Spatial Analysis of Determinants of COVID-19 Vaccine Hesitancy in Portugal.

Vaccine hesitancy tends to exhibit geographical patterns and is often associated with social deprivation and migrant status. We aimed to estimate COVID-19 vaccination hesitancy in a high-vaccination-acceptance country, Portugal, and determine its association with sociodemographic risk factors. We used the Registry of National Health System Users to determine the eligible population and the Vaccination Registry to determine individuals without COVID-19 vaccine doses. Individuals older than five with no COVID-19 vaccine dose administered by 31 March 2022 were considered hesitant. We calculated hesitancy rates by municipality, gender, and age group for all municipalities in mainland Portugal. We used the spatial statistical scan method to identify spatial clusters and the Besag, Yorke, and Mollié (BYM) model to estimate the effect of age, gender, social deprivation, and migrant proportion across all mainland municipalities. The eligible population was 9,852,283, with 1,212,565 (12%) COVID-19 vaccine-hesitant individuals. We found high-hesitancy spatial clusters in the Lisbon metropolitan area and the country's southwest. Our model showed that municipalities with higher proportions of migrants are associated with an increased relative risk (RR) of vaccine hesitancy (RR = 8.0; CI 95% 4.6; 14.0). Social deprivation and gender were not associated with vaccine hesitancy rates. We found COVID-19 vaccine hesitancy has a heterogeneous distribution across Portugal and has a strong association with the proportion of migrants per municipality.

A standardised protocol for relative SARS-CoV-2 variant severity assessment, applied to Omicron BA.1 and Delta in six European countries, October 2021 to February 2022.

Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of new variants. Therefore, a joint WHO Regional Office for Europe and ECDC working group was formed to produce and pilot a standardised study protocol to estimate relative case-severity of SARS-CoV-2 variants during periods when two variants were co-circulating. The study protocol and its associated statistical analysis code was applied by investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the severity of cases with the Omicron BA.1 virus variant relative to Delta. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio (aHR) = 0.41; 95% confidence interval (CI): 0.31-0.54), admission to intensive care unit (aHR = 0.12; 95% CI: 0.05-0.27) and death (aHR = 0.31; 95% CI: 0.28-0.35) was lower for Omicron BA.1 compared with Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study demonstrates the feasibility of conducting variant severity analyses in a multinational collaborative framework and adds evidence for the reduced severity of the Omicron BA.1 variant.

Viral genetic clustering and transmission dynamics of the 2022 mpox outbreak in Portugal.

Pathogen genome sequencing during epidemics enhances our ability to identify and understand suspected clusters and investigate their relationships. Here, we combine genomic and epidemiological data of the 2022 mpox outbreak to better understand early viral spread, diversification and transmission dynamics. By sequencing 52% of the confirmed cases in Portugal, we identified the mpox virus sublineages with the highest impact on case numbers and fitted them into a global context, finding evidence that several international sublineages probably emerged or spread early in Portugal. We estimated a 62% infection reporting rate and that 1.3% of the population of men who have sex with men in Portugal were infected. We infer the critical role played by sexual networks and superspreader gatherings, such as sauna attendance, in the dissemination of mpox virus. Overall, our findings highlight genomic epidemiology as a tool for the real-time monitoring and control of mpox epidemics, and can guide future vaccine policy in a highly susceptible population.

Task Force for a rapid response to an outbreak of severe acute hepatitis of unknown aetiology in children in Portugal in 2022.

On 5 April 2022, the United Kingdom reported an increase of cases of severe acute hepatitis of unknown aetiology in children, several needing hospitalisation and some required liver transplant or died. Thereafter, 35 countries reported probable cases, almost half of them in Europe. Facing the alert, on 28 April, Portugal created a multidisciplinary Task Force (TF) for rapid detection of probable cases and response. The experts of the TF came from various disciplines: clinicians, laboratory experts, epidemiologists, public health experts and national and international communication. Moreover, Portugal adopted the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) case definition and recommendations. By 31 December 2022, 28 probable cases of severe acute hepatitis of unknown aetiology were reported: 16 male and 17 aged under 2 years. Of these cases, 23 were hospitalised but none required liver transplant or died. Adenovirus was detected from nine of 26 tested cases. No association was observed between adenovirus infection and hospital admission after adjusting for age, sex and region in a binomial regression model. The TF in Portugal may have contributed to increase awareness among clinicians, enabling early detection and prompt management of the outbreak.

LOCUS (LOng Covid-Understanding Symptoms, events and use of services in Portugal): A three-component study protocol.

Approximately 10% of patients experience symptoms of Post COVID-19 Condition (PCC) after a SARS-CoV-2 infection. Akin acute COVID-19, PCC may impact a multitude of organs and systems, such as the cardiovascular, respiratory, musculoskeletal, and neurological systems. The frequency and associated risk factors of PCC are still unclear among both community and hospital settings in individuals with a history of COVID-19. The LOCUS study was designed to clarify the PCC's burden and associated risk factors. LOCUS is a multi-component study that encompasses three complementary building blocks. The "Cardiovascular and respiratory events following COVID-19" component is set to estimate the incidence of cardiovascular and respiratory events after COVID-19 in eight Portuguese hospitals via electronic health records consultation. The "Physical and mental symptoms following COVID-19" component aims to address the community prevalence of self-reported PCC symptoms through a questionnaire-based approach. Finally, the "Treating and living with Post COVID-19 Condition" component will employ semi-structured interviews and focus groups to characterise reported experiences of using or working in healthcare and community services for the treatment of PCC symptoms. This multi-component study represents an innovative approach to exploring the health consequences of PCC. Its results are expected to provide a key contribution to the optimisation of healthcare services design.

Comparative complete scheme and booster effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infections with SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2) variants: A case-case study based on electronic health records.

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.

Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, Portugal.

We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.

Spatiotemporal evolution of COVID-19 in Portugal's Mainland with self-organizing maps.

BACKGROUND: Self-Organizing Maps (SOM) are an unsupervised learning clustering and dimensionality reduction algorithm capable of mapping an initial complex high-dimensional data set into a low-dimensional domain, such as a two-dimensional grid of neurons. In the reduced space, the original complex patterns and their interactions can be better visualized, interpreted and understood. METHODS: We use SOM to simultaneously couple the spatial and temporal domains of the COVID-19 evolution in the 278 municipalities of mainland Portugal during the first year of the pandemic. Temporal 14-days cumulative incidence time series along with socio-economic and demographic indicators per municipality were analyzed with SOM to identify regions of the country with similar behavior and infer the possible common origins of the incidence evolution. RESULTS: The results show how neighbor municipalities tend to share a similar behavior of the disease, revealing the strong spatiotemporal relationship of the COVID-19 spreading beyond the administrative borders of each municipality. Additionally, we demonstrate how local socio-economic and demographic characteristics evolved as determinants of COVID-19 transmission, during the 1st wave school density per municipality was more relevant, where during 2nd wave jobs in the secondary sector and the deprivation score were more relevant. CONCLUSIONS: The results show that SOM can be an effective tool to analysing the spatiotemporal behavior of COVID-19 and synthetize the history of the disease in mainland Portugal during the period in analysis. While SOM have been applied to diverse scientific fields, the application of SOM to study the spatiotemporal evolution of COVID-19 is still limited. This work illustrates how SOM can be used to describe the spatiotemporal behavior of epidemic events. While the example shown herein uses 14-days cumulative incidence curves, the same analysis can be performed using other relevant data such as mortality data, vaccination rates or even infection rates of other disease of infectious nature.

Measuring the impact of COVID-19 vaccination and immunity waning: A modelling study for Portugal.

Vaccination strategies to control COVID-19 have been ongoing worldwide since the end of 2020. Understanding their possible effect is key to prevent future disease spread. Using a modelling approach, this study intends to measure the impact of the COVID-19 Portuguese vaccination strategy on the effective reproduction number and explore three scenarios for vaccine effectiveness waning. Namely, the no-immunity-loss, 1-year and 3-years of immunity duration scenarios. We adapted an age-structured SEIR deterministic model and used Portuguese hospitalisation data for the model calibration. Results show that, although the Portuguese vaccination plan had a substantial impact in reducing overall transmission, it might not be sufficient to control disease spread. A significant vaccination coverage of those above 5 years old, a vaccine effectiveness against disease of at least 80% and softer non-pharmaceutical interventions (NPIs), such as mask usage and social distancing, would be necessary to control disease spread in the worst scenario considered. The immunity duration scenario of 1-year displays a resurgence of COVID-19 hospitalisations by the end of 2021, the same is observed in 3-year scenario although with a lower magnitude. The no-immunity-loss scenario presents a low increase in hospitalisations. In both the 1-year and 3-year scenarios, a vaccination boost of those above 65 years old would result in a 53% and 38% peak reduction of non-ICU hospitalisations, respectively. These results suggest that NPIs should not be fully phased-out but instead be combined with a fast booster vaccination strategy to reduce healthcare burden.

Comparative Effectiveness of Coronavirus Vaccine in Preventing Breakthrough Infections among Vaccinated Persons Infected with Delta and Alpha Variants.

We developed a case-case study to compare mRNA vaccine effectiveness against Delta versus Alpha coronavirus variants. We used data on 2,097 case-patients with PCR-positive severe acute respiratory syndrome coronavirus 2 infections reported in Portugal during May-July 2021. We estimated the odds of vaccine breakthrough infection in Delta-infected versus Alpha-infected patients by using conditional logistic regression adjusted for age group and sex and matched by the week of diagnosis. We compared reverse-transcription PCR cycle threshold values by vaccination status and variant as an indirect measure of viral load. We found significantly higher odds of vaccine breakthrough infection in Delta-infected patients than in Alpha-infected patients (odds ratio 1.96 [95% CI 1.22-3.14]), suggesting lower effectiveness of the mRNA vaccines in preventing infection with the Delta variant. We estimated lower mean cycle threshold values for the Delta cases (mean difference -2.10 [95% CI -2.74 to -1.47]), suggesting higher infectiousness than the Alpha variant.

The neglected epidemic-Risk factors associated with road traffic injuries in Mozambique: Results of the 2016 INCOMAS study.

In 2019, 93% of road traffic injury related mortality occurred in low- and middle-income countries, an estimated burden of 1.3 million deaths. This problem is growing; by 2030 road traffic injury will the seventh leading cause of death globally. This study both explores factors associated with RTIs in the central region of Mozambique, as well as pinpoints geographical "hotspots" of RTI incidence. A cross-sectional, population-level survey was carried out in two provinces (Sofala and Manica) of central Mozambique where, in addition to other variables, the number of road traffic injuries sustained by the household within the previous six months, was collected. Urbanicity, household ownership of a car or motorcycle, and socio-economic strata index were included in the analysis. We calculated the prevalence rate ratios using a generalized linear regression with a Poisson distribution, as well as the spatial prevalence rate ratio using an Integrated Nested Laplace Approximation. The survey included 3,038 households, with a mean of 6.29 (SD 0.06) individuals per household. The road traffic injury rate was 6.1% [95%CI 7.1%, 5.3%]. Urban residence was associated with a 47% decrease in rate of injury. Household motorbike ownership was associated with a 92% increase in the reported rate of road traffic injury. Higher socio-economic status households were associated with a 26% increase in the rate of road traffic injury. The rural and peri-urban areas near the "Beira corridor" (national road N6) have higher rates of road traffic injuries. In Mozambique, living in the rural areas near the "Beira corridor", higher household socio-economic strata, and motorbike ownership are risk factors for road traffic injury.

Increasing risk of breakthrough COVID-19 in outbreaks with high attack rates in European long-term care facilities, July to October 2021.

We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July-October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8-52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.

Initial assessment of the COVID-19 vaccination's impact on case numbers, hospitalisations and deaths in people aged 80 years and older, 15 EU/EEA countries, December 2020 to May 2021.

Prioritisation of elderly people in COVID-19 vaccination campaigns aimed at reducing severe outcomes in this group. Using EU/EEA surveillance and vaccination uptake, we estimated the risk ratio of case, hospitalisation and death notifications in people 80 years and older compared with 25-59-year-olds. Highest impact was observed for full vaccination uptake 80% or higher with reductions in notification rates of cases up to 65% (IRR: 0.35; 95% CI: 0.13-0.99), hospitalisations up to 78% (IRR: 0.22; 95% CI: 0.13-0.37) and deaths up to 84% (IRR: 0.16; 95% CI: 0.13-0.20).

Association of enteropathogen detection with diarrhoea by age and high versus low child mortality settings: a systematic review and meta-analysis.

BACKGROUND: The odds ratio (OR) comparing pathogen presence in diarrhoeal cases versus asymptomatic controls is a measure for diarrhoeal disease cause that has been integrated into burden of disease estimates across diverse populations. This study aimed to estimate the OR describing the association between pathogen detection in stool and diarrhoea for 15 common enteropathogens by age group and child mortality setting. METHODS: We did a systematic review to identify case-control and cohort studies published from Jan 1, 1990, to July 9, 2019, which examined at least one enteropathogen of interest and the outcome diarrhoea. The analytical dataset included data extracted from published articles and supplemented with data from the Global Enteric Multicenter Study and the Malnutrition and Enteric Disease study. Random effects meta-analysis models were fit for each enteropathogen, stratified by age group and child mortality level, and adjusted for pathogen detection method and study design to produce summary ORs describing the association between pathogen detection in stool and diarrhoea. FINDINGS: 1964 records were screened and 130 studies (over 88 079 cases or diarrhoea samples and 135 755 controls or non-diarrhoea samples) were available for analysis. Heterogeneity (I2) in unadjusted models was substantial, ranging from 27·6% to 86·6% across pathogens. In stratified and adjusted models, summary ORs varied by age group and setting, ranging from 0·4 (95% CI 0·2-0·6) for Giardia lamblia to 54·1 (95% CI 7·4-393·5) for Vibrio cholerae. INTERPRETATION: Incorporating effect estimates from diverse data sources into diarrhoeal disease cause and burden of disease models is needed to produce more representative estimates. FUNDING: WHO, Bill & Melinda Gates Foundation, and National Institutes of Health.

mRNA vaccine effectiveness against COVID-19-related hospitalisations and deaths in older adults: a cohort study based on data linkage of national health registries in Portugal, February to August 2021.

Through deterministic data linkage of health registries, mRNA vaccine effectiveness (VE) against COVID-19-related hospitalisations and deaths was measured in 1,880,351 older adults. VE against hospitalisations was 94% (95% confidence interval (CI): 88-97) and 82% (95% CI: 72-89) for those 65-79 and ≥ 80 years old, with no evidence of waning 98 days after dose two. VE against mortality was 96% (95% CI: 92-98) and 81% (95% CI: 74-87) in these two age groups.

Tracking SARS-CoV-2 lineage B.1.1.7 dissemination: insights from nationwide spike gene target failure (SGTF) and spike gene late detection (SGTL) data, Portugal, week 49 2020 to week 3 2021.

We show that the SARS-CoV-2 B.1.1.7 lineage is highly disseminated in Portugal, with the odds of B.1.1.7 proportion increasing at an estimated 89% (95% confidence interval: 83-95%) per week until week 3 2021. RT-PCR spike gene target late detection (SGTL) can constitute a useful surrogate to track B.1.1.7 spread, besides the spike gene target failure (SGTF) proxy. SGTL/SGTF samples were associated with statistically significant higher viral loads, but not with substantial shift in age distribution compared to non-SGTF/SGTL cases.

Telehealth Opportunities in the COVID-19 Pandemic Early Days: What Happened, Did Not Happen, Should Have Happened, and Must Happen in the Near Future?

The objective of this communication is to offer a better understanding of the value of telemedicine in health care, particularly its role in creating opportunities for continuity of care to patients in a complex and novel setting as were the circumstances of the early COVID-19 pandemic times. Crisis time is also a time for opportunities. With regard to telehealth, all players (providers, staff, and patients) should be informed about its benefits and should also become familiar with the use of the various telehealth options and this will only be achieved through large information campaigns necessary enriched by local teaching and training programs in both public and private institutions. The final aim is to launch the debate and foster ideas useful throughout the pandemic. This article covers the experiences of physicians as well as health professionals in the Iberian Peninsula (Spain and Portugal), to provide a clearer idea of what has happened and how we can improve it with the possibilities provided by telemedicine, while at the same time to put in evidence that public health systems need to be rethought to provide solutions to situations such as that we are experiencing.

The comparative politics of COVID-19: The need to understand government responses.

COVID-19 has created a ramifying public health, economic, and political crisis throughout many countries in the world. While globally the pandemic is at different stages and far from under control in some countries, now is the time for public health researchers and political scientists to start understanding how and why governments responded the way they have, explore how effective these responses appear to be, and what lessons we can draw about effective public health policymaking in preparation of the next wave of COVID-19 or the next infectious disease pandemic. We argue that there will be no way to understand the different responses to COVID-19 and their effects without understanding policy and politics. We propose four key focuses to understand the reasons for COVID-19 responses: social policies to crisis management as well as recovery, regime type (democracy or autocracy), formal political institutions (federalism, presidentialism), and state capacity (control over health care systems and public administration). A research agenda to address the COVID-19 pandemic that takes politics as a serious focus can enable the development of more realistic, sustainable interventions in policies and shape our broader understanding of the politics of public health.

Who wants to cross borders in the EU for healthcare? An analysis of the Eurobarometer data in 2007 and 2014.

Background: The European Union (EU) Directive on Patients' Rights in Cross-border Healthcare clarified the entitlements to medical care in other EU Member states. However, little is known about whether EU citizens have been travelling or are willing to travel to receive care. This study aimed to measure the determinants of cross-border patient mobility and willingness to travel to receive medical care in the EU, before and after the adoption of the Directive. Methods: We used individual data from the Eurobarometer 210 (2007) and 425 (2014). In the 2 years, 53 439 EU citizens were randomly selected. We performed a logistic regression on the cross-border patient mobility and willingness to travel to other EU countries to use healthcare services as a function of the year (2007 or 2014), adjusting for age, gender, education and country size. Results: In 2007, 3.3% of citizens reported cross-border mobility and 4.6% in 2014. The odds of cross-border patients' mobility were 11% higher in 2014, compared with 2007 [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Also, mobility was 19% higher in males (OR 1.19, 95% CI 1.08-1.30) and 20% higher amongst the more educated (OR 1.20, 95% CI 1.09-1.31). However, the odds decreased 11% per decade of age (OR 0.89 per decade, 95% CI 0.85-0.93) and country size. In 2014, the willingness to travel decreased by 20% compared with 2007. Conclusions: Cross-border patient mobility is more likely amongst the younger, the more educated and those from smaller countries. The directive does not seem to have promoted mobility at a large scale among the neediest citizens.