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1.
Nat Commun ; 13(1): 1251, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-1740439

ABSTRACT

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antiviral Agents , Humans , Longitudinal Studies , Spike Glycoprotein, Coronavirus
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322827

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is normally controlled by effective host immunity including innate, humoral and cellular responses. However, the trajectories and correlates of acquired immunity, and the capacity of memory responses months after infection to neutralise variants of concern - which has important public health implications - is not fully understood. To address this, we studied a cohort of 78 UK healthcare workers who presented in April to June 2020 with symptomatic PCR-confirmed infection or who tested positive during an asymptomatic screening programme and tracked virus-specific B and T cell responses longitudinally at 5-6 time points each over 6 months, prior to vaccination. We observed a highly variable range of responses, some of which - T cell interferon-gamma (IFN-γ) ELISpot, N-specific antibody waned over time across the cohort, while others (spike-specific antibody, B cell memory ELISpot) were stable. In such cohorts, antiviral antibody has been linked to protection against re-infection. We used integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling Over Night) to explore this heterogeneity and to identify predictors of sustained immune responses. Hierarchical clustering defined a group of high and low antibody responders, which showed stability over time regardless of clinical presentation. These antibody responses correlated with IFN-γ ELISpot measures of T cell immunity and represent a subgroup of patients with a robust trajectory for longer term immunity. Importantly, this immune-phenotype associates with higher levels of neutralising antibodies not only against the infecting (Victoria) strain but also against variants B.1.1.7 (alpha) and B.1.351 (beta). Overall memory responses to SARS-CoV-2 show distinct trajectories following early priming, that may define subsequent protection against infection and severe disease from novel variants.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312365

ABSTRACT

This paper explores the intersection of transnational law with contemporary corporate governance laws and principles. Transnational law, it must be said, is a far from settled concept. There is uncertainty as to what the term actually means, and how it differs from other concepts, such as national legal ordering or global law. For early theorists, the essence of transnational law was whether it regulated conduct or events that crossed national boundaries. More recent scholarship, however, has focused not on what is being regulated, but rather on how laws and norms are transmitted between supranational and local levels.Corporate governance, with its complex array of public and private actors, fits naturally within the modern conception of transnational law as a species of law that “can no longer be viewed through a purely national lens”. Financial markets today are global and interconnected and events, such as the 2007-2009 global financial crisis and the current COVID-19 crisis, exemplify the risk of contagion across those markets.Not only can corporate governance problems transcend national boundaries, so too can their solutions, which often involve regulatory efforts that operate at a transnational level. In this environment, the corporation has taken on a greater societal role. Indeed, according to The British Academy’s influential Future of the Corporation project, the main purpose of business today is “to solve the problems of people and planet profitably”.This paper explores, from a transnational perspective, the transmission of laws and norms that are designed to constrain directors’ conduct and enhance corporate accountability. It focuses on two key examples of such accountability mechanisms —fiduciary duties and corporate codes.The paper begins with a comparative and historical examination of directors’ fiduciary duties in the United States, the United Kingdom and Australia, analyzing the extent to which the transfer of fiduciary law to these common law jurisdictions has resulted in a unified approach to directors’ duties, as is often assumed by studies such as the law matters hypothesis. The paper then moves on to discuss the modern phenomenon of codes, such as corporate governance codes and shareholder stewardship codes. Corporate codes originated in the United Kingdom in the early 1990s, but have subsequently spread throughout the world. The paper explores the global transmission of these codes, which constitute powerful “norm creators”. The rise of corporate codes epitomizes the fact that transnational legal ordering occurs “multi-directionally and recursively up from and down to the national and local levels”. It also demonstrates the importance of “who writes the rules”, because this can affect the substance of those rules and result in significant divergence between national codes.The paper assesses these various developments against the backdrop of convergence and path dependence theories in corporate governance.

4.
Teaching & Learning Inquiry ; 9(2):1-21, 2021.
Article in English | ProQuest Central | ID: covidwho-1615173

ABSTRACT

Assessment feedback should be an integral part of learning In higher education, but students can find this process emotionally and cognitively challenging. Instructors need to consider how to manage students' responses to feedback so that students feel capable of improving their work and maintaining their wellbeing. In this paper, we examine the role of instructor-student relational feed-forward, enacted as a dialogue relating to ongoing assessment, in dissipating student anxiety, enabling productive learning attitudes and behaviours, and supporting wellbeing. We undertook qualitative data collection within two undergraduate teaching units that were adopting a relational feed-forward intervention over the 2019-2020 academic year. Student responses were elicited via small group, semi-structured interviews and personal reflective diaries, and were analysed inductively using thematic analysis. The results demonstrate that relational feed-forward promotes many elements of student feedback literacy, such as appreciating the purpose and value of feedback, judging work against a rubric, exercising volition and agency to act, and managing affect. Students were keen for instructors to help them manage their emotions related to assessment, believing this would promote their wellbeing. We conclude by exploring academic strategies and pedagogies that position relational instructor feed-forward as an act of care, and we summarize the key characteristics of emotionally resonant relational feed-forward meetings.

5.
Am J Obstet Gynecol MFM ; 4(1): 100515, 2022 01.
Article in English | MEDLINE | ID: covidwho-1465997
6.
Journal of Early Childhood Literacy ; : 14687984211044187, 2021.
Article in English | Sage | ID: covidwho-1390458

ABSTRACT

COVID-19 has changed the daily lives of families, impacted on work, social interactions, and mental health. Since spring 2020, parents have been working from home and children have been home from daycare and school. Parents are experiencing stress in an attempt to satisfy the demands of work, family, and COVID-19 concerns. Due to the fact that children have been home from daycare and school, parents have the sole responsibility of caring for and teaching their children until schools are able to fully and effectively meet the needs of educating students in an adapted format. Research provides a wealth of information documenting the advantages of parents reading to their children. Children benefit from read-alouds with parental interaction, and these benefits include an increase in oral language skills, reading comprehension, vocabulary, and an increase in motivation to read. The purpose of this study is to answer two questions: (1) Since parents were home more often with their children, were parents spending more quality time reading to their two-to four-year-old children? This can be defined as reading developmentally appropriate books to their children with their undivided attention;and (2) Since parents were home more often with their two-to four-year-old children, were parents reading more to their young children? Parents of pre-kindergarten students were surveyed to determine the answers to these questions.

7.
Am J Obstet Gynecol MFM ; 3(6): 100454, 2021 11.
Article in English | MEDLINE | ID: covidwho-1347472

ABSTRACT

BACKGROUND: Universal testing for COVID-19 on admission to the labor and delivery unit identifies asymptomatic patients. Whether or not these patients are at increased risk for adverse outcomes and go on to develop clinically significant disease is uncertain. OBJECTIVE: This study aimed to assess the prevalence of asymptomatic COVID-19 presentation among pregnant patients admitted for delivery and to determine whether these patients become symptomatic or require hospital readmission after discharge. STUDY DESIGN: We performed a multicenter, prospective cohort study of pregnant patients who delivered between 200/7 and 416/7 weeks' gestation and who were found to have COVID-19 based on universal screening on admission for delivery at 1 of 4 medical centers in New Jersey (exposed group). The unexposed group, comprising patients who tested negative for COVID-19, were identified at the primary study site. The primary outcomes were the rates of asymptomatic COVID-19 presentation, the development of symptoms among the asymptomatic positive patients, and hospital readmission rates in the 2 weeks following discharge. We compared the frequency of the distribution of risk factors and outcomes in relation to the COVID-19 status among patients with COVID-19 across all centers and among those without COVID-19 at the primary site. Associations between categorical risk factors and COVID-19 status were expressed as relative risks with 95% confidence intervals. RESULTS: Between April 10, 2020, and June 15, 2020, there were 218 patients with COVID-19 at the 4 sites and 413 patients without COVID-19 at the primary site. The majority (188 [83.2%]) of patients with COVID-19 were asymptomatic. Compared with the negative controls, these asymptomatic patients were not at increased risk for obstetrical complications that may increase the risk associated with COVID-19, including gestational diabetes (8.2% vs 11.4%; risk ratio, 0.72; 95% confidence interval, 0.24-2.01) and gestational hypertension (6.1% vs 7.0%; risk ratio, 0.88; 95% confidence interval, 0.29-2.67). Postpartum follow-ups via telephone surveys revealed that these patients remained asymptomatic and had low rates of family contacts acquiring the disease, but their adherence to social distancing guidelines waned during the 2-week postpartum period. Review of inpatient and emergency department records revealed low rates of hospital readmission. CONCLUSION: Most of the pregnant patients who screened positive for COVID-19 are asymptomatic and do not go on to develop clinically significant infection after delivery. Routine surveillance of these patients after hospital discharge appears to be sufficient.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19 Testing , Female , Follow-Up Studies , Humans , Pregnancy , Prospective Studies , SARS-CoV-2
9.
Nat Med ; 27(2): 279-288, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065913

ABSTRACT

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.


Subject(s)
Antibody Formation/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunization, Secondary , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/immunology , Dose-Response Relationship, Drug , Genetic Vectors/immunology , Humans , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Young Adult
10.
Am J Obstet Gynecol ; 224(4): 389.e1-389.e9, 2021 04.
Article in English | MEDLINE | ID: covidwho-871684

ABSTRACT

BACKGROUND: Coronavirus disease 2019 may be associated with adverse maternal and neonatal outcomes in pregnancy, but there are few controlled data to quantify the magnitude of these risks or to characterize the epidemiology and risk factors. OBJECTIVE: This study aimed to quantify the associations of coronavirus disease 2019 with adverse maternal and neonatal outcomes in pregnancy and to characterize the epidemiology and risk factors. STUDY DESIGN: We performed a matched case-control study of pregnant patients with confirmed coronavirus disease 2019 cases who delivered between 16 and 41 weeks' gestation from March 11 to June 11, 2020. Uninfected pregnant women (controls) were matched to coronavirus disease 2019 cases on a 2:1 ratio based on delivery date. Maternal demographic characteristics, coronavirus disease 2019 symptoms, laboratory evaluations, obstetrical and neonatal outcomes, and clinical management were chart abstracted. The primary outcomes included (1) a composite of adverse maternal outcome, defined as preeclampsia, venous thromboembolism, antepartum admission, maternal intensive care unit admission, need for mechanical ventilation, supplemental oxygen, or maternal death, and (2) a composite of adverse neonatal outcome, defined as respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, 5-minute Apgar score of <5, persistent category 2 fetal heart rate tracing despite intrauterine resuscitation, or neonatal death. To quantify the associations between exposure to mild and severe or critical coronavirus disease 2019 and adverse maternal and neonatal outcomes, unadjusted and adjusted analyses were performed using conditional logistic regression (to account for matching), with matched-pair odds ratio and 95% confidence interval based on 1000 bias-corrected bootstrap resampling as the effect measure. Associations were adjusted for potential confounders. RESULTS: A total of 61 confirmed coronavirus disease 2019 cases were enrolled during the study period (mild disease, n=54 [88.5%]; severe disease, n=6 [9.8%]; critical disease, n=1 [1.6%]). The odds of adverse composite maternal outcome were 3.4 times higher among cases than controls (18.0% vs 8.2%; adjusted odds ratio, 3.4; 95% confidence interval, 1.2-13.4). The odds of adverse composite neonatal outcome were 1.7 times higher in the case group than to the control group (18.0% vs 13.9%; adjusted odds ratio, 1.7; 95% confidence interval, 0.8-4.8). Stratified analyses by disease severity indicated that the morbidity associated with coronavirus disease 2019 in pregnancy was largely driven by the severe or critical disease phenotype. Major risk factors for associated morbidity were black and Hispanic race, advanced maternal age, medical comorbidities, and antepartum admissions related to coronavirus disease 2019. CONCLUSION: Coronavirus disease 2019 during pregnancy is associated with an increased risk of adverse maternal and neonatal outcomes, an association that is primarily driven by morbidity associated with severe or critical coronavirus disease 2019. Black and Hispanic race, obesity, advanced maternal age, medical comorbidities, and antepartum admissions related to coronavirus disease 2019 are risk factors for associated morbidity.


Subject(s)
COVID-19/epidemiology , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2 , Adult , COVID-19/complications , COVID-19/ethnology , Case-Control Studies , Female , Humans , Infant, Newborn , Logistic Models , Maternal Age , Perinatal Death/etiology , Pregnancy , Pregnancy Complications, Infectious/ethnology , Pregnancy Outcome , Risk Factors
11.
Ann Med ; 52(7): 354-360, 2020 11.
Article in English | MEDLINE | ID: covidwho-630185

ABSTRACT

BACKGROUND: There is limited data on outcomes in patients with coronavirus disease 2019 (Covid-19) in rural United States (US). This study aimed to describe the demographics, and outcomes of hospitalized Covid-19 patients in rural Southwest Georgia. METHODS: Using electronic medical records, we analyzed data from all hospitalized Covid-19 patients who either died or survived to discharge between 2 March 2020 and 6 May 2020. RESULTS: Of the 522 patients, 92 died in hospital (17.6%). Median age was 63 years, 58% were females, and 87% African-Americans. Hypertension (79.7%), obesity (66.5%) and diabetes mellitus (42.3%) were the most common comorbidities. Males had higher overall mortality compared to females (23 v 13.8%). Immunosuppression [odds ratio (OR) 3.6; (confidence interval (CI): 1.52-8.47, p=.003)], hypertension (OR 3.36; CI:1.3-8.6, p=.01), age ≥65 years (OR 3.1; CI:1.7-5.6, p<.001) and morbid obesity (OR 2.29; CI:1.11-4.69, p=.02), were independent predictors of in-hospital mortality. Female gender was an independent predictor of decreased in-hospital mortality. Mortality in intubated patients was 67%. Mortality was 8.9% in <50 years, compared to 20% in ≥50 years. CONCLUSIONS: Immunosuppression, hypertension, age ≥ 65 years and morbid obesity were independent predictors of mortality, whereas female gender was protective for mortality in hospitalized Covid-19 patients in rural Southwest Georgia. KEY MESSAGES Patients hospitalized with Covid-19 in rural US have higher comorbidity burden. Immunosuppression, hypertension, age ≥ 65 years and morbid obesity are independent predictors of increased mortality. Female gender is an independent predictor of reduced mortality.


Subject(s)
Coronavirus Infections/epidemiology , Hospital Mortality , Hospitalization/statistics & numerical data , Pneumonia, Viral/epidemiology , Rural Population/statistics & numerical data , Adolescent , Adult , African Americans/statistics & numerical data , Age Factors , Aged , COVID-19 , Child , Child, Preschool , Comorbidity , Coronavirus Infections/mortality , Female , Georgia/epidemiology , Humans , Hypertension/epidemiology , Immunocompromised Host , Infant , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Retrospective Studies , Risk Factors , Sex Factors , Young Adult
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