om as , F e r na n d o G on zález Candelas, SeqCOVID-SPAIN consortium, Tanja Stadler & Richard A. NeherThis is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

We study the clinical, management and outcome differences between respiratory syncytial virus (RSV) positive and negative bronchiolitis. A retrospective review of the medical records of children ≤ 2 years of age with acute bronchiolitis between January 1995 and December 2006 was done. There were 2,384 patients hospitalized for acute bronchiolitis, and 1,495 (62.7%) were RSV infections. Overall, hospitalization rate was 55/1,000 admissions. Mortality occurred in 0.08% of cases. Bronchiolitis due to RSV was more frequent from November to March (97%). RSV bronchiolitis had longer hospital stays (6 vs. 5 days, P<0.0001), higher risk of intensive care unit (ICU) admission (OR 2.7; 95%CI 1.87-3.9) and more oxygen use (OR 2.2; 95%CI 1.8-2.6). Infants < 2 months had longer median hospital stay (6 vs. 5 days, P <0.0001) and higher risk of ICU admission (OR 3.4; 95%CI 2.5-4.6). Prematures of < 32 gestational weeks, congenital heart disease, and atelectasis/condensation were the main risk factors for ICU admission in both RSV and non-RSV bronchiolitis. The introduction of palivizumab in prematures diminished hospitalization for RSV bronchiolitis, oxygen need, length of hospital stay and mechanical ventilation. In conclusion, this study supports that RSV bronchiolitis seems to be a more severe disease than that caused by other viruses.

Hand, foot and mouth disease (HFMD) is a childhood illness frequently caused by genotypes belonging to the enterovirus A species, including coxsackievirus (CV)-A16 and enterovirus (EV)-71. Between 2010 and 2012, several outbreaks and sporadic cases of HFMD occurred in different regions of Spain. The objective of the present study was to describe the enterovirus epidemiology associated with HFMD in the country. A total of 80 patients with HFMD or atypical rash were included. Detection and typing of the enteroviruses were performed directly in clinical samples using molecular methods. Enteroviruses were detected in 53 of the patients (66%). CV-A6 was the most frequent genotype, followed by CV-A16 and EV-71, but other minority types were also identified. Interestingly, during almost all of 2010, CV-A16 was the only causative agent of HFMD but by the end of the year and during 2011, CV-A6 became predominant, while CV-A16 was not detected. In 2012, however, both CV-A6 and CV-A16 circulated. EV-71 was associated with HFMD symptoms only in three cases during 2012. All Spanish CV-A6 sequences segregated into one major genetic cluster together with other European and Asian strains isolated between 2008 and 2011, most forming a particular clade. Spanish EV-71 strains belonged to subgenogroup C2, as did most of the European sequences circulated. In conclusion, the recent increase of HFMD cases in Spain and other European countries has been due to a larger incidence of circulating species A enteroviruses, mainly CV-A6 and CV-A16, and the emergence of new genetic variants of these viruses.

Influenza has a major impact on healthcare systems and society, but can be prevented using vaccination. The World Health Organization (WHO) currently recommends that influenza vaccines should include at least two virus A and one virus B lineage (trivalent vaccine; TIV). A new quadrivalent vaccine (QIV), which includes an additional B virus strain, received regulatory approval and is now recommended by several countries. The present study estimates the cost-effectiveness of replacing TIVs with QIV for risk groups and elderly population in Spain. A static, lifetime, multi-cohort Markov model with a one-year cycle time was adapted to assess the costs and health outcomes associated with a switch from TIV to QIV. The model followed a cohort vaccinated each year according to health authority recommendations, for the duration of their lives. National epidemiological data allowed the determination of whether the B strain included in TIVs matched the circulating one. Societal perspective was considered, costs and outcomes were discounted at 3% and one-way and probabilistic sensitivity analyses were performed. Compared to TIVs, QIV reduced more influenza cases and influenza-related complications and deaths during periods of B-mismatch strains in the TIV. The incremental cost-effectiveness ratio (ICER) was 8,748€/quality-adjusted life year (QALY). One-way sensitivity analysis showed mismatch with the B lineage included in the TIV was the main driver for ICER. Probabilistic sensitivity analysis shows ICER below 30,000€/QALY in 96% of simulations. Replacing TIVs with QIV in Spain could improve influenza prevention by avoiding B virus mismatch and provide a cost-effective healthcare intervention.

We report the in vitro antibiotic susceptibility of 1,220 strains belonging to the thermotolerant Campylobacter species, isolated from the feces of pediatric patients with diarrhea in the period from 1987 to 1993. The strains were identified as 1,148 C.jejuni isolates and 72 C. coli isolates. The overall results show that the strains showed drug resistance as follows: 51.8% to ampicillin, 4.4% to clindamycin, 2.6% to chloramphenicol, 21.2% to tetracycline, and 1% to gentamicin. Twenty-one strains (1.7%) displayed resistance to the combination of amoxicillin-clavulanic acid, and 3.2% of the strains were resistant to erythromycin (MIC of .4 ,ug/ml), with a notable diference according to the species under consideration. While C. jejuni remained stable at 0.9 to 4% resistance to erythromycin, for C. coli the percentages detected ranged from 0 to 33%, with overall rates of 2.5 and 15.2% for the two species, respectively. Resistance to nalidixic acid (MIC of .32 ,ug/ml) was found in 27.2% of the strains (27.8% for C. jejuni and 18% for C. col), and resistance to ciprofloxacin (MIC of .4 ,Ig/ml) was found in 24.2% of the strains for C. jejuni and 15.2% for C. coli). Cross-resistance between nalidixic acid and ciprofloxacin was found in 89.1% of the strains (type 1 mutants), while 10.9% were resistant to nalidixic acid but susceptible to ciprofloxacin (type 2 mutants).