Covid-19: virology, variants, and vaccines

Abstract

As of 25 January 2022, over 349 million individuals have received a confirmed diagnosis of covid-19, with over 5.59 million confirmed deaths associated with the SARS-CoV-2 virus. The covid-19 pandemic has prompted an extensive global effort to study the molecular evolution of the virus and develop vaccines to prevent its spread. Although rigorous determination of SARS-CoV-2 infectivity remains elusive, owing to the continuous evolution of the virus, steps have been made to understand its genome, structure, and emerging genetic mutations. The SARS-CoV-2 genome is composed of several open reading frames and structural proteins, including the spike protein, which is essential for entry into host cells. As of 25 January 2022, the World Health Organization has reported five variants of concern, two variants of interest, and three variants under monitoring. Additional sublineages have since been identified, and are being monitored. The mutations harboured in these variants confer an increased transmissibility, severity of disease, and escape from neutralising antibodies compared with the primary strain. The current vaccine strategy, including booster doses, provides protection from severe disease. As of 24 January 2022, 33 vaccines have been approved for use in 197 countries. In this review, we discuss the genetics, structure, and transmission methods of SARS-CoV-2 and its variants, highlighting how mutations provide enhanced abilities to spread and inflict disease. This review also outlines the vaccines currently in use around the world, providing evidence for every vaccine's immunogenicity and effectiveness.

Keywords: COVID-19; Covid-19; Virology.

Figure 1

Genome and structure of SARS-CoV-2. (A) SARS-CoV-2 genome and spike (S) protein amino acid composition. The SARS-CoV-2 genome is about 30 000 base pairs (bp) long and consists of open reading frames (ORF) and elements that are essential for the virus’ structure. The S protein is responsible for binding and entry into host cells. SARS-CoV-2 variants of concern contain various S protein non-synonymous mutations that result in amino acid changes in the receptor binding domain (orange bracketed text) and the S1/S2 subunit interface (black bracketed text), which have been shown to enhance transmissibility of the virus. Variants of concern include alpha (α), beta (β), gamma (γ), delta (δ), and omicron (O). (B) SARS-CoV-2 structure. SARS-CoV-2 is an RNA virus that has a crown-like appearance and contains four major structural proteins: nucleocapsid (N), spike (S), envelope (E), and membrane (M). (C) Viral S protein and human angiotensin converting enzyme 2 (ACE2) interaction. The SARS-CoV-2 S protein directly interacts with human ACE2 receptors in order to gain entry into host cells. The receptor binding domain (RBD) of the S protein tightly binds to ACE2. (D) S protein structure. The S protein protrudes out from the main SARS-CoV-2 bulk and is comprised of two subunits: S1 and S2. S1 contains the RBD, which directly interacts with the human ACE2 receptor, while the S1/S2 interface contains a furin cleavage site that is cleaved to allow S2 to fuse with the host cell membrane. Both the RBD and the S1/S2 interface contain transmissibility increasing mutations that are harboured in variants of concern

Figure 2

Viral entry and host response. (A) At the alveolar epithelial cell layer. Epithelial cells in the lungs express both angiotensin converting enzyme 2 (ACE2) receptors and transmembrane protease serine 2 (TMPRSS2), allowing for infection by SARS-CoV-2. Replication of the virus within these cells induces an intense immune response that attracts monocytes, T cells, and macrophages and, in some instances, can result in a cytokine storm. (B) Within nearby blood vessels. Cytokines produced by the epithelial cell layer are released into blood vessels supplying the infected tissue, which causes the recruitment of further immune cells to the area, driving the damaging inflammatory response further. Circulating cytokines also create a systemic inflammatory environment. (C) Adaptive immune response. Circulating lymphocytes carry viral antigens to lymph nodes and bone marrow to begin the adaptive immune system processes whereby B cells, and later antibodies, are activated. (D) SARS-CoV2 host replication. The SARS-CoV-2 virus uses the ACE2 receptor and TMPRSS2 to gain entry into human cells. Following release of the viral RNA within the host cell, the virus uses the host endoplasmic reticulum (ER) and Golgi apparatus to produce and manufacture new viral particles, which are released out of the cell to infect other cells and new hosts