Systems vaccinology identifies clinical and immunological correlates of SARS-CoV-2 vaccine response in solid-organ transplant recipients (preprint)

Solid organ transplant (SOT) recipients are at enhanced risk of adverse outcomes following infectious challenges due to immunosuppressive treatment and additional comorbidities. Unfortunately, SOT recipients are also poor responders to the key medical intervention to preventing infection: vaccines. Here we performed a systems vaccinology study on a cohort of 59 kidney transplant recipients and 31 lung transplant recipients who received the mRNA Pfizer-BioNTech COVID-19 vaccine. Analyzing the immunological status of the patients prior to vaccination, we were able to identify multiple immunological associates of relatively improved vaccine responses following two or three doses of mRNA-based SARS-CoV-2 vaccine. These immunological associates predicted, with 95.0% and 93.3% accuracy, vaccine response after the second and third dose, respectively. Comparison of the immunological associates with vaccine response in SOT recipients revealed two distinct immune configurations: a non-classical configuration, distinct from the immune state of healthy subjects, associated with responses to two doses of mRNA vaccine and that could be mediated partly by the presence of double negative B cell subsets which are more prominently represented in responsive SOT recipients, and a "normalized" configuration, closer to the immune state of healthy subjects, associated with potent antibody responses to three doses of mRNA vaccine. These results suggest that immunosuppression in SOT recipients can result in distinct immune states associated with different trade-offs in vaccine responsiveness. Immune phenotyping of SOT recipients for immune constellation may be an effective approach for identifying patients most at risk of poor vaccine responses and susceptibility to vaccine-preventable diseases. One-sentence summarySOT recipients showed distinct immune states at baseline associated with different profiles of vaccine-associated immune response.

System and transcript dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2) (preprint)

Statistical laws arise in many complex systems and can be explored to gain insights into their structure and behavior. Here, we investigate the dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2) at the system and individual gene levels; and demonstrate that the statistical frameworks used here are robust in spite of the technical noise associated with single-cell RNA sequencing (scRNA-seq) data. A biphasic fit to Taylor's power law was observed, and it is likely associated with the larger sampling noise inherent to the measure of less expressed genes. The type of the distribution of the system, as assessed by Taylor's parameters, varies along the course of infection in a cell type-dependent manner, but also sampling noise had a significant influence on Taylor's parameters. At the individual gene level, we found that genes that displayed signals of punctual rank stability and/or long-range dependence behavior, as measured by Hurst exponents, were associated with translation, cellular respiration, apoptosis, protein-folding, virus processes, and immune response.

Design of virtual learning experiences for microcontroller programming during COVID-19 pandemic

The social distancing imposed by Covid-19 impacted the development of educational activities at all levels. Engineering education was specially challenged by the suspension of face-to-face activities, which paused the development of laboratory practices. The present work accounts for the design of virtual learning experiences in a Microcontrollers course. The free online tools 'Tinkercad Circuits' and 'Arduino' were used to simulate circuit programming and connections. These tools also allowed remote collaboration between students and teachers during lockdown. The results of the Mechatronics Engineering students (n=30) show that programming skills and hardware knowledge were developed. Additionally, the activities had a positive response from the students. On the other hand, according to the psychomotor domain taxonomy, the students had obstacles to their full development. It is concluded on the importance of integrating simulation to the development of activities and laboratory practices, as well as the advantages of hybrid teaching formats. © 2023 IEEE.

HERDING BEHAVIOR OF BUSINESS GROUPS DURING COVID-19: EVIDENCE IN CHILE

This article investigates whether herding behavior is present in stock returns of business groups during the COVID-19 pandemic. Using series of prices and daily traded volume of the companies that make up the General Index of Stock Prices of the Santiago de Chile Stock Exchange (S & P/CLIGPA) from January 1, 2010 to October 9, 2020 the results show herding behavior during COVID-19. Nevertheless, the herding behavior is weaker in business group firms compared to companies which are not affiliated to business groups. Then, when analyzing how herding behavior evolves in business groups during the presence of COVID-19, it is found that herding behavior changes to reverse herding behavior during May 2020 onwards. When inquiring about this point, it is found that herding behavior in business groups is lower under increasing uncertainty (number of cases and deaths due to COVID-19 increases).Alternate :Este artículo investiga si la conducta de manada está presente en los rendimientos de las acciones de los grupos empresariales durante la pandemia COVID-19. Utilizando series de precios y volumen diario negociado de las empresas que integran el Índice General de Precios de Acciones de la Bolsa de Comercio de Santiago de Chile (S&P/CLIGPA) del 1 de enero de 2010 al 9 de octubre de 2020, los resultados muestran una conducta de manada durante el COVID-19. Sin embargo, esta conducta es más débil en las empresas afiliadas al grupo empresarial, en comparación con las no afiliadas. Es así como encontramos que la conducta de manada para el grupo de interés evoluciona durante el periodo del COVID-19 a tal punto que cambia a lo que se denomina conducta de manada inversa durante mayo de 2020 en adelante. Al analizar este comportamiento nos encontramos con que la conducta de manada en grupos empresariales es menor en presencia de un aumento de la incertidumbre (número de casos de muertes debido al COVID-19).

Advocating for students during distance learning: The role of the school counselor

The COVID-19 pandemic forced schools to rush into distance learning, prioritizing academics and limiting consideration of students' socioemotional needs. Given that distance learning is likely to be a recurring experience, school counselors should understand this unique context to better advocate for student needs. Through this illustrative case study, we sought to understand the distance learning experience of students, specifically examining barriers experienced and desired support, in an urban school district in the Western United States. We conducted classroom observations, interviews, and town hall observation with students who were part of an action civics program in the district. Following thematic data analysis, we found that student participants described themes of challenges (with subthemes of online learning and outside of school), needs (with subthemes of community and student voice), and communication. Based on these findings, we argue for school counselors to use student voice to inform advocacy efforts in addressing student needs during distance learning. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Correction: The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: The case of the spike A222V mutation.

[This corrects the article DOI: 10.1371/journal.ppat.1010631.].

Subclinical Acute Kidney Injury in COVID-19: Possible Mechanisms and Future Perspectives.

Since the outbreak of COVID-19 disease, a bidirectional interaction between kidney disease and the progression of COVID-19 has been demonstrated. Kidney disease is an independent risk factor for mortality of patients with COVID-19 as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to the development of acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with COVID-19. However, the detection of kidney damage in patients with COVID-19 may not occur until an advanced stage based on the current clinical blood and urinary examinations. Some studies have pointed out the development of subclinical acute kidney injury (subAKI) syndrome with COVID-19. This syndrome is characterized by significant tubule interstitial injury without changes in the estimated glomerular filtration rate. Despite the complexity of the mechanism(s) underlying the development of subAKI, the involvement of changes in the protein endocytosis machinery in proximal tubule (PT) epithelial cells (PTECs) has been proposed. This paper focuses on the data relating to subAKI and COVID-19 and the role of PTECs and their protein endocytosis machinery in its pathogenesis.

SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells.

Patients with COVID-19 have high prevalence of albuminuria which is used as a marker of progression of renal disease and is associated with severe COVID-19. We hypothesized that SARS-CoV-2 spike protein (S protein) could modulate albumin handling in proximal tubule epithelial cells (PTECs) and, consequently contribute to the albuminuria observed in patients with COVID-19. In this context, the possible effect of S protein on albumin endocytosis in PTECs was investigated. Two PTEC lines were used: HEK-293A and LLC-PK1. Incubation of both cell types with S protein for 16 h inhibited albumin uptake at the same magnitude. This effect was associated with canonical megalin-mediated albumin endocytosis because: (1) DQ-albumin uptake, a marker of the lysosomal degradation pathway, was reduced at a similar level compared with fluorescein isothiocyanate (FITC)-albumin uptake; (2) dextran-FITC uptake, a marker of fluid-phase endocytosis, was not changed; (3) cell viability and proliferation were not changed. The inhibitory effect of S protein on albumin uptake was only observed when it was added at the luminal membrane, and it did not involve the ACE2/Ang II/AT1R axis. Although both cells uptake S protein, it does not seem to be required for modulation of albumin endocytosis. The mechanism underlying the inhibition of albumin uptake by S protein encompasses a decrease in megalin expression without changes in megalin trafficking and stability. These results reveal a possible mechanism to explain the albuminuria observed in patients with COVID-19.

The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: The case of the spike A222V mutation.

The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has since reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness.

Advocating for Students During Distance Learning: The Role of the School Counselor

The COVID-19 pandemic forced schools to rush into distance learning, prioritizing academics and limiting consideration of students’ socioemotional needs. Given that distance learning is likely to be a recurring experience, school counselors should understand this unique context to better advocate for student needs. Through this illustrative case study, we sought to understand the distance learning experience of students, specifically examining barriers experienced and desired support, in an urban school district in the Western United States. We conducted classroom observations, interviews, and town hall observation with students who were part of an action civics program in the district. Following thematic data analysis, we found that student participants described themes of challenges (with subthemes of online learning and outside of school), needs (with subthemes of community and student voice), and communication. Based on these findings, we argue for school counselors to use student voice to inform advocacy efforts in addressing student needs during distance learning.

Tracking changes in tourism demand with point-of-sale data: The case of Portugal

This study extends the literature on big data applied to tourism by validating the significance of point-of-sale (POS) electronic transactions, which have received little attention within tourism literature, as a reliable and effective alternative to surveys on guests stays at tourist accommodation establishments. Compared with official statistics on occupancy of tourist accommodation establishments, data on POS transactions tend to exhibit greater volatility and a less adverse year-on-year variation during the COVID-19 pandemic in Portugal. Still, both data sources reveal the same underlying trend. POS electronic payments, namely, at lodging establishments, deliver timely data for most municipalities in Portugal, filling in significant data gaps in many low-density areas, where statistical confidentiality is imposed in tourism indicators. This supports POS data?s effectiveness to analyse regional inequalities at the municipal level, allowing to gain a clearer understanding of the impacts of COVID-19 in domestic tourism.

The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: the case of the spike A222V mutation (preprint)

The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has now reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness.

Molecular docking and molecular dynamics studies of sars-cov-2 inhibitors: Crocin, digitoxigenin, beta-eudesmol and favipiravir: Comparative study

In this study, Crocin, Digitoxigenin, Beta-Eudesmol, and Favipiravir were docked in the active site of SARS-CoV-2 main protease (PDB code: 6LU7). The docking study was followed by Molecular Dynamics simulation. The result indicates that Crocin and Digitoxigenin are the structures with the best affinity in the studied enzyme's binding site. Still, Molecular Dynamics simulation showed that Digitoxigenin is the molecule that fits better in the active site of the main protease. Therefore, this molecule could have a more potent antiviral treatment of COVID-19 than the other three studied compounds. © 2021 by the authors.

Production of high-quality SARS-CoV-2 antigens: Impact of bioprocess and storage on glycosylation, biophysical attributes, and ELISA serologic tests performance.

Serological assays are valuable tools to study SARS-CoV-2 spread and, importantly, to identify individuals that were already infected and would be potentially immune to a virus reinfection. SARS-CoV-2 Spike protein and its receptor binding domain (RBD) are the antigens with higher potential to develop SARS-CoV-2 serological assays. Moreover, structural studies of these antigens are key to understand the molecular basis for Spike interaction with angiotensin converting enzyme 2 receptor, hopefully enabling the development of COVID-19 therapeutics. Thus, it is urgent that significant amounts of this protein became available at the highest quality. In this study, we produced Spike and RBD in two human derived cell hosts: HEK293-E6 and Expi293F™. We evaluated the impact of different and scalable bioprocessing approaches on Spike and RBD production yields and, more importantly, on these antigens' quality attributes. Using negative and positive sera collected from human donors, we show an excellent performance of the produced antigens, assessed in serologic enzyme-linked immunosorbent assay (ELISA) tests, as denoted by the high specificity and sensitivity of the test. We show robust Spike productions with final yields of approx. 2 mg/L of culture that were maintained independently of the production scale or cell culture strategy. To the best of our knowledge, the final yield of 90 mg/L of culture obtained for RBD production, was the highest reported to date. An in-depth characterization of SARS-CoV-2 Spike and RBD proteins was performed, namely the antigen's oligomeric state, glycosylation profiles, and thermal stability during storage. The correlation of these quality attributes with ELISA performance show equivalent reactivity to SARS-CoV-2 positive serum, for all Spike and RBD produced, and for all storage conditions tested. Overall, we provide straightforward protocols to produce high-quality SARS-CoV-2 Spike and RBD antigens, that can be easily adapted to both academic and industrial settings; and integrate, for the first time, studies on the impact of bioprocess with an in-depth characterization of these proteins, correlating antigen's glycosylation and biophysical attributes to performance of COVID-19 serologic tests.

Asthma and COVID-19: a systematic review.

BACKGROUND: Severe coronavirus disease-19 (COVID-19) presents with progressive dyspnea, which results from acute lung inflammatory edema leading to hypoxia. As with other infectious diseases that affect the respiratory tract, asthma has been cited as a potential risk factor for severe COVID-19. However, conflicting results have been published over the last few months and the putative association between these two diseases is still unproven. METHODS: Here, we systematically reviewed all reports on COVID-19 published since its emergence in December 2019 to June 30, 2020, looking into the description of asthma as a premorbid condition, which could indicate its potential involvement in disease progression. RESULTS: We found 372 articles describing the underlying diseases of 161,271 patients diagnosed with COVID-19. Asthma was reported as a premorbid condition in only 2623 patients accounting for 1.6% of all patients. CONCLUSIONS: As the global prevalence of asthma is 4.4%, we conclude that either asthma is not a premorbid condition that contributes to the development of COVID-19 or clinicians and researchers are not accurately describing the premorbidities in COVID-19 patients.

OPTIMIZING COVID-19 VACCINE USAGE (preprint)

As the worldwide vaccination, it is imperative to minimize vaccine wastage by effectively using all doses available. Vaccine wastage can occur at multiple points during the vaccination process, but it is mainly because the device dead space and the filling process technique. However, there are no studies discussing the waste volume effect of COVID-19 vaccines in clinical practice. There is an increasing COVID-19 vaccine demand that we estimate up to several billion dual doses. The objective of this study was to assess the number of 0.3mL doses obtained from a multiple-dose vial using 1ml and 3ml syringes with different type of needles replicating the first COVID-19 vaccination protocol. Our results suggest that it is possible to obtain six or seven doses from each vial instead five. We provide evidence to optimize between 20% and 40% additional vaccine doses per vial if the current 5-dose vials are used, making scarce supplies go further. It is our duty, as researchers, to ensure the efficacy and efficiency of the worldwide COVID-19 vaccination process. However, if standard syringes-needles and technique are used, there may not be sufficient volume to draw extra doses from a single vial.

When Being “Essential” Illuminates Disparities: Counseling Clients Affected by COVID-19

The 2019 novel coronavirus (COVID-19) has highlighted social disparities in the United States. This article examines how preexisting racial and ethnic disparities, exacerbated by COVID-19, have negatively affected communities of color that tend to be overrepresented in lower socioeconomic groups, have limited access to health care and education, have an undocumented status, and work in jobs considered ?essential.? Counselors are encouraged to use creative strategies to design and facilitate telecounseling and reduced- or no-cost workshops in which attendees can participate safely. Specific cultural considerations, aspects of crisis management, and creative interventions that can be used with clients of color at an appropriate social distance are discussed. Counselors can also instill hope in their clients by promoting sociopolitical development. As the impact of COVID-19 will be felt for years, it is crucial that counselors be prepared to address the needs of those disproportionately affected.

Increased IL-10-producing regulatory T cells are characteristic of severe cases of COVID-19.

OBJECTIVES: The pandemic spread of the coronavirus SARS-CoV-2 is due, in part, to the immunological properties of the host-virus interaction. The clinical presentation varies from individual to individual, with asymptomatic carriers, mild-to-moderate-presenting patients and severely affected patients. Variation in immune response to SARS-CoV-2 may underlie this clinical variation. METHODS: Using a high-dimensional systems immunology platform, we have analysed the peripheral blood compartment of 6 healthy individuals, 23 mild-to-moderate and 20 severe COVID-19 patients. RESULTS: We identify distinct immunological signatures in the peripheral blood of the mild-to-moderate and severe COVID-19 patients, including T-cell lymphopenia, more consistent with peripheral hypo- than hyper-immune activation. Unique to the severe COVID-19 cases was a large increase in the proportion of IL-10-secreting regulatory T cells, a lineage known to possess anti-inflammatory properties in the lung. CONCLUSION: As IL-10-secreting regulatory T cells are known to possess anti-inflammatory properties in the lung, their proportional increase could contribute to a more severe COVID-19 phenotype. We openly provide annotated data (https://flowrepository.org/experiments/2713) with clinical correlates as a systems immunology resource for the COVID-19 research community.