SARS-CoV-2 Variants Show a Gradual Declining Pathogenicity and Pro-Inflammatory Cytokine Stimulation, an Increasing Antigenic and Anti-Inflammatory Cytokine Induction, and Rising Structural Protein Instability: A Minimal Number Genome-Based Approach.

Hyper-transmissibility with decreased disease severity is a typical characteristic of the SARS-CoV-2 Omicron variant. To understand this phenomenon, we used various bioinformatics approaches to analyze randomly selected genome sequences (one each) of the Gamma, Delta, and Omicron variants submitted to NCBI from December 15 to 31, 2021. We report that the pathogenicity of SARS-CoV-2 variants decreases in the order of Wuhan > Gamma > Delta > Omicron; however, the antigenic property follows the order of Omicron > Gamma > Wuhan > Delta. The Omicron spike RBD shows lower pathogenicity but higher antigenicity than other variants. The reported decreased disease severity by the Omicron variant may be due to its decreased pro-inflammatory and IL-6 stimulation and increased IFN-γ and IL-4 induction efficacy. The mutations in the N protein are probably associated with this decreased IL-6 induction and human DDX21-mediated increased IL-4 production for Omicron. Due to the mutations, the stability of S, M, N, and E proteins decreases in the order of Omicron > Gamma > Delta > Wuhan. Although a stronger spike RBD-hACE2 binding of Omicron increases its transmissibility, the lowest stability of its spike protein makes spike RBD-hACE2 interaction weak for systemic infection and for causing severe disease. Finally, the highest instability of the Omicron E protein may also be associated with decreased viral maturation and low viral load, leading to less severe disease and faster recovery. Our findings will contribute to the understanding of the dynamics of SARS-CoV-2 variants and the management of emerging variants. This minimal genome-based method may be used for other similar viruses avoiding robust analysis.

Associations and Disease-Disease Interactions of COVID-19 with Congenital and Genetic Disorders: A Comprehensive Review.

Since December 2019, the COVID-19 pandemic, which originated in Wuhan, China, has resulted in over six million deaths worldwide. Millions of people who survived this SARS-CoV-2 infection show a number of post-COVID complications. Although, the comorbid conditions and post-COVID complexities are to some extent well reviewed and known, the impact of COVID-19 on pre-existing congenital anomalies and genetic diseases are only documented in isolated case reports and case series, so far. In the present review, we analyzed the PubMed indexed literature published between December 2019 and January 2022 to understand this relationship from various points of view, such as susceptibility, severity and heritability. Based on our knowledge, this is the first comprehensive review on COVID-19 and its associations with various congenital anomalies and genetic diseases. According to reported studies, some congenital disorders present high-risk for developing severe COVID-19 since these disorders already include some comorbidities related to the structure and function of the respiratory and cardiovascular systems, leading to severe pneumonia. Other congenital disorders rather cause psychological burdens to patients and are not considered high-risk for the development of severe COVID-19 infection.