Tracking COVID-19 in England and Wales: Insights from Virus Watch - a prospective community cohort study (preprint)

BackgroundVirus Watch is a prospective community cohort study of COVID-19 of 28{square},527 households in England and Wales designed to estimate the incidence of PCR-confirmed COVID-19 in those with respiratory presentations and examine symptom profiles and transmission of COVID-19 in relation to population movement and behaviour. The Office for National Statistics (ONS) COVID-19 infection survey (CIS) was the largest regular survey of COVID-19 infections and antibodies in the UK and included 227,797 households. In this analysis, we aimed to compare incidence rate estimates from the two studies to understand differences in estimates from the two study designs. MethodsWe used the Virus Watch prospective community cohort study to estimate the overall SARS-CoV-2 incidence rate and incidence rate by age in England and Wales from June 2020 to February 2023. Virus Watch data consisted of self-reported laboratory COVID-19 test results and linkage to the Second Generation Surveillance System, the UK national database for COVID-19 testing. We compared our findings with modelled incidence rates from ONS CIS using 3-day rolling Pearsons correlation to measure synchrony. Results58,628 participants were recruited into the Virus Watch study between June 2020 and March 2022, of whom 52,526 (90%) were reported to be living in England and 1,532 (2.6%) in Wales. COVID-19 incidence rates were initially similar across age groups until the Delta wave when rates increased at different magnitudes. During the Omicron BA.1, the 0-14 age group had the highest incidence rates, which shifted to the 25-44 age group with Omicron BA.2, 4, and 5 dominance. We found strong synchrony between Virus Watch and ONS CIS COVID-19 incidence estimates for England and Wales, both with and without the incorporation of linked national testing data into the Virus Watch study. In particular, the magnitude and trend of Virus Watch- and ONS-estimated rates for England were generally consistent, although Virus Watch-estimated peaks of infection during the Omicron BA.1 and 2 waves were found to be lower than estimates from the ONS. ConclusionOur findings suggest that the Virus Watch research approach is a low-cost and effective method for on-going surveillance of COVID-19 regardless of the availability of national testing in the UK. Similar approaches can also be utilised by low-resource settings to provide accurate incidence rate estimates to better monitor and respond to COVID-19 as well as other acute respiratory diseases in the future.

Long-Term Outcomes of SARS-CoV-2 Variants and Other Respiratory Infections: Evidence from the Virus Watch Prospective Cohort in England (preprint)

BackgroundGiven the considerable prevalence of long-term sequelae following SARS-CoV-2 infection, understanding pathogen-related factors that influence long-term outcomes is warranted. We aimed to compare the likelihood of long-term symptoms for SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals. MethodData were from 5,630 individuals participating in Virus Watch, a prospective community cohort study of SARS-CoV-2 epidemiology in England. We used logistic regression to compare the predicted probability of developing long-term symptoms (>2 months duration) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status. ResultsPredicted probability of long-term sequelae was greater following SARS-CoV-2 infection during the Wild Type (adjusted predicted probability (PP) 0.28, 95% confidence interval (CI) =0.14-0.43), Alpha (PP= 0.28, 95% CI =0.14-0.42), Delta (PP= 0.34, 95% CI=0.25-0.43) and Omicron BA.1 periods (PP= 0.27, 95% CI =0.22-0.33) compared to later Omicron sub-variants (PP range from 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, estimates for long-term symptoms following both infection types substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00,0.02 to 0.03, 95% CI 0.01-0.06) across all variant periods. ConclusionsBetween-variant differences influenced the likelihood of post-infection sequelae for SARS-CoV-2, with lower predicted probabilities for recent Omicron sub-variants similar to those for other contemporaneous ARIs. Both SARS-CoV-2 and other ARIs were associated with long-term symptom development, and further aetiological investigation including between-pathogen comparison is recommended.

Examining the association of live virus neutralisation activity of capillary microsamples and risk of SARS-CoV-2 infections: a nested case control study within the Virus Watch community cohort (preprint)

Due to the proliferation of new SARS-CoV-2 variants, most COVID-19 cases are now caused by post-vaccine infections and a substantial proportion are reinfections. While prior research on correlates of protection has focused on the role of anti-spike antibodies, the results of the corresponding antibody assays may not accurately predict the risk of infection with new SARS-CoV-2 variants. In this study, we investigated the association between live virus neutralising antibody activity and SARS-CoV-2 infection risk using self-administered capillary microsample blood tests from VirusWatch participants. The study was conducted during the transition between the dominance of the B.1.617.2 (Delta) and B.1.1.529 (Omicron BA.1) SARS-CoV-2 variants, enabling us to investigate the association between variant-specific virus inhibition and subsequent infections within each dominance period. Greater inhibition of Omicron BA.1 live virus was associated with a reduction in infection risk during both the Delta and Omicron BA.1 dominance periods. Delta virus inhibition was associated with infection risk reduction during the Delta dominance period, but we found no association between Delta inhibition and protection against infection during the Omicron BA.1 dominance period. Our results are consistent with earlier findings and suggest that variant-specific serosurveillance of immunity and protection against SARS-CoV-2 infection at the population level could inform public health policy in near-real time using inexpensive and accessible home-based testing.

Cohort profile: Virus Watch: Understanding community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviour (preprint)

[bullet] Virus Watch is a national community cohort study of COVID-19 in households in England and Wales, established in June 2020. The study aims to provide evidence on which public health approaches are most effective in reducing transmission, and investigate community incidence, symptoms, and transmission of COVID-19 in relation to population movement and behaviours. [bullet] 28,527 households and 58,628 participants of age (0-98 years, mean age 48), were recruited between June 2020 - July 2022 [bullet] Data collected include demographics, details on occupation, co-morbidities, medications, and infection-prevention behaviours. Households are followed up weekly with illness surveys capturing symptoms and their severity, activities in the week prior to symptom onset and any COVID-19 test results. Monthly surveys capture household finance, employment, mental health, access to healthcare, vaccination uptake, activities and contacts. Data have been linked to Hospital Episode Statistics (HES), inpatient and critical care episodes, outpatient visits, emergency care contacts, mortality, virology testing and vaccination data held by NHS Digital. [bullet] Nested within Virus Watch are a serology & PCR cohort study (n=12,877) and a vaccine evaluation study (n=19,555). [bullet] Study data are deposited in the Office of National Statistics (ONS) Secure Research Service (SRS). Survey data are available under restricted access upon request to ONS SRS.

Public policy responses to COVID-19 and the survival of ethnic minority businesses (EMBs): does entrepreneurial orientation (EO) matter?

Purpose The global economic crisis triggered by the coronavirus disease 2019 (COVID-19) has caused the closure of countless ethnic minority businesses (EMBs) worldwide, partly due to the public policy responses. This paper investigates whether EMBs' entrepreneurial orientation (EO) mediates the impact of public policy responses to COVID-19 on their survival. Design/methodology/approach Utilizing institutional theory, the authors developed a novel conceptual framework that divides policy responses to COVID-19 into aggressive (imposing restrictions on movement, e.g. lockdowns) and less aggressive policy responses (not imposing restrictions on movement, e.g. social distancing). The authors then surveyed intra-regional EMBs, specifically businesses owned by ethnic minorities in the Kano and Katsina provinces of Nigeria, and analysed the data using structural equation modelling and analysis of variance (ANOVA). Findings The authors found that intra-regional EMBs in developing countries are very vulnerable to the public policy responses imposed by governments to curb COVID-19. Aggressive policy responses have a more significant negative effect on the survival of intra-regional EMBs than their less aggressive counterparts. Furthermore, the authors found that EO as a crisis response strategy significantly supports intra-regional EMBs in managing their vulnerability to the hostile institutional environment, reduces the adverse effect of public policy responses and stimulates their survival during the COVID-19 pandemic. Originality/value This paper contributes to the institutional theory of small and medium-sized enterprises (SMEs)/entrepreneurship and the literature on EMBs by showing the role of EO in mediating the effects of COVID-19 institutional policies on the survival of intra-regional EMBs.

Epigenetic modifications associated with genes implicated in cytokine storm: The potential biotherapeutic effects of vitamins and minerals in COVID‐19

Cytokine storm is a phrase used to refer to an abrupt upsurge in the circulating levels of various pro‐inflammatory cytokines, causing increased stimulation and activity of immune cells during disease conditions. The binding of pattern recognition receptors to pathogen‐associated molecular patterns during COVID‐19 infection recruits response machinery involving the activation of transcription factors and proteins required for a robust immune response by host cells. These immune responses could be influenced by epigenetic modifications as evidenced by significant variations in COVID‐19 pathophysiology and response to therapy observed among patients across the globe. Considering that circulating levels of interleukin 1, tumor necrosis factor‐α, and interleukin 6 are significantly elevated during cytokine storm in COVID‐19 patients, genetic and epigenetic variations in the expression and function of these proteins could enhance our understanding of the disease pathogenesis. Treatment options that repress the transcription of specific cytokine genes during COVID‐19 infection could serve as possible targets to counteract cytokine storm in COVID‐19. Therefore, the present article reviews the roles of cytokines and associated genes in the COVID‐19 cytokine storm, identifies epigenetic modifications associated with the disease progression, and possible ameliorative effects of some vitamins and minerals obtained as epigenetic modifiers for the control of cytokine storm and disease severity in COVID‐19 patients. PRACTICAL APPLICATIONS: COVID‐19 causes mortality and morbidity that adversely affect global economies. Despite a global vaccination campaign, side effects associated with vaccination, misconceptions, and a number of other factors have affected the expected successes. Cytokine storm in COVID‐19 patients contributes to the disease pathogenesis and response to therapy. Epigenetic variations in the expression of various cytokines could be implicated in the different outcomes observed in COVID‐19 patients. Certain vitamins and minerals have been shown to interfere with the expression and activity of cytokines implicated in cytokine storm, thereby counteracting observed pathologies. This review examines cytokines implicated in cytokine storm in COVID‐19, epigenetic modifications that contribute to increased expression of identified cytokines, specific foods rich in the identified vitamins and minerals, and suggests their possible ameliorative benefits. The article will be beneficial to both scientists and the general public who are interested in the role of vitamins and minerals in ameliorating COVID‐19.

Incidence Rate of COVID-19 Mortality and its Associated Factors During the First and Second Waves in Nigeria: A Retrospective Cohort Study (preprint)

Background: COVID-19 mortality rate has not been formally assessed in Nigeria. We therefore aimed to address this gap and identify associated mortality risk factors during the first and second waves in Nigeria.Methods: We conducted a retrospective cohort study using the national surveillance database between February 27, 2020, and April 3, 2021. The outcome was deaths amongst persons with a laboratory diagnosis of COVID-19. Incidence rates of COVID-19 death per 100,000 person-days were estimated. Adjusted negative binomial regression was used to identify factors associated with COVID-19 death, and presented as adjusted Incidence Rate Ratios (aIRR) with 95% confidence intervals (CI). Results: The first wave included 65,790 COVID-19 patients, of whom 994 (1∙51%) died; the second wave included 91,089 patients, of whom 513 (0∙56%) died. The incidence rate of deaths related to COVID-19 was higher in the first wave [54∙25 (95% CI: 50∙98-57∙73)] than in the second wave [19∙19 (17∙60-20∙93)]. Factors independently associated with increased risk of death in both waves were: age ≥45 years, male gender [first wave aIRR 1∙65 (1∙35-2∙02) and second wave 1∙52 (1∙11-2∙06)], being symptomatic [aIRR 3∙17 (2∙59-3∙89) and 3∙04 (2∙20-4∙21)], and being hospitalised [aIRR 4∙19 (3∙26-5∙39) and 7∙84 (4∙90-12∙54)].Interpretation: The incidence rate of COVID-19 death in Nigeria was higher in the first wave, suggesting improved public health response and care during the second wave. Regional mortality differences suggest that policy makers focus on regional equity in access to testing and quality of care to mitigate the impact of another COVID-19 wave in Nigeria.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Ethical approval for the study was given by the Nigeria National Health Research Ethics Committee (NHREC/01/01/2007-22/06/2020).

Ethnicity and COVID-19 outcomes among healthcare workers in the United Kingdom: UK-REACH ethico-legal research, qualitative research on healthcare workers' experiences, and stakeholder engagement protocol (preprint)

Introduction: As the world continues to grapple with the COVID-19 pandemic, emerging evidence suggests that individuals from ethnic minority backgrounds may be disproportionately affected. The UK-REACH project has been initiated to understand ethnic differentials in COVID-19 outcomes among healthcare workers (HCWs) in the United Kingdom (UK) through five inter-linked work packages. The ethico-legal work package (Work Package 3) aims to understand and address legal, ethical and acceptability issues around big data research; the healthcare workers' experiences work package (Work Package 4) is a qualitative study exploring healthcare workers' experiences during COVID-19 and; the stakeholder engagement work package (Work Package 5) aims to provide feedback and support with the formulation and dissemination of the project recommendations. Methods and Analysis: Work Package 3 has two different research strands: (a) desk-based doctrinal research; and (b) empirical qualitative research with key opinion leaders. For the empirical research, in-depth interviews will be conducted digitally and recorded with participants' permission. Recordings will be transcribed, coded and analysed using thematic analysis. In Work Package 4, online in-depth interviews and focus groups will be conducted with approximately 150 HCWs, from across the UK, and these will be recorded with participants' consent. The recordings will be transcribed, coded and data will be analysed using thematic analysis. Work Package 5 will achieve its objectives through regular group meetings and in-group discussions. Ethics and Dissemination: Ethical approval has been received from the London - Brighton & Sussex Research Ethics Committee of the Health Research Authority (Ref No. 20/HRA/4718). Results of the study will be published in open access journals, and disseminated through conference presentations, project website, stakeholder organisations, media and scientific advisory groups.

Development and immunogenic potentials of chitosan-saponin encapsulated DNA vaccine against avian infectious bronchitis coronavirus.

Infectious Bronchitis (IB) is an economically important avian disease that considerably threatens the global poultry industry. This is partly, as a result of its negative consequences on egg production, weight gain as well as mortality rate.The disease is caused by a constantly evolving avian infectious bronchitis virus whose isolates are classified into several serotypes and genotypes that demonstrate little or no cross protection. In order to curb the menace of the disease therefore, broad based vaccines are urgently needed. The aim of this study was to develop a recombinant DNA vaccine candidate for improved protection of avian infectious bronchitis in poultry. Using bioinformatics and molecular cloning procedures, sets of monovalent and bivalent DNA vaccine constructs were developed based on the S1 glycoprotein from classical and variants IBV strains namely, M41 and CR88 respectively. The candidate vaccine was then encapsulated with a chitosan and saponin formulated nanoparticle for enhanced immunogenicity and protective capacity. RT-PCR assay and IFAT were used to confirm the transcriptional and translational expression of the encoded proteins respectively, while ELISA and Flow-cytometry were used to evaluate the immunogenicity of the candidate vaccine following immunization of various SPF chicken groups (A-F). Furthermore, histopathological changes and virus shedding were determined by quantitative realtime PCR assay and lesion scoring procedure respectively following challenge of various subgroups with respective wild-type IBV viruses. Results obtained from this study showed that, groups vaccinated with a bivalent DNA vaccine construct (pBudCR88-S1/M41-S1) had a significant increase in anti-IBV antibodies, CD3+ and CD8+ T-cells responses as compared to non-vaccinated groups. Likewise, the bivalent vaccine candidate significantly decreased the oropharyngeal and cloacal virus shedding (p < 0.05) compared to non-vaccinated control. Chickens immunized with the bivalent vaccine also exhibited milder clinical signs as well as low tracheal and kidney lesion scores following virus challenge when compared to control groups. Collectively, the present study demonstrated that bivalent DNA vaccine co-expressing dual S1 glycoprotein induced strong immune responses capable of protecting chickens against infection with both M41 and CR88 IBV strains. Moreso, it was evident that encapsulation of the vaccine with chitosan-saponin nanoparticle further enhanced immune responses and abrogates the need for multiple booster administration of vaccine. Therefore, the bivalent DNA vaccine could serve as efficient and effective alternative strategy for the control of IB in poultry.

Development and validation of the 4C Deterioration model for adults hospitalised with COVID-19 (preprint)

Prognostic models to predict the risk of clinical deterioration in acute COVID-19 are required to inform clinical management decisions. Among 75,016 consecutive adults across England, Scotland and Wales prospectively recruited to the ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC4C) study, we developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) using 11 routinely measured variables. We used internal-external cross-validation to show consistent measures of discrimination, calibration and clinical utility across eight geographical regions. We further validated the final model in held-out data from 8,252 individuals in London, with similarly consistent performance (C-statistic 0.77 (95% CI 0.75 to 0.78); calibration-in-the-large 0.01 (-0.04 to 0.06); calibration slope 0.96 (0.90 to 1.02)). Importantly, this model demonstrated higher net benefit than using other candidate scores to inform decision-making. Our 4C Deterioration model thus demonstrates unprecedented clinical utility and generalisability to predict clinical deterioration among adults hospitalised with COVID-19.

Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: An observational cohort study (preprint)

BackgroundThe number of proposed prognostic models for COVID-19, which aim to predict disease outcomes, is growing rapidly. It is not known whether any are suitable for widespread clinical implementation. We addressed this question by independent and systematic evaluation of their performance among hospitalised COVID-19 cases. MethodsWe conducted an observational cohort study to assess candidate prognostic models, identified through a living systematic review. We included consecutive adults admitted to a secondary care hospital with PCR-confirmed or clinically diagnosed community-acquired COVID-19 (1st February to 30th April 2020). We reconstructed candidate models as per their original descriptions and evaluated performance for their original intended outcomes (clinical deterioration or mortality) and time horizons. We assessed discrimination using the area under the receiver operating characteristic curve (AUROC), and calibration using calibration plots, slopes and calibration-in-the-large. We calculated net benefit compared to the default strategies of treating all and no patients, and against the most discriminating predictor in univariable analyses, based on a limited subset of a priori candidates. ResultsWe tested 22 candidate prognostic models among a cohort of 411 participants, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration and mortality, respectively. The highest AUROCs were achieved by the NEWS2 score for prediction of deterioration over 24 hours (0.78; 95% CI 0.73-0.83), and a novel model for prediction of deterioration <14 days from admission (0.78; 0.74-0.82). Calibration appeared generally poor for models that used probability outcomes. In univariable analyses, admission oxygen saturation on room air was the strongest predictor of in-hospital deterioration (AUROC 0.76; 0.71-0.81), while age was the strongest predictor of in-hospital mortality (AUROC 0.76; 0.71-0.81). No prognostic model demonstrated consistently higher net benefit than using the most discriminating univariable predictors to stratify treatment, across a range of threshold probabilities. ConclusionsOxygen saturation on room air and patient age are strong predictors of deterioration and mortality among hospitalised adults with COVID-19, respectively. None of the prognostic models evaluated offer incremental value for patient stratification to these univariable predictors.

Modelling SARS-COV2 Spread in London: Approaches to Lift the Lockdown (preprint)

Objective: To use mathematical models to predict the epidemiological impact of lifting the lockdown in London, UK, and alternative strategies to help inform policy in the UK. Methods: A mathematical model for the transmission of SARS-CoV2 in London. The model was parametrised using data on notified cases, deaths, contacts, and mobility to analyse the epidemic in the UK capital. We investigated the impact of multiple non pharmaceutical interventions (NPIs) and combinations of these measures on future incidence of COVID-19. Results: Immediate action at the early stages of an epidemic in the affected districts would have tackled spread. While an extended lockdown is highly effective, other measures such as shielding older populations, universal testing and facemasks can all potentially contribute to a reduction of infections and deaths. However, based on current evidence it seems unlikely they will be as effective as continued lockdown. In order to achieve elimination and lift lockdown within 5 months, the best strategy seems to be a combination of weekly universal testing, contact tracing and use of facemasks, with concurrent lockdown. This approach could potentially reduce deaths by 48% compared with continued lockdown alone. Conclusions: A combination of NPIs such as universal testing, contact tracing and mask use while under lockdown would be associated with least deaths and infections. This approach would require high uptake and sustained local effort but it is potentially feasible as may lead to elimination in a relatively short time scale.