Value of the Lymphocyte Transformation Test for the Diagnosis of Drug-Induced Hypersensitivity Reactions in Severe Hospitalized COVID-19 Patients (preprint)

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all the cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays of PBMC. We included 5 nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT to at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.

Differential abundance of lipids and metabolites related to SARS- CoV-2 infection and susceptibility (preprint)

Background: The mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why unvaccinated individuals remain uninfected despite high-risk exposures.  Objective: to understand lipid and metabolite profiles related with COVID-19 susceptibility and disease progression. Methods: we collected samples from an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 but not infected (‘non-susceptible’) and subjects who became infected during the follow-up (‘susceptible’), including non-hospitalized and hospitalized patients with different disease severity providing samples at early disease stages. Then, we analyzed their plasma metabolomic profiles using mass spectrometry coupled with liquid and gas chromatography. Results:we show specific lipids profiles and metabolites that could explain SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, non-susceptible individuals show a unique lipidomic pattern characterized by the upregulation of most lipids, especially ceramides and sphingomyelin, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. Conclusion: this study strengthens the findings of other researchers about the importance of studying lipid profiles as relevant markers of SARS-CoV-2 pathogenesis.

Lung Ultrasound Score severity cut-off points in COVID-19 pneumonia. A systematic review and validating cohort

Objetivos: Establecer diferentes puntos de corte basados ​​en el Lung Ultrasound Score (LUS) para clasificar la gravedad de la neumonía COVID-19. Métodos: Inicialmente, realizamos una revisión sistemática entre los puntos de corte LUS propuestos previamente. Estos resultados fueron validados por una cohorte prospectiva de un unicéntrica de pacientes adultos con infección confirmada por SARS-CoV-2. Las variables analizadas fueron mala evolución y mortalidad a los 28 días. Resultados: De 510 artículos, se incluyeron 11. Entre los puntos de corte propuestos en los artículos incluidos, solo LUS >15 pudo ser validado para su objetivo original, demostrando también la relación más fuerte con mala evolución (odds ratio [OR] = 3,636, intervalo de confianza [IC] 1.411-9.374). Respecto a nuestra cohorte, se incluyeron 127 pacientes. En estos pacientes, la LUS se asoció estadísticamente con mala evolución (OR = 1,303, IC 1,137-1,493) y con mortalidad a los 28 días (OR = 1,024, IC 1,006-1,042). LUS > 15 mostró el mejor rendimiento diagnóstico al elegir un único punto de corte en nuestra cohorte (área bajo la curva 0,650). LUS ≤7 mostró una alta sensibilidad para descartar mal resultado (0,89, IC 0,695-0,955), mientras que LUS >20 reveló gran especificidad para predecir mala evolución (0,86, IC 0,776-0,917). Conclusiones: LUS es un buen predictor de mala evolución y mortalidad a 28 días en COVID-19. LUS ≤7 se asocia con neumonía leve, LUS 8-20 con neumonía moderada y ≥20 con neumonía grave. Si se utilizara un único punto de corte, LUS > 15 sería el que mejor discriminaría la enfermedad leve de la grave.

Characteristics and clinical outcome in 312 patients with moderate to severe pneumonia due to SARS-COV-2 and hyperinflammation treated with anakinra and corticosteroids: A retrospective cohort study.

OBJECTIVE: To assess the clinical outcome (death and/or Intensive Care Unit (ICU) admission) based on the time from hospital admission to the administration of anakinra and the possible usefulness of a "simplified" SCOPE score to stratify the risk of worse prognosis in our cohort of patients with moderate/severe SARS-CoV-2 pneumonia, both vaccinated and unvaccinated, that received anakinra and corticosteroids. In addition, the clinical, analytical, and imaging characteristics of patients at admission are described. METHODS: Retrospective cohort study of 312 patients admitted to Hospital Clínico San Cecilio in Granada for moderate/severe pneumonia caused by SARS-CoV-2 that received anakinra and corticosteroids between March 2020 and January 2022. Clinical and analytical data were collected as well as the patient outcome at 30 and 60 days after admission. Three treatment groups were established according to the time from hospital admission to administration of anakinra: early (1st-2nd day), intermediate (3rd-5th day), and late (after the 5th day). RESULTS: The median age was 67.4 years (IQR 22-97 years) and 204 (65.4%) were male. The most common comorbidity was hypertension (58%). The median time from the start of symptoms to anakinra administration was 6 days (IQR 5-10) and the SaFi (SaO2/FiO2) was 228 (IQR 71-471). The cure rate was higher in the early-onset anakinra group versus the late-onset group (73% vs 56.6%). The latter had a higher percentage of deaths (27.4%) and a greater number of patients remained hospitalized for a month (16%). On admission, the patients had elevated C-reactive protein (CRP), ferritin, and D-dimer values and decreased total lymphocytes. Analytical improvement was observed at both 72 hours and one month after treatment. 42 (13.5%) required ICU admission, and 23 (7.3%) orotracheal intubation. At 60 days, 221 (70.8%) were discharged, 87 (27.8%) had died and 4 (1.4%) remained hospitalized. The mean dose of anakinra was 1000 mg (100-2600 mg) with differences found between the dose administered and the clinical outcome. There were no differences in the primary outcome based on vaccination. A simplified SCOPE score at the start of anakinra administration was lower in patients with better clinical evolution. CONCLUSIONS: Early treatment with anakinra and corticosteroids was associated with a better outcome regardless of vaccination status. A simplified SCOPE was found to be a good prognostic tool.

Impact of COVID-19 on the Care of Patients With HIV Infection (preprint)

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Methods: Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the “pandemic period” (March 2020 to February 2021) to the “pre-pandemic period” (the equivalent timeframe in 2019) and the “post-pandemic period” (March to September 2021). Results: During the pandemic period, the number of new patients seen at the HIV clinic (116), as well as the requested viral load tests (2414), decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively)(p<0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, 93%, respectively), and the number of hospital admissions among PLWH remained constant. Conclusions: Despite the COVID-19 pandemic impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates and all-cause mortality.

Vino, Turismo y COVID-19: El impacto de la COVID-19 en las Rutas del Vino de España

Diversas investigaciones han abordado el papel jugado por las Rutas del Vino de España para dinamizar la competitividad de un territorio, incrementar la producción vinícola, mejorar la calidad de vida de los ciudadanos y respetar el medioambiente. Sin embargo, hasta donde sabemos, el impacto de la COVI-19 sobre dichas rutas enológicas no ha sido abordado en la literatura académica. Para superar este gap de investigación, el trabajo pretende analizar el impacto del patógeno sobre la oferta y la demanda de las actividades turísticas a través de, por un lado, el análisis de la evolución de las instituciones adheridas a las rutas del vino españolas y, por otro lado, el estudio del impacto económico de las 32 rutas que conforman dicho producto turístico.Alternate : Several studies have addressed the role played by the Spanish Wine Routes in boosting the competitiveness of a territory, increasing wine production, improving the quality of life of citizens and respecting the environment. However, to our knowledge, the impact of COVID-19 on these wine routes has not been addressed in the academic literature. In order to overcome this research gap, this paper aims to analyse the impact of the pathogen on the supply and demand of tourist activities by analysing the evolution of the institution members of the Spanish wine routes and the economic impact of the 32 routes that make up this tourist product.

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with critical COVID-19 (preprint)

Background We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and autoantibodies against type I IFN in another 15-20% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI:1.5-528.7, P=1.1x10-4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2], P=2.1x10-4). Adding the recently reported TYK2 COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4]; P=3.4x10-3). When these 14 loci and TLR7 were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0], P=4.7x10-7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9], P=0.02). Finally, the patients 13 with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10-5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie lifethreatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Assessing the impact of SARS-CoV-2 lineages and mutations on patient survival (preprint)

After more than two years of COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations whose impact on COVID-19 severity and patient survival is uncertain. A total of 764 SARS-CoV-2 genomes sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30st April 2021, along with their clinical data, were used for survival analysis. A significant association of B.1.1.7, the alpha lineage, with patient mortality (Log Hazard ratio LHR=0.51, C.I.=[0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome rendered 27 of them significantly associated with higher mortality of patients. Most of these mutations were located in the S, ORF8 and N proteins. This study illustrates how a combination of genomic and clinical data provide solid evidence on the impact of viral lineage on patient survival.

The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies (preprint)

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

CAN A MACHINE LEARNING ALGORITHM IDENTIFY SARS-COV-2 VARIANTS BASED ON CONVENTIONAL rRT-PCR? PROOF OF CONCEPT (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been and remains one of the major challenges humanity has faced thus far. Over the past few months, large amounts of information have been collected that are only now beginning to be assimilated. In the present work, the existence of residual information in the massive numbers of rRT-PCRs that tested positive out of the almost half a million tests that were performed during the pandemic is investigated. This residual information is believed to be highly related to a pattern in the number of cycles that are necessary to detect positive samples as such. Thus, a database of more than 20,000 positive samples was collected, and two supervised classification algorithms (a support vector machine and a neural network) were trained to temporally locate each sample based solely and exclusively on the number of cycles determined in the rRT-PCR of each individual. Finally, the results obtained from the classification show how the appearance of each wave is coincident with the surge of each of the variants present in the region of Galicia (Spain) during the development of the SARS-CoV-2 pandemic and clearly identified with the classification algorithm.

Compositional analysis of Sindbis virus ribonucleoproteins reveals an extensive co-opting of key nuclear RNA-binding proteins (preprint)

The expansion of tropical mosquito habitats and associated arboviruses is a risk for human health, and it thus becomes fundamental to identify new antiviral strategies. In this study we employ a new approach to elucidate the composition of the ribonucleoproteins (RNPs) of a prototypical arbovirus called Sindbis (SINV). SINV RNPs contain 453 cellular and 6 viral proteins, many of these proteins are nuclear in uninfected cells and redistribute to the cytoplasm upon infection. These findings suggest that SINV RNAs act as spiderwebs, capturing host factors required for viral replication and gene expression in the cytoplasm. Functional perturbation of several of these host proteins causes profound effects in virus infection, as illustrated here with the tRNA ligase complex. Moreover, inhibition of viral RNP components with available drugs hampers the infection of a wide range of viruses, opening new avenues for the development of broad-spectrum therapies. Research highlightsO_LISINV RNA interactome includes 453 cellular and 6 viral proteins. C_LIO_LINuclear RBPs that interact with SINV RNA are selectively redistributed to the cytoplasm upon infection C_LIO_LIThe tRNA ligase complex plays major regulatory roles in SINV and SARS-CoV- 2 replication C_LIO_LIThe SINV RNA interactome is enriched in pan-viral regulators with therapeutic potential. C_LI

Metabolic snapshot of plasma samples reveals new pathways implicated in SARS-CoV-2 pathogenesis (preprint)

Despite of the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking differences in the susceptibility to infection and the risk of severe disease. Here, we used untargeted metabolomics to examine novel metabolic pathways related to SARS-CoV-2 susceptibility and COVID-19 clinical severity using capillary electrophoresis coupled to a time-of-flight mass spectrometer (CE-TOF-MS) in plasma samples. We included 27 patients with confirmed COVID-19 early after symptom onset who were prospectively followed and 29 healthcare workers heavily exposed to SARS-CoV-2 but with low susceptibility to infection ( nonsusceptible). We found that the metabolite profile was predictive of the study group. We identified a total of 55 metabolites as biomarkers of SARS-CoV-2 susceptibility or COVID-19 clinical severity. We report the discovery of new plasma biomarkers for COVID-19 that provide mechanistic explanations for the clinical consequences of SARS-CoV-2, including mitochondrial and liver dysfunction as a consequence of hypoxemia (citrulline, citrate, and BAIBA), energy production and amino acid catabolism (L-glycine, L-alanine, L-serine, L-proline, L-aspartic acid and L-histidine), endothelial dysfunction and thrombosis (citrulline, L-ADMA, 2-AB, and Neu5Ac), and we found interconnections between these pathways. In summary, in this first report of the metabolomic profile of individuals with severe COVID-19 and SARS-CoV-2 susceptibility by CE-MS, we define several metabolic pathways implicated in SARS-CoV-2 susceptibility and COVID-19 clinical progression that could be developed as biomarkers of COVID-19.

Evaluating SARS-CoV-2 infection under tenofovir-based antiviral prophylaxis: a multi-scale modeling analysis upon experimental data (preprint)

Tenofovir has shown promising evidence of improving COVID-19 clinical outcomes in observational studies, still to be confirmed in clinical trials. Disease severity might be reduced under prophylaxis with the prodrug tenofovir disoproxil fumarate (TDF), while the protection seems to decrease, or even to lack, when using the alternative prodrug tenofovir alafenamide fumarate (TAF).  Aiming to understand why TDF-prophylaxis might reduce COVID-19 severity upon infection we developed a multi-scale analysis framework combining  in vitro  susceptibility data, molecular docking, and within-host dynamics modeling, and using remdesivir–the only antiviral approved to date against COVID-19– as a point of reference.First, our docking model predicted that intracellularly active tenofovir diphosphate binds into the SARS-CoV-2 RNA polymerase in the same site as the antiviral remdesivir triphosphate, but presents lower binding energy, likely reducing the overall inhibition of viral replication and making the antiviral efficacy more susceptible to the drug intracellular concentration. Second, using data from  in vitro  viral   cultures with plausible TDF therapeutic concentrations, we estimated that the drug can inhibit SARS-COV-2 replication at an efficacy ranging between 54-99%  conditional to the viral cycle length. Third, assuming values approximating this range of inhibition for  in vivo  viral replication during human SARS-COV-2 infection, we found that prophylaxis with TDF with high penetration into viral target cells is capable of delaying viral replication, mitigating direct cell damage and allowing time for the host to mount the adaptive immunity. Last, we found that the potential antiviral effect can be substantially reduced when TDF is given after infection begins. Our work provides a potential mechanistic explanation of the observed clinical effect of TDF against SARS-CoV-2 infection. The proposed inference framework can help to optimize the evaluation of antiviral therapies for COVID-19, in particular those targeting the RNA dependent RNA polymerase.

Optimal COVID-19 Adapted Table Disposition in Hostelry for Guaranteeing the Social Distance through Memetic Algorithms

The COVID-19 pandemic has challenged all physical interactions. Social distancing, face masks and other rules have reshaped our way of living during the last year. The impact of these measures for indoor establishments, such as education or hostelry businesses, resulted in a considerable organisation problem. Achieving a table distribution inside these indoor spaces that fulfilled the distancing requirements while trying to allocate the maximum number of tables for enduring the pandemic has proved to be a considerable task for multiple establishments. This problem, defined as the Table Location Problem (TLP), is categorised as NP-Hard, thus a metaheuristic resolution is recommended. In our previous works, a Genetic Algorithm (GA) optimisation was proposed for optimising the table distribution in real classrooms. However, the proposed algorithm performed poorly for high obstacle density scenarios, especially when allocating a considerable number of tables due to the existing dependency between adjacent tables in the distance distribution. Therefore, in this paper, we introduce for the first time, to the authors’ best knowledge, a Memetic Algorithm (MA) optimisation that improves the previously designed GA through the introduction of a Gradient Based Local Search. Multiple configurations have been analysed for a real hostelry-related scenario and a comparison between methodologies has been performed. Results show that the proposed MA optimisation obtained adequate solutions that the GA was unable to reach, demonstrating a superior convergence performance and an overall greater flexibility. The MA performance denoted its value not only from a COVID-19 distancing perspective but also as a flexible managing algorithm for daily table arrangement, thus fulfilling the main objectives of this paper.

Siglec-1 on dendritic cells mediates SARS-CoV-2 trans-infection of target cells while on macrophages triggers proinflammatory responses (preprint)

COVID-19 pandemic is not yet under control by vaccination, and effective antivirals are critical for preparedness. Here we report that macrophages and dendritic cells, key antigen presenting myeloid cells (APCs), are largely resistant to SARS-CoV-2 infection. APCs effectively captured viruses within cellular compartments that lead to antigen degradation. Macrophages sense SARS-CoV-2 and released higher levels of cytokines, including those related to cytokine storm in severe COVID-19. The sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169) present on APCs, which interacts with sialylated gangliosides on membranes of retroviruses or filoviruses, also binds SARS-CoV-2 via GM1. Blockage of Siglec-1 receptors by monoclonal antibodies reduces SARS-CoV-2 uptake and transfer to susceptible target cells. APCs expressing Siglec-1 and carrying SARS-CoV-2 are found in pulmonary tissues of non-human primates. Single cell analysis reveals the in vivo induction of cytokines in those macrophages. Targeting Siglec-1 could offer cross-protection against SARS-CoV-2 and other enveloped viruses that exploit APCs for viral dissemination, including those yet to come in future outbreaks.

Sistemas de recuperación de información implementados a partir de CORD-19: herramientas clave en la gestión de la información sobre COVID-19

La investigación sobre el coronavirus ha generado una producción de documentos científicos extraordinaria. Su tratamiento y asimilación por parte de la comunidad científica ha necesitado de la ayuda de sistemas de recuperación de información diseñados específicamente. Algunas de las principales instituciones mundiales dedicadas a la lucha contra la pandemia han desarrollado el conjunto de datos CORD-19 que destaca sobre otros proyectos de similar naturaleza. Los documentos recopilados en esta fuente han sido procesados por distintas herramientas de recuperación de información, a veces prototipos o sistemas que ya estaban implementados. Se ha analizado la tipología y características principales de estos sistemas concluyendo que hay tres grandes categorías no excluyentes entre ellas: búsqueda terminológica, visualización de información y procesamiento de lenguaje natural. Destaca enormemente que la gran mayoría de ellos emplean preferentemente tecnologías de búsqueda semántica con el objeto de facilitar la adquisición de conocimiento s los investigadores y ayudarlas en su ingente tarea. La crisis provocada por la pandemia ha sido aprovechada por los buscadores semánticos para encontrar su sitio.Alternate abstract:Research on the coronavirus has generated an extraordinary production of scientific documents. Their treatment and assimilation by the scientific community has required the help of specifically designed information retrieval systems. Some of the world's leading institutions involved in the fight against the pandemic have developed the CORD-19 dataset that stands out from other projects of a similar nature. The documents collected in this source have been processed by various information retrieval tools, sometimes prototypes or previously implemented systems. The typology and main characteristics of these systems have been analysed, concluding that there are three main non-exclusive categories among them: terminological search, information visualisation and natural language processing. It should be noted that most of them use semantic search technologies in order to facilitate the acquisition of knowledge by researchers and to help them in their enormous task. The crisis caused by the pandemic has been taken advantage of by semantic search engines to find their site.

Players' physical performance in LaLiga across the season: insights for competition continuation after COVID-19.

Due to the COVID-19 outbreak, professional football players competing in LaLiga were confined at home for ~8 weeks and then they were allowed to train to prepare the first competitive match for 4 weeks. As the duration of summer break in the prior four seasons of LaLiga (from 2015-2016 to 2018-2019) was of similar length to the suspension of the championship due to COVID-19 (~12 weeks), we have analysed the running performance of teams competing in LaLiga in these four seasons to anticipate players' physical performance after the resumption of the competition. The analysis includes the average running distance per game for each of the 38 matchdays that compose LaLiga. One-way ANOVA revealed that there was a main effect of the matchday on total running distance per match (p = 0.001), and in the distance covered between 14.0 and 20.9 km/h (p < 0.001), between 21.0 and 23.9 km/h (p < 0.001) and at above 24.0 km/h (p < 0.001). Overall, the post-hoc analysis revealed that the running patterns progressively increased during the first 8-10 matchdays and then reached a plateau which was significantly different to matchday-1 (p < 0.05). This analysis reveals that, in the prior four competitive seasons of LaLiga, players' physical performance was lower at the beginning of the season and the teams needed approximately 8-10 matchdays to reach a steady state running performance. These data suggest that football players will progressively increase their performance across the 11 matchdays remaining to complete LaLiga.

Global analysis of protein-RNA interactions in SARS-CoV-2 infected cells reveals key regulators of infection (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. SARS-CoV-2 relies on cellular RNA-binding proteins (RBPs) to replicate and spread, although which RBPs control SARS-CoV-2 infection remains largely unknown. Here, we employ a multi-omic approach to identify systematically and comprehensively which cellular and viral RBPs are involved in SARS-CoV-2 infection. We reveal that the cellular RNA-bound proteome is remodelled upon SARS-CoV-2 infection, having widespread effects on RNA metabolic pathways, non-canonical RBPs and antiviral factors. Moreover, we apply a new method to identify the proteins that directly interact with viral RNA, uncovering dozens of cellular RBPs and six viral proteins. Amongst them, several components of the tRNA ligase complex, which we show regulate SARS-CoV-2 infection. Furthermore, we discover that available drugs targeting host RBPs that interact with SARS-CoV-2 RNA inhibit infection. Collectively, our results uncover a new universe of host-virus interactions with potential for new antiviral therapies against COVID-19.