical severity predictive algorithm. Using a previously published algorithm, we compared the viral genome-based severity predictions to clinically derived PCR-based viral load of 716 viral genomes. For those samples predicted to be "severe" (probability of severe illness >0.5), we observed an average cycle threshold (Ct) of 18.3, whereas those in in the "mild" category (severity probability <0.5) had an average Ct of 20.4 (P=0.0017). We also found a nontrivial correlation between predicted severity probability and cycle threshold (r = -0.199). Finally, when divided into severity probability quartiles, the group most likely to experience severe illness (≥75% probability) had a Ct of 16.6 (n = 10), whereas the group least likely to experience severe illness (<25% probability) had a Ct of 21.4 (n = 350) (P=0.0045). Taken together, our results suggest that the severity predicted by a genome-based algorithm can be related to clinical diagnostic tests and that relative severity may be inferred from diagnostic values.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/genetics , Humans , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , Severity of Illness Index , Viral Load/genetics
11.
International Journal of Environmental Research and Public Health ; 19(11):6401, 2022.
Article in English | MDPI | ID: covidwho-1857166

ABSTRACT

Sedentary behavior negatively impacts mental health, which can decrease employee productivity. Employee mental well-being and work performance may improve with sedentary reduction interventions, especially strategies that include environmental workplace modifications and behavior-changing strategies. However, such interventions have not been examined among employees working remotely during the COVID-19 pandemic. As part of the Stand Up Kansas program, 95 sedentary university employees working from home were randomized into one of four intervention arms: height-adjustable desk provision (Desk Only), online sedentary behavior modification program (Program Only), Desk + Program, or Control. The outcomes were measured at a baseline (November 2020) and following the 12-week intervention (February 2021). Employees reported mood (positive and negative affect), stress, fatigue (duration, interference with activities and severity) and work performance (irritability, focus, work satisfaction, non-work satisfaction and productivity) were measured using established self-report instruments. The effect sizes, by comparing the Control arm to the Desk + Program arm, revealed large improvements in mood (positive affect, d = 1.106). Moderate improvements were also seen in fatigue (duration, d = −0.533, and interference with activities, d = −0.648) and several aspects of work performance (focus, d = 0.702, work satisfaction, d = 0.751, and productivity, d = 0.572). Moderate effect sizes were also seen for positive affect (d = 0.566) and fatigue severity (d = 0.577) among the Program Only arm, whereas no noteworthy effect sizes were observed among the Desk Only arm. Combining an online sedentary behavior modification program with height-adjustable desk provisions appeared to positively affect mental well-being and work performance among remote employees.

13.
Viruses ; 14(4)2022 03 29.
Article in English | MEDLINE | ID: covidwho-1810313

ABSTRACT

Surface plasmon resonance and biolayer interferometry are two common real-time and label-free assays that quantify binding events by providing kinetic parameters. There is increased interest in using these techniques to characterize whole virus-ligand interactions, as the methods allow for more accurate characterization than that of a viral subunit-ligand interaction. This review aims to summarize and evaluate the uses of these technologies specifically in virus-ligand and virus-like particle-ligand binding cases to guide the field towards studies that apply these robust methods for whole virus-based studies.


Subject(s)
Biosensing Techniques , Surface Plasmon Resonance , Biological Assay , Interferometry/methods , Kinetics , Ligands
14.
Managing Sport and Leisure ; 27(1/2):93-101, 2022.
Article in English | CAB Abstracts | ID: covidwho-1769092

ABSTRACT

This commentary considers the impacts of COVID-19 on sport governance and management, given the global threat to sport services and organizations evident as a result of the disease since early 2020. To frame this analysis of the impacts and lessons to be learned, the researchers use a Critical Realist (CR) perspective, which takes a multi-level view of reality and seeks to establish how and why something occurs in reality [Byers, T. (2013). Using critical realism: A new perspective on control of volunteers in sport clubs. European Sport Management Quarterly, 13(1), 5-31. https://doi.org/10.1080/16184742.2012.744765]. While the existing commentaries and emerging research on COVID19 have focused on a superficial level of reality (i.e. what stakeholder responses have been), a CR view encourages a more holistic account of what and why something happens. Specifically, this commentary contributes to the discussion of COVID-19 impacts focusing on sport governance, using a philosophy that encourages examination of what is happening in sport organizations, how different stakeholder's perspectives and assessment of the legitimacy of COVID-19 may reveal underlying social structures and biases that help explain sport administrator's responses and value systems. The researchers hope this novel perspective on sport governance encourages readers to think of new ways of organizing and governing that is more inclusive of diversity (e.g. race, gender, disability) in sport.

15.
Sci Rep ; 12(1): 4082, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1735288

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV), is a highly infectious RNA virus. A percentage of patients develop coronavirus disease 2019 (COVID-19) after infection, whose symptoms include fever, cough, shortness of breath and fatigue. Acute and life-threatening respiratory symptoms are experienced by 10-20% of symptomatic patients, particularly those with underlying medical conditions. One of the main challenges in the containment of COVID-19 is the identification and isolation of asymptomatic/pre-symptomatic individuals. A number of molecular assays are currently used to detect SARS-CoV-2. Many of them can accurately test hundreds or even thousands of patients every day. However, there are presently no testing platforms that enable more than 10,000 tests per day. Here, we describe the foundation for the REcombinase Mediated BaRcoding and AmplificatioN Diagnostic Tool (REMBRANDT), a high-throughput Next Generation Sequencing-based approach for the simultaneous screening of over 100,000 samples per day. The REMBRANDT protocol includes direct two-barcoded amplification of SARS-CoV-2 and control amplicons using an isothermal reaction, and the downstream library preparation for Illumina sequencing and bioinformatics analysis. This protocol represents a potentially powerful approach for community screening of COVID-19 that may be modified for application to any infectious or non-infectious genome.


Subject(s)
COVID-19/diagnosis , DNA-Binding Proteins/metabolism , Membrane Proteins/metabolism , Nucleic Acid Amplification Techniques/methods , SARS-CoV-2/genetics , Viral Proteins/metabolism , COVID-19/virology , High-Throughput Nucleotide Sequencing , Humans , Mass Screening , RNA, Viral/analysis , RNA, Viral/metabolism , SARS-CoV-2/isolation & purification
16.
Cytometry A ; 2022 Mar 04.
Article in English | MEDLINE | ID: covidwho-1729117

ABSTRACT

We evaluated the number of CD26 expressing cells in peripheral blood of patients with COVID-19 within 72 h of admission and on day 4 and day 7 after enrollment. The majority of CD26 expressing cells were presented by CD3+ CD4+ lymphocytes. A low number of CD26 expressing cells were found to be associated with critical-severity COVID-19 disease. Conversely, increasing numbers of CD26 expressing T cells over the first week of standard treatment was associated with good outcomes. Clinically, the number of circulating CD26 cells might be a marker of recovery or the therapeutic efficacy of anti-COVID-19 treatment. New therapies aimed at preserving and increasing the level of CD26 expressing T cells may prove useful in the treatment of COVID-19 disease.

17.
Int J Environ Res Public Health ; 19(3)2022 01 25.
Article in English | MEDLINE | ID: covidwho-1649004

ABSTRACT

Mask wearing and physical distancing are effective at preventing COVID-19 transmission. Little is known about the practice of these behaviors during physical activity (PA). In this longitudinal study, direct observation was used to describe COVID-19 prevention behaviors among physically active individuals. The Viral Transmission Scan (VT-Scan) was used to assess COVID-19 prevention behaviors of people standing, sitting, walking, jogging, and cycling in educational, retail, and residential areas. The VT-Scan was performed once per week over 22 weeks between 11:00 a.m. and 2:30 p.m. Information was manually extracted from videos collected during VT-Scans. A total of 4153 people were described, of which 71.2% were physically active, 80.0% were 18-30 years of age, 14.0% were non-white, 61.0% were female, and were 19.6% obese. Individuals not engaged in PA were less compliant with COVID-19 prevention behaviors than physically active people. Compliance differed by PA type, with walkers less compliant with COVID-19 prevention behaviors than joggers and cyclists. Among those physically active, non-compliance with COVID-19 prevention behaviors was higher in 18-30-year-olds, whites, and men. Engagement in COVID-19 prevention behaviors varies as a function of PA. Efforts to promote compliance with recommendations may benefit from tailored messaging, taking into account PA participation, PA type, and characteristics of physically active individuals.


Subject(s)
COVID-19 , Adolescent , Environment , Exercise , Female , Humans , Longitudinal Studies , Male , SARS-CoV-2
18.
Sci Rep ; 11(1): 22463, 2021 11 17.
Article in English | MEDLINE | ID: covidwho-1592758

ABSTRACT

SARS-CoV-2 infection results in a spectrum of outcomes from no symptoms to widely varying degrees of illness to death. A better understanding of the immune response to SARS-CoV-2 infection and subsequent, often excessive, inflammation may inform treatment decisions and reveal opportunities for therapy. We studied immune cell subpopulations and their associations with clinical parameters in a cohort of 26 patients with COVID-19. Following informed consent, we collected blood samples from hospitalized patients with COVID-19 within 72 h of admission. Flow cytometry was used to analyze white blood cell subpopulations. Plasma levels of cytokines and chemokines were measured using ELISA. Neutrophils undergoing neutrophil extracellular traps (NET) formation were evaluated in blood smears. We examined the immunophenotype of patients with COVID-19 in comparison to that of SARS-CoV-2 negative controls. A novel subset of pro-inflammatory neutrophils expressing a high level of dual endothelin-1 and VEGF signal peptide-activated receptor (DEspR) at the cell surface was found to be associated with elevated circulating CCL23, increased NETosis, and critical-severity COVID-19 illness. The potential to target this subpopulation of neutrophils to reduce secondary tissue damage caused by SARS-CoV-2 infection warrants further investigation.


Subject(s)
COVID-19/immunology , Neutrophils/immunology , Pseudogenes/immunology , Aged , Chemokines/metabolism , Cohort Studies , Critical Illness , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay/methods , Extracellular Traps/metabolism , Female , Humans , Inflammation/metabolism , Male , Middle Aged , Neutrophils/metabolism , Pseudogenes/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index
19.
Hastings Cent Rep ; 52(1): 51-58, 2022 01.
Article in English | MEDLINE | ID: covidwho-1568055

ABSTRACT

Covid-19 raised many novel ethical issues including regarding the allocation of opportunities to participate in clinical trials during a public health emergency. In this article, we explore how hospitals that have a scarcity of trial opportunities, either overall or in a specific trial, can equitably allocate those opportunities in the context of an urgent medical need with limited therapeutic interventions. We assess the three main approaches to allocating trial opportunities discussed in the literature: patient choice, physician referral, and randomization/lottery. As, we argue, none of the three typical approaches are ethically ideal for allocating trial opportunities in the pandemic context, many hospitals have instead implemented hybrid solutions. We offer practical guidance to support those continuing to face these challenges, and we analyze options for the future.


Subject(s)
COVID-19 , Clinical Trials as Topic , Pandemics , Patient Selection , Emergencies , Humans , Pandemics/prevention & control , Public Health
20.
Infectious Disease Alert ; 41(3), 2021.
Article in English | ProQuest Central | ID: covidwho-1525222

ABSTRACT

[...]other oral options remain an important goal. Since being approved by the Food and Drug Administration (FDA) in 1997, fluvoxamine has had a good safety record and generally is well tolerated. [...]whether fluvoxamine can help those already hospitalized (e.g., prevent intensive care unit admission) is uncertain. [...]the study was conducted in one geographic area with a relatively homogeneous population, so the results might not be applicable to other regions and should be considered preliminary.

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