Actions and attitudes on the immunized patients against SARS-CoV-2.

The access to COVID vaccines by millions of human beings and their high level of protection against the disease, both in its mild and severe forms, together with a plausible decrease in the transmission of the infection from vaccinated patients, has prompted a series of questions from the members of the College of Physicians of Madrid (ICOMEM) and the society. The ICOMEM Scientific Committee on this subject has tried to answer these questions after discussion and consensus among its members. The main answers can be summarized as follows: The occurrence of new SARS-CoV-2 infections in both vaccinated and previously infected patients is very low, in the observation time we already have. When breakthrough infections do occur, they are usually asymptomatic or mild and, purportedly, should have a lower capacity for transmission to other persons. Vaccinated subjects who have contact with a SARS-CoV-2 infected patient can avoid quarantine as long as they are asymptomatic, although this decision depends on variables such as age, occupation, circulating variants, degree of contact and time since vaccination. In countries with a high proportion of the population vaccinated, it is already suggested that fully vaccinated persons could avoid the use of masks and social distancing in most circumstances. Systematic use of diagnostic tests to assess the immune response or the degree of protection against reinfection after natural infection or vaccination is discouraged, since their practical consequences are not known at this time. The existing information precludes any precision regarding a possible need for future revaccination. This Committee considers that when mass vaccination of health care workers and the general population is achieved, SARS-CoV-2 screening tests could be avoided at least in outpatient care and in the case of exploratory procedures that do not require hospitalization.post-print156 K

Respiratory symptoms and their determinants in the general Spanish population: changes over 20 years

Epidemiology; Respiratory symptomsEpidemiología; Síntomas respiratoriosEpidemiologia; Símptomes respiratorisBackground Few large epidemiological studies have analysed the prevalence of respiratory symptoms and their determinants in the general adult population. We investigated the prevalence and determinants of respiratory symptoms and compared their prevalence with that of two previous studies conducted in 1999 and 2009. Method EPISCAN II was a multicentre, cross-sectional, population-based epidemiological study in individuals older than 40 years. Results A total of 9092 individuals were included. Up to 47.5% reported at least one respiratory symptom, being more frequent in women than in men (49.4% versus 45.5%, p=0.0002) and with wheezing being the most frequent (33.7%) followed by dyspnoea (26.8%). The presence of any symptom was associated with female sex, higher body mass index (BMI), lower forced expiratory volume in 1 s (FEV1 % pred), reduced physical activity, a higher Charlson index and the presence of anxiety and depression. Smoking was also significantly associated with having at least one respiratory symptom in a dose–response fashion (OR: 1.415, 1.916, 2.192 and 2.987 for 0–10, 10–20, 20–30 and >30 pack-years, respectively, all p<0.0001). The prevalence of symptoms remained quite similar over the last 20 years (wheezing 40%, 36% and 33.7% and dyspnoea 10.4%, 9.9% and 13.1% in 1999, 2009 and 2019, respectively). Conclusions Approximately half of the adult Spanish population have respiratory symptoms and this prevalence has remained quite stable over the last 20 years. Smoking remains the main factor associated with respiratory symptoms, but female sex, comorbidities, high BMI and low FEV1 and low physical activity are also significantly associated with respiratory symptoms.The EPISCAN II study was sponsored by GlaxoSmithKline. Funding information for this article has been deposited with the Crossref Funder Registry

‘Smoking Genes’: A Genetic Association Study

Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (−48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A −1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1)

Factors Associated with Non-Adherence to Drugs in Patients with Chronic Diseases Who Go to Pharmacies in Spain

Background. Pharmacological non-adherence in chronic diseases is 40–65%. No predictive profile of non-adherence exists in patients with multiple chronic diseases. Our study aimed to quantify the prevalence of non-adherence to pharmacological treatment and its associated factors in patients who visit pharmacies in Spain. Methods. This observational cross-sectional study included patients with one or more chronic diseases. The variables analyzed were demographics, diseases involved, self-medication, information about disease, and lifestyle. The main variable was adherence using the Morisky–Green test. A total of 132 pharmacies collaborated, providing 6327 patients representing all Spain regions (April–December 2016). Bivariate and multivariate analyses were performed and the area under the receiver operating characteristic (ROC) curve was calculated. Results. Non-adherence was 48.4% (95% confidence interval (CI): 47.2–49.7%). The variables that reached significance in the multivariate model were: difficulty in taking medication, self-medication, desire for more information, smoking, lower physical activity, younger age and number of chronic treatments. Discrimination was satisfactory (area under the ROC curve = 70%). Our study found that 50% patients was non-adherent and we obtained a profile of variables associated with therapeutic non-adherence. Conclusions. It is cause for concern that in patients with multiple diseases and taking multiple medications, there is an association between non-adherence, self-medication and worse lifestyle

Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits

It has been proposed that deregulation of neuronal glycogen synthase kinase 3 (GSK3) activity may be a key feature in Alzheimer disease pathogenesis. We have previously generated transgenic mice that overexpress GSK3β in forebrain regions including dentate gyrus (DG), a region involved in learning and memory acquisition. We have found that GSK3 overexpression results in DG degeneration. To test whether tau protein modified by GSK3 plays a role in that neurodegeneration, we have brought GSK3 overexpressing mice to a tau knockout background. Our results indicate that the toxic effect of GSK3 overexpression is milder and slower in the absence of tau. Thus, we suggest that the hyperphosphorylated tau mediates, at least in part, the pathology observed in the brain of GSK3 overexpressing mice.This work was supported by grants from Spanish Plan Nacional, Comunidad de Madrid, Fundación Botín, CIBERNED, and an institutional grant from Fundación Ramón Areces.Peer reviewe

New variants of SARS-CoV-2

The emergence and spread of new variants of SARS-CoV-2 has produced enormous interest due to their possible implication in the improved transmissibility of the virus, their consequences in the individual evolution of the infection, as well as in the possible escape from the immunity generated by the current vaccines. The variants that attract most attention are those of public health concern, including B.1.1.7 (UK), P.1 (Brazilian) and B.1.351 (South African). This list is extended by the variants of interest that emerge and are expanding in certain countries but are found sporadically in others, such as B.1.427 and B.1.429 (Californians) or B.1.617 (Indian). Whole genome sequencing or strategies specifically targeting the spicule gene are used in the microbiology laboratories for characterization and detection. The number of infected individuals, the sanitary situation of each country, epidemiological measures and vaccination strategies influence its dispersion and new variants are expected to emerge. This emergence can only be avoided today by increasing the vaccinated population in all countries and by not relaxing epidemiological containment measures. It is not excluded that in the future it will be necessary to revaccinate against new variants.post-print186 K

Persistence and viability of SARS-CoV-2 in primary infection and reinfections

Since the beginning of the SARS-CoV-2 epidemic, virus isolation in the infected patient was only possible for a short period of time and it was striking that this occurred constantly and did not provide guidance on the clinical course. This fact led to confusion about the efficacy of some of the drugs initially used, which seemed to have a high efficiency in viral clearance and proved ineffective in modifying the course of the disease. The immune response also did not prove to be definitive in terms of evolution, although most of the patients with very mild disease had a weak or no antibody response, and the opposite was true for the most severe patients. With whatever the antibody response, few cases have been re-infected after a first infection and generally, those that have, have not reproduced a spectrum of disease similar to the first infection. Among those re-infected, a large number have been asymptomatic or with very few symptoms, others have had a moderate picture and very few have had a poor evolution. Despite this dynamic of rapid viral clearance, laboratory tests were still able to generate positive results in the recovery of genomic sequences and this occurred in patients who were already symptom-free, in others who were still ill and in those who were very seriously ill. There was also no good correlate. For this reason and with the perspective of this year and the half of pandemic, we compiled what the literature leaves us in these aspects and anticipating that, as always in biology, there are cases that jump the limits of the general behavior of the dynamics of infection in genera

Actions and attitudes on the immunized patients against SARS-CoV-2

The access to COVID vaccines by millions of human beings and their high level of protection against the disease, both in its mild and severe forms, together with a plausible decrease in the transmission of the infection from vaccinated patients, has prompted a series of questions from the members of the College of Physicians of Madrid (ICOMEM) and the society. The ICOMEM Scientific Committee on this subject has tried to answer these questions after discussion and consensus among its members. The main answers can be summarized as follows: The occurrence of new SARS-CoV-2 infections in both vaccinated and previously infected patients is very low, in the observation time we already have. When breakthrough infections do occur, they are usually asymptomatic or mild and, purportedly, should have a lower capacity for transmission to other persons. Vaccinated subjects who have contact with a SARS-CoV-2 infected patient can avoid quarantine as long as they are asymptomatic, although this decision depends on variables such as age, occupation, circulating variants, degree of contact and time since vaccination. In countries with a high proportion of the population vaccinated, it is already suggested that fully vaccinated persons could avoid the use of masks and social distancing in most circumstances. Systematic use of diagnostic tests to assess the immune response or the degree of protection against reinfection after natural infection or vaccination is discouraged, since their practical consequences are not known at this time. The existing information precludes any precision regarding a possible need for future revaccination. This Committee considers that when mass vaccination of health care workers and the general population is achieved, SARS-CoV-2 screening tests could be avoided at least in out-patient care and in the case of exploratory procedures that do not require hospitalizatio

COVID-19: Some unresolved issues

Two years after the COVID-19 pandemic, many uncertainties persist about the causal agent, the disease and its future. This document contains the reflection of the COVID-19 working group of the Official College of Physicians of Madrid (ICOMEM) in relation to some questions that remain unresolved. The document includes considerations on the origin of the virus, the current indication for diagnostic tests, the value of severity scores in the onset of the disease and the added risk posed by hypertension or dementia. We also discuss the possibility of deducing viral behavior from the examination of the structure of the complete viral genome, the future of some drug associations and the current role of therapeutic resources such as corticosteroids or extracorporeal oxygenation (ECMO). We review the scarce existing information on the reality of COVID 19 in Africa, the uncertainties about the future of the pandemic and the status of vaccines, and the data and uncertainties about the long-term pulmonary sequelae of those who suffered severe pneumonia.post-print462 K