The Impact of COVID-19 on Mortality in Spain: Monitoring Excess Mortality (MoMo) and the Surveillance of Confirmed COVID-19 Deaths

Measuring mortality has been a challenge during the COVID-19 pandemic. Here, we compared the results from the Spanish daily mortality surveillance system (MoMo) of excess mortality estimates, using a time series analysis, with those obtained for the confirmed COVID-19 deaths reported to the National Epidemiological Surveillance Network (RENAVE). The excess mortality estimated at the beginning of March 2020 was much greater than what has been observed in previous years, and clustered in a very short time. The cumulated excess mortality increased with age. In the first epidemic wave, the excess mortality estimated by MoMo was 1.5 times higher than the confirmed COVID-19 deaths reported to RENAVE, but both estimates were similar in the following pandemic waves. Estimated excess mortality and confirmed COVID-19 mortality rates were geographically distributed in a very heterogeneous way. The greatest increase in mortality that has taken place in Spain in recent years was detected early by MoMo, coinciding with the spread of the COVID-19 pandemic. MoMo is able to identify risk situations for public health in a timely manner, relying on mortality in general as an indirect indicator of various important public health problems.S

Perimeter confinements of basic health zones and COVID-19 incidence in Madrid, Spain

Background: A unique policy of perimeter closures of Basic Health Zones (small administrative health units) was implemented in the Autonomous Community of Madrid from September 21st 2020 to May 23rd 2021 to face the COVID-19 pandemic. Aim: To assess the impact of local perimeter confinements on the 14-days cumulative incidence of SARS-CoV-2 during the second wave of the pandemic in Madrid, Spain. Methods: We compare the errors in estimation of two families of mathematical models: ones that include the perimeter closures as explanatory covariables and ones that do not, in search of a significant improvement in estimation of one family over the other. We incorporate leave-one-out cross-validation, and at each step of this process we select the best model in AIC score from a family of 15 differently tuned ones. Results: The two families of models provided very similar estimations, for a 1- to 3-weeks delay in observed cumulative incidence, and also when restricting the analysis to only those Basic Health Zones that were subject to at least one closure during the time under study. In all cases the correlation between the errors yielded by both families of models was higher than 0.98 (±10- 3 95% CI), and the average difference of estimated 14-days cumulative incidence was smaller than 1.49 (±0.33 95% CI). Conclusion: Our analysis suggests that the perimeter closures by Basic Health Zone did not have a significant effect on the epidemic curve in Madrid.This research has been financed by Carlos III Health Institute (ISCIII) under the project COV20–00881.S

Real time surveillance of COVID-19 space and time clusters during the summer 2020 in Spain

Background: On June 21st de-escalation measures and state-of-alarm ended in Spain after the COVID-19 first wave. New surveillance and control strategy was set up to detect emerging outbreaks. Aim: To detect and describe the evolution of COVID-19 clusters and cases during the 2020 summer in Spain. Methods: A near-real time surveillance system to detect active clusters of COVID-19 was developed based on Kulldorf's prospective space-time scan statistic (STSS) to detect daily emerging active clusters. Results: Analyses were performed daily during the summer 2020 (June 21st - August 31st) in Spain, showing an increase of active clusters and municipalities affected. Spread happened in the study period from a few, low-cases, regional-located clusters in June to a nationwide distribution of bigger clusters encompassing a higher average number of municipalities and total cases by end-August. Conclusion: STSS-based surveillance of COVID-19 can be of utility in a low-incidence scenario to help tackle emerging outbreaks that could potentially drive a widespread transmission. If that happens, spatial trends and disease distribution can be followed with this method. Finally, cluster aggregation in space and time, as observed in our results, could suggest the occurrence of community transmission.This research has been financed by Carlos III Health Institute (ISCIII) under the project COV20–00881.S

Effectiveness of mRNA vaccine boosters against infection with the SARS-CoV-2 omicron (B.1.1.529) variant in Spain: a nationwide cohort study

Factor de impacto: 25,71 Q1Background: The omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster. Methods: In this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR. Findings: Between Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2-52·4). Estimated effectiveness was 52·5% (51·3-53·7) for an mRNA-1273 booster and 46·2% (43·5-48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5-61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford-AstraZeneca), 55·3% (52·3-58·2) with mRNA-1273 (Moderna), 49·7% (48·3-51·1) with BNT162b2 (Pfizer-BioNTech), and 48·0% (42·5-53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0-47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0-53·3) if administered more than 180 days after primary scheduled completion. Interpretation: Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster.S

Assessing the effect of non-pharmaceutical interventions on COVID-19 transmission in Spain, 30 August 2020 to 31 January 2021

Background: After a national lockdown during the first wave of the COVID-19 pandemic in Spain, regional governments implemented different non-pharmaceutical interventions (NPIs) during the second wave. Aim: To analyse which implemented NPIs significantly impacted effective reproduction number (Rt) in seven Spanish provinces during 30 August 2020-31 January 2021. Methods: We coded each NPI and levels of stringency with a 'severity index' (SI) and computed a global SI (mean of SIs per six included interventions). We performed a Bayesian change point analysis on the Rt curve of each province to identify possible associations with global SI variations. We fitted and compared several generalised additive models using multimodel inference, to quantify the statistical effect on Rt of the global SI (stringency) and the individual SIs (separate effect of NPIs). Results: The global SI had a significant lowering effect on the Rt (mean: 0.16 ± 0.05 units for full stringency). Mandatory closing times for non-essential businesses, limited gatherings, and restricted outdoors seating capacities (negative) as well as curfews (positive) were the only NPIs with a significant effect. Regional mobility restrictions and limited indoors seating capacity showed no effect. Our results were consistent with a 1- to 3-week-delayed Rt as a response variable. Conclusion: While response measures implemented during the second COVID-19 wave contributed substantially to a decreased reproduction number, the effectiveness of measures varied considerably. Our findings should be considered for future interventions, as social and economic consequences could be minimised by considering only measures proven effective.This research was financed by Carlos III Health Institute (ISCIII) under the project COV20–00881.S

Impacto de la COVID-19 en la mortalidad en España: exceso de mortalidad por MoMo y muertes confirmadas por COVID-19

Comunicación presentada en las II Jornada del Centro Nacional de Epidemiología - 2021.Se estudia el impacto de la COVID-19 en la mortalidad en España. Los objetivos del estudio son: 1. Analizar la mortalidad por COVID-19 en España, describiendo las tres primeras olas pandémicas de COVID-19 y proporcionando estimaciones por grupo de edad y regiones españolas; y 2. Comparar el exceso de mortalidad por todas las causas de MoMo durante la pandemia de COVID-19 con las muertes confirmadas por COVID-19 notificadas al sistema nacional de vigilancia. Las conclusiones son: 1. MoMo identificó un exceso de mortalidad sin precedentes, en la primera ola pandémica de COVID-19 en España, que coincidió con la aparición de la pandemia COVID-19, 2. El sistema MoMo puede proporcionar estimaciones de exceso de mortalidad por todas las causas por edad y región geográfica, y 3. A pesar de ser un sistema inespecífico que no permite establecer causalidad directa en el análisis de exceso de mortalidad, MoMo constituye una herramienta esencial de vigilancia a tiempo real, como sistema de alerta temprana para la acción en salud pública, y para realizar estimaciones del impacto de diferentes eventos de salud en la mortalidad de la población

Epidemic Diffusion Network of Spain: A Mobility Model to Characterize the Transmission Routes of Disease

Human mobility drives the geographical diffusion of infectious diseases at different scales, but few studies focus on mobility itself. Using publicly available data from Spain, we define a Mobility Matrix that captures constant flows between provinces by using a distance-like measure of effective distance to build a network model with the 52 provinces and 135 relevant edges. Madrid, Valladolid and Araba/Álaba are the most relevant nodes in terms of degree and strength. The shortest routes (most likely path between two points) between all provinces are calculated. A total of 7 mobility communities were found with a modularity of 63%, and a relationship was established with a cumulative incidence of COVID-19 in 14 days (CI14) during the study period. In conclusion, mobility patterns in Spain are governed by a small number of high-flow connections that remain constant in time and seem unaffected by seasonality or restrictions. Most of the travels happen within communities that do not completely represent political borders, and a wave-like spreading pattern with occasional long-distance jumps (small-world properties) can be identified. This information can be incorporated into preparedness and response plans targeting locations that are at risk of contagion preventively, underscoring the importance of coordination between administrations when addressing health emergencies.This research has been financed by Carlos III Health Institute (ISCIII) under the project COV20-00881 and the project Fundación BBVA.DGVI 256/22 “COVID-19 Urban Atlas Spain”.S

Traffic Density Exposure, Oxidative Stress Biomarkers and Plasma Metabolomics in a Population-Based Sample: The Hortega Study

Exposure to traffic-related air pollution (TRAP) generates oxidative stress, with downstream effects at the metabolic level. Human studies of traffic density and metabolomic markers, however, are rare. The main objective of this study was to evaluate the cross-sectional association between traffic density in the street of residence with oxidative stress and metabolomic profiles measured in a population-based sample from Spain. We also explored in silico the potential biological implications of the findings. Secondarily, we assessed the contribution of oxidative stress to the association between exposure to traffic density and variation in plasma metabolite levels. Traffic density was defined as the average daily traffic volume over an entire year within a buffer of 50 m around the participants' residence. Plasma metabolomic profiles and urine oxidative stress biomarkers were measured in samples from 1181 Hortega Study participants by nuclear magnetic resonance spectroscopy and high-performance liquid chromatography, respectively. Traffic density was associated with 7 (out of 49) plasma metabolites, including amino acids, fatty acids, products of bacterial and energy metabolism and fluid balance metabolites. Regarding urine oxidative stress biomarkers, traffic associations were positive for GSSG/GSH% and negative for MDA. A total of 12 KEGG pathways were linked to traffic-related metabolites. In a protein network from genes included in over-represented pathways and 63 redox-related candidate genes, we observed relevant proteins from the glutathione cycle. GSSG/GSH% and MDA accounted for 14.6% and 12.2% of changes in isobutyrate and the CH2CH2CO fatty acid moiety, respectively, which is attributable to traffic exposure. At the population level, exposure to traffic density was associated with specific urine oxidative stress and plasma metabolites. Although our results support a role of oxidative stress as a biological intermediary of traffic-related metabolic alterations, with potential implications for the co-bacterial and lipid metabolism, additional mechanistic and prospective studies are needed to confirm our findings.This research was funded by the State Agency for Research (PID2019-108973RB-C21 and C22), by Strategic Action for Research in Health Sciences (PI15/00071 and PI22CIII/00029) from the Spanish Ministry of Economy and Competitiveness and co-funded with European Funds for Regional Development (FEDER), and IDIFEDER/2021/072, CIAICO/2022/181 and INVEST/2023/180 from the Generalitat Valenciana of Spain.S

Vigilancia del COVID-19 en centros de larga estancia: el efecto de la pandemia en las residencias de mayores

[ES] Este informe muestra la situación epidemiológica de la COVID-19 en los centros residenciales de mayores a lo largo del año 2021 y hasta la semana 17 del 2022. Desde su puesta en marcha en enero de 2021, esta vigilancia ha proporcionado datos semanales nacionales agregados, con información sobre la proporción de residencias afectadas por la COVID-19, la incidencia de COVID-19 y la letalidad entre una población vulnerable donde los efectos de la pandemia han sido y están siendo especialmente graves. La comparación con la incidencia y mortalidad de casos COVID-19 en población mayor no institucionalizada, nos demuestra cómo el impacto de la COVID-19 ha sido y está siendo mayor entre las personas mayores que viven en residencias de ancianos, con tasas de mortalidad superiores al resto de la población de la misma edad. [EN] This report shows the epidemiological situation of COVID-19 in the long-term care facilities (LTCF) for elderly throughout 2021 and until the 17th week of 2022. Since its start-up in January 2021, this surveillance has provided aggregated national weekly data, with information on the proportion of LTCF for elderly affected by COVID-19, the incidence of COVID-19 and fatal cases among a vulnerable population where the effects of the pandemic have been and are being especially severe. The comparison with the incidence and mortality of COVID-19 cases in non institutionalized elderly shows how the impact of COVID-19 is being greater among the elderly living in nursing homes, with more fatal cases than the rest of the population of the same age

Effectiveness of vaccines against SARS-CoV-2 used in Spain: infection, hospitalization and mortality in people aged fifty/fifty-nine

[ES] En este trabajo se comparó la efectividad de la vacuna contra la COVID-19 (EV) durante agosto de 2021, en personas nacidas entre 1962 y 1971 y vacunadas durante junio, según la marca utilizada. La protección frente a infección por SARS-CoV-2 sintomática fue menor para la vacuna de Janssen (56%; IC95%: 53-59) y AstraZeneca [Vaxzevria] (68%; IC95%: 65-70), en comparación con Pfizer [Comirnaty] (78%; IC95%: 77-78), AZ/Pfizer (86%; IC95%: 80-90) y Moderna [Spikevax] (89%; IC95%: 88-90). La EV contra la hospitalización osciló entre el 86% de Janssen y el 97%-98% de las demás vacunas. [EN]In this paper we compared brand-specific COVID-19 vaccine effectiveness (VE) during August 2021 in persons born 1962-1971 and vaccinated during June. For SARS-CoV-2 symptomatic infection, protection was lower for Janssen (56%; CI95%: 53-59) or AstraZeneca [Vaxzevria] (68%; CI95%: 65-70), compared to Pfizer-BioNTech [Comirnaty] (78%; CI95%: 77-78), AstraZeneca/Pfizer (86%; CI95%: 80-90) or Moderna [Spikevax] (89%; CI95%: 88-90). VE against hospitalization was ranged 86% for Janssen to 97%-98% for other vaccines.S