Explore the vast range of titles available.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the coronavirus strain causing the respiratory pandemic COVID-19 (coronavirus disease 2019). To understand the pathobiology of SARS-CoV-2 in humans it is necessary to unravel the metabolic changes that are produced in the individuals once the infection has taken place. The goal of this work is to provide new information about the altered biomolecule profile and with that the altered biological pathways of patients in different clinical situations due to SARS-CoV-2 infection. This is done via metabolomics using HPLC–QTOF–MS analysis of plasma samples at COVID-diagnose from a total of 145 adult patients, divided into different clinical stages based on their subsequent clinical outcome (25 negative controls (non-COVID); 28 positive patients with asymptomatic disease not requiring hospitalization; 27 positive patients with mild disease defined by a total time in hospital lower than 10 days; 36 positive patients with severe disease defined by a total time in hospital over 20 days and/or admission at the ICU; and 29 positive patients with fatal outcome or deceased). Moreover, follow up samples between 2 and 3 months after hospital discharge were also obtained from the hospitalized patients with mild prognosis. The final goal of this work is to provide biomarkers that can help to better understand how the COVID-19 illness evolves and to predict how a patient could progress based on the metabolites profile of plasma obtained at an early stage of the infection. In the present work, several metabolites were found as potential biomarkers to distinguish between the end-stage and the early-stage (or non-COVID) disease groups. These metabolites are mainly involved in the metabolism of carnitines, ketone bodies, fatty acids, lysophosphatidylcholines/phosphatidylcholines, tryptophan, bile acids and purines, but also omeprazole. In addition, the levels of several of these metabolites decreased to “normal” values at hospital discharge, suggesting some of them as early prognosis biomarkers in COVID-19 at diagnose.

Background and purpose Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza. Methods All consecutive patients who met the definition criteria of influenza‐like illness during the influenza seasons 2010–2011 through 2021–2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage. Results During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020–2021) and 21.69 cases per 1000 patients (season 2017–2018). The prevalence of headache was 66.1% (95% CI = 65.1%–67.1%), varying between 49.6% (season 2021–2022) and 80.1% (season 2010–2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection. Conclusions Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections.

Background: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.

SARS-CoV-2 infection can cause an inflammatory syndrome (COVID-19) leading, in many cases, to bilateral pneumonia, severe dyspnea, and in ~5% of these, death. DNA methylation is known to play an important role in the regulation of the immune processes behind COVID-19 progression, however it has not been studied in depth. In this study, we aim to evaluate the implication of DNA methylation in COVID-19 progression by means of a genome-wide DNA methylation analysis combined with DNA genotyping. The results reveal the existence of epigenomic regulation of functional pathways associated with COVID-19 progression and mediated by genetic loci. We find an environmental trait-related signature that discriminates mild from severe cases and regulates, among other cytokines, IL-6 expression via the transcription factor CEBP. The analyses suggest that an interaction between environmental contribution, genetics, and epigenetics might be playing a role in triggering the cytokine storm described in the most severe cases. Genetic associations with severe COVID-19 have been discovered, but epigenetic associations are not as well described. Here, the authors perform a genome-wide epigenetic analysis of COVID-19 patients, discovering an interaction between environmental exposure, genetics, and epigenetics which might play a role in severe disease.

Smallpox vaccination may confer cross-protection to mpox. We evaluated vaccinia virus antibodies in 162 persons ≥50 years of age in Spain; 68.5% had detectable antibodies. Highest coverage (78%) was among persons 71-80 years of age. Low antibody levels in 31.5% of this population indicates that addressing their vaccination should be a priority.

Background and Objective The clinical relevance of the detection of multiple respiratory viruses in acute bronchiolitis (AB) has not been established. Our goal was to evaluate the effect of viral coinfections on the progression and severity of AB. Methods A retrospective observational study was conducted in a tertiary hospital in Spain from September 2012 to March 2020. Infants admitted for AB with at least one respiratory virus identified by molecular diagnostic techniques were included. A comparison was made between single-virus infections and viral coinfections. The evolution and severity of AB were determined based on the days of hospitalization and admission to the pediatric intensive care unit (PICU). Results Four hundred forty-five patients were included (58.4% male). The median weight was 5.2 kg (IQR 4.2–6.5), and the median age was 2.5 months (IQR 1.4–4.6). A total of 105 patients (23.6%) were admitted to the PICU. Respiratory syncytial virus (RSV) was the most frequent etiological agent (77.1%). A single virus was detected in 270 patients (60.7%), and viral coinfections were detected in 175 (39.3%), of which 126 (28.3%) had two viruses and 49 (11%) had three or more viruses. Hospital length of stay (LOS) increased in proportion to the number of viruses detected, with a median of 6 days (IQR 4–8) for single infections, 7 days (IQR 4–9) for coinfections with two viruses and 8 days (IQR 5–11) for coinfections with ≥ 3 viruses (p = 0.003). The adjusted Cox regression model showed that the detection of ≥ 3 viruses was an independent risk factor for a longer hospital LOS (HR 0.568, 95% CI 0.410–0.785). No significant association was observed between viral coinfections and the need for PICU admission (OR 1.151; 95% CI 0.737–1.797). Conclusions Viral coinfections modified the natural history of AB, prolonging the hospital LOS in proportion to the number of viruses detected without increasing the need for admission to the PICU.

Influenza A viruses (IAV) can infect and replicate in multiple mammalian and avian species. Avian influenza virus (AIV) is a highly contagious viral disease that occurs primarily in poultry and wild water birds. Due to the lack of population immunity in humans and ongoing evolution of AIV, there is a continuing risk that new IAV could emerge and rapidly spread worldwide, causing a pandemic, if the ability to transmit efficiently among humans was gained. The aim of this study is to analyze the basal protection and presence of antibodies against IAV H5N1 and H7N9 subtypes in the population from different ages. Moreover, we have evaluated the humoral response after immunization with a seasonal influenza vaccine. This study is strategically important to evaluate the level of population immunity that is a major factor when assessing the impact that an emerging IAV strain would have, and the role of seasonal vaccines to mitigate the effects of a pandemic.

SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection + vaccination) is affected by the moment of vaccination and number of doses received. We conducted a retrospective study in 746 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(t RI ) between unvaccinated, vaccinated before 6 months, and later; and comparing one, two or three doses (incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan–Meier estimator. Also, an adjusted Cox-regression was performed to evaluate the risk of reinfection in all groups. The t RI was significantly higher in those vaccinated vs. non-vaccinated (p < 0.001). However, an early incomplete regime protects similar time than not receiving a vaccine. Vaccination before 6 months after infection showed a lower t RI compared to those vaccinated later with the same regime (adj-p < 0.001). Actually, early vaccination with complete and booster regimes provided lower length of protection compared to vaccinating later with incomplete and complete regime, respectively. Vaccination with complete and booster regimes significantly increases the t RI (adj-p < 0.001). Vaccination increases the time it takes for a person to become reinfected with SARS-CoV-2. Increasing the time from infection to vaccination increases the time in which a person could be reinfected and reduces the risk of reinfection, especially in complete and booster regimes. Those results emphasize the role of vaccines and boosters during the pandemic and can guide strategies on future vaccination policy.

Background Influenza causes 650,000 deaths, 3–5 million hospitalizations, and 1 billion cases worldwide each year. There is a limited repertoire of antivirals available to tackle this burden, highlighting the risk of developing resistance to current drugs. An effort to develop new influenza antivirals has been made, leading to the approval of baloxavir. Some mutations leading to reduced susceptibility to baloxavir have been reported, but information about their epidemiology is scarce. Thus, we aim to evaluate the prevalence of substitutions in the polymerase acidic (PA) subunit associated with baloxavir susceptibility over 16 epidemiological seasons in Europe. Methods We evaluated 87,266 sequences collected from 2009 to 2025 in Europe, annotated the mutations, and identified all known amino acid substitutions related to changes in baloxavir susceptibility to assess their prevalence. Results A total of 149 (0.2%) sequences with at least one substitution were identified, 81 (0.09%) exhibiting reduced susceptibility. Overall, 17 different substitutions were detected, located both inside and outside baloxavir binding site. The number of substitutions detected ranged from 0 to 15 per season, with E23K, E23R, K34R, A36V, I38F, I38L, and E120D emerging after baloxavir approval in Europe. Double and triple concurrent substitutions were also identified. Conclusion While the prevalence of sequences with substitutions that alter baloxavir susceptibility remains stable, the number of circulating substitutions increases over time. This implies the emergence of amino acid substitutions that did not circulate before and the concurrence of double and triple substitutions that might synergize their individual effects. These results highlight the need for virological surveillance and novel antiviral treatments.

Background Human metapneumovirus (hMPV) is a respiratory pathogen often underestimated in the elderly. Although studies suggest it causes around 10% of respiratory hospitalizations in the United States, national and local data remain scarce. This study aimed to describe patients hospitalized with hMPV and identify risk factors for hospitalization and severe disease. Methods A retrospective study included adults aged ≥ 60 years diagnosed with hMPV infection in two hospitals in Valladolid, Spain, during three consecutive seasons (2021–2024). Data on demographics, comorbidities, clinical presentation, laboratory results and severity parameters were collected. Severe disease was defined as hospital stay ≥ 11 days, ICU admission, need for mechanical ventilation, readmission within 90 days or in‐hospital death. Results Among 703 hMPV‐confirmed cases, 608 required hospitalization, following a clear seasonal epidemic pattern (November–March). The hospitalization rate was 123.2 per 100,000 > 60 years old inhabitants (95% CI: 113.6–133.4), representing 20.5% of respiratory virus detections. Mean hospital stay was 10.5 days; 6.4% of the patients were admitted to ICU, 3.3% required mechanical ventilation, 6.9% died, and 14.0% were readmitted within 90 days. Advanced age (≥ 75 years) increased hospitalization risk threefold to fivefold compared to people between 60 and 74 years old. Co‐infections, particularly bacterial, and living in nursing homes were also associated with a 1.5–2.7 fold higher risk of severe disease and hospitalization. Conclusions hMPV infections pose a significant health burden among the elderly. The findings underscore the need for greater awareness, surveillance, and development of preventive strategies, including vaccination, against hMPV in older adults.