a case–case study based on electronic health records

Funding Information: The acquisition of sequencing equipment and reagents used in this study by the Instituto Nacional de Saúde Doutor Ricardo Jorge was partially funded by the HERA project (grant no. 2021/PHF/23776), supported by the European Commission through the European Centre for Disease Control, and also partially funded by the Genome PT project (grant no. POCI‐01‐0145‐FEDER‐022184), supported by COMPETE 2020–Operational Programme for Competitiveness and Internationalisation, Lisboa Portugal Regional Operational Programme, Algarve Portugal Regional Operational, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund, and by the Portuguese Science and Technology Foundation. The Algarve Biomedical Center Laboratory received public funding through the Project ALG‐D2‐2021‐06 Variants Screen in Southern Portugal–Monitoring Variants of Concern in Southern Portugal and the Portuguese Science and Technology Foundation national support through the Comprehensive Health Research Center (grant no. UIDP/04923/2020). Funding information Funding Information: The acquisition of sequencing equipment and reagents used in this study by the Instituto Nacional de Saúde Doutor Ricardo Jorge was partially funded by the HERA project (grant no. 2021/PHF/23776), supported by the European Commission through the European Centre for Disease Control, and also partially funded by the Genome PT project (grant no. POCI-01-0145-FEDER-022184), supported by COMPETE 2020–Operational Programme for Competitiveness and Internationalisation, Lisboa Portugal Regional Operational Programme, Algarve Portugal Regional Operational, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund, and by the Portuguese Science and Technology Foundation. The Algarve Biomedical Center Laboratory received public funding through the Project ALG-D2-2021-06 Variants Screen in Southern Portugal–Monitoring Variants of Concern in Southern Portugal and the Portuguese Science and Technology Foundation national support through the Comprehensive Health Research Center (grant no. UIDP/04923/2020). Publisher Copyright: © 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.Background: Information on vaccine effectiveness in a context of novel variants of concern (VOC) emergence is of key importance to inform public health policies. This study aimed to estimate a measure of comparative vaccine effectiveness between Omicron (BA.1) and Delta (B.1.617.2 and sub-lineages) VOC according to vaccination exposure (primary or booster). Methods: We developed a case–case study using data on RT-PCR SARS-CoV-2-positive cases notified in Portugal during Weeks 49–51, 2021. To obtain measure of comparative vaccine effectiveness, we compared the odds of vaccination in Omicron cases versus Delta using logistic regression adjusted for age group, sex, region, week of diagnosis, and laboratory of origin. Results: Higher odds of vaccination were observed in cases infected by Omicron VOC compared with Delta VOC cases for both complete primary vaccination (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.8 to 2.4) and booster dose (OR = 5.2; 95% CI: 3.1 to 8.8), equivalent to reduction of vaccine effectiveness from 44.7% and 92.8%, observed against infection with Delta, to −6.0% (95% CI: 29.2% to 12.7%) and 62.7% (95% CI: 35.7% to 77.9%), observed against infection with Omicron, for complete primary vaccination and booster dose, respectively. Conclusion: Consistent reduction in vaccine-induced protection against infection with Omicron was observed. Complete primary vaccination may not be protective against SARS-CoV-2 infection in regions where Omicron variant is dominant.publishersversionpublishe

A proteomic survival predictor for COVID-19 patients in intensive care

© 2022 Demichev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. https://creativecommons.org/licenses/by/4.0/Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.Peer reviewedFinal Published versio

The Your COVID-19 risk assessment tool and the accompanying open access data and materials repositories

In March 2020, the Your COVID-19 Risk tool was developed in response to the global spread of SARS-CoV-2. The tool is an online resource based on key behavioural evidence-based risk factors related to contracting and spreading SARS-CoV-2. This article describes the development of the tool, the produced resources, the associated open repository, and initial results. This tool was developed by a multidisciplinary research team consisting of more than 150 international experts. This project leverages knowledge obtained in behavioural science, aiming to promote behaviour change by assessing risk and supporting individuals completing the assessment tool to protect themselves and others from infection. To enable iterative improvements of the tool, tool users can optionally answer questions about behavioural determinants. The data and results are openly shared to support governments and health agencies developing behaviour change interventions. Over 60 000 users in more than 150 countries have assessed their risk and provided data.info:eu-repo/semantics/publishedVersio

Variations across Europe in hospitalization and management of pregnant women with SARS-CoV-2 during the initial phase of the pandemic: Multi-national population-based cohort study using the International Network of Obstetric Survey Systems (INOSS)

INTRODUCTION: The majority of data on COVID-19 in pregnancy are not from sound population-based active surveillance systems. MATERIAL AND METHODS: We conducted a multi-national study of population-based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS-CoV-2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID-19-related or non-COVID-19-related. The primary outcome of interest was incidence of COVID-19-related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID-19-directed medical treatment. RESULTS: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS-CoV-2; among them 940 (40%) were COVID-19-related admissions. The pooled incidence estimate for COVID-19-related admission was 0.59 (95% confidence interval 0.27-1.02) per 1000 maternities, with notable heterogeneity across countries (I 2  = 97.3%, P = 0.00). In the COVID-19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%-13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID-19-related admission (range 14%-55%). Among 908 infants born to women in the COVID-19-related admission group, 5 (0.6%) stillbirths were reported. CONCLUSIONS: During the initial months of the pandemic, we found substantial variations in incidence of COVID-19-related admissions in nine European countries. Few pregnant women received COVID-19-directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics

Combating the COVID-19 pandemic in a resource-constrained setting: insights from initial response in India.

The low-and-middle-income country (LMIC) context is volatile, uncertain and resource-constrained. India, an LMIC, has put up a complex response to the COVID-19 pandemic. Using an analytic approach, we have described India's response to combat the pandemic during the initial months (from 17 January to 20 April 2020). India issued travel advisories and implemented graded international border controls between January and March 2020. By early March, cases started to surge. States scaled up movement restrictions. On 25 March, India went into a nationwide lockdown to ramp up preparedness. The lockdown uncovered contextual vulnerabilities and stimulated countermeasures. India leveraged existing legal frameworks, institutional mechanisms and administrative provisions to respond to the pandemic. Nevertheless, the cross-sectoral impact of the initial combat was intense and is potentially long-lasting. The country could have further benefited from evidence-based policy and planning attuned to local needs and vulnerabilities. Experience from India offers insights to nations, especially LMICs, on the need to have contextualised pandemic response plans

Benefits of early aggressive immunomodulatory therapy (tocilizumab and methylprednisolone) in COVID-19: Single center cohort study of 685 patients

Introduction: A growing evidence suggests that immune dysregulation and thrombotic phenomena are key features in the pathophysiology of COVID-19. Apart from antivirals and respiratory support, anticoagulants, corticoids and immunomodulators are increasingly being prescribed, especially for more severe cases. We describe the clinical outcome of a large cohort of patients preferentially treated with glucocorticoids and interleukin inhibitors. Methods: Single center and retrospective case series. Adult patients admitted with COVID-19 related respiratory insufficiency were included. Patients who died within 2 days after admission and those testing positive but asymptomatic were excluded. We defined two study periods: from March 3rd to March 31 st, 2020 (beginning of epidemic until peak of incidence) and April 1 st to May 7 th, 2020 (second half of epidemic). The majority of patients received respiratory support, combinations of antimicrobials, anticoagulants, corticoids and interleukin inhibitors. Antivirals were preferentially given in the first period. The clinical outcome (death and ventilator dependency) of both periods was compared. Results: From March 3 rd to May 7 th, 685 patients were included for analysis (58.4% males, mean age 68.9 years). Patients in the first period (n = 408) were younger (66.6 vs 71.1 years, p = 0.003), presented lower mean P a O2/FiO2 ratio at admission (256.5 vs 270.4 mm Hg,p = 0.0563), higher ferritin (1520 vs 1221 ng/ml, p = 0.01), higher IL-6 (679 vs 194 pg/ml, p < 0.0001) and similar D-dimer levels (3.59 vs 3.39 mu g/mL, p = 0.65) compared to the second period (n = 277). Lopinavir/ritonavir and interferon were preferentially given in the first period (23.8% and 32% vs 1.8% and 11.9%, p < 0.0001). Use of corticoids (88.2% vs 87.4%, p = 0,74) and tocilizumab (26.29 vs 20.22% p = 0.06) were similarly administered in both periods. Patients in the second period needed less mechanical ventilation (4.9% vs 16.9%, p < 0.0001), fewer ICU admission (6.1% vs 20.1%,p < 0.0001) and showed similar mortality (17.7% vs 15.4%, p = 0.43). Infectious and thrombotic complications were comparable in both periods (both around 8%, with no statistical difference). Patients treated with tocilizumab (n = 163) had lower mortality rate compared to those untreated under the same indication (7.9% vs 24.2%, p < 0.0001). Conclusions: In this large retrospective COVID-19 in-hospital cohort, lopinavir/ritonavir and interferon showed no significant impact on survival. Extensive use of corticosteroids and tocilizumab resulted in good overall outcome and showed acceptable complication rates

Recommendations for the re-opening of dental services : a rapid review of international sources

The COVID-19 Dental Services Evidence Review Working Group would like to thank and acknowledge the contribution of the following individuals for providing the advice and access to the international guidance documents necessary for this rapid review: Colette Bridgman, Chief Dental Officer, Wales; Alonso Carrasco-Labra, Director, ADA Science & Research Institute; Riana Clarke, National Clinical Director Oral Health, New Zealand; Michael Donaldson, Chief Dental Officer, Northern Ireland; Tom Ferris, Chief Dental Officer, Scotland; Sara Hurley, Chief Dental Officer, England; Marco Landi, Council of European Dentists; Timothy Ricks, Chief Dental Officer, US Public Health Service; James Taylor, Chief Dental Officer, Canada; Benoit Varenne, Dental Officer, World Health Organization. The COVID-19 Dental Services Evidence Review Working Group are grateful for the help and support provided by Shona Floate, University of Glasgow; Anne Littlewood, Laura MacDonald and Helen Worthington from Cochrane Oral Health; David Felix, Postgraduate Dental Dean, NES and colleagues from NES’s Clinical Effectiveness workstream: Samantha Rutherford; Douglas Stirling; Michele West; Linda Young.Publisher PD

COVID-19 vaccination in Sindh province, Pakistan: A modelling study of health impact and cost-effectiveness

Background: Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).Methods and findings: We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70$27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.Conclusions: COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries

The importance of saturating density dependence for population-level predictions of SARS-CoV-2 resurgence compared with density-independent or linearly density-dependent models, England, 23 March to 31 July 2020.

BackgroundPopulation-level mathematical models of outbreaks typically assume that disease transmission is not impacted by population density ('frequency-dependent') or that it increases linearly with density ('density-dependent').AimWe sought evidence for the role of population density in SARS-CoV-2 transmission.MethodsUsing COVID-19-associated mortality data from England, we fitted multiple functional forms linking density with transmission. We projected forwards beyond lockdown to ascertain the consequences of different functional forms on infection resurgence.ResultsCOVID-19-associated mortality data from England show evidence of increasing with population density until a saturating level, after adjusting for local age distribution, deprivation, proportion of ethnic minority population and proportion of key workers among the working population. Projections from a mathematical model that accounts for this observation deviate markedly from the current status quo for SARS-CoV-2 models which either assume linearity between density and transmission (30% of models) or no relationship at all (70%). Respectively, these classical model structures over- and underestimate the delay in infection resurgence following the release of lockdown.ConclusionIdentifying saturation points for given populations and including transmission terms that account for this feature will improve model accuracy and utility for the current and future pandemics