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Neutralizing Antibodies Response against SARS-CoV-2 Variants of Concern Elicited by Prior Infection or mRNA BNT162b2 Vaccination
Full text linkIn order to determine the humoral protective response against SARS-CoV-2, the vaccine-induced and naturally induced neutralizing antibodies (NtAbs) responses against SARS-CoV-2 variants circulating in Italy through in vitro live virus neutralization assay were evaluated. A total of 39 SARS-CoV-2 recovered subjects (COVID-19+) and 63 subjects with a two-dose cycle of the BNT16262 vaccine were enrolled. A single serum sample was tested for COVID-19+ at 35–52 days post-positive swab, while vaccinees blood samples were taken at one (V1) and at three months (V3) after administration of the second vaccine dose. Significantly higher NtAb titers were found against B.1 and Alpha in both COVID-19+ and vaccinees, while lower NtAb titers were detected against Delta, Gamma, and Omicron variants. A comparison between groups showed that NtAb titers were significantly higher in both V1 and V3 than in COVID-19+, except against the Omicron variant where no significant difference was found. COVID-19+ showed lower neutralizing titers against all viral variants when compared to the vaccinees. Two-dose vaccination induced a sustained antibody response against each analyzed variant, except for Omicron. The evolution process of SARS-CoV-2, through variants originating from an accumulation of mutations, can erode the neutralizing effectiveness of natural and vaccine-elicited immunity. Therefore, a need for new vaccines should be evaluated to contain the ongoing pandemic
Confidence in a Vaccine against COVID-19 among Registered Nurses in Barcelona, Spain across Two Time Periods
Full text linkObjective: To report the vaccine hesitancy (VH) for a vaccine against COVID-19 in registered nurses in Barcelona, with measurements taken at two stages, prior to the vaccination campaign and once 75% vaccination coverage had been reached. Methods: A self-completed online survey was administered in December 2020 and again in July 2021 through the College of Nurses of Barcelona. It measured the prevalence of VH against a government-approved vaccine recommended by their employer, their intention to be vaccinated, perceptions of disease risk and vaccine protection, attitudes and beliefs to vaccination and social norm. Bivariate analysis according to VH and application time are presented. Results: 2430 valid responses were obtained in the first measurement and 2027 in the second. At both times, 86% were women and 69% worked mainly in the public sector. Prior to the vaccine availability, VH was 34.2%, decreasing to 17.9%. Risk perceptions were significantly lower in those with VH compared to non-VH, in all groups studied and at both times, while safety and efficacy perceptions increased in all groups, significantly less in VH. The greatest benefit of the COVID-19 vaccine is perceived by pharmaceutical companies. VH nurses perceived a more hesitant social environment. Conclusion: As the vaccination was rolled out, VH in nurses declined, with time improving the confidence in the safety and efficacy of the vaccines. Risk perceptions also decreased over time, except for the perception of severity in HCW where it increased. Trust in institutions impacts trust in vaccines
Seroprevalence of Pertussis in Adults at Childbearing Age Pre- and Post- COVID-19 in Beijing, China
Full text linkThe number of reported pertussis cases has significantly decreased during the coronavirus disease 2019 (COVID-19) pandemic under the influence of strict public health measures in many countries including China. This study evaluated the prevalence of serum anti-pertussis toxin (anti-PT) IgG antibodies in adults at childbearing age pre- and post- COVID-19 in Beijing, China. Altogether, 2021 serum samples collected from individuals aged 20 to 39 years who attended an annual health examination at the Sixth Medical Center of PLA General Hospital, Beijing, in 2018~2020 were measured by ELISA. The median concentration of anti-PT IgG antibodies among participants in 2020 (2.96 IU/mL) was significantly lower than that in 2018 (3.27 IU/mL) (p = 0.011) and in 2019 (3.24 IU/mL) (p = 0.014). The percentage of participants with anti-PT IgG antibodies higher than 40 IU/mL (indicating a pertussis infection within the past few years) was 1.79% (9/503) in 2018, 2.04% (15/735) in 2019 and 1.66% (13/783) in 2020, respectively. The corresponding numbers of the non-detectable (<5 IU/mL) rate of anti-PT IgG antibodies were 66.60%, 65.99% and 70.24%. Our results showed that there was a significant difference between true and reported incidence rates even during the COVID-19 pandemic. The proportion of adults at childbearing age without pertussis-specific antibodies is high, suggesting that booster vaccinations in adults should be considered in this country
Pulmonary Embolism after Moderna Vaccination in Kidney Transplant Patients: Two Case Reports and Literature Review
Full text linkCurrently, the coronavirus disease 2019 (COVID-19) pandemic is still an ongoing and constant medical issue, and with upcoming new variants, vaccinations and boosters remain important. The safety of vaccines in patients after kidney transplantation is an essential problem, with thrombosis being one of the severe side effects and vaccine-induced immune thrombotic thrombocytopenia (VITT) revealed as the most commonly reported syndrome for thromboembolic events following COVID-19 vaccination. Here, we present two cases of kidney transplantation developing pulmonary embolism post-Moderna vaccination within 30 days without thrombocytopenia. The first case was a 52-year-old man with history of type II diabetes, hypertension and hyperlipidemia who had had cadaveric kidney transplantation in September 2008, where right leg swelling with claudication occurred 23 days after the second Moderna vaccination. The second case was a 57-year-old man with history of type II diabetes and glaucoma who had had living-related kidney transplantation in April 2013 and then complained of exertional dyspnea 26 days after administration of the third Moderna vaccine. The advantages of vaccination even in immunocompromised patients far outweigh the disadvantages, although clinicians must understand the risks of deep-vein thrombosis or even pulmonary embolism for such patients, which might not occur after just the first vaccination
Retention of Neutralizing Response against SARS-CoV-2 Omicron Variant in Sputnik V-Vaccinated Individuals
Full text linkThe new Omicron variant of SARS-CoV-2, first identified in November 2021, is rapidly spreading all around the world. Omicron has become the dominant variant of SARS-CoV-2. There are many ongoing studies evaluating the effectiveness of existing vaccines. Studies on the neutralizing activity of vaccinated sera against the Omicron variant are currently being carried out in many laboratories. In this study, we have shown the neutralizing activity of sera against the SARS-CoV-2 Omicron variant compared to the reference Wuhan D614G variant in individuals vaccinated with two doses of Sputnik V up to 6 months after vaccination and in individuals who experienced SARS-CoV-2 infection either before or after vaccination. As a control to our study we also measured neutralizing antibody titers in individuals vaccinated with two doses of BNT162b2. The decrease in NtAb titers to the Omicron variant was 8.1-fold for the group of Sputnik V-vaccinated individuals. When the samples were stratified for the time period after vaccination, a 7.6-fold or 8.8-fold decrease in NtAb titers was noticed after up to 3 and 3-to-6 months after vaccination. We observed a 6.7- and 5-fold decrease in Sputnik V-vaccinated individuals experiencing asymptomatic or symptomatic infection, respectively. These results highlight the observation that the decrease in NtAb to the SARS-CoV-2 Omicron variant compared to the Wuhan variant occurs for different COVID-19 vaccines in use, with some showing no neutralization at all, confirming the necessity of a third booster vaccination
Short-Term Drop in Antibody Titer after the Third Dose of SARS-CoV-2 BNT162b2 Vaccine in Adults
Full text linkLittle is known about the longevity of antibodies after a third dose of the mRNA-based SARS-CoV-2 vaccine BNT162b2 (BioNTech/Pfizer, Mainz, Germany). Therefore, serum antibody levels were evaluated after a third dose of BNT162b2 in healthy adult healthcare workers in Germany. These antibody levels dropped significantly within a short period of 11 weeks from 4155.59 ± 2373.65 BAU/mL to 2389.10 ± 1433.90 BAU/mL, p-value < 0.001 but remained higher than after the second dose (611.92 ± 450.31 BAU/mL). To evaluate the quality of the humoral immune response, we additionally measured neutralizing antibodies, which also showed a small but significant decrease within this short period. These data underline the positive effect of a third dose of BNT162b2 concerning antibody re-induction but also shows a drop of Anti-SARS-CoV-2-IgG within a short span of time
Omicron Infection Evokes Cross-Protection against SARS-CoV-2 Variants in Vaccinees
Full text linkDue to the rapid global spread of the Omicron (B.1.1.529) variant, efforts to scale up COVID-19 booster vaccination have been improved, especially in light of the increasing evidence of reduced neutralizing antibody (NT Ab) over time in vaccinated subjects. In this study, neutralizing antibody responses against the Wild-Type, Delta, and Omicron strains were evaluated among vaccinees, both infected with Omicron or uninfected, and non-vaccinated subjects infected with Omicron. The aim of the study was to compare the cross-protective humoral response to the variant strains induced by vaccination and/or Omicron infection. The results showed a significant difference in the neutralizing antibody response between the vaccinees and the Omicron-infected vaccinated subjects against the three tested strains (p < 0.001), confirming the booster effect of the Omicron infection in the vaccinees. By contrast, Omicron infection only did not enhance the antibody response to the other variants, indicating a lack of cross-protection. These results suggest the importance of updating the current formulation of the SARS-CoV-2 vaccine to protect people against the Omicron subvariants. A specific Omicron vaccine, administered as a booster for the previously adopted mRNA vaccines, may protect against a wider range of SARS-CoV-2 variants. However, it is unlikely that the Omicron vaccine alone would be able to protect non-vaccinated subjects against other circulating variants
Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis
Full text linkNon-small-cell lung cancer (NSCLC) is considered as one of the malignant cancers that causes premature death. The present study aimed to identify a few potential novel genes highlighting their functions, pathways, and regulators for diagnosis, prognosis, and therapies of NSCLC by using the integrated bioinformatics approaches. At first, we picked out 1943 DEGs between NSCLC and control samples by using the statistical LIMMA approach. Then we selected 11 DEGs (CDK1, EGFR, FYN, UBC, MYC, CCNB1, FOS, RHOB, CDC6, CDC20, and CHEK1) as the hub-DEGs (potential key genes) by the protein–protein interaction network analysis of DEGs. The DEGs and hub-DEGs regulatory network analysis commonly revealed four transcription factors (FOXC1, GATA2, YY1, and NFIC) and five miRNAs (miR-335-5p, miR-26b-5p, miR-92a-3p, miR-155-5p, and miR-16-5p) as the key transcriptional and post-transcriptional regulators of DEGs as well as hub-DEGs. We also disclosed the pathogenetic processes of NSCLC by investigating the biological processes, molecular function, cellular components, and KEGG pathways of DEGs. The multivariate survival probability curves based on the expression of hub-DEGs in the SurvExpress web-tool and database showed the significant differences between the low- and high-risk groups, which indicates strong prognostic power of hub-DEGs. Then, we explored top-ranked 5-hub-DEGs-guided repurposable drugs based on the Connectivity Map (CMap) database. Out of the selected drugs, we validated six FDA-approved launched drugs (Dinaciclib, Afatinib, Icotinib, Bosutinib, Dasatinib, and TWS-119) by molecular docking interaction analysis with the respective target proteins for the treatment against NSCLC. The detected therapeutic targets and repurposable drugs require further attention by experimental studies to establish them as potential biomarkers for precision medicine in NSCLC treatmen
The Prognosis and Predictive Value of Estrogen Negative/Progesterone Positive (ER−/PR+) Phenotype: Experience of 1159 Primary Breast Cancer from a Single Institute
Full text linkBreast cancer is a serious worldwide public health problem and is currently the most common cancer overall. Its endocrine therapy is related to the expression of the steroid hormones, estrogen receptor (ER), and progesterone receptor (PR). Breast cancers can be presented under multiple profiles of steroid hormones: ER(−)/PR(+), ER(+)/PR(−), double-positive/negative ER, and PR. 2–8% of all breast cancers express only PR (ER−/PR+) which is an abnormal phenotype, with less known about their behaviors and outcomes. Our study was performed on a large and well-characterized database of primary breast cancer from 2012 to 2019, up to 1159 cases. These cases were divided according to ER and PR expression, as we put all of our focus on ER-negative/PR-positive group, more specifically ER−/PR+/HER2+ and ER−/PR+/HER2− gene expressions, to highlight their features and find a pattern that links HR (hormone receptors) profiles and breast cancer subtypes. Out of the informative cases, 94 patients (8%) had ER−/PR+ breast cancers, while 676 (58.4%) had ER+/PR+, 88 (7.6%) had ER+/PR−, and 164 (14.2%) had ER−/PR− tumors. The ER−/PR+ group was statistically correlated with a high risk of recurrence and death in midway between the double-negative and double-positive HR. According to HER2 status, a low DFS was observed in patients ER−/PR+/HER2−, which is closer to the DFS of TNBC cases but worse than ER+/PR any. On the other side, the ER−/PR+/HER2+ showed also a poorer DFS closer to the HER2+ subgroup in between TNBC and ER+/PR any. The clinicopathological features of the ER−/PR+/HER2− and ER−/PR+ HER2+ have distinguished the patients into two groups with a difference in some clinicopathological characteristics: both groups had closer OS estimation, which was worse than ER−/PR any and better than TNBC and HER2. The ER−/PR+/HER2− seems to increase the risk of recurrence than ER−/PR+/HER2+ when compared to ER+/PR any. On the other hand, the ER−/PR+/HER2+ seems to increase the risk of death more than ER−/PR+/HER2− in comparison with ER+/PR any. Our results support that ER−/PR+ tumors really exist and are rare and clinically and biologically distinct subtypes of breast cancer. In addition, our analysis, which was based on dividing the groups according to HER2 expression, has revealed the existence of two distinct groups; this gave the ER−/PR+ subgroup a heterogeneity characterization. Moreover, this breast cancer subtype should not be treated as a luminal tumor but rather according to the HER2 expression status.
1. Introduction
Breast cancer is a serious worldwide public health problem and is currently the most common cancer overall [1], causing the highest number of cancer-related deaths among women. Due to its complexity and heterogeneity, breast cancer presents veritable variation in clinical, morphological, and molecular management [2]. The molecular classification by immunohistochemical expression of estrogen receptor ER, progesterone receptor PR, human epidermal growth factor receptor 2 (HER2), and proliferation index Ki-67 established by St. Gallen surrogate for breast cancer subtypes reveals five main entities: luminal-A, luminal-B HER2-negative, luminal B HER2-positive, HER2 enriched, and TNBC (triple negative: lack of expression of ER, PR, and no overexpression of HER2) [3, 4].
Breast cancer endocrine therapy is actually related to the expression of the steroid hormones, estrogen receptor (ER), and progesterone receptor (PR). The estrogen receptor (ER) and progesterone receptor (PR) are expressed in more than 75% of breast cancers [5, 6]. They are one of the most powerful prognostic factors and predictive markers in hormonal treatment [7–9]. Therefore, breast cancers can be presented in multiple profiles of steroid hormones: ER(−)/PR(+), ER(+)/PR(−), double-positive/negative ER, and PR [3].
The treatment strategies decisions in cases of double-positive/negative steroid hormones can be taken easily [9]. Not to mention, hormone-receptor-positive breast tumors are qualified by less aggressive clinicopathological outcomes and a high prognosis in reason of the benefits from endocrine therapy [10].
Estrogen receptors (ER) status on its own is useful in predicting benefits from antiestrogenic treatment, but not from hormonal treatment. Thus, progesterone receptors are often tested in parallel with estrogen receptors, as studies have shown that PR expression is conditional on ER activity [3, 4, 11, 12]. Consequently, the luminal tumors are the most common breast cancer phenotypes, presenting more than 50% of all breast cancers [9]. Moreover, only 15–20% of all breast cancer cases have expressed one hormone receptor at a time, with a predominance of tumors expressing ER, but not PR (ER+/PR−) [13, 14].
The existence of breast cancer with ER-negative/PR-positive phenotype is still debated. The biological significance, prognosis, and predictive impact of ER−/PR+ breast cancers have been discussed; there are some hypotheses about considering this profile as a technical artifact. The HR status of breast cancer may be altered due to several factors, resulting in a false-negative ER and/or false-positive PR assay. Antibody selection for ER testing, improper tissue fixations, and different thresholds for reporting immunostaining or less sensitive immunohistochemistry, are some of these factors [15–17]. The American Society of Clinical Oncology/College of American Pathologists recommended that ER−/PR+ tumors should be tested repeatedly to avoid false negative ER results [7, 18]
The Neurophysiological Impact of Subacute Stroke: Changes in Cortical Oscillations Evoked by Bimanual Finger Movement
Full text linkntroduction. To design more effective interventions, such as neurostimulation, for stroke rehabilitation, there is a need to understand early physiological changes that take place that may be relevant for clinical monitoring. We aimed to study changes in neurophysiology following recent ischemic stroke, both at rest and with motor planning and execution. Materials and Methods. We included 10 poststroke patients, between 7 and 10 days after stroke, and 20 age-matched controls to assess changes in cortical motor output via transcranial magnetic stimulation and in dynamics of oscillations, as recorded using electroencephalography (EEG). Results. We found significant differences in cortical oscillatory patterns comparing stroke patients with healthy participants, particularly in the beta rhythm during motor planning () and execution () of a complex movement with fingers from both hands simultaneously. Discussion. The stroke lesion induced a decrease in event-related desynchronization in patients, in comparison to controls, providing evidence for decreased disinhibition. Conclusions. After a stroke lesion, the dynamics of cortical oscillations is changed, with an increasing neural beta synchronization in the course of motor preparation and performance of complex bimanual finger tasks. The observed patterns may provide a potential functional measure that could be used to monitor and design interventional approaches in subacute stages.
1. Introduction
Stroke represents the third major cause of death and is one of the leading sources of disability, contributing to a decline in the global quality of life. Although several approaches are applied to the rehabilitation of patients, current interventions lack efficacy [1].
In order to develop new and more effective interventions for neurorehabilitation, and particularly, for the rehabilitation of stroke patients, it is fundamental to understand subacute physiological changes of potential neuroplastic significance following the event. After a brain lesion, neural networks are damaged, which triggers the reorganization of neural connectivity and brain rhythms. Plastic changes may occur not only on the lesioned but also in the contralateral hemisphere [2]. It is frequently reported in the literature that the activity of the unaffected hemisphere increases in the first days after the cerebrovascular accident [2, 3]. After this period, at 3 to 6 months following the event, a relative increase in the activity of the areas adjacent to the lesion is frequently observed, concurrent with functional improvements [3].
Functional techniques to assess brain changes include electroencephalography, magnetoencephalography, and functional magnetic resonance imaging [2]. Electroencephalography (EEG) can potentially contribute to the understanding of the physiology of brain reorganization [4], in particular in which concerns the study of dynamics of oscillations [5].
Brain oscillations can appear at diverse frequencies, associated to distinct levels of synchrony in neuronal networks [6]. The visual alpha rhythm is known to respond to a stimulus or instruction with a decrease in amplitude or power, resulting in an event-related desynchronization (ERD). Synchronization (ERS) occurs in the absence of stimuli or idle states. It is therefore believed that alpha ERS is associated to cortical inhibition, whereas ERD is related to the reduction of inhibition, in turn [7]. Current knowledge, nevertheless, also points out a role for other types of alpha rhythm in attention and conscious awareness [8].
Performing a voluntary movement or receiving instructions to execute a motor task are generally associated with a decrease in upper alpha (mu rhythm) and in beta rhythms [6, 7], in those regions around sensorimotor areas [6, 9]. This reduction of movement-related beta power is thought to be associated with the excitability of the primary motor cortex and to be affected by GABA (gamma-aminobutyric acid) levels [10].
Preparation and execution of motor tasks might reveal altered activity patterns in stroke, which may have significant implications for the design of therapeutic interventions [11]. Changes in neural synchronization and oscillatory activities can play a role in the pathophysiology of distinct disorders, such as in stroke [7]. The poststroke changes in brain oscillations, particularly those accompanying movements of the impaired limbs, are worthy of further research [10]. Therefore, exploration of biomarkers to strengthen stroke investigation has been advocated [12], and recent works have been studying EEG activity in stroke, along with motor tasks, such as unilateral [11–13] or bilateral wrist movements [13].
Here, we determined motor thresholds as a measure of cortical excitability and assessed ERD and ERS in the course of motor tasks, both in healthy subjects and in poststroke patients. To the best of our knowledge, this is the first time that the neurophysiology of stroke patients is analysed shortly after the event (between 7 and 10 days poststroke) by EEG preceding and during simple and complex fine-tuned unilateral and bilateral motor tasks performed with both the affected and unaffected arms and hands, and a direct comparison with a control healthy sample that did the same experiment is provided. Our aim was to study the impact of a subacute ischemic stroke in brain neurophysiology at rest and during motor preparation and execution. Moreover, we investigated whether significant changes in the EEG brain activity pattern following stroke could be correlated with the motor performance of the affected upper limb, assessed by the Wolf Motor Function Test