zoonotic viruses that can be transmitted from animal to human; and the first time that occurs, it is referred to as a spillover event. The SARS-CoV-2 has been found to be closely related to coronaviruses found in the bat population and to the SARS-CoV [2]. Two coronaviruses found in bat populations, RaTG13 and RmYN02 were found to have 96.2% and 93.3% sequence homology, respectively with SARS-CoV-2 [3, 4]. Coronaviruses in Malayan pangolins have also been found to have sequence homology to SARS-CoV-2 [5]. The zoonotic source for SARS-CoV-2 is yet to be established. The bat and pangolin coronaviruses lack the polybasic cleavage site and mutations in the spike (S) protein, which SARS-CoV-2 possesses making the theory of human to human transmission at undetectable rates post spillover, a possibility for the virus to have acquired these genomic features prior to starting off the pandemic [6]. December 31, 2019 was the day the World Health Organisation (WHO) China Country Office was made aware of cases of pneumonia of an unknown etiology occurring in the city of Wuhan in the Hubei Province of China [7]. The virus once isolated from the airway epithelial cells of the infected Manuscript submitted May 4, 2021, accepted June 3, 2021 Published online June 25, 2021 a Department of Pediatrics, Pediatric Group of Acadiana, Lafayette, LA, USA bDepartment of Medicine, Oregon Health and Science University, Portland, OR, USA c Physicians for American Health Care Access, Philadelphia, PA, USA dDepartment of Medicine, Jeanes Campus-Temple University Hospital, Philadelphia, PA, USA e Department of Medicine, Bay Area Hospital, Coos Bay, OR, USA f Corresponding Author: Deepa Vasireddy, Department of Pediatrics, Pediatric Group of Acadiana, 7053 Johnston Street, Lafayette, LA, USA. Email: deepa26vasi@gmail.com doi: https://doi.org/10.14740/jocmr4518 318 Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press Inc™ | www.jocmr.org COVID-19 Vaccines Versus the Variants J Clin Med Res. 2021;13(6):317-325 patients was temporarily assigned the name 2019-nCoV [8]. Once it was determined that the virus is related to SARS-CoV, it was designated the name SARS-CoV-2 by the Coronavirus Research Group (CSG) of the International Committee for the classification of viruses on February 11, 2020 [9]. Genetics and pathogenesis SARS-CoV-2 is an enveloped spherical-shaped virus [1]. It has four structural proteins and 16 nonstructural proteins. The structural proteins are the nucleocapsid (N) protein, the membrane (M), the S protein and the envelope (E) protein. The RNA is oriented in a 5’-3’direction which makes it a positive sense RNA virus, and the RNA can be read directly as a messenger RNA (mRNA, Fig. 1). The RNA replicase is encoded at the 5’ terminal end. The nonstructural protein 14 (nsp14) has proofreading activity which allows the rate of mutations to stay low. The S protein causes the attachment of the virus to the host cell at the angiotensin-converting enzyme 2 (ACE2) receptor, which is present on the membrane of the host cell. The ACE2 receptors are found in abundance on alveolar cells. The attachment causes fusion of the viral lipid membrane with the cell membrane of the host thus internalising the virus. The host machinery translates the viral RNA and leads to the production of the replicase and structural proteins of the virus. The replicase is cleaved into nonstructural proteins of which RNA-dependent RNA polymerase (RdRp) is one of them. Viral replication and amplification is carried out and assembly of the virions is carried out in the host cell endoplasmic reticulum and Golgi apparatus. During the process of replication, errors can occur in the genome leading to mutations which give rise to variants. The virions are finally released out of the cell by exocytosis [10, 11]. Coronavirus Disease 2019 (COVID-19) Mutations and Variants A change in the genetic sequence is called a mutation (Table 1 [12]). Genomes that differ from each other in genetic sequence are called variants. Variants can differ from each other by one or more mutations. When a phenotypic difference is demonstrated among the variants, they are called strains [13]. In 2008 a global science initiative and primary source, Global Influenza Surveillance and Response System (GISAID) was established to provide open access to genomic data of influenza viruses. In January 2020, the SARS-CoV-2 genome sequences were made available on GISAID [14]. Nextstrain curates and analyses the genetics of SARS-CoV-2, and is a collaborative effort of researchers between Seattle, USA and Basel, Switzerland [12]. The interagency of the USA government has divided the SARS-CoV-2 variants into three classes. Based on the scientific evidence, the variant status can sometimes be escalated or deescalated and hence, the Center of Disease Control and Prevention (CDC) will update the variant strains in the different classes (Table 2) [15]. According to the report of April 21, 2021, the classes are: variant of interest, variant of concern, and variant of high consequence. Variant of interest This class includes variants with specific markers that are associated with changes to receptor binding, decreased antibody neutralization developed against previous infection or vaccination, decreased efficacy of