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The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02-0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56-0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5-0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07-1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97-1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95-1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19., (© 2024. The Author(s).)

Long-COVID (LC) is characterised by persistent symptoms for at least 3 months after acute infection. A dysregulation of the immune system and a persistent hyperinflammatory state may cause LC. LC patients present differences in activation and exhaustion states of innate and adaptive compartments. Different T CD4 + cell subsets can be identified by differential expression of chemokine receptors (CCR). However, changes in T cells with expression of CCRs such as CCR6 and CXCR3 and their relationship with CD8 + T cells remains unexplored in LC. Here, we performed unsupervised analysis and found CCR6 + CD4 + subpopulations enriched in COVID-19 convalescent individuals upon activation with SARS-CoV-2 peptides. SARS-CoV-2 specific CCR6 + CD4 + are decreased in LC patients, whereas CXCR3 + CCR6 - and CCR4 + CCR6 - CD4 + T cells are increased. LC patients showed lower IFN-γ-secreting CD8 + T cells after stimulation with SARS-CoV-2 Spike protein. This work underscores the role of CCR6 in the pathophysiology of LC., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity., Materials and Methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed., Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 ( HMOX1 ; T/T genotype OR 9.9 p  < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p  = 0.04 and T/T genotype OR 12.9, p  < 0.0001), and rs713400 (eQTL for TMPRSS2 ; C/T + T/T genotype OR 1.86, p  = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 ( CD69 ; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p  = 0.01), rs2660 ( OAS1 ; A/G genotype OR 0.6, p  = 0.08), rs896 ( VIPR1 ; T/T genotype OR 0.4, p  = 0.02) and rs33980500 ( TRAF3IP2 ; C/T + T/T genotype OR 0.3, p  = 0.01) were associated with lower risk of viremia., Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population., Competing Interests: FA, has been consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Aptatargets, Chemo, FAES, Farmalíder, Ferrer, Galenicum, GlaxoSmithKline, Gilead, Italfarmaco, Janssen-Cilag, Kern, Normon, Novartis, Servier, Teva and Zambon. IG-Á reports grants from Instituto de Salud Carlos III, during the course of the study; personal fees from Lilly and Sanofi; personal fees and non-financial support from BMS; personal fees and non-financial support from Abbvie; research support, personal fees and non-financial support from Roche Laboratories; research support from Gebro Pharma; non-financial support from MSD, Pfizer and Novartis, not related to the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Roy-Vallejo, Fernández de Córdoba-Oñate, Delgado-Wicke, Triguero-Martínez, Montes, Carracedo-Rodríguez, Zurita-Cruz, Marcos-Jiménez, Lamana, Galván-Román, Villapalos García, Zubiaur, Ciudad, Rabes, Sanz, Rodríguez, Villa, Rodríguez, Marcos, Hernando, Díaz-Fernández, Abad, de los Santos, Rodríguez Serrano, García-Vicuña, Suárez Fernández, P. Gomariz, Muñoz-Calleja, Fernández-Ruiz, González-Álvaro Cardeñoso and the PREDINMUN-COVID Group.)

Objective: To study the respiratory patterns and the hemodynamic variations related to postural changes in inpatients with coronavirus disease (COVID-19)., Methods: This report is a prospective study in a cohort of inpatients admitted with COVID-19. We recruited 10 patients admitted to the hospital with moderate or severe COVID-19 who showed improvement in oxygen saturation with prone positioning. We performed cardiorespiratory polygraphy and hemodynamic evaluations by thoracic electrical bioimpedance., Results: We observed a median minimum oxygen saturation of 85.00% (IQR: 7.00) in the supine position versus 91.00% (IQR: 8.00) ( P = 0.173) in the prone position. The airflow restriction in the supine position was 2.70% (IQR: 6.55) versus 1.55% (IQR: 2.80) ( P = 0.383) in the prone position. A total of 36.4% of patients were classified as having a normo-hemodynamic state in the supine position, whereas 54.5% were classified in this group in the prone position ( P = 0.668). A decrease in vascular resistance was observed in the prone position (18.2% of vasoconstriction) compared to the supine position (36.4% of vasoconstriction) ( P = 0.871)., Conclusion: This brief report describes the effects of prone positioning on respiratory and hemodynamic variables in 10 patients with moderate or severe COVID-19.

Background and Objective: Clinical ethics consultation services (CEC) have arisen from Healthcare Ethics Committees (HEC) to address ethical conflicts in real-time. Our aim was to determine the perception of usefulness of a CEC service among healthcare workers one year after its creation as well as to assess changes in trends in the use of the CEC and HEC between 2015 and 2021., Materials and Methods: This observational, cross-sectional study was based on a standardized survey of healthcare workers at an urban tertiary care hospital. The results were also compared to those from an identical survey conducted in the same population in 2015., Results: A total of 213 professionals participated (mean age 44 ± 11 years, 69% women). The professionals were more familiar with the HEC than the CEC service (94% vs 61%; p < 0.001). Forty-five individuals (21%) had consulted the CEC since its implementation; 95% of them found the consultation useful. Physicians knew about and used the CEC more than other groups of professionals. The degree of knowledge of the HEC increased significantly by 2021 compared to 2015 (94% v. 76%; p < 0.001). Some areas for improvement identified were the need for greater dissemination of the service, guaranteeing institutional resources to maintain the service, and encouraging greater participation from different professional groups., Conclusions: Knowledge of the institutional HEC and CEC services has increased in recent years among healthcare workers, who considered the CEC service to be useful for addressing ethical conflicts in daily practice., (Copyright © 2022 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

To describe congenital and acquired heart diseases in a Spanish cohort of adults with Down syndrome (DS), which could inform potential health recommendations for this population. Cross-sectional, observational study of adults with DS evaluated consecutively at a tertiary care, outpatient center between January 1 and December 31, 2019. The study population comprised 937 patients (51.8% men; median [IQR] age, 42 [18] years). An echocardiogram was available in the clinical chart of 420 patients (44.8%). The diagnosis of any form of heart disease was confirmed in 211 patients (22.5%): 101 (10.8%) had congenital heart defects, 80 (8.5%) simultaneous congenital and valvular heart diseases, and 30 (3.2%) isolated valvular heart disease. 111 patients (52.6% of those with congenital or valvular heart disease) had received corrective cardiac surgery. A total of 65 individuals were receiving medical management alone (30.8%), while 35 did not require any treatment because their cardiac disease was mild (16.6%). We found a high overall prevalence of heart disease in patients with DS, higher than previously reported for the pediatric population. Management of cardiovascular disease in adults with DS differs from that of the general population and should include universal echocardiography-based screening., (© 2022. The Author(s).)

Introduction: Clinical ethics consultation services (CEC) are useful model for ethical counselling, albeit with scarce implementation in European countries. This article shares the experience of one of the first ethics consultation services in Spain., Materials and Methods: This work is a retrospective, observational study of all consultations received by the CEC service at La Princesa University Hospital (Madrid, Spain) from September 1, 2019 to August 31, 2021. The demographic, logistic, and ethical variables of the cases were analyzed., Results: A total of 63 cases were analyzed in which a total of 124 ethical conflicts were identified. Forty-one percent of the cases (n = 26) were emergency consultations and 38% (n = 24) were preferential inquiries. An initial evaluation was performed with 24 h in 50 cases (79%). The department that consulted most often was the Intensive Care Unit (9; 14%). The preferred contact methods were via pager (36; 57%), the electronic medical record system (13; 21%), or direct conversations with consulting team (7; 11%). The most common ethical conflicts were those related to the adequacy of treatment measures (24; 19%), refusal of treatment (19; 15%), communication with the patient or his/her family (29; 23%), or the patient's capacity (13; 11%)., Conclusion: CEC services provide quick, efficient assistance for resolving ethical problems in daily practice. Their implementation in Spain is feasible., (Copyright © 2022 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Among patients affected by the virus COVID-19, physicians have observed ventilation disorders. It is relevant to assess neurological involvement, including the role of diaphragmatic function. Its possible impairment could be related to the systemic inflammatory response and disease progression that both typify COVID-19 infection. We distinguished two groups (severe group (SG) and mild group (MG)) according to the severity of respiratory symptomatology. We performed neurophysiological and sonography studies to evaluate the diaphragmatic function. Regarding the sonography variables, we identified statistically significant differences in the right mean diaphragmatic thickness along with the expiration, showing 1.56 mm (SEM: 0.11) in the SG vs 1.92 mm (SEM: 0.19) in the MG (p = 0.042). The contractibility of both hemidiaphragms was 15% lower in the severe group, though this difference is not statistically significant. In our examination of the neurophysiological variables, in the amplitude responses, we observed a greater difference between responses from both phrenic nerves as follows: the raw differences in amplitude were 0.40 μV (SEM: 0.14) in the SG vs 0.35 μV (SEM: 0.19) in the MG and the percentage difference was 25.92% (SEM: 7.22) in the SG vs 16.28% (SEM: 4.38%) in the MG. Although diaphragmatic dysfunction is difficult to detect, our combined functional and morphological approach with phrenic electroneurograms and chest ultrasounds could improve diagnostic sensitivity. We suggest that diaphragmatic dysfunction could play a relevant role in respiratory disturbance in hospitalised patients with severe COVID-19.

Background: Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort., Methods: Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata., Results: A total of 57 patients were recruited, with median age of 63 years (IQR [53-81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age., Conclusion: In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Roy-Vallejo, Cardeñoso, Triguero-Martínez, Chicot Llano, Zurita, Ávalos, Barrios, Hernando, Ortiz, Rodríguez-García, Ciudad Sañudo, Marcos, García Castillo, Fontán García-Rodrigo, González, Méndez, Iturrate, Sanz-García, Villa, Sánchez-Azofra, Quicios, Arribas, Álvarez Rodríguez, Patiño, Trigueros, Uriarte, Martín-Ramírez, Arévalo Román, Galván-Román, García-Vicuña, Ancochea, Muñoz-Calleja, Fernández-Ruiz, de la Cámara, Suárez Fernández, González-Álvaro, Rodríguez-Serrano and the PREDINMUN-COVID Group.)

Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a signature of 15 dysregulated miRNAs between COVID-19 and CAP patients. Additionally, multivariate analysis displayed a combination of 4 miRNAs (miR-106b-5p, miR-221-3p, miR-25-3p and miR-30a-5p) that significantly discriminated between both pathologies. Search for targets of these miRNAs, combined with plasma protein measurements, identified a differential cytokine signature between COVID-19 and CAP that included EGFR, CXCL12 and IL-10. Significant differences were also detected in plasma levels of CXCL12, IL-17, TIMP-2 and IL-21R between mild and severe COVID-19 patients. These findings provide new insights into the etiopathological mechanisms underlying COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martínez-Fleta, Vera-Tomé, Jiménez-Fernández, Requena, Roy-Vallejo, Sanz-García, Lozano-Prieto, López-Sanz, Vara, Lancho-Sánchez, Martín-Gayo, Muñoz-Calleja, Alfranca, González-Álvaro, Galván-Román, Aspa, de la Fuente and Sánchez-Madrid.)