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1.
J Public Health Manag Pract ; 29(Suppl 1): S35-S44, 2023.
Article in English | MEDLINE | ID: covidwho-2318634

ABSTRACT

CONTEXT: The Public Health Workforce Interests and Needs Survey (PH WINS) was fielded in 2014 and 2017 and is the largest survey of the governmental public health workforce. It captures individual employees' perspectives on key issues such as workplace engagement and satisfaction, intention to leave, training needs, ability to address public health issues, as well as collects demographic information. This article describes the methods used for the 2021 PH WINS fielding. PH WINS: PH WINS 2021 was fielded to a nationally representative sample of staff in State Health Agency-Central Offices (SHA-COs) and local health departments (LHDs) from September 13, 2021, to January 14, 2022. The instrument was revised to assess the pandemic's potential toll on the workforce, including deployment to COVID-19 response roles and well-being, and the country's renewed focus on health equity and "Racism as a Public Health Crisis." PH WINS 2021 had 3 sampling frames: SHAs, Big Cities Health Coalition (BCHC) members, and LHDs. All participating agencies were surveyed using a census approach. PARTICIPATION: Overall, staff lists for 47 SHAs, 29 BCHC members, and 259 LHDs were collected, and the survey was sent to 137 446 individuals. PH WINS received a total of 44 732 responses, 35% of eligible respondents. The nationally representative SHA-CO frame includes a total of 14 957 individuals, and the nationally representative LHD frame includes 26 933 individuals from 439 LHDs (decentralized and nondecentralized). CONSIDERATIONS FOR ANALYSIS: PH WINS now offers a multiyear, nationally representative sample of both SHA-CO and LHD staff. Both practice and academia can use PH WINS to better understand the strengths, needs, and opportunities of the workforce. When using PH WINS for additional data analysis, there are a number of considerations both within the 2021 data set and when conducting multiyear and multiple cross-sectional analyses.


Subject(s)
COVID-19 , Public Health , Humans , Public Health/methods , Job Satisfaction , Cross-Sectional Studies , COVID-19/epidemiology , Workforce , Surveys and Questionnaires
2.
Lancet ; 401(10389): 1681-1690, 2023 05 20.
Article in English | MEDLINE | ID: covidwho-2310676

ABSTRACT

BACKGROUND: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality globally, with 83% of ARI mortality occurring in low-income and middle-income countries (LMICs) before the COVID-19 pandemic. We aimed to estimate the effect of interventions promoting handwashing with soap on ARI in LMICs. METHODS: In our systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, Global Health, and Global Index Medicus for studies of handwashing with soap interventions in LMICs from inception to May 25, 2021. We included randomised and non-randomised controlled studies of interventions conducted in domestic, school, or childcare settings. Interventions promoting hand hygiene methods other than handwashing with soap were excluded, as were interventions in health-care facilities or the workplace. The primary outcome was ARI morbidity arising from any pathogen for participants of any age. Secondary outcomes were lower respiratory infection, upper respiratory infection, influenza confirmed by diagnostic test, COVID-19 confirmed by diagnostic test, and all-cause mortality. We extracted relative risks (RRs), using random-effects meta-analysis to analyse study results, and metaregression to evaluate heterogeneity. We assessed risk of bias in individual studies using an adapted Newcastle-Ottawa scale, and assessed the overall body of evidence using a Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The study is registered with PROSPERO, CRD42021231414. FINDINGS: 26 studies with 161 659 participants met inclusion criteria, providing 27 comparisons (21 randomised). Interventions promoting handwashing with soap reduced any ARI compared with no handwashing intervention (RR 0·83 [95% CI 0·76-0·90], I2 88%; 27 comparisons). Interventions also reduced lower respiratory infections (0·78 [0·64-0·94], I2 64%; 12 comparisons) and upper respiratory infections (0·74 [0·59-0·93], I2 91%; seven comparisons), but not test-confirmed influenza (0·94 [0·42-2·11], I2 90%; three comparisons), test-confirmed COVID-19 (no comparisons), or all-cause mortality (prevalence ratio 0·95 [95% CI 0·71-1·27]; one comparison). For ARI, no heterogeneity covariates were significant at p<0·1 and the GRADE rating was moderate certainty evidence. INTERPRETATION: Interventions promoting handwashing with soap can reduce ARI in LMICs, and could help to prevent the large burden of respiratory disease. FUNDING: Bill & Melinda Gates Foundation, Reckitt Global Hygiene Institute, and UK FCDO.


Subject(s)
COVID-19 , Influenza, Human , Respiratory Tract Infections , Humans , COVID-19/prevention & control , Developing Countries , Soaps , Pandemics/prevention & control , Respiratory Tract Infections/prevention & control
3.
Clin Infect Dis ; 2022 May 17.
Article in English | MEDLINE | ID: covidwho-2235596

ABSTRACT

BACKGROUND: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 RT-PCR positivity. Of the remaining 168 participants, 12/81 (14·8%) CCP and 13/87 (14·9%) control recipients developed SARS-CoV-2 infection; 6 (7·4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25·3 vs. 25·2 days; p = 0·49) and COVID-19 (26·3 vs. 25·9 days; p = 0·35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, while appearing safe, did not prevent SARS-CoV-2 infection.

4.
Int J Infect Dis ; 128: 230-243, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2165390

ABSTRACT

OBJECTIVES: Investigate risk factors for SARS-CoV-2 infections in school students and staff. METHODS: In the 2020/2021 school year, we administered polymerase chain reaction, antibody tests, and questionnaires to a sample of primary and secondary school students and staff, with data linkage to COVID-19 surveillance. We fitted logistic regression models to identify the factors associated with infection. RESULTS: We included 6799 students and 5090 staff in the autumn and 11,952 students and 4569 staff in the spring/summer terms. Infections in students in autumn 2020 were related to the percentage of students eligible for free school meals. We found no statistical association between infection risk in primary and secondary schools and reported contact patterns between students and staff in either period in our study. Using public transports was associated with increased risk in autumn in students (adjusted odds ratio = 1.72; 95% confidence interval 1.31-2.25) and staff. One or more infections in the same household during either period was the strongest risk factor for infection in students and more so among staff. CONCLUSION: Deprivation, community, and household factors were more strongly associated with infection than contacts patterns at school; this suggests that the additional school-based mitigation measures in England in 2020/2021 likely helped reduce transmission risk in schools.


Subject(s)
COVID-19 , Humans , Longitudinal Studies , SARS-CoV-2 , Risk Factors , England , Schools , Students
5.
Transfusion ; 62(11): 2271-2281, 2022 11.
Article in English | MEDLINE | ID: covidwho-2070536

ABSTRACT

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, the transfusion medicine community has experienced unprecedented blood supply shortages since March 2020. As such, numerous changes to everyday practice have occurred with a specific emphasis on blood conservation. We sought to determine the strategies used to mitigate blood shortages and promote blood conservation during the pandemic. METHODS: An anonymous, 37-question survey was developed using Research Electronic Data Capture and distributed via e-mail to transfusion medicine specialists across the US obtained via publicly available databases. RESULTS: Amongst surveyed [41.1% response rate (51/124 institutions)], 98.0% experienced a product shortage, with the greatest number reporting red blood cell (RBC) shortages (92.0%). This led to 35.3% of institutions altering the composition and/or number of blood product suppliers, including a 100% increase in the number of institutions acquiring blood from organizations that connect hospital transfusion services with blood collection centers (e.g., Blood Buy) compared to before March 2020. Prospective triaging of blood products was the most common blood conservation strategy (68.1%), though 35.4% altered their RBC exchange or transfusion program for patients receiving chronic RBC transfusion/exchange. As a result of these changes, 78.6% of institutions reported that these changes resulted in a reduction in blood product usage, and 38.1% reported a decrease in product wastage. CONCLUSIONS: Most hospitals experienced the effects of the supply shortage, and many of them implemented blood conserving measures. Conservation strategies were associated with decreased blood utilization and waste, and future studies could evaluate whether these changes persist.


Subject(s)
Bloodless Medical and Surgical Procedures , COVID-19 , Humans , United States/epidemiology , Pandemics , COVID-19/epidemiology , Prospective Studies , Blood Transfusion , Hospitals
6.
J Infect Dis ; 226(Suppl 3): S340-S345, 2022 10 07.
Article in English | MEDLINE | ID: covidwho-2062916

ABSTRACT

BACKGROUND: People experiencing homelessness (PEH) are disproportionately affected by many infectious diseases, including coronavirus disease 2019 (COVID-19). However, communication efforts during public health emergencies like the COVID-19 pandemic often do not consider the unique needs of PEH. We examined how PEH seek and receive health information and how traditional health communication methods resonate with them. METHODS: We conducted in-person focus groups with PEH in 4 jurisdictions (Cincinnati, Ohio; Denver, Colorado; Sacramento, California; and the Bronx, New York) during July 2021. RESULTS: Findings from 15 focus groups with PEH (n = 53) revealed the need for trusted messengers and consistent messaging across local organizations, as PEH seek to verify information they receive from multiple sources. PEH overwhelmingly preferred to receive health information through face-to-face conversations, especially with healthcare providers with whom they had an established relationship, but they also cited news media, the internet, and social media as their main sources for obtaining health information. PEH reported that effective communication products pair a recommended action with instructions and resources about how to take that action within their community. CONCLUSIONS: These findings support healthcare providers collaborating with public health agencies to ensure that infectious disease prevention messages for PEH are provided by trusted messengers, multimodal, paired with resources, and consistent.


Subject(s)
COVID-19 , Communicable Diseases , Ill-Housed Persons , COVID-19/prevention & control , Communicable Diseases/epidemiology , Humans , Pandemics , Public Health
7.
Lancet Reg Health Eur ; 21: 100471, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1996406

ABSTRACT

Background: There remains uncertainty about the epidemiology of SARS-CoV-2 among school students and staff and the extent to which non-pharmaceutical-interventions reduce the risk of school settings. Methods: We conducted an open cohort study in a sample of 59 primary and 97 secondary schools in 15 English local authority areas that were implementing government guidance to schools open during the pandemic. We estimated SARS-CoV-2 infection prevalence among those attending school, antibody prevalence, and antibody negative to positive conversion rates in staff and students over the school year (November 2020-July 2021). Findings: 22,585 staff and students participated. SARS-CoV-2 infection prevalence among those attending school was highest during the first two rounds of testing in the autumn term, ranging from 0.7% (95% CI 0.2, 1.2) among primary staff in November 2020 to 1.6% (95% CI 0.9, 2.3) among secondary staff in December 2020. Antibody conversion rates were highest in the autumn term. Infection patterns were similar between staff and students, and between primary and secondary schools. The prevalence of nucleoprotein antibodies increased over the year and was lower among students than staff. SARS-CoV-2 infection prevalence in the North-West region was lower among secondary students attending school on normal school days than the regional estimate for secondary school-age children. Interpretation: SARS-CoV-2 infection prevalence in staff and students attending school varied with local community infection rates. Non-pharmaceutical interventions intended to prevent infected individuals attending school may have partially reduced the prevalence of infection among those on the school site. Funding: UK Department of Health and Social Care.

8.
Ann Intern Med ; 175(9): 1310-1321, 2022 09.
Article in English | MEDLINE | ID: covidwho-1994458

ABSTRACT

DESCRIPTION: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP. METHODS: These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations. RECOMMENDATION 1 (OUTPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence). RECOMMENDATION 2 (INPATIENT): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. RECOMMENDATION 3 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence). RECOMMENDATION 4 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence). RECOMMENDATION 5 (PROPHYLAXIS): The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence). GOOD CLINICAL PRACTICE STATEMENT: CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/therapy , Hospitalization , Humans , Immunization, Passive/methods , COVID-19 Serotherapy
9.
JMIR Res Protoc ; 11(11): e34075, 2022 11 10.
Article in English | MEDLINE | ID: covidwho-1875278

ABSTRACT

BACKGROUND: One of the most debated questions in the COVID-19 pandemic has been the role of schools in SARS-CoV-2 transmission. The COVID-19 Schools Infection Survey (SIS) aims to provide much-needed evidence addressing this issue. OBJECTIVE: We present the study protocol and participation profile for the SIS study, aimed at assessing the role of schools in SARS-CoV-2 infection and transmission within school settings, and investigating how transmission within and from schools could be mitigated through the implementation of school COVID-19 control measures. METHODS: SIS was a multisite, prospective, observational cohort study conducted in a stratified random sample of primary and secondary schools in selected local authorities in England. A total of 6 biobehavioral surveys were planned among participating students and staff during the 2020-2021 academic year, between November 2020 and July 2021. Key measurements were SARS-CoV-2 virus prevalence, assessed by nasal swab polymerase chain reaction; anti-SARS-CoV-2 (nucleocapsid protein) antibody prevalence and conversion, assessed in finger-prick blood for staff and oral fluid for students; student and staff school attendance rates; feasibility and acceptability of school-level implementation of SARS-CoV-2 control measures; and investigation of selected school outbreaks. The study was approved by the United Kingdom Health Security Agency Research Support and Governance Office (NR0237) and London School of Hygiene & Tropical Medicine Ethics Review Committee (reference 22657). RESULTS: Data collection and laboratory analyses were completed by September 2021. A total of 22,585 individuals-1891 staff and 4654 students from 59 primary schools and 5852 staff and 10,188 students from 97 secondary schools-participated in at least one survey. Across all survey rounds, staff and student participation rates were 45.2% and 16.4%, respectively, in primary schools and 30% and 15.2%, respectively, in secondary schools. Although primary student participation increased over time, and secondary student participation remained reasonably consistent, staff participation declined across rounds, especially for secondary school staff (3165/7583, 41.7% in round 1 and 2290/10,374, 22.1% in round 6). Although staff participation overall was generally reflective of the eligible staff population, student participation was higher in schools with low absenteeism, a lower proportion of students eligible for free school meals, and from schools in the least deprived locations (in primary schools, 446/4654, 9.6% of participating students were from schools in the least deprived quintile compared with 1262/22,225, 5.7% of eligible students). CONCLUSIONS: We outline the study design, methods, and participation, and reflect on the strengths of the SIS study as well as the practical challenges encountered and the strategies implemented to address these challenges. The SIS study, by measuring current and incident infection over time, alongside the implementation of control measures in schools across a range of settings in England, aims to inform national guidance and public health policy for educational settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/34075.

10.
EBioMedicine ; 77: 103902, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1700817

ABSTRACT

BACKGROUND: There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins. METHODS: In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351). FINDINGS: We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), an increase in binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) is observed following each additional dose. In addition, a strong and polyfunctional T cell response was measured all booster regimens. INTERPRETATION: Real world data is demonstrating that one or more doses of licensed SARS-CoV-2 vaccines confer reduced protection against hospitalisation and deaths caused by divergent VoC, including Omicron. Our data support the ongoing clinical development and testing of booster vaccines to increase immunity against highly mutated VoC. FUNDING: This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines , ChAdOx1 nCoV-19 , Humans , SARS-CoV-2/genetics
11.
BMJ Open ; 11(12), 2021.
Article in English | ProQuest Central | ID: covidwho-1592768

ABSTRACT

ObjectivesThe aim of this study is to fill a key information gap on the nutrition-related epidemiology of orphaned and vulnerable children living within institution-based care (IBC) across six countries.DesignA retrospective analysis with Shewhart control charts and funnel plots to explore intersite and over time variations in nutritional status.SettingWe conducted a retrospective analysis of records from Holt International’s Child Nutrition Programme from 35 sites in six countries;Mongolia, India, Ethiopia, Vietnam, China and the Philippines.ParticipantsDeidentified health records from Holt International’s online nutrition screening database included records from 2926 children, 0–18 years old. Data were collected from 2013 to 2020 and included demographic and health information.ResultsAt initial screening, 717 (28.7%) children were anaemic, 788 (34.1%) underweight, 1048 (37.3%) stunted, 212 (12.6%) wasted, 135 (12%) overweight or obese and 339 (31%) had small head circumference. Many had underlying conditions: low birth weight, 514 (57.5%);prematurity, 294 (42.2%) and disabilities, 739 (25.3%). Children with disabilities had higher prevalence of malnutrition compared with counterparts without disabilities at baseline and 1-year screenings. There was marked intersite variation. Funnel plots highlight sites with malnutrition prevalence outside expected limits for this specific population taking into consideration natural variation at baseline and at 1 year. Control charts show changes in site mean z-scores over time in relation to site control limits.ConclusionsMalnutrition is prevalent among children living within IBC, notably different forms of undernutrition (stunting, underweight, wasting). Underlying risk factors are also common: prematurity, low birth weight and disability. Nutrition interventions should take into account the needs of this vulnerable population, especially for infants and those with disabilities. Using control charts to present data could be especially useful to programme managers as sites outside control limits could represent: problems to be investigated;good practices to be shared.

12.
Mol Ther ; 29(6): 1970-1983, 2021 06 02.
Article in English | MEDLINE | ID: covidwho-1386766

ABSTRACT

A self-transcribing and replicating RNA (STARR)-based vaccine (LUNAR-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full-length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolongs SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell-mediated immunity produced a strong viral antigen-specific CD8+ T lymphocyte response. Assaying for intracellular cytokine staining for interferon (IFN)γ and interleukin-4 (IL-4)-positive CD4+ T helper (Th) lymphocytes as well as anti-spike glycoprotein immunoglobulin G (IgG)2a/IgG1 ratios supported a strong Th1-dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 µg and 10 µg doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of LUNAR-COV19 as a single-dose vaccine.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/administration & dosage , Alphavirus/genetics , Alphavirus/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , COVID-19 Vaccines/biosynthesis , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Female , Gene Expression , Humans , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-4/genetics , Interleukin-4/immunology , Mice , Mice, Transgenic , Replicon/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/virology , Transgenes , Treatment Outcome , Vaccination/methods , Vaccines, Synthetic/biosynthesis , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
13.
Transfusion ; 61(9): 2756-2767, 2021 09.
Article in English | MEDLINE | ID: covidwho-1367368

ABSTRACT

BACKGROUND: The AABB Clinical Transfusion Medicine Committee (CTMC) compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine (TM), which has been made available as a manuscript published in Transfusion since 2018. METHODS: CTMC committee members reviewed original manuscripts including TM-related topics published electronically (ahead) or in print from December 2019 to December 2020. The selection of topics and manuscripts was discussed at committee meetings and chosen based on relevance and originality. Next, committee members worked in pairs to create a synopsis of each topic, which was then reviewed by two additional committee members. The first and senior authors of this manuscript assembled the final manuscript. Although this synopsis is extensive, it is not exhaustive, and some papers may have been excluded or missed. RESULTS: The following topics are included: COVID-19 effects on the blood supply and regulatory landscape, COVID convalescent plasma, adult transfusion practices, whole blood, molecular immunohematology, pediatric TM, cellular therapy, and apheresis medicine. CONCLUSIONS: This synopsis provides easy access to relevant topics and may be useful as an educational tool.


Subject(s)
Transfusion Medicine/trends , Humans
14.
Nat Commun ; 12(1): 2893, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1232068

ABSTRACT

Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , RNA, Viral/administration & dosage , SARS-CoV-2/immunology , Vaccination/methods , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , ChAdOx1 nCoV-19 , Immunization, Secondary , Immunogenicity, Vaccine , Mice , RNA, Viral/genetics , RNA, Viral/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes, Cytotoxic/immunology , Th1 Cells/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
15.
BMJ Open ; 10(12): e039546, 2020 12 02.
Article in English | MEDLINE | ID: covidwho-1228877

ABSTRACT

OBJECTIVE: Post-randomisation exclusions in randomised controlled trials are common and may include participants identified as not meeting trial eligibility criteria after randomisation. We report how a decision might be reached and reported on, to include or exclude these participants. We illustrate using a motivating scenario from the BREATHE trial (Trial registration ClinicalTrials.gov, NCT02426112) evaluating azithromycin for the treatment of chronic lung disease in people aged 6-19 years with HIV in Zimbabwe and Malawi. KEY POINTS: Including all enrolled and randomised participants in the primary analysis of a trial ensures an unbiased estimate of the intervention effect using intention-to-treat principles, and minimises the effects of confounding through balanced allocation to trial arm. Ineligible participants are sometimes enrolled, due to measurement or human error. Of 347 participants enrolled into the BREATHE trial, 11 (3.2%) were subsequently found to be ineligible based on lung function criteria. We assumed no safety risk of azithromycin treatment; their inclusion in the trial and subsequent analysis of the intervention effect therefore mirrors clinical practice. Senior trial investigators considered diurnal variations in the measurement of lung function, advantages of retaining a higher sample size and advice from the Data Safety and Monitoring Board and Trial Steering Committee, and decided to include these participants in primary analysis. We planned and reported analyses including and excluding these participants, and in our case the interpretation of treatment effect was consistent. CONCLUSION: The decision, by senior investigators, on whether to exclude enrolled participants, should reflect issues of safety, treatment efficacy, statistical power and measurement error. As long as decisions are made prior to finalising the statistical analysis plan for the trial, the risk of exclusions creating bias should be minimal. The decision taken should be transparently reported and a sensitivity analysis can present the opposite decision.


Subject(s)
COVID-19 , Adolescent , Adult , Child , Humans , Malawi , SARS-CoV-2 , Treatment Outcome , Young Adult , Zimbabwe
16.
ACS Cent Sci ; 7(4): 594-602, 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1225486

ABSTRACT

Vaccine development against the SARS-CoV-2 virus focuses on the principal target of the neutralizing immune response, the spike (S) glycoprotein. Adenovirus-vectored vaccines offer an effective platform for the delivery of viral antigen, but it is important for the generation of neutralizing antibodies that they produce appropriately processed and assembled viral antigen that mimics that observed on the SARS-CoV-2 virus. Here, we describe the structure, conformation, and glycosylation of the S protein derived from the adenovirus-vectored ChAdOx1 nCoV-19/AZD1222 vaccine. We demonstrate native-like post-translational processing and assembly, and reveal the expression of S proteins on the surface of cells adopting the trimeric prefusion conformation. The data presented here confirm the use of ChAdOx1 adenovirus vectors as a leading platform technology for SARS-CoV-2 vaccines.

17.
Pediatr Pulmonol ; 56(7): 1951-1956, 2021 07.
Article in English | MEDLINE | ID: covidwho-1179015

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic profoundly impacted health care utilization. We evaluated asthma-related emergency department (ED) and inpatient health care utilization by a county-specific Medicaid population, ages 2-18, during the COVID-19 pandemic and compared it to utilization from a 3-year average including 2017-2019. All-cause ED utilization and asthma medication fill rates were evaluated during the same timeframes. Relative to the 2017-2019 3-year average, cumulative asthma-related ED visits from January through June decreased by 45.8% (p = .03) and inpatient admission rates decreased by 50.5% (p = .03). The decline in asthma-related ED utilization was greater than the reduction of overall ED use during the same time period, suggesting that the decline involved factors specific to asthma and was not due solely to avoidance of health care facilities. Fill rates for asthma controller medications decreased during this time (p = .03) and quick relief medication fill rates had no significant change (p = .31). Multiple factors may have contributed to the decrease in acute asthma health care visits. Locally, decreased air pollution and viral exposures coincided with the "Stay-at-home" order in Ohio, and increased utilization of telehealth for assessment during exacerbations may have impacted outcomes. Identification of the cause of the decline in visit rates could spur new interventions to limit the need for ED and inpatient visits for asthma patients, leading to both economic and health-associated benefits.


Subject(s)
Asthma/physiopathology , COVID-19/epidemiology , Pandemics , Adolescent , Air Pollution , Asthma/complications , Asthma/drug therapy , COVID-19/complications , COVID-19/virology , Child , Child, Preschool , Emergency Service, Hospital , Female , Humans , Inpatients , Male , Medicaid , Morbidity , Ohio/epidemiology , Patient Acceptance of Health Care , Patient Admission/statistics & numerical data , SARS-CoV-2 , Telemedicine , United States
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