Long-Term Antibody Response to SARS-CoV-2 in Children.

Almost 2 years into the pandemic and with vaccination of children significantly lagging behind adults, long-term pediatric humoral immune responses to SARS-CoV-2 are understudied. The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study is a prospective cohort study designed to identify and follow up children and their household contacts infected in the early 2020 first wave of SARS-CoV-2. We screened 6113 children < 18 years by nasopharyngeal swab-PCR in a low-incidence setting after general lockdown, from May 11 to June 30, 2020. A total of 4657 participants underwent antibody testing. Positive tests were followed up by repeated PCR and serological testing of all household contacts over 6 months. In total, the study identified 67 seropositive children (1.44%); the median time after infection at first presentation was 83 days post-symptom onset (PSO). Follow-up of household contacts showed less than 100% seroprevalence in most families, with higher seroprevalence in families with adult index cases compared to pediatric index cases (OR 1.79, P = 0.047). Most importantly, children showed sustained seroconversion up to 9 months PSO, and serum antibody concentrations persistently surpassed adult levels (ratio serum IgG spike children vs. adults 90 days PSO 1.75, P < 0.001; 180 days 1.38, P = 0.01; 270 days 1.54, P = 0.001). In a low-incidence setting, SARS-CoV-2 infection and humoral immune response present distinct patterns in children including higher antibody levels, and lower seroprevalence in families with pediatric index cases. Children show long-term SARS-CoV-2 antibody responses. These findings are relevant to novel variants with increased disease burden in children, as well as for the planning of age-appropriate vaccination strategies.

SARS-CoV-2 Omicron BA.1 Challenge after Ancestral or Delta Infection in Mice.

We assessed cross-reactivity to BA.1, BA.2, and BA.5 of neutralizing antibodies elicited by ancestral, Delta, and Omicron BA.1 SARS-CoV-2 infection in mice. Primary infection elicited homologous antibodies with poor cross-reactivity to Omicron strains. This pattern remained after BA.1 challenge, although ancestral- and Delta-infected mice were protected from BA.1 infection.

Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection.

Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.

Specific CD4+ T Cell Responses to Ancestral SARS-CoV-2 in Children Increase With Age and Show Cross-Reactivity to Beta Variant.

SARS-CoV-2 is still a major burden for global health despite effective vaccines. With the reduction of social distancing measures, infection rates are increasing in children, while data on the pediatric immune response to SARS-CoV-2 infection is still lacking. Although the typical disease course in children has been mild, emerging variants may present new challenges in this age group. Peripheral blood mononuclear cells (PBMC) from 51 convalescent children, 24 seronegative siblings from early 2020, and 51 unexposed controls were stimulated with SARS-CoV-2-derived peptide MegaPools from the ancestral and beta variants. Flow cytometric determination of activation-induced markers and secreted cytokines were used to quantify the CD4+ T cell response. The average time after infection was over 80 days. CD4+ T cell responses were detected in 61% of convalescent children and were markedly reduced in preschool children. Cross-reactive T cells for the SARS-CoV-2 beta variant were identified in 45% of cases after infection with an ancestral SARS-CoV-2 variant. The CD4+ T cell response was accompanied most predominantly by IFN-γ and Granzyme B secretion. An antiviral CD4+ T cell response was present in children after ancestral SARS-CoV-2 infection, which was reduced in the youngest age group. We detected significant cross-reactivity of CD4+ T cell responses to the more recently evolved immune-escaping beta variant. Our findings have epidemiologic relevance for children regarding novel viral variants of concern and vaccination efforts.

ARPIP: Ancestral sequence Reconstruction with insertions and deletions under the Poisson Indel Process.

Modern phylogenetic methods allow inference of ancestral molecular sequences given an alignment and phylogeny relating present day sequences. This provides insight into the evolutionary history of molecules, helping to understand gene function and to study biological processes such as adaptation and convergent evolution across a variety of applications. Here we propose a dynamic programming algorithm for fast joint likelihood-based reconstruction of ancestral sequences under the Poisson Indel Process (PIP). Unlike previous approaches, our method, named ARPIP, enables the reconstruction with insertions and deletions based on an explicit indel model. Consequently, inferred indel events have an explicit biological interpretation. Likelihood computation is achieved in linear time with respect to the number of sequences. Our method consists of two steps, namely finding the most probable indel points and reconstructing ancestral sequences. First, we find the most likely indel points and prune the phylogeny to reflect the insertion and deletion events per site. Second, we infer the ancestral states on the pruned subtree in a manner similar to FastML. We applied ARPIP on simulated datasets and on real data from the Betacoronavirus genus. ARPIP reconstructs both the indel events and substitutions with a high degree of accuracy. Our method fares well when compared to established state-of-the-art methods such as FastML and PAML. Moreover, the method can be extended to explore both optimal and suboptimal reconstructions, include rate heterogeneity through time and more. We believe it will expand the range of novel applications of ancestral sequence reconstruction.

Incidence of pulmonary embolism in COVID-19 infection in the ED: ancestral, Delta, Omicron variants and vaccines.

PURPOSE: This retrospective review examines the incidence of pulmonary embolism (PE) during computed tomography pulmonary angiography (CTPA) exams performed in the emergency room setting of a tertiary care center over dominant periods of the ancestral, Delta, and Omicron variants of COVID-19. MATERIALS/METHODS: Demographic information, patient comorbidities and risk factors, vaccination status, and COVID-19 infection status were collected from patient's charts. Incidence of PE in COVID positive patients was compared between variant waves. Subgroup analysis of vaccination effect was performed. RESULTS: CTPA was ordered in 18.3% of COVID-19 positive patients during the ancestral variant period, 18.3% during the Delta period and 17.3% during the Omicron wave. PE was seen in 15.0% of the ancestral COVID-19 variant cohort, 10.6% in the Delta COVID cohort and 9.23% of the Omicron cohort, reflecting a 41% and 60% increased risk of PE with ancestral variants compared to Delta and Omicron periods respectively. The study however was underpowered and the difference in rate of PE did not reach statistically significance (p = 0.43 and p = 0.22). Unvaccinated patients had an 2.75-fold increased risk of COVID-associated PE during the Delta and Omicron periods (p = .02) compared to vaccinated or recovered patients. CONCLUSION: Vaccination reduces the risk of COVID-19 associated PE. Patients infected with the Delta and Omicron COVID-19 variants may have a lower incidence of pulmonary embolism, though a larger or multi-institution study is needed to prove definitively.

Increasing contributions of airborne route in SARS-CoV-2 omicron variant transmission compared with the ancestral strain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant lineage worldwide. Experimental studies have shown that SARS-CoV-2 Omicron variant is more stable on various environmental surfaces than the ancestral strains of SARS-CoV-2. However, the influences on the role of the contact route in SARS-CoV-2 transmission are still unknown. In this study, we built a Markov chain model to simulate the transmission of the Omicron and ancestral strains of SARS-CoV-2 within a household over a 1-day period from multiple pathways; that is, airborne, droplet, and contact routes. We assumed that there were two adults and one child in the household, and that one of the adults was infected with SARS-CoV-2. We assumed two scenarios. (1) Asymptomatic/presymptomatic infection, and (2) symptomatic infection. During asymptomatic/presymptomatic infection, the contact route contributing the most (37%-45%), followed by the airborne (34%-38%) and droplet routes (21%-28%). During symptomatic infection, the droplet route was the dominant pathway (48%-71%), followed by the contact route (25%-42%), with the airborne route playing a negligible role (<10%). Compared to the ancestral strain, although the contribution of the contact route increased in Omicron variant transmission, the increase was slight, from 25%-41% to 30%-45%. With the growing concern about the increase in the proportion of asymptomatic/presymptomatic infection in Omicron strain transmissions, the airborne route, rather than the fomite route, should be of focus. Our findings suggest the importance of ventilation in the SARS-CoV-2 Omicron variant prevention in building environment.

Math Crafts, Educational Activities: 400 Indigenous Kids Learning Math from Engineers and Scientists

This paper provides a framework for the planning and implementation stages involved in teaching a math class, in full compliance with local educational programs, Additional content based on native/indigenous numerical systems is also provided. The educational program includes a combination of theory and practice to help kids appreciate technical concepts and provides a wide-range of learning possibilities for other applications. These 'Math Crafts' activities will be implemented in five schools within the Arhuaco School System, part of an indigenous community of approximately 30, 000 people. Four hundred children in 5th grade of elementary school are our initial audience. Future projects are expected to include reaching out to urban students. Note: Due to the COVID-19 global pandemic, prerecorded and remote classes will be provided. © 2021 IEEE.

Agroecological System from the administrative sciences in the Province of Azuay-Ecuador, exceeds the requirements of Covid-19

The objective of this work was to analyze the agroecological system from the management sciences, in the province of Azuay in Ecuador. For this, systems theory was used from administrative sciences in Ecuadorian agriculture, through analytical research and field design. The population was made up of all the agroecological associations and a stratified sampling was applied;To collect the data, a structured questionnaire with a Likert scale was used, the results of which were treated from descriptive statistics. Among the results, a favorable trend prevails to maintain the strengths of an integral system that provides food to the entire nation. It is concluded that the complications of the environment were strengthened by the pandemic;however, the associations demonstrated in general terms their willingness and capabilities to overcome the demands of COVID-19, as they have a system with four flexible subsystems, capable of adapting to market influences. © 2022, Associacao Iberica de Sistemas e Tecnologias de Informacao. All rights reserved.

WATER KEFIR, A FERMENTED BEVERAGE CONTAINING PROBIOTIC MICROORGANISMS: FROM ANCIENT AND ARTISANAL MANUFACTURE TO INDUSTRIALIZED AND REGULATED COMMERCIALIZATION

Throughout the COVID-19 pandemic, there was a demand for natural products able to enhance consumers health. Many people discovered the benefits of fermented products such as milk and water kefir and kombucha. Specifically, water kefir has aroused great interest from people interested in consuming foods that do not come from animals (plant-based and vegan diets) or people allergic to milk proteins or lactose intolerant, while increasing the scientific evidence of water kefir health enhancement. This review deals with the needing for the establishment of quality parameters found in traditional and flavoured water kefir drink, for their implementation in the industrially produced beverage. Such industrialization must seek the sustainable development of this economic activity for the implementation of circular economy guidelines. The benefits and safety of this non-dairy fermented drink have been demonstrated since its ancestral consumption and have been documented by many scientific works around the world. The scientific community must accompany this rapid advance of fermented foods containing probiotic microorganisms, given the changing priorities within the food industry. In addition, the quality parameters for the inclusion of this product in the Codex Alimentarius of many countries must be established, in order to regulate its production on an industrial scale and marketing.

Ancestral Food Sources Rich in Polyphenols, Their Metabolism, and the Potential Influence of Gut Microbiota in the Management of Depression and Anxiety.

The relationship between a population's diet and the risk of suffering from mental disorders has gained importance in recent years, becoming exacerbated due to the COVID-19 lockdown. This review concentrates relevant literature from Scopus, PubMed, and Google Scholar analyzed with the aim of rescuing knowledge that promotes mental health. In this context, it is important to highlight those flowers, seeds, herbaceous plants, fungi, leaves, and tree barks, among other ancestral matrices, that have been historically part of the eating habits of human beings and have also been a consequence of the adaptation of collectors, consuming the ethnoflora present in different ecosystems. Likewise, it is important to note that this knowledge has been progressively lost in the new generations. Therefore, this review concentrates an important number of matrices used particularly for food and medicinal purposes, recognized for their anxiolytic and antidepressant effects, establishing the importance of metabolism and biotransformation mainly of bioactive compounds such as polyphenols by the action of the gut microbiota.

Customs and beliefs of ancestral medicine to reduce COVID-19, in the town of mariscal sucre – Otavalo

The objective of this research work was to develop an intervention proposal rescuing the customs and beliefs of ancestral medicine that contribute to the care of patients with COVID-19 aimed at the indigenous population of the Mariscal Sucre community in the city of Otavalo. In its development, the theoretical foundations were determined that allowed knowing which are the elements of nature that are used in the healing process, as well as the different rites, rituals and relevant procedures. The methodology used was based on a quantitative, descriptive, non-experimental field design, and bibliographic research was also used to obtain the pertinent theoretical bases. The population is made up of 393 citizens of the population, over 14 years of age, from which a representative sample of 256 inhabitants of the community and 13 men and women of wisdom were extracted, to whom a questionnaire was applied as a data collection instrument, designed with closed response options, Likert-type scale, which were processed by the SPSS statistical program to obtain a descriptive analysis. The main results stand out, through the use of customs and beliefs of ancestral medicine, based on infusions of herbs and plants with medicinal properties, it is possible to treat the symptoms of COVID-19, however, it is necessary to achieve a relevant articulation with the National Public Health System to achieve the integral care of the patient, complementing with pharmacological treatment. © 2021, University of Cienfuegos, Carlos Rafael Rodriguez. All rights reserved.

Phylogenetic and Ancestral Sequence Reconstruction of SARS-CoV-2 Reveals Latent Capacity to Bind Human ACE2 Receptor.

SARS-CoV-2 is a unique event, having emerged suddenly as a highly infectious viral pathogen for human populations. Previous phylogenetic analyses show its closest known evolutionary relative to be a virus detected in bats (RaTG13), with a common assumption that SARS-CoV-2 evolved from a zoonotic ancestor via recent genetic changes (likely in the Spike protein receptor-binding domain or RBD) that enabled it to infect humans. We used detailed phylogenetic analysis, ancestral sequence reconstruction, and in situ molecular dynamics simulations to examine the Spike-RBD's functional evolution, finding that the common ancestral virus with RaTG13, dating to no later than 2013, possessed high binding affinity to the human ACE2 receptor. This suggests that SARS-CoV-2 likely possessed a latent capacity to bind to human cellular targets (though this may not have been sufficient for successful infection) and emphasizes the importance of expanding efforts to catalog and monitor viruses circulating in both human and non-human populations.

Genomic and Ancestral Variation Underlies the Severity of COVID-19 Clinical Manifestation in Individuals of European Descent.

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a wide spectrum of clinical phenotypes ranging from asymptomatic to symptomatic with mild or moderate presentation and severe disease. COVID-19 susceptibility, severity and recovery have demonstrated high variability worldwide. Variances in the host genetic architecture may underlie the inter-individual and population-scale differences in COVID-19 presentation. We performed a genome-wide association analysis employing the genotyping data from AncestryDNA for COVID-19 patients of European descent and used asymptomatic subjects as the control group. We identified 621 genetic variants that were significantly distinct between asymptomatic and acutely symptomatic COVID-19 patients (multiple-testing corrected p-value < 0.001). These variants were found to be associated with pathways governing host immunity, such as interferon, interleukin and cytokine signalling, and known COVID-19 comorbidities, such as obesity and cholesterol metabolism. Further, our ancestry analysis revealed that the asymptomatic COVID-19 patients possess discernibly higher proportions of the Ancestral North Eurasian (ANE) and Eastern Hunter-Gatherer (EHG) ancestry, which was introduced to Europe through Bell Beaker culture (Yamnaya related) and lower fractions of Western Hunter-Gatherer (WHG) ancestry, while severely symptomatic patients have higher fractions of WHG and lower ANE/EHG ancestral components, thereby delineating the likely ancestral differences between the two groups.

Ongoing global and regional adaptive evolution of SARS-CoV-2.

Understanding the trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution is paramount to control the COVID-19 pandemic. We analyzed more than 300,000 high-quality genome sequences of SARS-CoV-2 variants available as of January 2021. The results show that the ongoing evolution of SARS-CoV-2 during the pandemic is characterized primarily by purifying selection, but a small set of sites appear to evolve under positive selection. The receptor-binding domain of the spike protein and the region of the nucleocapsid protein associated with nuclear localization signals (NLS) are enriched with positively selected amino acid replacements. These replacements form a strongly connected network of apparent epistatic interactions and are signatures of major partitions in the SARS-CoV-2 phylogeny. Virus diversity within each geographic region has been steadily growing for the entirety of the pandemic, but analysis of the phylogenetic distances between pairs of regions reveals four distinct periods based on global partitioning of the tree and the emergence of key mutations. The initial period of rapid diversification into region-specific phylogenies that ended in February 2020 was followed by a major extinction event and global homogenization concomitant with the spread of D614G in the spike protein, ending in March 2020. The NLS-associated variants across multiple partitions rose to global prominence in March to July, during a period of stasis in terms of interregional diversity. Finally, beginning in July 2020, multiple mutations, some of which have since been demonstrated to enable antibody evasion, began to emerge associated with ongoing regional diversification, which might be indicative of speciation.

Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context.

The human leukocyte antigen (HLA) is a complex genetic system that encodes proteins which predominantly regulate immune/inflammatory processes. It can be involved in a variety of immuno-inflammatory disorders ranging from infections to autoimmunity and cancers. The HLA system is also suggested to be involved in neurodevelopment and neuroplasticity, especially through microglia regulation and synaptic pruning. Consequently, this highly polymorphic gene region has recently emerged as a major player in the etiology of several major psychiatric disorders, such as schizophrenia, autism spectrum disorder and bipolar disorder and with less evidence for major depressive disorders and attention deficit hyperactivity disorder. We thus review here the role of HLA genes in particular subgroups of psychiatric disorders and foresee their potential implication in future research. In particular, given the prominent role that the HLA system plays in the regulation of viral infection, this review is particularly timely in the context of the Covid-19 pandemic.

Phylogenetic network analysis of SARS-CoV-2 genomes.

In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.

New insights into the evolutionary features of viral overlapping genes by discriminant analysis.

Overlapping genes originate by a mechanism of overprinting, in which nucleotide substitutions in a pre-existing frame induce the expression of a de novo protein from an alternative frame. In this study, I assembled a dataset of 319 viral overlapping genes, which included 82 overlaps whose expression is experimentally known and the respective 237 homologs. Principal component analysis revealed that overlapping genes have a common pattern of nucleotide and amino acid composition. Discriminant analysis separated overlapping from non-overlapping genes with an accuracy of 97%. When applied to overlapping genes with known genealogy, it separated ancestral from de novo frames with an accuracy close to 100%. This high discriminant power was crucial to computationally design variants of de novo viral proteins known to possess selective anticancer toxicity (apoptin) or protection against neurodegeneration (X protein), as well as to detect two new potential overlapping genes in the genome of the new coronavirus SARS-CoV-2.