Differential contribution for ERK1 and ERK2 kinases in BRAFV600E-triggered phenotypes in adult mouse models.

The BRAF gene is mutated in a plethora of human cancers. The majority of such molecular lesions result in the expression of a constitutively active BRAF variant (BRAFV600E) which continuously bolsters cell proliferation. Although we recently addressed the early effects triggered by BRAFV600E-activation, the specific contribution of ERK1 and ERK2 in BRAFV600E-driven responses in vivo has never been explored. Here we describe the first murine model suitable for genetically dissecting the ERK1/ERK2 impact in multiple phenotypes induced by ubiquitous BRAFV600E-expression. We unveil that ERK1 is dispensable for BRAFV600E-dependent lifespan shortening and for BRAFV600E-driven tumor growth. We show that BRAFV600E-expression provokes an ERK1-independent lymphocyte depletion which does not rely on p21CIP1-induced cell cycle arrest and is unresponsive to ERK-chemical inhibition. Moreover, we also reveal that ERK1 is dispensable for BRAFV600E-triggered cytotoxicity in lungs and that ERK-chemical inhibition abrogates some of these detrimental effects, such as DNA damage, in Club cells but not in pulmonary lymphocytes. Our data suggest that ERK1/ERK2 contribution to BRAFV600E-driven phenotypes is dynamic and varies dependently on cell type, the biological function, and the level of ERK-pathway activation. Our findings also provide useful insights into the comprehension of BRAFV600E-driven malignancies pathophysiology as well as the consequences in vivo of novel ERK pathway-targeted anti-cancer therapies.

A Prospective Observational Study of Frailty in Geriatric Revitalization Aimed at Community-Dwelling Elderly.

(1) Background: The increasing life expectancy brings an increase in geriatric syndromes, specifically frailty. The literature shows that exercise is a key to preventing, or even reversing, frailty in community-dwelling populations. The main objective is to demonstrate how an intervention based on multicomponent exercise produces an improvement in frailty and pre-frailty in a community-dwelling population. (2) Methods: a prospective observational study of a multicomponent exercise program for geriatric revitalization with people aged over 65 holding Barthel Index scores equal to, or beyond, 90. The program was developed over 30 weeks, three times a week, in sessions lasting 45-50 min each. Frailty levels were registered by the Short Physical Performance Battery, FRAIL Questionnaire Screening Tool, and Timed "Up & Go" at the beginning of the program, 30 weeks later (at the end of the program), and following 13 weeks without training; (3) Results: 360 participants completed the program; a greater risk of frailty was found before the program started among older women living in urban areas, with a more elevated fat percentage, more baseline pathologies, and wider baseline medication use. Furthermore, heterogeneous results were observed both in training periods and in periods without physical activity. However, they are consistent over time and show improvement after training. They show a good correlation between TUG and SPPB; (4) Conclusions: A thirty-week multicomponent exercise program improves frailty and pre-frailty status in a community-dwelling population with no functional decline. Nevertheless, a lack of homogeneity is evident among the various tools used for measuring frailty over training periods and inactivity periods.

Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

Medical deserts in Spain-Insights from an international project.

INTRODUCTION: Medical deserts are a growing phenomenon across many European countries. They are usually defined as (i) rural areas, (ii) underserved areas or (iii) by applying a measure of distance/time to a facility or a combination of the three characteristics. The objective was to define medical deserts in Spain as well as map their driving factors and approaches to mitigate them. METHODS: A mixed methods approach was applied following the project "A Roadmap out of medical deserts into supportive health workforce initiatives and policies" work plan. It included the following elements: (i) a scoping literature review; (ii) a questionnaire survey; (iii) national stakeholders' workshop; (iv) a descriptive case study on medical deserts in Spain. RESULTS: Medical deserts in Spain exist in the form of mostly rural areas with limited access to health care. The main challenge in their identification and monitoring is local data availability. Diversity of both factors contributing to medical deserts and solutions applied to eliminate or mitigate them can be identified in Spain. They can be related to demand for or supply of health care services. More national data, analyses and/or initiatives seem to be focused on the health care supply dimension. CONCLUSIONS: Addressing medical deserts in Spain requires a comprehensive and multidimensional approach. Effective policies are needed to address both the medical staff education and planning system, working conditions, as well as more intersectoral approach to the population health management.

Clinical outcome prediction of acute neurological patients admitted to the emergency department: Sequential Organ Failure Assessment score and modified SOFA score.

Background: The aim of this study was to determine the ability of the Sequential Organ Failure Assessment score (SOFA) and modified SOFA score (mSOFA) as predictive tools for 2-day and 28-day mortality and ICU admission in patients with acute neurological pathology treated in hospital emergency departments (EDs). Methods: An observational, prospective cohort study in adults with acute neurological disease transferred by ambulance to an ED was conducted from 1 January 2019 to 31 August 2022 in five hospitals in Castilla-León (Spain). Score discrimination was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the score. Results: A total of 640 adult patients with neurological disease were included. For the prediction of 2-day mortality (all-cause), mSOFA presented a higher AUC than SOFA (mSOFA = 0.925 vs. SOFA = 0.902). This was not the case for 28-day mortality, for which SOFA was higher than mSOFA (mSOFA = 0.852 vs. SOFA = 0.875). Finally, ICU admission showed that SOFA was higher than mSOFA (mSOFA = 0.834 vs. SOFA = 0.845). Conclusion: Both mSOFA and SOFA presented similar predictive ability, with mSOFA being the best predictor for short-term mortality and SOFA being the best predictor for medium-term mortality, as well as for ICU admission. These results in a cohort of patients with acute neurological pathology pave the way for the use of both predictive tools in the ED. The inclusion of these tools could improve the clinical assessment and further treatment of neurological patients, who commonly present the worst outcomes.

The Distribution of Eight Antimicrobial Resistance Genes in Streptococcus oralis, Streptococcus sanguinis, and Streptococcus gordonii Strains Isolated from Dental Plaque as Oral Commensals.

It has been proposed that oral commensal bacteria are potential reservoirs of a wide variety of antimicrobial resistance genes (ARGs) and could be the source of pathogenic bacteria; however, there is scarce information regarding this. In this study, three common streptococci of the mitis group (S. oralis, S. sanguinis, and S. gordonii) isolated from dental plaque (DP) were screened to identify if they were frequent reservoirs of specific ARGs (blaTEM, cfxA, tetM, tetW, tetQ, ermA, ermB, and ermC). DP samples were collected from 80 adults; one part of the sample was cultured, and from the other part DNA was obtained for first screening of the three streptococci species and the ARGs of interest. Selected samples were plated and colonies were selected for molecular identification. Thirty identified species were screened for the presence of the ARGs. From those selected, all of the S. sanguinis and S. oralis carried at least three, while only 30% of S. gordonii strains carried three or more. The most prevalent were tetM in 73%, and blaTEM and tetW both in 66.6%. On the other hand, ermA and cfxA were not present. Oral streptococci from the mitis group could be considered frequent reservoirs of specifically tetM, blaTEM, and tetW. In contrast, these three species appear not to be reservoirs of ermA and cfxA.

Presence of methanogenic archaea in necrotic root canals of patients with or without type 2 diabetes mellitus.

Theoretically, a necrotic root canal fulfils all requirements as a niche for methanogens to inhabit. However, their presence in it and its implication in apical periodontitis (AP) is controversial. Therefore, to contribute to ending the controversy, this study aimed to detect and compare methanogens' presence in two distinct niches with supposedly different microenvironments; both were necrotic root canals associated with AP but one from patients with type 2 diabetes mellitus (T2DM) while the other from non-diabetic patients. A clinical examination was performed on 65 T2DM patients and 73 non-diabetic controls. Samples from necrotic root canals were obtained, and methanogens were identified. The presence of methanogens was three times higher (27.6%) in the T2DM group than in non-diabetic patients (8.2%). In addition, methanogens' presence was associated with a higher prevalence of periapical symptoms.

Cell-autonomous and differential endocannabinoid signaling impacts the development of presynaptic retinal ganglion cell axon connectivity in vivo.

Cannabis exposure during gestation evokes significant molecular modifications to neurodevelopmental programs leading to neurophysiological and behavioral abnormalities in humans. The main neuronal receptor for Δ9-tetrahydrocannabinol (THC) is the type-1 cannabinoid receptor CB1R, one of the most abundant G-protein-coupled receptors in the nervous system. While THC is the major psychoactive phytocannabinoid, endocannabinoids (eCBs) are the endogenous ligands of CB1R and are known to act as retrograde messengers to modulate synaptic plasticity at different time scales in the adult brain. Accumulating evidence indicates that eCB signaling through activation of CB1R plays a central role in neural development. During development, most CB1R localized to axons of projection neurons, and in mice eCB signaling impacts axon fasciculation. Understanding of eCB-mediated structural plasticity during development, however, requires the identification of the precise spatial and temporal dynamics of CB1R-mediated modifications at the level of individual neurons in the intact brain. Here, the cell-autonomous role of CB1R and the effects of CB1R-mediated eCB signaling were investigated using targeted single-cell knockdown and pharmacologic treatments in Xenopus. We imaged axonal arbors of retinal ganglion cells (RGCs) in real time following downregulation of CB1R via morpholino (MO) knockdown. We also analyzed RGC axons with altered eCB signaling following treatment with URB597, a selective inhibitor of the enzyme that degrades Anandamide (AEA), or JZL184, an inhibitor of the enzyme that blocks 2-Arachidonoylglycerol (2-AG) hydrolysis, at two distinct stages of retinotectal development. Our results demonstrate that CB1R knockdown impacts RGC axon branching at their target and that differential 2-AG and AEA-mediated eCB signaling contributes to presynaptic structural connectivity at the time that axons terminate and when retinotectal synaptic connections are made. Altering CB1R levels through CB1R MO knockdown similarly impacted dendritic morphology of tectal neurons, thus supporting both pre- and postsynaptic cell-autonomous roles for CB1R-mediated eCB signaling.

Validation of N Protein Antibodies to Diagnose Previous SARS-CoV-2 Infection in a Large Cohort of Healthcare Workers: Use of Roche Elecsys® Immunoassay in the S Protein Vaccination Era.

The aim of this study was to validate the detection of anti-nucleocapsid protein (N protein) antibodies for the diagnosis of SARS-CoV-2 infection in light of the fact that most COVID-19 vaccines use the spike (S) protein as the antigen. Here, 3550 healthcare workers (HCWs) were enrolled from May 2020 (when no S protein vaccines were available). We defined SARS-CoV-2 infection if HCWs were found to be positive by RT-PCR or found to be positive in at least two different serological immunoassays. Serum samples from Biobanc I3PT-CERCA were analyzed by Roche Elecsys® (N protein) and Vircell IgG (N and S proteins) immunoassays. Discordant samples were reanalyzed with other commercial immunoassays. Roche Elecsys® showed the positivity of 539 (15.2%) HCWs, 664 (18.7%) were found to be positive by Vircell IgG immunoassays, and 164 samples (4.6%) showed discrepant results. According to our SARS-CoV-2 infection criteria, 563 HCWs had SARS-CoV-2 infection. The Roche Elecsys® immunoassay has a sensitivity, specificity, accuracy, and concordance with the presence of infection of 94.7%, 99.8%, 99.3%, and 0.96, respectively. Similar results were observed in a validation cohort of vaccinated HCWs. We conclude that the Roche Elecsys® SARS-CoV-2 N protein immunoassay demonstrated good performance in diagnosing previous SARS-CoV-2 infection in a large cohort of HCWs.

Root canal microbiota as an augmented reservoir of antimicrobial resistance genes in type 2 diabetes mellitus patients.

BACKGROUND: Antimicrobial resistance is a global public health problem. Root canal microbiota associated with apical periodontitis represents a well-known reservoir of antimicrobial resistance genes (ARGs). However, the effect of type 2 diabetes mellitus (T2DM) in this reservoir is unknown. This study aimed to establish if root canal microbiota associated with apical periodontitis in T2DM patients is an augmented reservoir by identifying the prevalence of nine common ARGs and comparing it with the prevalence in nondiabetic patients. METHODOLOGY: This cross-sectional study included two groups: A T2DM group conformed of 20 patients with at least ten years of living with T2DM and a control group of 30 nondiabetic participants. Premolar or molar teeth with pulp necrosis and apical periodontitis were included. A sample was collected from each root canal before endodontic treatment. DNA was extracted, and ARGs were identified by polymerase chain reaction. RESULTS: tetW and tetM genes were the most frequent (93.3 and 91.6%, respectively), while ermA was the least frequent (8.3%) in the total population. The distribution of the ARGs was similar in both groups, but a significant difference (p<0.005) was present in ermB, ermC, cfxA, and tetQ genes, being more frequent in the T2DM group. A total of eighty percent of the T2DM patients presented a minimum of four ARGs, while 76.6% of the control group presented a maximum of three. CONCLUSIONS: Root canal microbiota associated with apical periodontitis in T2DM patients carries more ARGs. Therefore, this pathological niche could be considered an augmented reservoir.

Modified Sequential Organ Failure Assessment Score vs. Early Warning Scores in Prehospital Care to Predict Major Adverse Cardiac Events in Acute Cardiovascular Disease.

(1) Background: The Modified Sequential Organ Failure Assessment (mSOFA) is an Early Warning Score (EWS) that has proven to be useful in identifying patients at high risk of mortality in prehospital care. The main objective of this study was to evaluate the predictive validity of prehospital mSOFA in estimating 2- and 90-day mortality (all-cause) in patients with acute cardiovascular diseases (ACVD), and to compare this validity to that of four other widely-used EWS. (2) Methods: We conducted a prospective, observational, multicentric, ambulance-based study in adults with suspected ACVD who were transferred by ambulance to Emergency Departments (ED). The primary outcome was 2- and 90-day mortality (all-cause in- and out-hospital). The discriminative power of the predictive variable was assessed and evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC). (3) Results: A total of 1540 patients met the inclusion criteria. The 2- and 90-day mortality rates were 5.3% and 12.7%, respectively. The mSOFA showed the highest AUC of all the evaluated scores for both 2- and 90-day mortality, AUC = 0.943 (0.917-0.968) and AUC = 0.874 (0.847-0.902), respectively. (4) Conclusions: The mSOFA is a quick and easy-to-use EWS with an excellent ability to predict mortality at both 2 and 90 days in patients treated for ACVD, and has proved to be superior to the other EWS evaluated in this study.

Can Intrapartum Ultrasonography Improve the Placement of the Vacuum Cup in Operative Vaginal Deliveries?

Although the fetal head position has traditionally been evaluated by digital examination (DE), it has a failure rate ranging between 20 and 70%; hence, intrapartum transabdominal ultrasonography (TUS) has become relevant. We aimed to evaluate the utility of the TUS to identify the fetal head positions in vacuum-assisted deliveries. We performed a prospective observational study including 101 pregnant patients in active labor who required a vacuum-assisted delivery. The fetal head position was assessed by a DE and a TUS prior to vacuum cup placement. After delivery, the optimal vacuum cup placement was evaluated as the distance between the chignon and the flexion point ≤2 cm. The general concordance rate between the DE and TUS was 72.2%, with the poorest concordance rate for occiput posterior positions at 46.1%. In five cases (4.9%), it was not possible to determine the fetal head position through the DE. The correlation was higher in low and medium planes, with 77% and 68.1% concordance rates, respectively, while it was lower in high planes (60%). In 90.1% of cases, the vacuum cup placement was optimal. Our findings show that intrapartum transabdominal ultrasonography is a useful technique to identify the fetal head position allowing optimal placement of the vacuum cup necessary for correct vacuum-assisted delivery.

Identification of decreased intrinsic capacity: Performance of diagnostic measures of the ICOPE Screening tool in community dwelling older people in the VIMCI study.

BACKGROUND: The World Health Organization (WHO) has developed the Integrated Care for Older People (ICOPE) strategy to face the challenges of ageing societies. This strategy is focused on person centered care and the assessment intrinsic capacity (IC). Early identification of five domains of IC (cognition, locomotion, vitality, sensory (hearing and vision), and psychological) has been shown to be related with adverse outcomes and can guide actions towards primary prevention and healthy ageing. IC assessment proposed by the WHO ICOPE guidelines is composed by two steps: First, Screening for decreased IC by the ICOPE Screening tool; second, by the reference standard methods. The aim was to assess the performance of diagnostic measures (sensibility, specificity, diagnostic accuracy, and agreement of the ICOPE Screening tool) compared to the reference standard methods in European community-dwelling older adults. METHODS: Cross-sectional analysis of the baseline of the ongoing VIMCI (Validity of an Instrument to Measure Intrinsic Capacity) cohort study, which was carried out in Primary Care centers and outpatient clinics from 5 rural and urban territories in Catalonia (Spain). Participants were 207community dwelling persons ≥ 70-year-old with Barthel ≥ 90, without dementia or advanced chronic conditions who provided their consent to participate. The 5 IC domains were assessed by the ICOPE Screening tool and the reference methods (SPPB, gait speed, MNA, Snellen chart, audiometry, MMSE, GDS5) during patients' visit. Agreement was assessed with the Gwet AC1 index. RESULTS: ICOPE Screening tool sensitivity was higher for cognition (0.889) and ranged between 0.438 and 0.569 for most domains. Specificity ranged from 0.682 to 0.96, diagnostic accuracy from 0.627 to 0.879, Youden index from 0.12 to 0.619, and Gwet AC1 from 0.275 to 0.842. CONCLUSION: The ICOPE screening tool showed fair performance of diagnostic measures; it was helpful to identify those participants with satisfactory IC and showed a modest ability to identify decreased IC in older people with high degree of autonomy. Since low sensitivities were found, a process of external validation would be recommended to reach better discrimination. Further studies about the ICOPE Screening tool and its performance of diagnostic measures in different populations are urgently required.

Impact of experience on the sensitivity, acceptability, and intrusive of two subjective mental workload techniques: The NASA TLX and workload profile.

BACKGROUND: Today's work environments have high cognitive demands, and mental workload is one of the main causes of work stress, human errors, and accidents. While several mental workload studies have compared the mental workload perceived by groups of experienced participants to that perceived by novice groups, no comparisons have been made between the same individuals performing the same tasks at different times. OBJECTIVE: This work aims to compare NASA Task Load Index (NASA-TLX) to Workload Profile (WP) in terms of their sensitivity. The comparison considers the impact of experience and task differentiation in the same individual once a degree of experience has been developed in the execution of the same tasks. It also considers the acceptability and intrusivity of the techniques. METHODS: The sample consisted of 30 participants who performed four tasks in two sessions. The first session was performed when participants had no experience; the second session was performed after a time of practice. Mental workload was assessed after each session. Statistical methods were used to compare the results. RESULTS: The NASA-TLX proved to be more sensitive to experience, while the WP showed greater sensitivity to task differentiation. In addition, while both techniques featured a similar degree of intrusivity, the NASA-TLX received greater acceptability. CONCLUSION: The acceptability of WP is low due to the high complexity of its dimensions and clarifying explanations of these may be necessary to increase acceptability. Future research proposals should be expanded to consider mental workload when designing work environments in current manufacturing environments.

Gender Differences in Anxiety, Attitudes, and Fear among Nursing Undergraduates Coping with CPR Training with PPE Kit for COVID.

BACKGROUND: The aim of this study was to examine the attitudes, fears, and anxiety level of nursing students faced with a critical clinical simulation (cardiopulmonary reanimation) with and without personal protective equipment (PPE). METHODS: A pilot before-after study as conducted from 21 to 25 June 2021, with 24 students registered in the nursing degree of the Faculty of Health Sciences of the Castilla-La Mancha University (UCLM) in the city of Talavera de la Reina (Toledo, Spain). From 520 possible participants, only 24 were selected according to the exclusion and inclusion criteria. The STAI Manual for the State-Trait Anxiety Inventory, a self-evaluation questionnaire, was used to study trait STAI (basal anxiety), trait STAI before CPR, state STAI after CPR, total STAI before CPR, and total STAI after CPR as the main variables. A t-test was used to study the STAI variables according to sex and the physiological values related to the anxiety level of participants. An ANOVA statistical test was used to perform a data analysis of the STAI variables. RESULTS: A total of 54.2% of participants (IC 95% 35.1-72.1) suffered from global anxiety before the cardiopulmonary reanimation maneuvers (CPR). The results of the STAI before CPR maneuvers showed significant differences according to gender in state anxiety (p = 0.04), with a higher level of anxiety in women (22.38 ± 7.69 vs. 15.82 ± 7.18). CONCLUSIONS: This study demonstrates different levels of anxiety in terms of gender suffered by nursing students in high-pressure environments, such as a CPR situation.

Isothiocyanate-Rich Extracts from Cauliflower (Brassica oleracea Var. Botrytis) and Radish (Raphanus sativus) Inhibited Metabolic Activity and Induced ROS in Selected Human HCT116 and HT-29 Colorectal Cancer Cells.

Cruciferous vegetables such as cauliflower and radish contain isothiocyanates exhibiting chemoprotective effects in vitro and in vivo. This research aimed to assess the impact of cauliflower (CIE) and radish (RIE) isothiocyanate extracts on the metabolic activity, intracellular reactive oxygen species (ROS), and LDH production of selected human colorectal adenocarcinoma cells (HCT116 and HT-29 for early and late colon cancer development, respectively). Non-cancerous colon cells (CCD-33Co) were used as a cytotoxicity control. The CIE samples displayed the highest allyl isothiocyanate (AITC: 12.55 µg/g) contents, whereas RIE was the most abundant in benzyl isothiocyanate (BITC: 15.35 µg/g). Both extracts effectively inhibited HCT116 and HT-29 metabolic activity, but the CIE impact was higher than that of RIE on HCT116 (IC50: 0.56 mg/mL). Assays using the half-inhibitory concentrations (IC50) of all treatments, including AITC and BITC, displayed increased (p < 0.05) LDH (absorbance: 0.25-0.40 nm) and ROS release (1190-1697 relative fluorescence units) in both cell lines. BITC showed the highest in silico binding affinity with all the tested colorectal cancer molecular markers (NF-kB, ß-catenin, and NRF2-NFE2). The theoretical evaluation of AITC and BITC bioavailability showed high values for both compounds. The results indicate that CIE and RIE extracts display chemopreventive effects in vitro, but additional experiments are needed to validate their effects.

A machine learning COVID-19 mass screening based on symptoms and a simple olfactory test.

The early detection of symptoms and rapid testing are the basis of an efficient screening strategy to control COVID-19 transmission. The olfactory dysfunction is one of the most prevalent symptom and in many cases is the first symptom. This study aims to develop a machine learning COVID-19 predictive tool based on symptoms and a simple olfactory test, which consists of identifying the smell of an aromatized hydroalcoholic gel. A multi-centre population-based prospective study was carried out in the city of Reus (Catalonia, Spain). The study included consecutive patients undergoing a reverse transcriptase polymerase chain reaction test for presenting symptoms suggestive of COVID-19 or for being close contacts of a confirmed COVID-19 case. A total of 519 patients were included, 386 (74.4%) had at least one symptom and 133 (25.6%) were asymptomatic. A classification tree model including sex, age, relevant symptoms and the olfactory test results obtained a sensitivity of 0.97 (95% CI 0.91-0.99), a specificity of 0.39 (95% CI 0.34-0.44) and an AUC of 0.87 (95% CI 0.83-0.92). This shows that this machine learning predictive model is a promising mass screening for COVID-19.

SARS-CoV-2 Spike Protein Vaccine-Induced Immune Imprinting Reduces Nucleocapsid Protein Antibody Response in SARS-CoV-2 Infection.

Immune imprinting or original antigenic sin (OAS) is the process by which the humoral memory response to an antigen can inhibit the response to new epitopes of that antigen originating from a second encounter with the pathogen. Given the situation of the COVID-19 pandemic, multiple vaccines have been developed against SARS-CoV-2 infection. These vaccines are directed to the spike protein (S protein) of the original variant of Wuhan D614G. Vaccine memory immune response against S protein in noninfected subjects could inhibit, through the OAS mechanism, the response to new epitopes of SARS-CoV-2 after infection. The present study analyzes whether the memory antibody B cell response generated by mRNA vaccines against S protein can inhibit the primary antibody immune response to other SARS-CoV-2 antigens, such as nucleocapsid protein (N protein). SARS-CoV-2 primary infection in vaccinated healthcare workers (HCWs) produced significantly lower titers of anti-N antibodies than that in nonvaccinated HCWs: 5.7 (IQR 2.3-15.2) versus 12.2 (IQR 4.2-32.0), respectively (p = 0.005). Therefore, spike protein vaccine-induced immune imprinting (original antigenic sin) reduces N protein antibody response.

Antibody Response Induced by BNT162b2 and mRNA-1273 Vaccines against the SARS-CoV-2 in a Cohort of Healthcare Workers.

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.