Background COVID-19 patients can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation (IMV). Since interleukin-6 (IL-6) is a relevant cytokine in ARDS, the blockade of its receptor with Tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective To determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods Retrospective observational study performed in hospitalized patients diagnosed of COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with pre- and post-administration of TCZ. Multivariable logistic and linear regressions, and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio (PaO 2 /FiO 2 ) or mortality. Results One hundred and forty-six patients were studied, predominantly male (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels>30 pg/ml was the best predictor for IMV (OR:7.1; p<0.001). Early administration of TCZ was associated with improvement of oxygenation (PaO 2 /FiO 2 ) in patients with high IL-6 (p=0.048). Patients with high IL-6 not treated with TCZ showed high mortality (HR: 4.6; p=0.003), as well as those with low IL-6 treated with TCZ (HR: 3.6; p=0.016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusion Baseline IL-6>30 pg/ml predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.

Maintenance of genetic distinction in the face of gene flow is an important aspect of the speciation process. Here, we provide a detailed spatial and genetic characterization of a hybrid zone between two subspecies of the European rabbit. We examined patterns of allele frequency change for 22 markers located on the autosomes, X-chromosome, Y-chromosome, and mtDNA in 1078 individuals sampled across the hybrid zone. While some loci revealed extremely wide clines (w>=300 km) relative to an estimated dispersal of 1.95–4.22 km/generation, others showed abrupt transitions (w ≈ 10 km), indicating localized genomic regions of strong selection against introgression. The subset of loci showing steep clines had largely coincident centers and stepped changes in allele frequency that did not co-localize with any physical barrier or ecotone, suggesting that the rabbit hybrid zone is a tension zone. The steepest clines were for X and Y chromosome markers. Our results are consistent with previous inference based on DNA sequence variation of individuals sampled in allopatry in suggesting that a large proportion of each genome has escaped the overall barrier to gene flow in the middle of the hybrid zone. These results imply an old history of hybridization and high effective gene flow, and anticipate that isolation factors should often localize to small genomic regions.

Population units that merit separate management and are of conservation concern have been called evolutionary significant units. Two divergent lineages of the European rabbit Oryctolagus cuniculus occur naturally in Spain, with a well-marked geographical distribution. We analysed the frequency and importance of rabbit translocations in central-southern Spain and whether this practice, carried out by hunters and conservationists, could cause the mixture of two clearly different evolutionary significant units. We carried out interviews in 1993 and 2002 at 60 locations to determine the presence and intensity of translocations during both decades. The distribution of the lineages was obtained using mtDNA analysis of hunted rabbits in 2003-2005. We demonstrate that rabbit translocation was used frequently in the 1980s and increased in the 1990s. Up to 43% of the studied areas translocated rabbits in the latter decade, whereas only 25% did so in the 1980s. Our results show that neither the origin of the introduced rabbits nor their genetic lineage were taken into account in most of the translocations. We found rabbits of lineage A in several localities within the distribution area of lineage B, and vice versa, probably as a consequence of translocations. The distribution of both lineages is likely to have been altered by human activity and this could represent the loss of the results of 2 million years of genetic differentiation with possible attendent ecological consequences. Consequently, authorities should more closely regulate rabbit translocations and convey to both hunters and conservationists the importance of not mixing the lineages by translocations.

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COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48–72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50–60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8–22.6] for Roche, OR 10.3 [3.6–29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13–23.57] for TFS viremia and HR = 7.09 [3.3–14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.