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1.
J Med Internet Res ; 23(12): e31127, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1597005

ABSTRACT

BACKGROUND: The short form, 17-item version of the Pediatric Symptom Checklist-Youth Self-Report (PSC-17-Y) is a validated measure that assesses psychosocial problems overall (OVR) and in 3 major psychopathological domains (internalizing, externalizing, and attention-deficit/hyperactivity disorder), taking 5-10 min to complete. Prior research has established sound psychometric properties of the PSC-17-Y for English speakers. OBJECTIVE: This study extends psychometric evidence for the acceptability of the PSC-17-Y in a large sample of Spanish adolescents, providing proof of its reliability and structure, convergent and discriminant validity, and longitudinal and gender invariance. METHODS: Data were collected on 5430 adolescents, aged 12-18 years, who filled out the PSC-17-Y twice during 2018-2019 (7-month interval). We calculated the Cronbach alpha and the McDonald omega coefficients to test reliability, the Pearson correlation for convergent (distress) and criterion validity (well-being, quality of life, and socioemotional skills), confirmatory factor analysis (CFA) for structure validity, and multigroup and longitudinal measurement invariance analysis for longitudinal and gender stability. RESULTS: Within structural analysis for the PSC-17-Y, CFA supported a correlated 3-factor solution, which was also invariant longitudinally and across gender. All 3 subscales showed evidence of reliability, with coefficients near or above .70. Moreover, scores of PSC-17-Y subscales were positively related with convergent measures and negatively related with criterion measures. Normative data for the PSC-17-Y are presented in the form of percentiles (75th and 90th). CONCLUSIONS: This work provides the first evidence of the reliability and validity of the Spanish version of the PSC-17-Y administered over the internet to assess mental health problems among adolescents, maintaining the same domains as the long version.

2.
JCI Insight ; 2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1528616

ABSTRACT

Sangivamycin is a nucleoside analog that is well-tolerated by humans and broadly active against phylogenetically distinct viruses, including arenaviruses, filoviruses, and orthopoxviruses. Here, we show that sangivamycin is a potent antiviral against multiple variants of replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with half-maximal inhibitory concentration (IC50) in the nanomolar range in several cell types. Sangivamycin suppressed SARS-CoV-2 replication with greater efficacy than remdesivir (another broad-spectrum nucleoside analog). When we investigated sangivamycin's potential for clinical administration, pharmacokinetic, ADME (absorption, distribution, metabolism, and excretion), and toxicity properties were found to be favorable. When tested in combination with remdesivir, efficacy was additive rather than competitive against SARS-CoV-2. The proven safety in humans, long half-life, potent antiviral activity (compared to remdesivir), and combinatorial potential suggest that sangivamycin is likely to be efficacious alone or in combination therapy to suppress viremia in patients. Sangivamycin may also have the ability to help combat drug-resistant or vaccine-escaping SARS-CoV-2 variants since it is antivirally active against several tested variants. Our results support the pursuit of sangivamycin for further preclinical and clinical development as a potential coronavirus disease 2019 (COVID-19) therapeutic.

3.
Socioecol Pract Res ; : 1-7, 2021 Feb 25.
Article in English | MEDLINE | ID: covidwho-1516964

ABSTRACT

In this communication article, we share our scenario ideas at the request of the journal editor. These are (1) a scenario for building sustainable suburbs; (2) a counterfactual scenario for coping with the super wicked COVID problem; (3) envisioning alternative futures of cultural ecosystem services supplies in Southwestern Ghana; and (4) a path toward writing successful scenarios. The ideas will be fully developed in due course into scholarly articles for the journal.

4.
JCI Insight ; 6(22)2021 11 22.
Article in English | MEDLINE | ID: covidwho-1476916

ABSTRACT

Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 , Immunization, Secondary , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Lung/immunology , SARS-CoV-2/immunology , Adult , Aged , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Female , Follow-Up Studies , Humans , Immunity, Humoral/drug effects , Longitudinal Studies , Male , Middle Aged
5.
Viruses ; 12(5)2020 05 06.
Article in English | MEDLINE | ID: covidwho-1389513

ABSTRACT

SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.


Subject(s)
Antibodies, Viral/immunology , Neutralization Tests/methods , Spike Glycoprotein, Coronavirus/analysis , Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Containment of Biohazards , HEK293 Cells , Humans , Lentivirus , Peptidyl-Dipeptidase A/metabolism , Plasma/immunology
6.
Front Immunol ; 12: 710263, 2021.
Article in English | MEDLINE | ID: covidwho-1315952

ABSTRACT

The unprecedented global demand for SARS-CoV-2 vaccines has demonstrated the need for highly effective vaccine candidates that are thermostable and amenable to large-scale manufacturing. Nanoparticle immunogens presenting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S) in repetitive arrays are being advanced as second-generation vaccine candidates, as they feature robust manufacturing characteristics and have shown promising immunogenicity in preclinical models. Here, we used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the RBD. The selected mutations fill a cavity in the RBD that has been identified as a linoleic acid binding pocket. Screening of several designs led to the selection of two lead candidates that expressed at higher yields than the wild-type RBD. These stabilized RBDs possess enhanced thermal stability and resistance to aggregation, particularly when incorporated into an icosahedral nanoparticle immunogen that maintained its integrity and antigenicity for 28 days at 35-40°C, while corresponding immunogens displaying the wild-type RBD experienced aggregation and loss of antigenicity. The stabilized immunogens preserved the potent immunogenicity of the original nanoparticle immunogen, which is currently being evaluated in a Phase I/II clinical trial. Our findings may improve the scalability and stability of RBD-based coronavirus vaccines in any format and more generally highlight the utility of comprehensive DMS data in guiding vaccine design.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization Schedule , Immunogenicity, Vaccine , Mutation , Protein Domains/genetics , Protein Domains/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/virology , COVID-19 Vaccines/immunology , Chlorocebus aethiops , Female , HEK293 Cells , Humans , Linoleic Acids , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Treatment Outcome , Vero Cells
7.
Nature ; 594(7862): 253-258, 2021 06.
Article in English | MEDLINE | ID: covidwho-1192479

ABSTRACT

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).


Subject(s)
Adjuvants, Immunologic , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccines, Subunit/immunology , Alum Compounds , Animals , Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , COVID-19/virology , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Disease Models, Animal , Immunity, Cellular , Immunity, Humoral , Macaca mulatta/immunology , Male , Oligodeoxyribonucleotides , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Squalene
10.
Sci Rep ; 11(1): 4290, 2021 02 22.
Article in English | MEDLINE | ID: covidwho-1096333

ABSTRACT

Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was conducted to assess whether existing B-cell epitope prediction methods, combined with comprehensive mining of sequence databases and structural data, could predict whether a particular protein would be suitable for serodiagnosis. Nine of the predictions were validated with recombinant SARS-CoV-2 proteins in the ELISA format using plasma and sera from patients with SARS-CoV-2 infection, and a further 11 predictions were compared to the recent literature. Results appeared to be in agreement with 12 of the predictions, in disagreement with 3, while a further 5 were deemed inconclusive. We showed that two of our top five candidates, the N-terminal fragment of the nucleoprotein and the receptor-binding domain of the spike protein, have the highest sensitivity and specificity and signal-to-noise ratio for detecting COVID-19 sera/plasma by ELISA. Mixing the two antigens together for coating ELISA plates led to a sensitivity of 94% (N = 80 samples from persons with RT-PCR confirmed SARS-CoV-2 infection), and a specificity of 97.2% (N = 106 control samples).


Subject(s)
COVID-19/diagnosis , COVID-19/immunology , Enzyme-Linked Immunosorbent Assay/methods , Epitopes, B-Lymphocyte/immunology , SARS-CoV-2/pathogenicity , Humans , Real-Time Polymerase Chain Reaction , SARS-CoV-2/immunology , Signal-To-Noise Ratio
11.
PS, Political Science & Politics ; 54(1):188-190, 2021.
Article in English | ProQuest Central | ID: covidwho-1012642
12.
Transfus Med Rev ; 35(1): 1-6, 2021 01.
Article in English | MEDLINE | ID: covidwho-960142
14.
Cell ; 183(5): 1367-1382.e17, 2020 11 25.
Article in English | MEDLINE | ID: covidwho-893667

ABSTRACT

A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Nanoparticles/chemistry , Protein Domains/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Vaccination , Adolescent , Adult , Aged , Animals , COVID-19/virology , Chlorocebus aethiops , Cohort Studies , Epitopes/immunology , Female , HEK293 Cells , Humans , Macaca nemestrina , Male , Mice, Inbred BALB C , Middle Aged , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells , Young Adult
15.
Journal of World - Systems Research ; 26(2):143-150, 2020.
Article in English | ProQuest Central | ID: covidwho-829065

ABSTRACT

There is far more consciousness that to be Black in the present world is to face a constant vulnerability to violence, premature death, incarceration, environmental havoc, and impoverishment. To be Black in the present world is to bear the weight of the irreparable loss and lingering physical and emotional scars caused by the abduction and enslavement of more than 15 million African people and their descendants. To be Black in the present world is to contend continually with the afterlife of slavery. And significantly today, it has become much more obvious that racism constitutes a "pre-existing societal condition" that now obstructs efforts at national and global levels to contain the COVID- 19 pandemic. Here, Murphy et al talk about the social movements for reparations.

16.
Br J Haematol ; 191(3): 340-346, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-824515

ABSTRACT

The emerging COVID-19 pandemic has overwhelmed healthcare resources worldwide, and for transfusion services this could potentially result in rapid imbalance between supply and demand due to a severe shortage of blood donors. This may result in insufficient blood components to meet every patient's needs resulting in difficult decisions about which patients with major bleeding do and do not receive active transfusion support. This document, which was prepared on behalf of the National Blood Transfusion Committee in England, provides a framework and triage tool to guide the allocation of blood for patients with massive haemorrhage during severe blood shortage. Its goal is to provide blood transfusions in an ethical, fair, and transparent way to ensure that the greatest number of life years are saved. It is based on an evidence- and ethics-based Canadian framework, and would become operational where demand for blood greatly exceeds supply, and where all measures to manage supply and demand have been exhausted. The guidance complements existing national shortage plans for red cells and platelets.


Subject(s)
Betacoronavirus , Blood Banks/methods , Blood Donors/supply & distribution , Coronavirus Infections/epidemiology , Health Care Rationing/methods , Pandemics , Pneumonia, Viral/epidemiology , Triage/methods , Blood Banks/standards , Blood Transfusion/methods , Bloodless Medical and Surgical Procedures , COVID-19 , Disaster Planning , Health Care Rationing/ethics , Health Care Rationing/standards , Hemorrhage/epidemiology , Hemorrhage/therapy , Humans , SARS-CoV-2 , Triage/ethics , Triage/standards , United Kingdom/epidemiology
17.
Oral Surgery ; n/a(n/a), 2020.
Article | Wiley | ID: covidwho-780996

ABSTRACT

Abstract We would like to bring to your readership?s attention to the drug phenindione. We came across this drug during a COVID-19 pandemic phone triage at our dental hospital. A 48-year-old was referred for the management of a right sided facial swelling related to a carious unrestorable upper right molar. She had a complex medical history, including rheumatic fever, total kidney failure with regular dialysis and was anticoagulated with phenindione following a tricuspid valve replacement as she was allergic to warfarin. When checked, her International Normalized Ratio (INR) was eight, likely due to untreated dental infection.

18.
Nat Commun ; 11(1): 4378, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-740036

ABSTRACT

Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children's Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Visitors to Patients , Adolescent , COVID-19 , COVID-19 Testing , Child , Child, Preschool , Clinical Laboratory Techniques/methods , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Hospitals , Humans , Infant , Infant, Newborn , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2 , Seroepidemiologic Studies , Serologic Tests/methods , United States/epidemiology
20.
Transfus Med Rev ; 34(3): 151-157, 2020 07.
Article in English | MEDLINE | ID: covidwho-625527

ABSTRACT

The collection and clinical use of COVID-19 convalescent plasma (CCP) as a therapy for COVID-19 infection is under development and early use in many centers worldwide. We conducted an international survey of centers undertaking studies of CCP to provide understanding of the common themes and differences between them. Sixty-four studies in 22 countries were identified from clinical trial registries and personal contacts of the authors. Twenty of the 64 centers (31%) from 12 of 22 countries (55%) responded to the survey. Of the 20 studies, 11 were randomized controlled trials (RCTs), and 9 were case series. Only 4 of the RCTs plan to recruit 400 patients or more, and only 3 RCTs were blinded. The majority of studies will study the effect of CCP on sick patients requiring hospitalization and those requiring critical care, and none is examining the role of CCP in non-infected at-risk individuals. A wide variety of primary and secondary outcomes are being used. The donor eligibility criteria among the studies are very similar, and the use of plasmapheresis for the collection of CCP is almost universal. The planned dose of CCP ranges from as little as 200 mL to well over 1 L, but is 400 to 800 mL or 4 mL/kg or greater in all the RCTs. There is considerable variability in donor antibody testing with no consistency regarding the cut-off for antibody titer for acceptance as CCP or the use of pathogen-inactivation. Our survey provides an understanding of the similarities and differences among the studies of CCP, and that by virtue of their design some studies may be more informative than others.


Subject(s)
Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Betacoronavirus , COVID-19 , Data Collection , Donor Selection , Global Health , Humans , Immunization, Passive , International Cooperation , Pandemics , Plasmapheresis , Randomized Controlled Trials as Topic , Research Design , SARS-CoV-2 , Surveys and Questionnaires , Tissue Donors , Treatment Outcome
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