Estimation and interpretation of vaccine efficacy in COVID-19 randomized clinical trials

Objectives: An exceptional effort by the scientific community has led to the development of multiple vaccines against COVID-19. Efficacy estimates for these vaccines have been widely communicated to the general public, but are nonetheless challenging to compare because they are based on phase 3 trials that differ in study design, definition of vaccine efficacy and the handling of cases arising shortly after vaccination. We investigate the impact of these choices on vaccine efficacy estimates, both theoretically and by re-analyzing the Janssen and Pfizer COVID-19 trial data under a uniform protocol. We moreover study the causal interpretation that can be assigned to per-protocol analyses typically performed in vaccine trials. Finally, we propose alternative estimands to measure the intrinsic vaccine efficacy in settings with delayed immune response. Methods: The data of the Janssen COVID-19 trials were recreated, based on the published Kaplan-Meier curves. An estimator for the alternative causal estimand was developed using a Structural Distribution Model. Results: In the data analyses, we observed rather large differences between intention-to-treat and per-protocol effect estimates. In contrast, the causal estimand and the different estimators used for per-protocol effects lead approximately to the same estimates. Conclusions: In these COVID-10 vaccine trials, per-protocol effects can be interpreted as the number of cases that can be avoided by vaccination, if the vaccine would immediately induce an immune response. However, it is unclear whether this interpretation also holds in other settings.

Advancing patient safety governance in the COVID-19 response

In the backdrop of the COVID-19 pandemic, ensuring the safety of health care services remains a serious, ongoing challenge. This once-in-a-century global health crisis exposed the vulnerability of healthcare delivery systems and the subsequent risks of patient harm. Given the scale of the occurrence and costs of preventable patient safety events, intervention and investment are still relatively modest. Good patient safety governance focuses on what leaders and policy makers can do to improve system performance and reduce the financial burden of avoidable care. Moreover, it is essential in driving progress in improving safety outcomes. This report examines how patient safety governance mechanisms in OECD countries have withstood the test of COVID-19 and provides recommendations for countries in further improving patient safety governance and strengthening health system resilience.

Improving the timeliness of health expenditure tracking in OECD and low-and middle-income countries

The COVID-19 pandemic has highlighted that access to timely health spending data is crucial for informed policy-making. This Health Working Paper summarises and compares the methodologies applied in around half of OECD countries to estimate public and private health spending for the most recent year (i.e. t-1) as well as the approaches taken by the OECD Secretariat to fill existing data gaps for the remaining OECD countries. For the first time, the paper also explores the feasibility of nowcasting health spending for the current year (i.e. t) and examines data sources that could be potentially useful in such an exercise. While this review should help OECD countries that do not yet have experience in estimating health spending for year t-1 to improve the timeliness in their data reporting, a special focus in this paper lies on testing the applicability of the methods in low- and middle-income countries (LMIC), using the WHO Western Pacific Region (WPRO) as an example. Generally, different data sources exist in many countries that would allow for a more timely estimation for health spending aggregates.

SARS-CoV-2 infections in farmed minks (Neovision vision) - current data on the disease, epidemiology and emerging threat for humans and other animals

SARS-CoV-2, the betacoronavirus that causes COVID-19, has spread rapidly around the world since December 2019. It was suspected from the beginning that the primary outbreak in China, was of a zoonotic origin, but the SARS- CoV-2 animal reservoir(s) has not been definitively identified yet. So far, it has been confirmed that numerous animal species are susceptible to infection and that experimentally infected cats, shrews, hamsters and ferrets can also shed the virus. The SARS-CoV-2 was also detected in farmed mink (Neovison vison), in which it caused both, the clinical and subclinical disease, with respiratory symptoms and increased mortality. In April 2020, the first SARS-CoV-2 cases were detected in minks in the Netherlands, and to date (November 2020), further outbreaks have been confirmed in Denmark, Italy, Spain, Sweden, the United States, Greece, France and Poland. It has also been shown that the transmission of infection from humans to minks and from minks to humans may occur. The OIE is working on the inclusion of mink in the WAHIS database and encouraging the Members to provide appropriate data for this species to improve the monitoring of the epidemiological situation worldwide and prevent the establishment of a possible new reservoir for SARS-CoV-2.

Existence of severe acute respiratory syndrome causing Coronavirus-2 (COVID-19) on aquatic animals and aquatic products: a review

Many pandemic diseases have emerged in the history and millions of people affected from these diseases. Among the marked pandemics in history, the plague, known as the black death, was recorded to cause the death of 17-54% of the world population. Similar to previous pandemics, as the SARS CoV-2, which emerged in 2019 and belonged to the coronavirus family, caused an epidemic and turned into a pandemic infection, positive cases were detected in more than 483 million people, and more than 6.1 million people died. While this emerging epidemic is still continuing its effects, it has been determined that there are positive cases in pets such as dogs and cats, especially in mink (Neovison vison). Especially in Denmark, Netherlands and Finland, positive animals for COVID-19 were accepted. Unlike the pandemic until today, the COVID-19 has spread to broader geographies and affected many animal species. With the reports that the SARS-CoV-2 - was first transmitted from bats to humans, this viral agent has been accepted as zoonotic, but a complete transmission route has not been shown for its transmission from other animals to humans except bats. It is reported that there is no significant risk of transmission of the virus, which is transmitted primarily by the respiratory route, from both pets and edible foods to humans. Although there are many reports in terrestrial animals, studies on the presence of SARS-CoV-2 - in aquatic animals or aquatic environments and COVID-19 transmission in aquatic animals have doubts. Here we reviewed the viability of the SARS-CoV-2 - in the aquatic environment, transmission to the aquatic ecosystem and aquatic animals, and therefore the risks to humans through water or aquatic products.

Implementation and methodological framework of the SHARE study in Croatia

This paper highlights the specific aspects of the eighth wave of SHARE in which face-to-face interviewing has been suspended due to the coronavirus pandemic, and a methodological turn has been made, i.e. face-to-face interviews have been replaced with a short CATI (telephone) survey called "SHARE Corona". From the database of insured persons of the Croatian Health Insurance Fund (HZZO), 4,990 persons born in 1963 and earlier were randomly selected. In all countries that had refresher samples, the response rate was 51.3% at the household level and 46.8% at the individual level. The seventh SHARE wave, called SHARELIFE, was mainly retrospective, accomplishing a full EU coverage. As a part of the seventh wave, a relatively small refresher sample was selected in Croatia i.e. 346 interviews were conducted in 234 households. The minimum satisfactory response rate of 30% was achieved at the household level. In Croatia, the retention rate of respondents in the seventh wave was 84.6%, which was the highest retention rate of respondents between waves six and seven. In Slovenia, it was 82.9%, in Greece 82.8%, in Estonia 82.2%, in Belgium 70.4%, in France 64.9%, and in Italy 62%. The sampling procedure for the refresher sample in wave eight in Croatia followed the standard phases of two-stage sampling. Primary sampling units were polling stations selected based on a probability proportional to the number of voters aged 50+ at each polling station. The sample was stratified by counties and by settlement size. In the second phase, the gross sample of individuals aged 50 or older was selected randomly. The SHARE study today faces a number of challenges, the most prominent ones being the retention of European coverage due to lack of funding and the future method of surveying in the light of COVID-19. In Croatia, joining the SHARE study was marked by significant challenges. Firstly, SHARE is the first longitudinal study on demographic ageing conducted in our country. Secondly, the SHARE survey requires ample financial resources, so the size of the Croatian sample had to be adjusted accordingly and to meet high scientific standards set by the SHARE study. The third significant challenge that the SHARE research team faced were barriers to accessing the sampling framework. Substantial efforts were undertaken to demonstrate that the SHARE study adheres to all ethical standards and regulations related to the protection of the personal data of respondents. Another issue was the limited number of survey agencies in Croatia that can conduct demanding surveys of this type.

Early discharge of patients with COVID-19

Introduction: Recently, this journal published a study on the experiences of 49 stable Covid-19 patients who were discharged early from hospital. These patients self-administered oxygen at home and were supervised remotely by a pulmonologist or lung nurse. In October 2020, a project started in Amsterdam in which Covid-19 patients were discharged early, received oxygen supplementation at home and were supervised by their own GP. We report the safety of this approach and describe the expectations beforehand and satisfaction afterwards of all involved. MethodAdult patients admitted to Amsterdam UMC, OLVG or BovenIJ hospital because of covid-19 were eligible for early discharge if they were clinically stable for at least 48 hours and had an oxygen saturation of 94% on oxygen therapy at 3 l/min (figure). Before discharge, patients were taught how to use a pulse oximeter (ihealth P03M, CE/FDA certified) and oxygen equipment. Treatment with dexamethasone and thrombosis prophylaxis were continued in accordance with current treatment guidelines as long as there was an indication. The participants were transferred verbally and in writing from the hospital to their own GP who then took over the supervision. In the period January 18-March 26, 2021, patients could be prospectively included in this evaluation. All patients discharged from October 23, 2020 to January 18, 2021 were retrospectively included. We collected clinical data from the patients and completed questionnaires among patients, general practitioners and caregivers, before hospital discharge and 14 days after.

Special Issue: Country responses to the COVID-19 pandemic. (Special Issue: Country responses to the COVID-19 pandemic.)

This special issue includes 9 articles focusing on France's response to the COVID-19 pandemic;response to COVID-19 in Italy;the Dutch policy response to the COVID-19 crisis;Belgium's response to the COVID-19 pandemic;a review of the Swedish policy response to COVID-19;United States response to the COVID-19 pandemic, January-November 2020;the federal government and Canada's COVID-19 responses;Australia's Response to COVID-19.

SARS-CoV-2 surveillance in imported meat and animal parts for food safety and security

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent for the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is contagious and fatal to humans. In the context of the COVID-19 pandemic, significant concerns on food safety and security are rising due to potential interspecies transmission. As such, surveillance of SARS-CoV-2 on imported meat and animal parts is carried out and reported in this study to safeguard food safety and security. Overall, none of the 225 samples from various livestock (buffaloes, cattle, goat and pig) imported from seven countries were tested positive for SARS-CoV-2 with quantitative reverse transcription polymerase chain reaction (RT-qPCR) from July 2020 to November 2021. This study finding serves as a baseline data for SARS-CoV-2 in imported meat and animal parts. Notably, this study accentuated the importance of active surveillance to prevent zoonosis and to safeguard food safety and security.

Democracy and COVID-19 mortality in Europe

Background: In Europe there is a great variability in mortality by Covid-19 among different countries. While some countries, such as Greece, Belarus or Ukraine, have a mortality rate of less than 5 cases/100,000 inhabitants, other countries such as Belgium, Spain or the United Kingdom have a mortality rate of well over 50 cases/100,000 inhabitants. It is generally considered that the reason for this variability is multifactorial (including political reasons), but there are few studies that associate factors related to this variability. The objective of this work was to analyse political risk factors/markers that could explain the variability in mortality due to Covid-19 among different European countries.

Normative analysis and ethical evaluation of clinical ethical guidelines published in the context of intensive care triage during COVID-19 pandemic

Throughout the COVID-19 pandemic, the rapid increase in the number of cases during certain periods has caused a high occupancy rate in intensive care units. Faced with a sudden and rapid increase in the number of patients, a lack of medical resources or its possibility led to ethical discussions on the immediate and equitable distribution of resources in intensive care units. This has not only given impetus to the ethical debate, but many medical professional organisations in Europe have published guidelines for triage of critical care which contain ethical criteria. In this study, some of the ethical triage guides have been normatively analyzed and ethically evaluated.

COVID-19, neoliberalism and health systems in 30 European countries: relationship to deceases

Background: The study was motivated by the need to understand the high number of deaths caused by COVID-19 in the global pandemic declared since December 2019, and how it impacted differently in European countries. The hypothesis was that less investment in the public health system, the number of doctors per inhabitant and the number of hospital beds available to the population led to a higher number of deaths after the arrival of COVID-19 in each country studied. The objective was to analyze the relationship between the number of deaths from COVID-19 in the global pandemic declared since December 2019 and health policies and investment in European countries.

Participatory sport events in times of COVID-19: analysing the (virtual) sport behaviour of event participants. (Special Issue: Sport and COVID-19: impact and challenges for the future: volume 2.)

Research question: Due to government restrictions because of COVID-19, all participatory sport events (PSEs) were cancelled. As a result, knowledge is needed as to how and to what extent participants of PSEs modified their sport behaviour to fill the void of event cancellation. Therefore, this study aimed to (1) investigate to what extent event participants have modified their sport behaviour as a result of the COVID-19 measures, and (2) analyse the factors that determine participation in virtual events (real activities using an online recording platform). Research methods: A total of 2869 respondents completed an online survey which was widely disseminated in Flanders (Belgium) six weeks after the announcement of the COVID-19 lockdown. The sample included both event and non-event participants. Descriptive and binary logistic regression analyses were used to investigate how event participants adapted their sport behaviour and which factors determined virtual event participation. Results and findings: Since the COVID-19 measures, event participants did not decrease the frequency but only the intensity of their sport behaviour. Based on social ecological theory, participation in virtual events could be explained by both individual determinants (e.g. motivation towards developing skills), and interpersonal determinants (e.g. previous participation in a virtual event). Implications: This study contributes to research on the impact of COVID-19 measures and consequently the cancellation of PSEs on sport behaviour of event participants. Confronted with an uncertain future, the findings provide insights for event organisers to develop and optimise virtual event experiences in order to reach non-event participants as well.

Experience of first COVID-19 patients in Northern part of the Netherlands: Information provision, source investigation, contact tracing and home isolation

Objective: The aim of this study was to investigate how patients experience the information, the source investigation and contact tracing and the measures in isolation at the start of a pandemic. Design: Secondary analysis of semi-structured interviews was conducted as part of a larger exploratory mixed-methods study on COVID-19 patient experiences.

The omicron strain of Coronavirus may be more transmissible than other variants and is partially resistant to existing vaccines

The study first interpreted all the data from the alpha to the delta strain. Then comparative data characterized the omicron of the coronavirus strain. Omicron, the SARS-CoV-2 variant responsible for a cluster of cases in South Africa and that is now spreading around the world, is the most heavily mutated variant to emerge so far and carries mutations similar to changes seen in previous variants of concern associated with enhanced transmissibility and partial resistance to vaccine induced immunity. Daily case numbers in South Africa had been fairly low but then rose rapidly from 273 on 16 November to more than 1200 by 25 November, more than 80% of which were in the northern province of Gauteng, where the first cases were seen. Europe's first case of the variant was confirmed in Belgium on 26 November in a person who tested positive for covid-19 on 22 November. By 29 November cases had been reported in the Netherlands, France, Germany, Portugal, and Italy. The UK had recorded nine cases by the morning of 29 November, six of them in Scotland. Elsewhere in the world cases have been reported in Botswana, Hong Kong, Canada, and Australia, which has had extremely tight border controls through the pandemic.

Inequality in mortality between Black and White Americans by age, place, and cause, and in comparison to Europe, 1990-2018

Although there is a large gap between Black and White American life expectancies, the gap fell 48.9% between 1990-2018, mainly due to mortality declines among Black Americans. We examine age-specific mortality trends and racial gaps in life expectancy in rich and poor U.S. areas and with reference to six European countries. Inequalities in life expectancy are starker in the U.S. than in Europe. In 1990 White Americans and Europeans in rich areas had similar overall life expectancy, while life expectancy for White Americans in poor areas was lower. But since then even rich White Americans have lost ground relative to Europeans. Meanwhile, the gap in life expectancy between Black Americans and Europeans decreased by 8.3%. Black life expectancy increased more than White life expectancy in all U.S. areas, but improvements in poorer areas had the greatest impact on the racial life expectancy gap. The causes that contributed the most to Black mortality reductions included: Cancer, homicide, HIV, and causes originating in the fetal or infant period. Life expectancy for both Black and White Americans plateaued or slightly declined after 2012, but this stalling was most evident among Black Americans even prior to the COVID-19 pandemic. If improvements had continued at the 1990-2012 rate, the racial gap in life expectancy would have closed by 2036. European life expectancy also stalled after 2014. Still, the comparison with Europe suggests that mortality rates of both Black and White Americans could fall much further across all ages and in both rich and poor areas.

COVID-19 patient mortality with convalescent plasma therapy: meta-analysis

Background: The use of convalescent plasma was recommended as empiric treatment during the Ebolavirus outbreak in 2014, and a protocol for the treatment of Middle East Respiratory Syndrome coronavirus (MERS) with convalescent plasma was created in 2015. These findings raise the hypothesis that the use of convalescent plasma transfusion may be beneficial in SARS-infected patients. -CoV-2. The aim of this study was to estimate the mortality risk of COVID-19 patients with convalescent plasma therapy. Subjects and method: A systematic review and meta-analysis was carried out by collecting articles from the Google Scholar, PubMed, and Science Direct databases. The articles were screened using the PICO model, including: (1) Population= confirmed COVID-19 patients, (2) Intervention= convalescent plasma therapy, (3) Comparison= standard of care, and (4) Outcome= mortality. The keywords used were "Convalescent plasma therapy" OR "Convalescent plasma transfusion" AND "Mortality" OR "death" AND "COVID-19" OR "Coronavirus disease 2019" OR "SARS-Cov-2'. Inclusion criteria were full text, randomized control trials, published from 2020 to 2021, and reported risk ratios. Articles were collected using PRISMA diagrams and quantitative syntheses were assessed using Review Manager (RevMan 5.3).

The system dynamic model of the labor migrant policy in economic growth affected by COVID-19. (Special Issue: Covid-19.)

At the end of 2019, the new virus called Coronavirus Disease (Covid-19) spread widely from China all over the world. In March 2020 the World Health Organization declared a new virus outbreak as "a global pandemic", and recommended social distancing and quarantine. Most countries in Europe have been quarantined. The social aspect of this issue is complicated by the fact that Europe nowadays hosts 82 million international migrants. If migrant workers leave the host country, it reduces the Covid-19 spread. Nevertheless, if migrant workers do not return, it will worsen the situation with the economic crisis. The subject of the study is the instrumental and mathematical aspects of impact simulation of labor migrants' policy on the economic growth of the host country affected by COVID-19 pandemic. The aim of the work is to develop the system dynamics model for assessing labor migrants' policy impact on the economic growth of the host country during COVID-19 pandemic. It examined through hypotheses of different scenarios of labor migrants policy impact on the host country economic growth in Covid-19 pandemic. The proposed model combines epidemiological and the economic growth models and relies upon real statistical data. The analysis was carried out in four European countries. The results of the study enabled to state that without migrant workers the gross domestic product may fall to 43% in Italy, 45% in Netherlands, 37% in Spain and 200% in Switzerland in 2020.

The first 100 COVID-19 patients admitted to the Elisabeth-Tweesteden hospital, Tilburg, the Netherlands

Here we describe the characteristics of the first 100 laboratory confirmed COVID-19 patients admitted to the Elisabeth-Tweesteden Hospital (Tilburg, The Netherlands). The median age was 72 years, 67% was male, approximately 80% had co-morbidity, approximately 50% of which consisted of hypertension, cardiac and or pulmonary conditions and 25% diabetes. At admission 61% of patients had fever and about 50% presented at day 6 or more after onset of symptoms. At the time of writing 38 patients were discharged, 19 admitted to the intensive care unit (ICU) and 20 patients had died. The median age of ICU patients was 67 years and 63% had co-morbidity. The median time to discharge or to death was 6 and 5.5 days, respectively.

Dealing with COVID-19-associated coagulopathy

COVID-19 is associated with a high prevalence of activation of the coagulation cascade. It has been suggested that this so-called COVID-19-associated coagulopathy is predictive of a poor outcome and of mortality. Consensus documents on how to manage patients with COVID-19-associated coagulopathy are based on the limited number of mainly retrospective studies that is currently available, and for this reason the recommendations are not always consistent with one another. In this article, we review the first studies into COVID-19-associated coagulopathy and give the most important do's and don'ts for diagnostics and the daily management of coagulopathy and the prevention of complications in patients with, or with strongly-suspected, COVID-19 in Dutch clinical practice.