[Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination]. / Gravedad comparativa de los casos de COVID-19 causados por las variantes Alfa, Delta u Ómicron de SARS-CoV-2 y su asociación con la vacunación.

BACKGROUND: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. METHODS: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted Odds Ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. RESULTS: We included 5,345 Alpha and 11,974 Delta infections in June-July and, 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years. CONCLUSION: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.

Gravedad comparativa de los casos de COVID-19 causados por las variantes Alfa, Delta u Ómicron de SARS-CoV-2 y su asociación con la vacunación Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination

Introducción: El objetivo es comprar la gravedad de las infecciones por las variantes Alfa, Delta y Ómicron del SARS-CoV-2 en periodos de co-circulación en España, y estimar la asociación entre vacunación y gravedad en cada variante. Métodos: Las infecciones por SARS-CoV-2 notificadas a la red nacional de vigilancia epidemiológica con información sobre la variante viral y el estado de vacunación se clasificaron como casos si habían requerido hospitalización, o como controles en caso contrario. Alfa y Delta se compararon durante Junio-Julio de 2021;y Delta y Ómicron durante Diciembre 2021-Enero 2022. Se estimaron Odds Ratios ajustadas (ORa) mediante regresión logística, comparando la variante y el estado de vacunación entre casos y controles. Resultados: Se incluyeron 5,345 infecciones por variante Alfa y 11,974 por Delta en Junio-Julio y 5,272 infecciones por Delta y 10,578 por Ómicron en Diciembre-Enero. Los casos no vacunados por Alfa (aOR: 0.57;95% CI: 0.46-0.69) u Ómicron (0.28;0.21-0.36) tuvieron menor probabilidad de hospitalización comparado con Delta. La vacunación completa se asoció a menor hospitalización de forma similar para Alfa (0.16;0.13-0.21) y Delta (Junio-Julio: 0.16;0.14-0.19;Diciembre-Enero: 0.36;0.30-0.44) pero menor para Ómicron (0.63;0.53-0.75) y para individuos con 65+ años. Conclusion: Los resultados indican una mayor gravedad intrínseca de la variante Delta comparada con Alfa u Ómicron, con menor diferencia entre personas vacunadas. La vacunación se asoció a menor hospitalización en todos los grupos.

Effectiveness of non-pharmaceutical interventions in nine fields of activity to decrease SARS-CoV-2 transmission (Spain, September 2020 - May 2021) (preprint)

Background We estimated the association between the level of restriction in nine different fields of activity and SARS-CoV-2 transmissibility in Spain, from 15 September 2020 to 9 May 2021.Methods A stringency index (0 to 1) was created for mobility, social distancing, commerce, indoor and outdoor bars and restaurants, culture and leisure, worship and ceremonies, indoor and outdoor sports, for each Spanish province (n = 50) daily. The logarithmic return (LR) of the weekly percentage variation of the 7-days COVID-19 cumulative incidence was used to measure COVID-19 transmission, lagged 12 days behind the stringency index. A hierarchical multiplicative model was fitted, and the median of coefficients across provinces (with 95% bootstrap confidence intervals) was used to quantify the effect of increasing one standard deviation (1SD) in the stringency index in each field.Results Highest levels of restriction were seen in mobility, sports and restaurants, particularly indoors. The increase in restrictions overall reduced SARS-CoV-2 transmission by 22% (RR = 0.78; one-sided 95%CI: 0,0.82) in one week, with highest effects for culture and leisure 14% (0.86; 0,0.98), social distancing 13% (0.87; 0,0.95), indoor restaurants 10% (0.90; 0,0.95) and indoor sports 6% (0.94; 0,0.98). In a reduced model with seven fields, culture and leisure no longer had a significant effect while ceremonies decreased transmission by 5% (0.95; 0,0.96). Models R2 was around 70%.Conclusion Increased restrictions decreased COVID-19 transmission. Limitations include remaining collinearity between fields, and somewhat artificial quantification of qualitative restrictions, so the exact attribution of the effect to specific areas must be done with caution.

Direct and indirect effectiveness of mRNA vaccination against SARS-CoV-2 infection in long-term care facilities in Spain (preprint)

Objectives: To estimate indirect and total (direct plus indirect) effects of COVID-19 vaccination in residents in long-term care facilities (LTCF). Design: Registries-based cohort study including all residents in LTCF 65 years or older offered vaccination between 27 December 2020 and 10 March 2021. Risk of SARS-CoV-2 infection following vaccination was compared with the risk in the same individuals in a period before vaccination. Risk in non-vaccinated was also compared to a period before the vaccination programme to estimate indirect protection. Standardized cumulative risk was computed adjusted by previous documented infection (before the start of follow-up) and daily-varying SARS-CoV-2 incidence and reproductive number. Participants: 573,533 records of 299,209 individuals in the National vaccination registry were selected; 99.0% had received at least 1 vaccine-dos, 99.8% was Pfizer/BioNTech (BNT162b2). Residents mean age was 85.9, 70.9% were females. A previous SARS-CoV-2 infection was found in around 25% and 13% of participants, respectively, at the time of vaccine offer and in the reference period. Main outcome measures: Documented SARS-CoV-2 infection identified in the National COVID-19 laboratory registry. Results: Total VE was 57.2% (95% Confidence Interval: 56.1%-58.3%), and was highest starting 28 days after the first vaccine-dose (proxy of more than 7 days after the second dose) and for individuals naive to SARS-CoV-2 [81.8% (81.0%-82.7%)] compared to those with previous infection [56.8% (47.1%-67.7%)]. Vaccination prevented up to 9.6 (9.3-9.9) cases per 10.000 vaccinated per day; 11.6 (11.3-11.9) if naive vs. 0.8 (0.5-1.0) if previous infection. Indirect protection in the non-vaccinated could only be estimated for naive individuals, at 81.4% (73.3%-90.3%) and up to 12.8 (9.4-16.2) infections prevented per 10.000 indirectly protected per day. Conclusions: Our results confirm the effectiveness of mRNA vaccination in institutionalized elderly population, endorse the policy of universal vaccination in this setting, including in people with previous infection, and suggest that even non-vaccinated individuals benefit from indirect protection.

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.