mRNA-1273 boost after BNT162b2 vaccination generates comparable SARS-CoV-2-specific functional responses in naïve and COVID-19-recovered individuals.

Introduction: COVID-19 vaccines based on mRNA have represented a revolution in the biomedical research field. The initial two-dose vaccination schedule generates potent humoral and cellular responses, with a massive protective effect against severe COVID-19 and death. Months after this vaccination, levels of antibodies against SARS-CoV-2 waned, and this promoted the recommendation of a third vaccination dose. Methods: We have performed an integral and longitudinal study of the immunological responses triggered by the booster mRNA-1273 vaccination, in a cohort of health workers previously vaccinated with two doses of the BNT162b2 vaccine at University Hospital La Paz located in Madrid, Spain. Circulating humoral responses and SARS-CoV-2-specific cellular reactions, after ex vivo restimulation of both T and B cells (cytokines production, proliferation, class switching), have been analyzed. Importantly, all along these studies, the analyses have been performed comparing naïve and subjects recovered from COVID-19, addressing the influence of a previous infection by SARS-CoV-2. Furthermore, as the injection of the third vaccination dose was contemporary to the rise of the Omicron BA.1 variant of concern, T- and B-cell-mediated cellular responses have been comparatively analyzed in response to this variant. Results: All these analyses indicated that differential responses to vaccination due to a previous SARS-CoV-2 infection were balanced following the boost. The increase in circulating humoral responses due to this booster dropped after 6 months, whereas T-cell-mediated responses were more stable along the time. Finally, all the analyzed immunological features were dampened in response to the Omicron variant of concern, particularly late after the booster vaccination. Conclusion: This work represents a follow-up longitudinal study for almost 1.5 years, analyzing in an integral manner the immunological responses triggered by the prime-boost mRNA-based vaccination schedule against COVID-19.

Development of a charged model of the SARS-CoV-2 viral surface.

A recent study provided experimental evidence of inactivation of viral activity after radio-frequency (RF) exposures in the 6-12 GHz band that was hypothesized to be caused by vibrations of an acoustic dipole mode in the virus that excited the viral membrane to failure. Here, we develop an atomic-scale molecular dynamics (MD) model of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral surface to estimate the electric fields necessary to rupture the viral membrane via dipole shaking of the virus. We computed the absorption spectrum of the system via unbiased MD simulations and found no particular strong absorption in the GHz band. We investigated the mechanical resiliency of the viral membrane by introducing uniaxial strains in the system and observed no pore formation in the membrane for strains up to 50%. Because the computed absorption spectrum was found to be essentially flat, and the strain required to break the viral membrane was >0.5, the field strength associated with rupture of the virus was greater than the dielectric breakdown value of air. Thus, RF disinfection of enveloped viruses would occur only once sufficient heat was transferred to the virus via a thermal mechanism and not by direct action (shaking) of the RF field oscillations on the viral membrane.

Detection of Pancreatic Cancer miRNA with Biocompatible Nitrogen-Doped Graphene Quantum Dots.

Early-stage pancreatic cancer remains challenging to detect, leading to a poor five-year patient survival rate. This obstacle necessitates the development of early detection approaches based on novel technologies and materials. In this work, the presence of a specific pancreatic cancer-derived miRNA (pre-miR-132) is detected using the fluorescence properties of biocompatible nitrogen-doped graphene quantum dots (NGQDs) synthesized using a bottom-up approach from a single glucosamine precursor. The sensor platform is comprised of slightly positively charged (1.14 ± 0.36 mV) NGQDs bound via π-π stacking and/or electrostatic interactions to the negatively charged (-22.4 ± 6.00 mV) bait ssDNA; together, they form a complex with a 20 nm average size. The NGQDs' fluorescence distinguishes specific single-stranded DNA sequences due to bait-target complementarity, discriminating them from random control sequences with sensitivity in the micromolar range. Furthermore, this targetability can also detect the stem and loop portions of pre-miR-132, adding to the practicality of the biosensor. This non-invasive approach allows cancer-specific miRNA detection to facilitate early diagnosis of various forms of cancer.

Differential Immune Checkpoint and Ig-like V-Type Receptor Profiles in COVID-19: Associations with Severity and Treatment.

Identifying patients' immune system status has become critical to managing SARS-CoV-2 infection and avoiding the appearance of secondary infections during a hospital stay. Despite the high volume of research, robust severity and outcome markers are still lacking in COVID-19. We recruited 87 COVID-19 patients and analyzed, by unbiased automated software, 356 parameters at baseline emergency department admission including: high depth immune phenotyping and immune checkpoint expression by spectral flow cytometry, cytokines and other soluble molecules in plasma as well as routine clinical variables. We identified 69 baseline alterations in the expression of immune checkpoints, Ig-like V type receptors and other immune population markers associated with severity (O2 requirement). Thirty-four changes in these markers/populations were associated with secondary infection appearance. In addition, through a longitudinal sample collection, we described the changes which take place in the immune system of COVID-19 patients during secondary infections and in response to corticosteroid treatment. Our study provides information about immune checkpoint molecules and other less-studied receptors with Ig-like V-type domains such as CD108, CD226, HVEM (CD270), B7H3 (CD276), B7H5 (VISTA) and GITR (CD357), defining these as novel interesting molecules in severe and corticosteroids-treated acute infections.

SARS-CoV-2: theoretical analysis of the proposed algorithms to the enhancement and segmentation of high-resolution microscopy images-Part II.

Today is a reality that the novel coronavirus SARS-Cov-2 has become a global pandemic. For this reason, the study of real microscopic images of this coronavirus is of great importance, as it allows us to carry out a more precise research on it. However, as we pointed out in a former paper as reported by Roberto Rodríguez (SARS-CoV-2: Enhancement and Segmentation of High-Resolution Microscopy Images. Part I", Sent to Signal, Image and Video Processing Video Processing, Springer, New York, 2020), many times these microscopic images present some blurring problems, which are always susceptible to be improved. The aim of this work is to carry out a theoretical analysis of the proposed algorithms to enhancement and segmentation of these microscopic images, which is important for the design and development of future algorithms before new epidemics.

Cellular and humoral functional responses after BNT162b2 mRNA vaccination differ longitudinally between naive and subjects recovered from COVID-19.

We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost 8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.

The utility of the Edmonton Obesity Staging System for the prediction of COVID-19 outcomes: a multi-centre study.

BACKGROUND: Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes. METHODS: 1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category. RESULTS: The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02-1.97 and 2.78, 95% CI 1.83-4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06-2.74, and 2.62, 95% CI 1.65-4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42-0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03-2.42). In patients with a BMI ≥ 25 kg/m2, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50-3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight. CONCLUSIONS: EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.

Evaluation of short-term safety of COVID-19 vaccines in patients with multiple sclerosis from Latin America.

BACKGROUND: To date, there are no data available on the safety of COVID-19 vaccines in Latin American patients with Multiple Sclerosis (MS). OBJECTIVE: Characterize safety of COVID-19 vaccines in Latin American (LATAM) patients with Multiple Sclerosis (pwMS). METHODS: A cross-sectional study between February 1, 2021, and April 30, 2021. Individuals with MS from LATAM countries were invited to participate in a self-administered web-based survey, through MS patient organizations from the region. RESULTS: 393 vaccinated pwMS from 10 different Latin American countries were included. The vaccines administered were: inactivated virus vaccines (IVV) in 38.2% of patients, adenovirus vector vaccines (AdV) in 48.8% and mRNA vaccines 13%. All patients received at least one dose of any of the COVID-19 vaccines and 123 (31.3%) declared receiving a second dose. Mean (SD) age 41.5 (11.8) years, 82.4% female, MS disease duration: 8.4 (8.2) years. No serious adverse events were reported with any of the COVID-19 vaccines after either the first or second dose. A lower frequency of adverse events was found with IVV (22%) in comparison with AdV (46.4%) and mRNA (35.3%) (p < 0.01). Five participants reported having an MS relapse after IVV first dose. CONCLUSION: COVID-19 vaccines applied in LATAM proved safe for MS patients.

SARS-CoV-2: preliminary study of infected human nasopharyngeal tissue by high resolution microscopy.

BACKGROUND: The novel coronavirus SARS-CoV-2 is the etiological agent of COVID-19. This virus has become one of the most dangerous in recent times with a very high rate of transmission. At present, several publications show the typical crown-shape of the novel coronavirus grown in cell cultures. However, an integral ultramicroscopy study done directly from clinical specimens has not been published. METHODS: Nasopharyngeal swabs were collected from 12 Cuban individuals, six asymptomatic and RT-PCR negative (negative control) and six others from a COVID-19 symptomatic and RT-PCR positive for SARS CoV-2. Samples were treated with an aldehyde solution and processed by scanning electron microscopy (SEM), confocal microscopy (CM) and, atomic force microscopy. Improvement and segmentation of coronavirus images were performed by a novel mathematical image enhancement algorithm. RESULTS: The images of the negative control sample showed the characteristic healthy microvilli morphology at the apical region of the nasal epithelial cells. As expected, they do not display virus-like structures. The images of the positive sample showed characteristic coronavirus-like particles and evident destruction of microvilli. In some regions, virions budding through the cell membrane were observed. Microvilli destruction could explain the anosmia reported by some patients. Virus-particles emerging from the cell-surface with a variable size ranging from 80 to 400 nm were observed by SEM. Viral antigen was identified in the apical cells zone by CM. CONCLUSIONS: The integral microscopy study showed that SARS-CoV-2 has a similar image to SARS-CoV. The application of several high-resolution microscopy techniques to nasopharyngeal samples awaits future use.

Changes on the health care of people with multiple sclerosis from Latin America during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in uncertain access to medical treatment for people with multiple sclerosis (pwMS) all over the world. However, there is no data regarding its impact on access to health care of pwMS from Latin America. OBJECTIVES: We investigated and described changes in health care delivery for pwMS from Latin America during the COVID-19 pandemic. METHODS: PwMS from 18 patient organizations of the region completed a web-based survey hosted from May to October 2020. RESULTS: A total of 602 pwMS completed the questionnaire. Changes in disease-modifying therapies (DMTs) use: 6.7% of pwMS on continuous DMTs claimed to stopped them; 14.1% of those on infusion therapies declared to postpone their dosing; 68.8% declared delaying the initiation of a DMT. Disruptions in accessing rehabilitation services were reported by 65.7%. Changes in laboratory and MRI monitoring were reported by 30% and 33%, respectively. In a multivariable-adjusted logistic regression model, changes in laboratory monitoring were significantly associated with increased odds of postponing MRI monitoring (OR 4.09 CI95% 2.79-6.00, p < 0.001). CONCLUSIONS: The COVID-19 pandemic has disrupted all aspects of the routine care for pwMS from Latin America. Consequences are yet to be determined.

SARS-CoV-2 Proteins Induce Endotoxin Tolerance Hallmarks: A Demonstration in Patients with COVID-19.

According to a large number of reported cohorts, sepsis has been observed in nearly all deceased patients with COVID-19. We and others have described sepsis, among other pathologies, to be an endotoxin tolerance (ET)-related disease. In this study, we demonstrate that the culture of human blood cells from healthy volunteers in the presence of SARS-CoV-2 proteins induced ET hallmarks, including impairment of proinflammatory cytokine production, low MHC class II (HLA-DR) expression, poor T cell proliferation, and enhancing of both phagocytosis and tissue remodeling. Moreover, we report the presence of SARS-CoV-2 blood circulating proteins in patients with COVID-19 and how these levels correlate with an ET status, the viral RNA presence of SARS-CoV-2 in plasma, as well as with an increase in the proportion of patients with secondary infections.

Potential Role of the Galectin-9/TIM-3 Axis in the Disparate Progression of SARS-CoV-2 in a Married Couple: A Case Report.

We report the disparate clinical progression of a couple infected by SARS-CoV-2 based on their immune checkpoint (IC) levels and immune cell distribution in blood from admission to exitus in patient 1 and from admission to discharge and recovery in patient 2. A detailed clinical follow-up accompanied by a longitudinal analysis of immune phenotypes and IC levels is shown. The continuous increase in the soluble IC ligand galectin-9 (Gal-9) and the increment in T-cell immunoglobulin and mucin domain-containing 3 (TIM-3) protein in T cells in patient 1 suggests an activation of the Gal-9/TIM-3 axis and, subsequently, a potential cell exhaustion in this patient that did not occur in patient 2. Our data indicate that the Gal-9/TIM-3 axis could be a potential target in this clinical setting, along with a patent effector memory T-cell reduction.

SARS-CoV-2: enhancement and segmentation of high-resolution microscopy images-Part I.

Possibly, and due to poor eating habits and unhealthy lifestyle, many viruses are transmitted to human people. Such is the case, of the novel coronavirus SARS-Cov-2, which has expanded of exponential way, practically, to whole world population. For this reason, the enhancement of real microscopic images of this coronavirus is of great importance. Of this way, one can highlight the S-spikes and visualizing those areas that show a high density, which are related to active zones of viral germination and major spread of the virus. The SARS-Cov-2 images were captured from nasopharyngeal samples of Cuban symptomatic individuals (RT-PCR positives for SARS-CoV-2) and processed via scanning electron microscopy. However, many times these microscopic images present some blurring problems, and the S-spikes do not look well defined. Therefore, the aim of this work is to propose new computational methods to carry out enhancement and segmentation of SARS-Cov-2 high-resolution microscopic images. The proposed strategy obtained very satisfactory results, and we validated its performance, together with specialist physicians, on a set of 1005 images. Due to the importance of the obtained results, this first work will be addressed to the application of the proposed algorithm. A second paper will deeply analyze the theory related to these algorithms.

Proteins from SARS-CoV-2 reduce T cell proliferation: A mirror image of sepsis.

Increased cytokine levels, acute phase reactants and immune checkpoint expression changes have been described in patients with Coronavirus Disease 2019 (COVID-19). Here, we have reported a monocyte polarization towards a low HLA-DR and high PD-L1 expression after long exposure to proteins from SARS-CoV-2. Moreover, CD86 expression was also reduced over SARS-CoV-2 proteins exposure. Additionally, T-cells proliferation was significantly reduced after stimulation with these proteins. Eventually, patients with long-term SARS-CoV-2 infection also exhibited a significant blockade of T-cells proliferation.

Consenso sobre la infección por COVID-19 (SARS-COV-2)

On January 15, 2020, the World Health Organization (WHO) made the first recommendations regarding the epidemiological surveillance of a new coronavirus detected on December 31, 2019 in the Hubei province of Wuhan city, China --which later (January 7, 2020) was identified as a new coronavirus, or an emerging corona-virus, initially called "2019-nCoV"-- and issued the first case definitions, when was detected 27 cases of acute respiratory syndrome of unknown etiology. This virus would eventually be called "COVID-19" or "SARS-CoV-2". It's spread around the world did not take long, and despite the fact that the WHO delayed declaring this outbreak as a pandemic event, it finally did so on March 11 of the current year. The Mexican Academy of Pediatrics (advisory body of the Secretary of Health) considered made up prudent to compile the facts to issue, as soon as possible, an expanded overview of infection-disease by this emerging virus and, at the same time, as its main objective is to contribute, support and work together with the Secretary of Health to combat the SARS-CoV-2 epidemic in order to provide the best care and treatment measures to mitigate its spread throughout the Mexican territory. (English) [ABSTRACT FROM AUTHOR] El 15 de enero de 2020, la Organización Mundial de la Salud (OMS) realizó las primeras recomendaciones respecto a la vigilancia epidemiológica de un nuevo co-ronavirus, detectado el 31 de diciembre de 2019 en la provincia de Hubei, ciudad de Wuhan, en China --que, posteriormente (07 de enero de 2020) fue identificado como un nuevo coronavirus, o bien, un coronavirus emergente, inicialmente denominado "2019-nCoV"--, y emitió las primeras definiciones de caso, tras haberse detectado en 27 sujetos con síndrome respiratorio agudo de etiología desconocida. Dicho virus, a la postre, se denominaría "COVID-19" o "SARS-CoV-2". Su diseminación en todo el mundo no tardó mucho, y a pesar de que la OMS retrasó la declaración del brote como un evento pandémico, finalmente lo hizo el 11 de marzo del año en curso. La Academia Mexicana de Pediatría (órgano asesor de la Secretaría de Salud) consideró prudente hacer una recopilación de los hechos para emitir, en lo posible, un panorama ampliado de la infección-enfermedad por este virus emergente y, a la vez, se planteó como principal objetivo contribuir, apoyar y trabajar en conjunto con la Secretaría de Salud para enfrentar la epidemia asociada con el SARS-CoV-2 para que se implementen las mejores medidas de atención y tratamiento a fin de mitigar su diseminación en el territorio mexicano. (Spanish) [ABSTRACT FROM AUTHOR] Copyright of Revista de Enfermedades Infecciosas en Pediatria is the property of Ediciones Franco S.A. de C.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Possible role of HLA class-I genotype in SARS-CoV-2 infection and progression: A pilot study in a cohort of Covid-19 Spanish patients.

Human Leukocyte Antigen (HLA) includes a large set of genes with important actions in immune response against viral infection. Numerous studies have revealed the existence of significant associations between certain HLA alleles and the susceptibility and prognosis of different infectious diseases. In this pilot study we analyse the binding affinity between 66 class I HLA alleles and SARS-CoV-2 viral peptides, and its association with the severity of the disease. A total of 45 Spanish patients with mild, moderate and severe SARS-CoV-2 infection were typed for HLA class I; after that, we analysed if an in silico model of HLA I-viral peptide binding affinity and classical HLA supertypes could be correlated to the severity of the disease. Our results suggest that patients with mild disease present Class I HLA molecules with a higher theoretical capacity for binding SARS-Cov-2 peptides and showed greater heterozygosity when comparing them with moderate and severe groups. In this regard, identifying HLA-SARS-CoV-2 peptides binding differences between individuals would help to clarify the heterogeneity of clinical responses to the disease and will also be useful to guide a personalized treatment according to its particular risk.

SARS-COV-2 infection presenting as ST-elevationmyocardial infarction.

We describe a patient presenting with chest discomfort, anterolateral ST elevation, and developing acute cardiogenic shock secondary to SARS-COV-2infection-patient zero presenting to our institution's cardiac catheterization laboratory. The emergent presentation with limited clinical information led to exposure of personnel. The diagnosis was complicated by two negative tests for SARS-COV-2, and high-clinical suspicion from the patient's occupational history led to additional testing in order to confirm the diagnosis.