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

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 vaccine effectiveness (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 sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta).The data of the study was originally collectedas part of the following projects run by the European Centre for Disease Prevention and Control:“Establishing Severe Acute Respiratory Infections (SARI) surveillance and performing hospital-based COVID-19 transmission studies”, “Developing an infrastructure and performing vaccine effectiveness studies for COVID-19 vaccines in the EU/EEA”, and the “Vaccine Effectiveness, Burden and Impact Studies(VEBIS) of COVID-19 and Influenza".S

multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021

Funding Information: This project received funding from the European Centre for Disease Prevention and Control (ECDC) under the contract ECD.11486. Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673. Publisher Copyright: © 2022 European Centre for Disease Prevention and Control (ECDC). All rights reserved.Introduction: In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. Aim: Using a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection. Methods: Individuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination. Results: Overall VE was 74% (95% CI: 69-79), 76% (95% CI: 71-80), 63% (95% CI: 48-75) and 63% (95% CI: 16-83) among those aged 30-44, 45-59, 60-74 and ≥ 75 years, respectively. VE among those aged 30-59 years was 78% (95% CI: 75-81), 66% (95% CI: 58-73), 91% (95% CI: 87-94) and 52% (95% CI: 40-61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52-77), 65% (95% CI: 48-76) and 83% (95% CI: 64-92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30-59 years was 87% (95% CI: 83-89) at 14-29 days and 65% (95% CI: 56-71%) at ≥ 90 days between vaccination and onset of symptoms. Conclusions: VE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.publishersversionpublishe

Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021

I-MOVE-COVID-19 primary care study team (in addition to authors above): Nick Andrews, Jamie Lopez Bernal, Heather Whitaker, Caroline Guerrisi, Titouan Launay, Shirley Masse, Sylvie van der Werf, Vincent Enouf, John Cuddihy, Adele McKenna, Michael Joyce, Cillian de Gascun, Joanne Moran, Ana Miqueleiz, Ana Navascués, Camino Trobajo-Sanmartín, Carmen Ezpeleta, Paula López Moreno, Javier Gorricho, Eva Ardanaz, Fernando Baigorria, Aurelio Barricarte, Enrique de la Cruz, Nerea Egüés, Manuel García Cenoz, Marcela Guevara, Conchi Moreno-Iribas, Carmen Sayón, Verónica Gomez, Baltazar Nunes, Rita Roquete, Adriana Silva, Aryse Melo, Inês Costa, Nuno Verdasca, Patrícia Conde, Diogo FP Marques, Anna Molesworth, Leanne Quinn, Miranda Leyton, Selin Campbell, Janine Thoulass, Jim McMenamin, Ana Martínez Mateo, Luca Basile, Daniel Castrillejo, Carmen Quiñones Rubio, Concepción Delgado-Sanz, Jesús Oliva.The I-MOVE-COVID-19 network collates epidemiological and clinical information on patients with coronavirus disease (COVID-19), including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virological characterisation in 11 European countries [1]. One component of I-MOVE-COVID-19 is the multicentre vaccine effectiveness (VE) study at primary care/outpatient level in nine European study sites in eight countries. We measured overall and product-specific COVID-19 VE against symptomatic SARS-CoV-2 infection among those aged 65 years and older. We also measured VE by time since vaccination.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673.info:eu-repo/semantics/publishedVersio

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021

Members of the I-MOVE-COVID-19 and VEBIS hospital study teams (in addition to the named authors): Svjetlana Karabuva, Petra Tomaš Petrić, Marija Marković, Sandra Ljubičić, Bojana Mahmutović, Irena Tabain, Petra Smoljo, Iva Pem Novosel, Tanya Melillo, John Paul Cauchi, Benédicte Lissoir, Xavier Holemans, Marc Hainaut, Nicolas Dauby, Benedicte Delaere, Marc Bourgeois, Evelyn Petit, Marijke Reynders, Door Jouck, Koen Magerman, Marieke Bleyen, Melissa Vermeulen, Sébastien Fierens, François Dufrasne, Siel Daelemans, Ala’a Al Kerwi, Francoise Berthet, Guy Fagherazzi, Myriam Alexandre, Charlene Bennett, Jim Christle, Jeff Connell, Peter Doran, Laura Feeney, Binita Maharjan, Sinead McDermott, Rosa McNamara, Nadra Nurdin, Salif Mamadou Cissé, Anne-Sophie L'Honneur, Xavier Duval, Yolande Costa, Fidouh Nadhira, Florence Galtier, Laura Crantelle, Vincent Foulongne, Phillipe Vanhems, Sélilah Amour, Bruno Lina, Fabrice Lainé, Laetitia Gallais, Gisèle Lagathu, Anna Maisa, Yacine Saidi, Christine Durier, Rebecca Bauer, Ana Paula Rodrigues, Adriana Silva, Raquel Guiomar, Margarida Tavares, Débora Pereira, Maria José Manata, Heidi Gruner, André Almeida, Paula Pinto, Cristina Bárbara, Itziar Casado, Ana Miqueleiz, Ana Navascués, Camino Trobajo-Sanmartín, Miguel Fernández-Huerta, María Eugenia Portillo, Carmen Ezpeleta, Nerea Egüés, Manuel García Cenoz, Eva Ardanaz, Marcela Guevara, Conchi Moreno-Iribas, Hana Orlíková, Carmen Mihaela Dorobat, Carmen Manciuc, Simin Aysel Florescu, Alexandru Marin, Sorin Dinu, Catalina Pascu, Alina Ivanciuc, Iulia Bistriceanu, Mihaela Oprea, Maria Elena Mihai, Silke Buda, Ute Preuss, Marianne Wedde, Auksė Mickienė, Giedrė Gefenaitė, Alain Moren, Anthony NardoneIntroduction: Two large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021. Aim: We aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March–June)- and Delta (June–December)-dominant periods, 2021. Methods: Forty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case–control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset. Results: We included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69–92) overall and 75% (95% CI: 42–90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18–74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57–98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90–179 days before onset. Conclusions: Our results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.Key public health message: - What did you want to address in this study? To understand how well the COVID-19 vaccine was performing in Europe against hospitalisation during SARS-CoV-2 Alpha and Delta variant periods, we present vaccine effectiveness results from a multi-country study of complete and booster dose COVID-19 vaccination among adults (aged 20 years and over). - What have we learnt from this study? Between March and June 2021 (Alpha period), vaccine effectiveness against hospitalisation with laboratory-confirmed SARS-CoV-2 was 43% for partial vaccination and 86% for complete vaccination. For June to December 2021 (Delta period), vaccine effectiveness for complete vaccination was lower (52%) but with addition of an mRNA booster dose, effectiveness reached 91%, and remained > 90% up to 119 days after the booster dose. - What are the implications of your findings for public health? In Europe in 2021, COVID-19 vaccine effectiveness results for the Alpha period indicated an excellent benefit for preventing hospitalisation after complete vaccination. During Delta variant circulation, however, a booster dose was required to achieve this level of effectiveness, and this was maintained for up to 4 months post booster.info:eu-repo/semantics/publishedVersio

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022

Introduction: The I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021. Aim: We aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period). Methods: In both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition. Results: We included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively. Conclusions: Our results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.Key public health message: 1. What did you want to address in this study? In order to understand how well the COVID-19 vaccine is performing in Europe against hospitalisation during the period when the SARS-CoV-2 Omicron variant was circulating, we investigated vaccine effectiveness using data from a multi-country study of complete and booster-dose COVID-19 vaccination among adults aged 20 years and over. 2. What have we learnt from this study? Between December 2021 and July 2022, vaccine effectiveness against hospitalisation with laboratory-confirmed SARS-CoV-2 was 43% for complete vaccination. With addition of an mRNA booster dose, effectiveness was 59% overall. It was higher when onset of illness was close to the date of the last vaccination, at 85% when last booster dose was 14–59 days before onset, at 70% for 60–119 days, and falling below 40% for 120–179 days. 3. What are the implications of your findings for public health? In European hospital settings in 2022, during the Omicron period, COVID-19 mRNA booster vaccine provided an improved benefit for preventing hospitalisation, particularly if disease onset was within 4 months of receiving the booster dose.info:eu-repo/semantics/publishedVersio

Qué debemos esperar en la próxima temporada de gripe

Artículo de divulgación publicado en The Conversation España el día 25/10/2021.La temporada gripal que acaba de comenzar deberá ser analizada detenidamente por lo diferente y excepcional, si se compara con temporadas epidémicas gripales anteriores.N

Comparison of real-time RT-PCR, shell vial culture, and conventional cell culture for the detection of the pandemic influenza A (H1N1) in hospitalized patients

The emergence of the pandemic influenza virus A H1N1 has made fast and accurate diagnosis essential. However, few well-validated diagnostic techniques exist. The real-time RT-PCR developed by the Centers for Disease Control and Prevention (CDC) is the recommended technique. Our objective was to compare the CDC real-time RT-PCR assay, shell vial (SV), and conventional cell culture [with Madine-Darby canine kidney (MDCK) cells and A549] for the detection of pandemic influenza A H1N1 in hospitalized patients. We performed a prospective study comparing the efficacy of 5 diagnostic techniques (RTPCR, SV in A549, SV in MDCK, conventional cell culture in A549, and conventional cell culture in MDCK) using nasopharyngeal swabs from patients ≥18 years of age hospitalized with clinical symptoms of influenza at our institution. Detection of the virus by conventional culture was considered the gold standard. An "extended gold standard" was also used to recalculate validity values. The sensitivities, specificities, positive predictive values, and negative predictive values (NPVs) for the detection of influenza A H1N1, determined using conventional culture as the gold standard, were, respectively, as follows: RT-PCR: 95.6, 82.3, 78.3, 96.5%; SVA549: 91.2, 99.01, 98.4, 94.4%; SV-MDCK: 82.3, 100, 100, 89.4%; tube-A549: 94.12, 100, 100, 96.2%; tube-MDCK: 86.7, 100, 100, 91.9%. Sensitivities and NPVs using an extended gold standard were as follows: RT-PCR: 96.5%, 96.6%; SV-A549: 73.3%, 78.5%; SV-MDCK: 65.1%, 73.7%; tube-A549: 74.4%, 79.2%; tube-MDCK: 68.6%, 75.7%. The average time to detect pandemic influenza A H1N1 by RT-PCR, SV culture, and conventional culture was, respectively, 4 h, 48 h, and 7 days. Real-time RT-PCR displayed high sensitivity and specificity for the detection of influenza A H1N1 in adult patients when compared with conventional techniques. In addition, the A549 cell line was not inferior to the MDCK line. © 2011 Elsevier Inc

Rabies in Spain. A Peculiarity in Eurasia

Spain accounts for some natural and political features which have influenced the situation of rabies, making it peculiar in the context of Europe. Dog rabies was eradicated from Spain in 1965 and the European vulpine epizootic was stopped by the French Oral Rabies Vaccination programs (ORVs) and it never crossed the Pyrenees this fact implying the first peculiarity. The possibility of the movement of infected animals from endemic territories in North Africa into the Spanish territories of Ceuta and Melilla by land, causing imported cases regularly is another peculiarity of rabies in Spain. Indeed, the existence of an intense maritime traffic from these endemic territories into the Spanish mainland is another peculiar feature which constitutes a permanent high risk for rabies introduction in Spain. European bat lyssavirus 1 is the most frequently lyssavirus found infecting bats in Spain, as occurs in most European countries. Eptesicus serotinus accounts for more than the 95% of infected bats declared in Europe and are considered the natural reservoir of EBLV-1. However, in the southern half of the Iberian Peninsula, E. serotinus is replaced by the sibling specie Eptesicus isabellinus, which has been found frequently infected by EBLV-1. E. isabellinus is present also in the other side of the Gibraltar Strait along a Mediterranean strip in Northern Africa. This constitutes another peculiarity of rabies in Spain. Finally, a new putative lyssavirus called Lleida Bat Lyssavirus (LLEBV) has been reported from a Miniopterus scheibersii bat from Catalonia. It still remains as another peculiarity of rabies in Spain.Patricia Mingo-Casas was part-funded by a Residencia de Estudiantes (CSIC) Postgraduate Fellowship from Spanish Ministry of Economy and Competitiveness (MINECO). This project was financially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) project MPY 1321/14 and Virginia Sandonís was supported by a contract of the internal research program of the Instituto de Salud Carlos III.S

Circulatory follicular helper T lymphocytes associate with lower incidence of CMV infection in kidney transplant recipients

Primary infection and/or reactivation of cytomegalovirus (CMV) in kidney transplant recipients (KTR) favor rejection and mortality. T follicular helper cells (TFH) could contribute to protection against CMV. Circulatory TFH (cTFH) were studied pretransplant and early posttransplant in 90 CMV seropositive KTR not receiving antithymocyte globulin or antiviral prophylaxis, followed-up for 1 year. Patients who presented CMV infection had significantly lower cTFH and activated cTFH pretransplant and early posttransplant. Pretransplant activated cTFH were also lower within patients who developed CMV disease. Pre- and 14 days posttransplant activated cTFH were an independent protective factor for CMV infection (HR 0.41, p = .01; and 0.52, p = .02, respectively). KTR with low cTFH 7 days posttransplant (<11.9%) had lower CMV infection-free survival than patients with high cTFH (28.2% vs. 67.6%, p = .002). cTFH were associated with CMV-specific neutralizing antibodies (Nabs). In addition, IL-21 increased interferon-γ secretion by CMV-specific CD8+ T cells in healthy controls. Thus, we show an association between cTFH and lower incidence of CMV infection, probably through their cooperation in CMV-specific Nab production and IL-21-mediated enhancement of CD8+ T cell activity. Moreover, monitoring cTFH pre- and early posttransplant could improve CMV risk stratification and help select KTR catalogued at low/intermediate risk who could benefit from prophylaxis

Identification of a Cluster of HIV-1 Controllers Infected with Low Replicating Viruses

<div><p>Long term non-progressor patients (LTNPs) are characterized by the natural control of HIV-1 infection. This control is related to host genetic, immunological and virological factors. In this work, phylogenetic analysis of the proviral nucleotide sequences in <i>env</i> gene from a Spanish HIV-1 LTNPs cohort identified a cluster of 6 HIV-1 controllers infected with closely-related viruses. The patients of the cluster showed common clinical and epidemiological features: drug user practices, infection in the same city (Madrid, Spain) and at the same time (late 70’s-early 80’s). All cluster patients displayed distinct host alleles associated with HIV control. Analysis of the virus envelope nucleotide sequences showed ancestral characteristic, lack of evolution and presence of rare amino-acids. Biological characterization of recombinant viruses with the envelope proteins from the cluster viruses showed very low replicative capacity in TZMbl and U87-CD4/CCR5 cells. The lack of clinical progression in the viral cluster patients with distinct combinations of protective host genotypes, but infected by low replicating viruses, indicate the important role of the virus in the non-progressor phenotype in these patients.</p></div