Relevance of TMPRSS2, CD163/CD206, and CD33 in clinical severity stratification of COVID-19.

Background: Approximately 13.8% and 6.1% of coronavirus disease 2019 (COVID-19) patients require hospitalization and sometimes intensive care unit (ICU) admission, respectively. There is no biomarker to predict which of these patients will develop an aggressive stage that we could improve their quality of life and healthcare management. Our main goal is to include new markers for the classification of COVID-19 patients. Methods: Two tubes of peripheral blood were collected from a total of 66 (n = 34 mild and n = 32 severe) samples (mean age 52 years). Cytometry analysis was performed using a 15-parameter panel included in the Maxpar® Human Monocyte/Macrophage Phenotyping Panel Kit. Cytometry by time-of-flight mass spectrometry (CyTOF) panel was performed in combination with genetic analysis using TaqMan® probes for ACE2 (rs2285666), MX1 (rs469390), and TMPRSS2 (rs2070788) variants. GemStone™ and OMIQ software were used for cytometry analysis. Results: The frequency of CD163+/CD206- population of transitional monocytes (T-Mo) was decreased in the mild group compared to that of the severe one, while T-Mo CD163-/CD206- were increased in the mild group compared to that of the severe one. In addition, we also found differences in CD11b expression in CD14dim monocytes in the severe group, with decreased levels in the female group (p = 0.0412). When comparing mild and severe disease, we also found that CD45- [p = 0.014; odds ratio (OR) = 0.286, 95% CI 0.104-0.787] and CD14dim/CD33+ (p = 0.014; OR = 0.286, 95% CI 0.104-0.787) monocytes were the best options as biomarkers to discriminate between these patient groups. CD33 was also indicated as a good biomarker for patient stratification by the analysis of GemStone™ software. Among genetic markers, we found that G carriers of TMPRSS2 (rs2070788) have an increased risk (p = 0.02; OR = 3.37, 95% CI 1.18-9.60) of severe COVID-19 compared to those with A/A genotype. This strength is further increased when combined with CD45-, T-Mo CD163+/CD206-, and C14dim/CD33+. Conclusions: Here, we report the interesting role of TMPRSS2, CD45-, CD163/CD206, and CD33 in COVID-19 aggressiveness. This strength is reinforced for aggressiveness biomarkers when TMPRSS2 and CD45-, TMPRSS2 and CD163/CD206, and TMPRSS2 and CD14dim/CD33+ are combined.

Association between periodontal diseases and cardiovascular diseases, diabetes and respiratory diseases: Consensus report of the Joint Workshop by the European Federation of Periodontology (EFP) and the European arm of the World Organization of Family Doctors (WONCA Europe).

AIM: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles. MATERIALS AND METHODS: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors. CONCLUSIONS: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated.

The association between respiratory diseases and periodontitis: A systematic review and meta-analysis.

AIM: To evaluate (1) whether periodontitis has an influence on the prevalence/incidence of respiratory diseases (chronic obstructive pulmonary disease [COPD], asthma, community-acquired pneumonia [CAP], obstructive sleep apnoea [OSA] and COVID-19), and (2) what is the impact of periodontal therapy on the onset or progression of respiratory diseases. MATERIALS AND METHODS: An electronic search was performed on Pubmed, Cochrane Library and Scopus databases up to October 2021, to identify studies answering the PECOS and PICOS questions. RESULTS: Seventy-five articles were selected. Meta-analyses identified statistically significant associations of periodontitis with COPD (nstudies  = 12, odds ratio [OR] = 1.28, 95% confidence interval [CI] [1.16; 1.42], p < .001), and OSA (ns  = 6, OR = 1.65, 95% CI [1.21; 2.25], p = .001), but not for asthma (ns  = 9, OR = 1.53, 95% CI [0.82; 2.86], p = .181). For acute conditions, two studies were found for CAP, while for COVID-19, significant associations were found for the need of assisted ventilation (ns  = 2, OR = 6.24, 95% CI [2.78; 13.99], p < .001) and COVID-related mortality (ns  = 3, OR = 2.26, 95% CI [1.36, 3.77], p = .002). Only four intervention studies were found, showing positive effects of periodontal treatment on COPD, asthma and CAP. CONCLUSIONS: A positive association between periodontitis and COPD, OSA and COVID-19 complications has been found, while there is a lack of intervention studies.

An Interplay between Oxidative Stress (Lactate Dehydrogenase) and Inflammation (Anisocytosis) Mediates COVID-19 Severity Defined by Routine Clinical Markers.

Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an involvement in the pathogenesis of the disease. The aim of this research was to study the role of the oxidative stress process assessed through lactate dehydrogenase (LDH) on the severity of COVID-19 measured by oxygen saturation (SaO2) and the putative interaction with inflammation. The investigation enrolled 1808 patients (mean age of 68 and 60% male) with COVID-19 from the HM Hospitals database. To explore interactions, a regression model and mediation analyses were performed. The patients with lower SaO2 presented lymphopenia and higher values of neutrophils-to-lymphocytes ratio and on the anisocytosis coefficient. The regression model showed an interaction between LDH and anisocytosis, suggesting that high levels of LDH (>544 U/L) and an anisocytosis coefficient higher than 10% can impact SaO2 in COVID-19 patients. Moreover, analysis revealed that LDH mediated 41% (p value = 0.001) of the effect of anisocytosis on SaO2 in this cohort. This investigation revealed that the oxidative stress marker LDH and the interaction with anisocytosis have an important role in the severity of COVID-19 infection and should be considered for the management and treatment of the oxidative phenomena concerning this within a precision medicine strategy.

Machine learning insights concerning inflammatory and liver-related risk comorbidities in non-communicable and viral diseases.

The liver is a key organ involved in a wide range of functions, whose damage can lead to chronic liver disease (CLD). CLD accounts for more than two million deaths worldwide, becoming a social and economic burden for most countries. Among the different factors that can cause CLD, alcohol abuse, viruses, drug treatments, and unhealthy dietary patterns top the list. These conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic fibrogenesis. High stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma (HCC). Despite the advances achieved in this field, new approaches are needed for the prevention, diagnosis, treatment, and prognosis of CLD. In this context, the scientific com-munity is using machine learning (ML) algorithms to integrate and process vast amounts of data with unprecedented performance. ML techniques allow the integration of anthropometric, genetic, clinical, biochemical, dietary, lifestyle and omics data, giving new insights to tackle CLD and bringing personalized medicine a step closer. This review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatory-related, hepatitis viruses-induced, and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development.

Potential protective effect against SARS-CoV-2 infection by APOE rs7412 polymorphism.

The pandemic burden caused by the SARS-CoV-2 coronavirus constitutes a global public health emergency. Increasing understanding about predisposing factors to infection and severity is now a priority. Genetic, metabolic, and environmental factors can play a crucial role in the course and clinical outcome of COVID-19. We aimed to investigate the putative relationship between genetic factors associated to obesity, metabolism and lifestyle, and the presence and severity of SARS-CoV-2 infection. A total of 249 volunteers (178 women and 71 men, with mean and ± SD age of 49 ± 11 years) characterized for dietary, lifestyle habits and anthropometry, were studied for presence and severity of COVID-19 infection, and genotyped for 26 genetic variants related to obesity, lipid profile, inflammation, and biorhythm patterns. A statistically significant association was found concerning a protective effect of APOE rs7412 against SARS-CoV-2 infection (p = 0.039; OR 0.216; CI 0.084, 0.557) after correction for multiple comparisons. This protective effect was also ascribed to the APOɛ2 allele (p = 0.001; OR 0.207; CI 0.0796, 0.538). The genetic variant rs7412 resulting in ApoE2, genetic determinant of lipid and lipoprotein levels, could play a significant role protecting against SARS-CoV-2 infection.

A Multicenter Analysis of the Outcome of Cancer Patients with Neutropenia and COVID-19 Optionally Treated with Granulocyte-Colony Stimulating Factor (G-CSF): A Comparative Analysis.

BACKGROUND: Approximately 15% of patients infected by SARS-CoV-2 develop a distress syndrome secondary to a host hyperinflammatory response induced by a cytokine storm. Myelosuppression is associated with a higher risk of infections and mortality. There are data to support methods of management for neutropenia and COVID-19. We present a multicenter experience during the first COVID-19 outbreak in neutropenic cancer patients infected by SARS-CoV-2. METHODS: Clinical retrospective data were collected from neutropenic cancer patients with COVID-19. Comorbidities, tumor type, stage, treatment, neutropenia severity, G-CSF, COVID-19 parameters, and mortality were analyzed. A bivariate analysis of the impact on mortality was carried out. Additionally, we performed a multivariable logistic regression to predict respiratory failure and death. RESULTS: Among the 943 cancer patients screened, 83 patients (11.3%) simultaneously had neutropenia and an infection with COVID-19. The lungs (26%) and breasts (22%) were the primary locations affected, and most patients had advanced disease (67%). In the logistic model, as adjusted covariates, sex, age, treatment (palliative vs. curative), tumor type, and the lowest level of neutrophils were used. A significant effect was obtained for the number of days of G-CSF treatment (OR = 1.4, 95% CI [1,1,03,92], p-value = 0.01). CONCLUSIONS: Our findings suggest that a prolonged G-CSF treatment could be disadvantageous for these cancer patients with infections by COVID-19, with a higher probability of worse outcome.

The Impact of COVID-19 in Collaborative Programming. Understanding the Needs of Undergraduate Computer Science Students

Collaborative learning activities have become a common practice in current university studies due to the implantation of the EHEA. However, the COVID-19 pandemic has led to a radical and abrupt change in the teaching–learning model used in most universities, and in the way students’ group work is carried out. Given this new situation, our interest is focused on discovering how computer science students have approached group programming tasks. For this purpose, we have designed a cross-sectional pilot study to explore, from both social and technological points of view, how students carried out their group programming activities during the shutdown of universities, how they are doing them now, when social distance must be maintained, and what they have missed in both situations. The results of the study indicate that during the imposed confinement, the students adopted a programming model based on work division or distributed peer programming, and very few made use of synchronous distributed collaboration tools. After the lockdown, the students mostly opted for a model based on collaborative programming and there was an increased use of synchronous distributed collaboration tools. The specific communication, synchronization, and coordination functionalities they considered most useful or necessary were also analyzed. Among the desirable features included in a software for synchronous distributed programming, the students considered that having an audio-channel can be very useful and, possibly, the most agile method to communicate. The video signal is not considered as very necessary, being in many cases rather a source of distraction, while textual communication through a chat, to which they are very accustomed, is also well valued. In addition, version control and the possibility of recovering previous states of the practical projects were highly appreciated by the students, and they considered it necessary to record the individual contributions of each member of the team to the result.

Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality.

BACKGROUND AND OBJECTIVES: In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS: The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, Hazard Ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox Regression models. RESULTS: The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS: The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.

ANTECEDENTES Y OBJETIVO: En los últimos meses se han realizado grandes esfuerzos para evaluar las terapias más eficaces en el manejo de pacientes con COVID-19. Actualmente ninguna combinación ha demostrado de manera consistente una relación clara con la mortalidad. Nuestro objetivo fue valorar el patrón de asociaciones observado entre los distintos tratamientos intrahospitalarios administrados a 238 pacientes ingresados por COVID-19 y la mortalidad. MATERIALES Y MÉTODOS: Se analizaron las historias clínicas electrónicas de aquellos pacientes dados de alta o que fallecieron por COVID-19 entre el 16 de marzo y el 10 de abril de 2020 en el Hospital Universitario San Cecilio (Granada, España). Se obtuvo información sobre sexo, edad, comorbilidades al ingreso, parámetros clínicos, analíticos, pruebas de imagen y tratamientos empíricos empleados. La variable de desenlace fue la mortalidad intrahospitalaria. Para estimar las asociaciones entre los diferentes tratamientos y el riesgo de mortalidad se estimaron, mediante modelos de regresión de Cox, hazard ratio ajustadas por edad, sexo, patologías previas y gravedad al ingreso. RESULTADOS: La combinación de fármacos más frecuentemente empleada fue la formada por heparinade bajo peso molecular (HBPM), hidroxicloroquina y ritonavir/lopinavir. Ninguno de los tratamientos utilizados mostró una asociación independiente con la mortalidad. Los fármacos que mostraron una asociación inversa de mayor magnitud fueron el tocilizumab y los corticoides. CONCLUSIONES: El patrón se asociaciones obtenido es consistente con lo reportado en la bibliografía. Parece oportuno diseñar ensayos aleatorizados que valoren el posible efecto protector de los corticoides y el tocilizumab sobre el riesgo de muerte en algunos subgrupos de pacientes hospitalizados por COVID-19.

The Role of Offspring Genotype-By-Sex Interactions, Independently of Environmental Cues, on the Phenotype Traits of an Obese Swine Model.

The present study aimed to assess the importance of offspring genotype on postnatal development, independently of confounding factors related to prenatal environment and postnatal lifestyle, using a translational model of obesity and metabolic syndrome (the Iberian pig). Hence, we compared two genotypes (purebred Iberian and crossbreds Iberian × Large White), produced in one single maternal environment (pure Iberian mothers) through artificial insemination of Iberian sows with Iberian and Large White heterospermic semen and maintained in the same conditions during postnatal development. The results indicate that, under same pre- and postnatal environments, the interaction genotype-by-sex has a determinant role on offspring phenotype (i.e., growth and development, metabolic and antioxidant status and fatty acid composition of different tissues). These results may set the basis for future preclinical and clinical research on the differences in the metabolic phenotype among genotypes.

Exploring Host Genetic Polymorphisms Involved in SARS-CoV Infection Outcomes: Implications for Personalized Medicine in COVID-19.

OBJECTIVE: To systematically explore genetic polymorphisms associated with the clinical outcomes in SARS-CoV infection in humans. METHODS: This comprehensive literature search comprised available English papers published in PubMed/Medline and SCOPUS databases following the PRISMA-P guidelines and PICO/AXIS criteria. RESULTS: Twenty-nine polymorphisms located in 21 genes were identified as associated with SARS-CoV susceptibility/resistance, disease severity, and clinical outcomes predominantly in Asian populations. Thus, genes implicated in key pathophysiological processes such as the mechanisms related to the entry of the virus into the cell and the antiviral immune/inflammatory responses were identified. CONCLUSIONS: Although caution must be taken, the results of this systematic review suggest that multiple genetic polymorphisms are associated with SARS-CoV infection features by affecting virus pathogenesis and host immune response, which could have important applications for the study and understanding of genetics in SARS-CoV-2/COVID-19 and for personalized translational clinical practice depending on the population studied and associated environments.

[Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality]. / Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad.

BACKGROUND AND OBJECTIVES: In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS: The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, hazard ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox regression models. RESULTS: The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS: The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.

Sociodemographic, clinical and laboratory factors on admission associated with COVID-19 mortality in hospitalized patients: A retrospective observational study.

BACKGROUND: To identify and quantify associations between baseline characteristics on hospital admission and mortality in patients with COVID-19 at a tertiary hospital in Spain. METHODS AND FINDINGS: This retrospective case series included 238 patients hospitalized for COVID-19 at Hospital Universitario Clínico San Cecilio (Granada, Spain) who were discharged or who died. Electronic medical records were reviewed to obtain information on sex, age, personal antecedents, clinical features, findings on physical examination, and laboratory results for each patient. Associations between mortality and baseline characteristics were estimated as hazard ratios (HR) calculated with Cox regression models. Series mortality was 25.6%. Among patients with dependence for basic activities of daily living, 78.7% died, and among patients residing in retirement homes, 80.8% died. The variables most clearly associated with a greater hazard of death were age (3% HR increase per 1-year increase in age; 95%CI 1-6), diabetes mellitus (HR 2.42, 95%CI 1.43-4.09), SatO2/FiO2 ratio (43% HR reduction per 1-point increase; 95%CI 23-57), SOFA score (19% HR increase per 1-point increase, 95%CI 5-34) and CURB-65 score (76% HR increase per 1-point increase, 95%CI 23-143). CONCLUSIONS: The patients residing in retirement homes showed great vulnerability. The main baseline factors that were independently associated with mortality in patients hospitalized for COVID-19 were older age, diabetes mellitus, low SatO2/FiO2 ratio, and high SOFA and CURB-65 scores.