An Insight into Association Between COVID-19 Infection and ABO Blood Group

Coronavirus disease 2019 (COVID-19), a pandemic that is triggered by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) or 2019-nCoV, causes primarily respiratory discomfort along with other mild symptoms/no symptoms, leading to severe illness and death, if proper care is not taken. At present, COVID-19 is the resilient reason for a large number of human casualties worldwide as well as a cause of crucial economic loss posturing global threat. There is a necessity of intensive research to elucidate the pathogenic mechanisms of COVID-19, which would assist in understating the susceptibility towards the infection as well as prompt development of effective prevention and treatment strategies. Over the years, clinical studies have indicated the risk of various pathogenic infections prejudiced due to preexisting chronic diseases as well as ABO blood group types to a larger extent. In line of this, current COVID-19 infection-associated clinical studies intensely endorse the relationship of blood group type of individual and risk of COVID-19 infection. In this chapter, various clinical studies from January 2020 to June 2020 have been summarized to highlight the eminence of ABO blood group and COVID-19 infection susceptibility in human population. These reports evidently support the fact that individuals with A histo blood group were found to be more vulnerable to COVID-19 infection whereas individuals with blood group O were less likely to get infected with virus. To get deeper insight in this fact, many more studies are desirable in order to further explicate the promising protective role of the blood group O and it will be supportive for designing and planning several additional countermeasures against COVID-19 infection. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Transcriptome Profiling in Autoimmune Diseases

Autoimmune diseases are a group of different inflammatory disorders characterized by systemic or localized inflammation, affecting approximately 0.1–1% of the general population. Several studies suggest that genetic risk loci are shared between different autoimmune diseases and pathogenic mechanisms may also be shared. The strategy of performing differential gene expression profiles in autoimmune disorders has unveiled new transcripts that may be shared among these disorders. Microarray technology and bioinformatics offer the most comprehensive molecular evaluations and it is widely used to understand the changes in gene expression in specific organs or in peripheral blood cells. The major goal of transcriptome studies is the identification of specific biomarkers for different diseases. It is believed that such knowledge will contribute to the development of new drugs, new strategies for early diagnosis, avoiding tissue autoimmune destruction, or even preventing the development of autoimmune disease. In this review, we primarily focused on the transcription profiles of three typical autoimmune disorders, including type 1 diabetes mellitus (destruction of pancreatic islet beta cells), systemic lupus erythematosus (immune complex systemic disorder affecting several organs and tissues), and multiple sclerosis (inflammatory and demyelinating disease of the nervous system). © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

T-Toxin Virulence Genes: Unconnected Dots in a Sea of Repeats.

In 1970, the Southern Corn Leaf Blight epidemic ravaged U.S. fields to great economic loss. The outbreak was caused by never-before-seen, supervirulent, Race T of the fungus Cochliobolus heterostrophus. The functional difference between Race T and O, the previously known, far less aggressive strain, is production of T-toxin, a host-selective polyketide. Supervirulence is associated with ~1 Mb of Race T-specific DNA; only a fraction encodes T-toxin biosynthetic genes (Tox1). Tox1 is genetically and physically complex, with unlinked loci (Tox1A, Tox1B) genetically inseparable from breakpoints of a Race O reciprocal translocation that generated hybrid Race T chromosomes. Previously, we identified 10 genes for T-toxin biosynthesis. Unfortunately, high-depth, short-read sequencing placed these genes on four small, unconnected scaffolds surrounded by repeated A+T rich sequence, concealing context. To sort out Tox1 topology and pinpoint the hypothetical Race O translocation breakpoints corresponding to Race T-specific insertions, we undertook PacBio long-read sequencing which revealed Tox1 gene arrangement and the breakpoints. Six Tox1A genes are arranged as three small islands in a Race T-specific sea (~634 kb) of repeats. Four Tox1B genes are linked, on a large loop of Race T-specific DNA (~210 kb). The race O breakpoints are short sequences of race O-specific DNA; corresponding positions in race T are large insertions of race T-specific, A+T rich DNA, often with similarity to transposable (predominantly Gypsy) elements. Nearby, are 'Voyager Starship' elements and DUF proteins. These elements may have facilitated Tox1 integration into progenitor Race O and promoted large scale recombination resulting in race T. IMPORTANCE In 1970 a corn disease epidemic ravaged fields in the United States to great economic loss. The outbreak was caused by a never-before seen, supervirulent strain of the fungal pathogen Cochliobolus heterostrophus. This was a plant disease epidemic, however, the current COVID-19 pandemic of humans is a stark reminder that novel, highly virulent, pathogens evolve with devastating consequences, no matter what the host-animal, plant, or other organism. Long read DNA sequencing technology allowed in depth structural comparisons between the sole, previously known, much less aggressive, version of the pathogen and the supervirulent version and revealed, in meticulous detail, the structure of the unique virulence-causing DNA. These data are foundational for future analysis of mechanisms of DNA acquisition from a foreign source.

Analysis of the Homozygosity of Microsatellite Markers by Using Fuzzy Sets

Genetics is a highly relevant field of science. During the time of COVID-19 pandemic, it has gained additional importance. In this paper, a novel approach to genetic research using fuzzy sets is presented. Such a synergy of two so far rarely interacting scientific disciplines opens new avenues of research. The proposed approach shows only a sample of the possibilities offered by interdisciplinary research. In this study, a new approach using fuzzy set-based techniques to analyze the phenomena of homozygosity of microsatellite markers is presented. The analyses carried out using one of the most intuitive types of membership functions allowed us to achieve results that shed new light on the examined data. Moreover, the analysis of the distributions of individual markers using fuzzy sets allowed for a more in-depth study of the problem under consideration. © 2022 IEEE.

Peptidomic analysis of mycobacterial secreted proteins enables species identification

Pulmonary disease arising from slow‐growing mycobacterial infections has emerged as an increasingly prevalent clinical concern over the past two to three decades. Proteins belonging to the family of ESAT‐6 secretion (Esx) systems play critical roles in the virulence of most pathogenic mycobacterial species and are associated with drug resistance. However, no clinical applications can detect and discriminate the expression of species‐specific variants of these proteins in clinical samples, such as early growth cultures, for rapid diagnosis of specific mycobacterial infections, which may require distinct interventions. Conventional immunoassay approaches are not suitable for this purpose due to the significant degree of conservation of Esx proteins among species. Herein we describe the development of a novel immunoprecipitation‐coupled mass spectrometry assay that can distinguish Esx proteins that are expressed by slow‐growing mycobacterial species commonly detected in clinical isolates. This approach uses custom antibodies raised against single semi‐conserved peptide regions in M. tuberculosis (Mtb) EsxB and EsxN to capture corresponding peptides from protein orthologs of mycobacteria associated with human respiratory infections, including Mtb, M. avium, M. intracellulare, M. kansasii, M. gordonae, and M. marinum, to detect these species in standard clinical cultures at the first sign mycobacterial growth to allow rapid disease diagnosis.

Association of tumor necrosis factor alpha ‐308 single nucleotide polymorphism with SARS CoV‐2 infection in an Iraqi Kurdish population

Uncovering risk factors playing roles in the severity of Coronavirus disease 2019 (Covid‐19) are important for understanding pathoimmunology of the disease caused by severe acute respiratory syndrome Coronavirus 2 (SARS CoV‐2). Genetic variations in innate immune genes have been found to be associated with Covid‐19 infections. A single‐nucleotide polymorphism (SNP) in a promoter region of tumor necrosis factor alpha (TNF‐α) gene, TNF‐α −308G>A, increases expression of TNF‐α protein against infectious diseases leading to immune dysregulations and organ damage. This study aims to discover associations between TNF‐α −308G>A SNP and Covid‐19 infection. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) was used for genotyping a general Kurdish population and Covid‐19 patients. The homozygous mutant (AA) genotype was found to be rare in the current studied population. Interestingly, the heterozygous (GA) genotype was significantly (p value = 0.0342) higher in the Covid‐19 patients than the general population. This suggests that TNF‐α −308G>A SNP might be associated with Covid‐19 infections. Further studies with larger sample sizes focusing on different ethnic populations are recommended.

Feedback and Control Course Labs for Distance Learning

Classic Feedback and Control is an undergraduate course that introduces students to concepts and methods for modeling, analysis, and design of single-input-single-output feedback control systems in the Electrical and/or Computer Engineering majors. In addition to using lectures to explain theories and assigning homework assignments for students to practice their modeling and analyses skills, instructors would usually supplement the course by a series of hardware-based experiments and software-based simulation labs so that students can apply the acquired knowledge to physical systems and real-world control problems. Similar to many other institutions, our ECE program offers a Feedback and Control course to junior students in the Electrical Engineering and Electromechanical Engineering majors. This course is a 3-hour lecture, 2-hour lab, as a 4-credit course. Topics discussed include modeling in both the time and the frequency domains, time response, model reduction, stability, steady-state error, root locus, design via root locus, frequency response, and design via frequency response. Due to the COVID-19 pandemic, both students and faculty in our institution were forced to work and study from home in summer 2020. In order to engage students in distance learning, application-oriented and active-learning opportunities were created. A series of exclusively software-based labs and projects were designed to help students gain a better understanding of how the knowledge are useful in real-world situations. Particularly, nine simulation labs and two simulation projects were used in the class of summer 2020. In order to evaluate the effectiveness of the designed simulation labs and projects in helping students to grasp and then apply the control concepts and ideas, surveys were conducted in the summer 2020 class to collect students' opinions and feedbacks. Among the 27 participating students, 81.4% of students “agree” or “strongly agree” that simulation laboratory exercises increased their interest in the subject, 85.1% of students “agree” or “strongly agree” that simulation laboratory exercises helped them better to learn course content, and 77.7% of the students thought simulation laboratory exercises were excellent or very good. We also compared the percentage of students who performed at the A, A-, B+, B, and B- levels with past records (while teaching was in-person), which turned out to be comparable and similar. This indicates the effectiveness of these simulation-based labs & projects, and their contribution in helping to maintain the course standard. © American Society for Engineering Education, 2021

New evidence of genetic factors related to severe infection of novel Coronavirus

Since the end of 2019, new coronavirus pneumonia caused by infection with a new type of coronavirus has become widespread in the world, posing a serious threat to life and health. However, after individuals are infected with SARS-CoV-2, significantly different outcomes occur, which can manifest as simple, mild, common, severe, and dangerous pneumonia. Previous research published in the New England Journal of Medicine suggested that severe infections in individuals may be related to genetic variation, but the genetic contribution and associated mechanisms of severe COVID-19 is still not well understood. Recently, JeanLaurent Casanova's team at Rockefeller University performed genomic testing on 1,193 patients with new coronary pneumonia and found that the critically ill patients carried rare harmful mutations. These mutations originate from 13 loci and related genes that are enriched in the TLR3/IRF7-dependent type I interferon pathway. Further studies of the function of all 118 non-synonymous mutations at these 13 loci revealed that cells harboring these mutations were more susceptible to SARS-CoV-2. This study suggests that TLR3/IRF7-dependent interferon immunity associated with dsRNA sensing may play an important role in the control of SARS-CoV-2, and that genetic defects in these genes are implicated in immunity may be responsible for the development of severe COVID-19 in some individuals.

The Genomic Physics of COVID-19 Pathogenesis and Spread.

Coronavirus disease (COVID-19) spreads mainly through close contact of infected persons, but the molecular mechanisms underlying its pathogenesis and transmission remain unknown. Here, we propose a statistical physics model to coalesce all molecular entities into a cohesive network in which the roadmap of how each entity mediates the disease can be characterized. We argue that the process of how a transmitter transforms the virus into a recipient constitutes a triad unit that propagates COVID-19 along reticulate paths. Intrinsically, person-to-person transmissibility may be mediated by how genes interact transversely across transmitter, recipient, and viral genomes. We integrate quantitative genetic theory into hypergraph theory to code the main effects of the three genomes as nodes, pairwise cross-genome epistasis as edges, and high-order cross-genome epistasis as hyperedges in a series of mobile hypergraphs. Charting a genome-wide atlas of horizontally epistatic hypergraphs can facilitate the systematic characterization of the community genetic mechanisms underlying COVID-19 spread. This atlas can typically help design effective containment and mitigation strategies and screen and triage those more susceptible persons and those asymptomatic carriers who are incubation virus transmitters.

Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19.

OBJECTIVES: COVID-19 has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies have identified potential genetic variants involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear. METHODS: We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19. RESULTS: In blood, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (ß [SE]=0.42 [0.09], P = 4.75 × 10-06 and ß [SE]=-0.48 [0.11], P = 6.76 × 10-06, respectively). Although no other probes were significant after correction for multiple testing in both blood and lung, multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation. CONCLUSIONS: We identified IFNAR2 and other potential genes that could be involved in the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism in COVID-19 and potential therapeutic targets for the effective treatment of COVID-19.

COVID-19 and Body Iron: A Survey on Phenomenological and Genetic Correlations.

To provide solid information about viral infection, disease, and body iron metabolism, the literature was surveyed for mutual correlations. Gender and age profiles of COVID-19 infection and disease correlate well with the profiles of serum iron and ferritin with correlation coefficients ≥ 0.75. There are further symptomatic hints that the ABO blood group system contributes to these correlations. Remarkably, the susceptibility to both the viral disease and iron dyshomeostasis can be traced back to the same gene loci of the ABO blood group system. The overlapping of susceptible gene loci together with the phenomenological correlations in gender and age are strong indicators for the interrelation of body iron dyshomeostasis with COVID-19 infection and disease.