Evolution of COVID-19 Spread in the Cohort of LaLiga Football (Soccer) Professionals between May 2020 and April 2021 (preprint)

Objectives: COVID-19 pandemic interrupted the Spanish professional football competition until May 2020, when it was restarted following a surveillance protocol established by LaLiga. The aims were to describe the infective and serological status of professional football players (PLY) and staff (STF) between May 5th 2020 until April 22nd 2021, to analyze the spatial-temporal distribution of the COVID-19 disease in this cohort and its comparison to the Spanish population. Methods: a prospective observational cohort study was carried out. Differences between PLY and STF were assessed by Chi-squared test and test of equality of proportions. Pearson correlation test was used to measure the presence of an association between the percentages of positivity in population and LaLiga cohort. Results: 137,420 RT-PCR and 20,376 IgG serology tests were performed in 7,112 professionals. Positive baseline serology was detected in 10.57% of PLY and 6.38% of STF. Among those who started the follow-up as not infected and before STF vaccination, 11.87% of PLY and 5.03% of STF became positive. Before summer 2020 the prevalence of infection was similar than the observed at national level. The percentage of positivity in the Spanish population was higher than in LaLiga cohort, but both series showed a similar decreasing trend.

COVID-19 vaccine effectiveness against hospitalization due to SARS-CoV-2: A test negative design study based on SARI sentinel surveillance in Spain (preprint)

Background: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for Acute Respiratory Infection (ARI) surveillance in Primary care, and a network of sentinel hospitals for Severe ARI (SARI) surveillance in hospitals. Methods: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 VE against hospitalization, by age group, vaccine type, time since vaccination and SARS-CoV-2 variant. Results: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. Conclusions: The SiVIRA surveillance system, with a network of sentinel hospitals in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations, monitor the circulation of SARS-CoV-2 and other respiratory viruses, and provide data to measure the effectiveness of COVID-19 vaccination in the population under surveillance. Our results add to evidence of high VE of mRNA vaccines against severe COVID-19 and waning protection with time since vaccination.

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.

Regional excess mortality during the 2020 COVID-19 pandemic: a study of five European countries (preprint)

The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.

Impact of Lockdown on COVID-19 Transmissibility During the First Pandemic Wave in Spain (preprint)

Background: The analysis of the evolution of the COVID-19 epidemic can provide evidence of the impact of measures implemented to reduce its progression. Our aim was to describe the evolution of the pandemic in the different Spanish regions and to examine the effect of the non-pharmaceutical public health interventions during the first epidemic wave on these trends. Methods: Daily incidence rates of cases were calculated at national and regional level between 31th of January and 10th of May 2020. Epidemic curves, important dates of interventions and effective reproduction number (Rt) were plotted and transmissibility parameters were calculated. To summarize the geographical heterogeneity in the evolution, regional epidemic curves have been classified into homogeneous groups using a clustering procedure. Findings: The incidence rate reached 5 cases per 100,000 on March 1 and peaked at March 20. The Rt gradually decreased after the national lockdown falling below 1 on March 24. Two homogeneous groups of epidemic curves were identified among regions, mainly differentiated by the magnitude of the daily incidence rate and the evolution of the Rt in the period prior to lockdown. However, irrespectively of the previous trend, the lockdown was followed by a steep decrease in the number of cases starting 6 days after its implementation. Interpretation: Our results confirm that the restrictive national lockdown efficiently reduced the progression of the epidemic in Spain during the first wave. This effect was similar in the two regional clusters, independent of the previous dynamics of the epidemic.Funding Statement: The study was supported by Instituto de Salud Carlos III, Spain (ISCIII) grant number COV20-008Declaration of Interests: All authors declare no competing interests.

Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data (preprint)

Designing public health responses to outbreaks requires close monitoring of population-level health indicators in real-time. Thus an accurate estimation of the epidemic curve is critical. We propose an approach to reconstruct epidemic curves in near real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between the months of March and April 2020. We address two data collection problems that affected the reliability of the available real-time epidemiological data, namely, the frequent missing information documenting when a patient first experienced symptoms, and the frequent retrospective revision of historical information (including right censoring). This is done by using a novel back-calculating procedure based on imputing patients dates of symptom onset from reported cases, according to a dynamically-estimated backward reporting delay conditional distribution, and adjusting for right censoring using an existing package, NobBS, to estimate in real time (nowcast) cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real-time. At each step, we evaluate how different assumptions affect the recovered epidemiological events and compare the proposed approach to the alternative procedure of merely using curves of case counts, by report day, to characterize the time-evolution of the outbreak. Finally, we assess how these real-time estimates compare with subsequently documented epidemiological information that is considered more reliable and complete that became available weeks to months later in time. Our approach may help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health surveillance systems in other locations.

SARS-CoV-2 infection fatality risk in a nationwide seroepidemiological study (preprint)

ObjectiveTo estimate the range of the age- and sex-specific infection fatality risk (IFR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on confirmed coronavirus disease 2019 (COVID-19) deaths and excess all-cause deaths. DesignNationwide population-based seroepidemiological study combined with two national surveillance systems. Setting and participantsNon-institutionalized Spanish population of all ages. Main outcome measuresThe range of IFR was calculated as the observed number of COVID-19 deaths and excess deaths divided by the estimated number of SARS-CoV-2 infections in the non-institutionalized Spanish population. Laboratory-confirmed COVID-19 deaths were obtained from the National Epidemiological Surveillance Network (RENAVE) and excess all-cause deaths from the Monitoring Mortality System (MoMo) up to July 15, 2020. SARS-CoV-2 infections were derived from the estimated seroprevalence by a chemiluminiscent microparticle immunoassay for IgG antibodies in 61,092 participants in the ENE-COVID nationwide serosurvey between April 27 and June 22, 2020. ResultsThe overall IFR (95% confidence interval) was 0.8% (0.8% to 0.9%) for confirmed COVID-19 deaths and 1.1% (1.0% to 1.2%) for excess deaths. The IFR ranged between 1.1% (1.0% to 1.2%) and 1.4% (1.3% to 1.5%) in men and between 0.6% (0.5% to 0.6%) and 0.8% (0.7% to 0.8%) in women. The IFR increased sharply after age 50, ranging between 11.6% (8.1% to 16.5%) and 16.4% (11.4% to 23.2%) in men [≥]80 years and between 4.6% (3.4% to 6.3%) and 6.5% (4.7% to 8.8%) in women [≥]80 years. ConclusionThe sharp increase in SARS-CoV-2 IFR after age 50 was more marked in men than in women. Fatality from COVID-19 is substantially greater than that reported for other common respiratory diseases such as seasonal influenza. WHAT IS ALREADY KNOWN ON THIS TOPICInfection fatality risk (IFR) for SARS-CoV-2 is a key indicator for policy decision making, but its magnitude remains under debate. Case fatality risk, which accounts for deaths among confirmed COVID-19 cases, overestimates SARS-CoV-2 fatality as it excludes a large proportion of asymptomatic and mild-symptomatic infections. Population-based seroepidemiological studies are a valuable tool to properly estimate the number of infected individuals, regardless of symptoms. Also, because ascertainment of deaths due to COVID-19 is often incomplete, the calculation of the IFR should be complemented with data on excess all-cause mortality. In addition, data on age- and sex-specific IFR are scarce, even though age and sex are well known modifiers of the clinical evolution of COVID-19. WHAT THIS STUDY ADDSUsing the ENE-COVID nationwide serosurvey and two national surveillance systems in Spain, this study provides a range of age- and sex-specific IFR estimates for SARS-CoV-2 based on laboratory-confirmed COVID-19 deaths and excess all-cause deaths. The risk of death was very low among infected individuals younger than 50 years, but it increased sharply with age, particularly among men. In the oldest age group ([≥]80 years), it was estimated that 12% to 16% of infected men and 5% to 6% of infected women died during the first epidemic wave.

Lockdown measures and relative changes in the age-specific incidence of SARS-CoV-2 in Spain (preprint)

BackgroundThe first months of the SARS-CoV-2 epidemic in Spain resulted in high incidence and mortality. A national sero-epidemiological survey suggests higher cumulative incidence of infection in older individuals than in younger individuals. However, little is known about the epidemic dynamics in different age groups, including the relative effect of the lockdown measures introduced on March 15, and strengthened on March 30 to April 14, 2020 when only essential workers continued to work. MethodsWe used data from the National Epidemiological Surveillance Network (RENAVE in Spanish) on the daily number of reported COVID-19 cases (by date of symptom onset) in eleven 5-year age groups: 15-19y through 65-69y. For each age group g, we computed the proportion E(g) of individuals in age group g among all reported cases aged 15-69y during the pre-lockdown period (March 1-10, 2020) and the corresponding proportion L(g) during two lockdown periods (March 25-April 3 and April 8-17, 2020). For each lockdown period, we computed the proportion ratios PR(g)= L(g)/E(g). For each pair of age groups g1,g2, PR(g1)>PR(g2) implies a relative increase in the incidence of detected SARS-CoV-2 infection in the age group g1 compared with g2 for the later vs. early period. ResultsFor the first lockdown period, the highest PR values were in age groups 50-54y (PR=1.21; 95% CI: 1.12,1.30) and 55-59y (PR=1.19; 1.11,1.27). For the second lockdown period, the highest PR values were in age groups 15-19y (PR=1.26; 0.95,1.68) and 50-54y (PR=1.20; 1.09,1.31). ConclusionsOur results suggest that different outbreak control measures led to different changes in the relative incidence by age group. During the first lockdown period, when non-essential work was allowed, individuals aged 40-64y, particularly those aged 50-59y presented with higher COVID-19 relative incidence compared to pre-lockdown period, while younger adults/older adolescents (together with persons aged 50-59y) had increased relative incidence during the later, strengthened lockdown. The role of different age groups during the epidemic should be considered when implementing future mitigation efforts.