Extrapulmonary complications were observed in different organs and systems, including myocarditis,437C439 arrhythmia,440C442 myocardial ischemia443C445 regarding the cardiovascular system, acute kidney injury446C448 and electrolyte abnormalities,449C451 hyperglycemia,452 and ketoacidosis453 in the urinary system, endocrine system, stroke,454C456 and encephalitis423,457,458 regarding the neurological system (Fig

Extrapulmonary complications were observed in different organs and systems, including myocarditis,437C439 arrhythmia,440C442 myocardial ischemia443C445 regarding the cardiovascular system, acute kidney injury446C448 and electrolyte abnormalities,449C451 hyperglycemia,452 and ketoacidosis453 in the urinary system, endocrine system, stroke,454C456 and encephalitis423,457,458 regarding the neurological system (Fig.?12).459 Open in a separate window Fig. Omicron variant even exacerbated the global anxiety in the continuous pandemic. Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity, which would greatly facilitate drug and vaccine development and benefit the global public health policymaking. Hence in this review, we summarized the molecular characteristics, immune evasion, and impacts of the SARS-CoV-2 variants and focused on the parallel comparison of different variants in mutational profile, transmissibility and tropism alteration, treatment effectiveness, and clinical manifestations, in order to provide a comprehensive landscape for SARS-CoV-2 variant research. strong class=”kwd-title” Subject terms: Vaccines, Infectious diseases, Infectious diseases Introduction The COVID-19 pandemic has lasted for over 2 years and caused over 6 million death cases.1 A wide variety of SARS-CoV-2 variants emerged during its persistence and displayed evolving adaptation to global populational immunity,2C5 leading to rapid worldwide spread and heterogenous escape from available therapeutic drugs and vaccines.6C9 The Saccharin 1-methylimidazole mutations harbored in the genome of SARS-CoV-2 variants have a significant MMP10 impact on viral protein structures, function, and immunogenicity, which was strongly associated with the immunological response and clinical outcome in humans.10C13 This review systematically describes the evolutionary and molecular characteristics of SARS-CoV-2 variants and summarizes the mutational impact on the critical viral proteins. Then it comprehensively describes the landscape of immune evasion of various critical variants from the currently approved antibody, small antiviral molecules, and vaccines. Lastly, it describes the epidemiological Saccharin 1-methylimidazole profile of SARS-CoV-2 variants and overview the different critical strains changes in infectivity, host tropism, and clinical manifestation and outcome. Detailed datasets for the parameterized depiction of the difference between SARS-CoV-2 variants in molecular characteristics, immune evasion, and clinical impact are also provided. Molecular characteristics of sequence and the encoded proteins of SARS-CoV-2 variants The genomic evolution of SARS-CoV-2 Since the emergency of SARS-CoV-2,14C17 its viral genome has been under constant and rapid mutation to adapt host system.18,19 Like other RNA virus,20C25 a high mutation rate benefits the emergence of novel variants with a significant change in viral phenotypes.20,26 Therefore, the global scientific community endeavors to construct systematic tracking systems of SARS-CoV-2 mutations and identified the clade with a genetically close relationship.27 The phylogenetic classification is widely used as a fundamental method for emergent SARS-CoV-2 strain classification in the clade-nomenclature system (terming the major strain as clade code such as GR) by Global Initiative of Sharing All Influenza Data (GISAID)28 or NextStrain29 or Pango lineage system (terming the major strain as letter and number with point interval such as B.1.1.7) by Pango Network30 (Fig.?1a). However, with the rapid increase in submitted sequence to the genomic database and wider observation of sequential distribution in the infected population, a more compact naming system for the critical variants was demanded to guide global anti-virus policy. Therefore World Health Organization (WHO) proposed using the Greek alphabet to name the critical SARS-CoV-2 clades or Pango lineages and raised the concept of Variant of Concern (VOCs) and Variants of Interest (VOIs) as a larger dynamic classification.17 Our review used the WHO naming system to indicate the strains in representing both sequence identity and their impact on disease control. Open in a separate window Fig. 1 SARS-CoV-2 evolution, prevalence, and genome architecture. a Phylogenetic analysis of sequence divergence of SARS-CoV-2 circulating variants based on Saccharin 1-methylimidazole clade classification in February 2022. The WHO labeling of clades is marked besides. b Sequential frequency of major clades of SARS-CoV-2 variants from April 2021 to February 2022. c Linear genome architecture of encoded viral protein and structural overview of SARS-CoV-2. The phylogenetic analysis and sequential frequency data come from the Nextstrain GISAID database (https://nextstrain.org/ncov/gisaid/global), and figures in related (a, b) are generated under the CC-BY 4.0 permission. BioRender is used to generate the structure diagram of SARS-CoV-2 virus in Fig.?1c Early 2020 has witnessed the emergence of the first widely reported spike mutation of SARS-CoV-2, D614G.31C36 In December 2020, the Alpha variant Saccharin 1-methylimidazole (B.1.1.7) harboring another critical mutation N501Y37,38 in spike protein, initially expanded in the southeast of.