Covid-19 emerged as a pandemic caused by severe acute respiratory syndrome- coronavirus (SARS-CoV-2) infected 4.9 million people and causing deaths of 0.3 million people worldwide. Originated from Wuhan province of China, COVID-19 spread all across the world and created unprecedented challenges among the healthcare facilities in both developed countries and developing countries equally. Previous SARS-CoV-1 also caused an outbreak back in 2003 but controlled with tracing and treatment methods globally. The current most efficient strategy in use to control the COVID-19 is, tracing, containing, treatment and social distancing and being followed worldwide as guided by World Health Organization (WHO).
A brief insight on the genome and structure of SARS-CoV2
Genome: SARS-CoV-2 is +ssRNA virus and its genome varies from 29.8kb to 29.9kb (largest known genome in viruses) with 10 ORF sequences. 5’ORF1a/b codes for polyproteins and apart from ORF1a/b, other ORF sequences codes for structural proteins such as nucleocapsid, membrane, envelope, and surface proteins.
Spike glycoprotein: CoV-2 uses spike glycoprotein to make entry into host cells and majorly responsible for the spread on infection and pathogenicity. In the host target cell it binds to the ACE2 (Angiotensin Converting Enzyme 2) receptor. Spike protein present in trimeric forms and each monomer is of 180kDa consisting of S1 and S2 subunits responsible for membrane fusion and virus entry. CoV-2 spike proteins are class 1 viral fusion proteins and proteolytic cleavage is necessary form the activation which is mediated by host furin enzyme (SARS-CoV-2). After cleavage of spike proteins, CoV-2 enters the cells via endocytosis. Further sequence analysis of spike glycoprotein reveals the addition of four amino acids between S1 and S2 subunits that ultimately increases the pathogenicity of the CoV-2.
Nucleocapsid protein: Nucleocapsid (NC) protein of CoV-2 is a 50kDa protein primarily involved in replication, transcription, and packaging of the viral genome. It is most abundant and highly immunogenic protein with conserved amino acid sequences among the other coronaviruses. In other coronaviruses, NC protein is responsible for the generation of humoral immunity and prolonged T-cell response upto 11 years and serves as suitable vaccine candidate. However, CoV-2 is a novel coronavirus with modified spike glycoproteins with high pathogenicity, suggesting immunity against spike protein is very crucial.
Membrane protein: Membrane (M) protein of CoV-2 is also conserved across all coronaviruses like β-CoVs and specially across SARS-CoVs. However having conserved sequences there is little variation at N-terminal region as an additional insertion of Serine residue at 4th position which is unique for CoV-2.
Envelope Protein: Envelope (E) protein is a membrane protein comprised of 76-109 amino acids and conserved across coronaviruses like β-CoVs & SARS-CoVs. Envelope proteins are oligomerize and forms ion channels. The E protein gene located nearby by Spike protein gene and thus play role in the assembly of viral genome, envelope formation, pathogenesis, budding and virion assembly. A short region at the starting of N-terminal region is hydrophobic and carboxy terminal hydrophilic. Hydrophobic region at N-terminal helps in oligomerization in extracellular space and from ion-channels in the membrane.
Clinical symptoms associated with COVID-19
While there is a diversity in clinical symptoms associated with COVID-19 ranges from mild to severe pneumonia. Majority of the patients are asymptomatic at al with mild cough or fever. Centre for Disease Control and Prevention (CDC), USA listed symptoms associated with COVID-19 like fever, dry cough, cold, pneumonia, loss of smell etc. Majority of affected population was male till date but there is variation among the age group like people with old age tend to acquire more severe symptoms as compared to children. As COVID-19 is causing wreak havoc onto the world, more complicated symptoms are coming into scenario. As per previous reports children were safe with COVID-19 but recent reports suggest young one are not safe the COVID-19 is inducing inflammatory syndrome in children that may have long term consequences.
Recent advances in immunology of SARS-CoV-2
COVID-19 like other major pandemics of history has put a halt to entire activities like scientific research, economic developments, and travel. In spite of this major challenge globally, studies on understanding the immunology associated with CoV-2 is keep going on. As per the reports intense cytokine storm is induced by COVID-19 into the body in which IL-6, also implicated in Cytokine Release Syndrome (CRS) major characteristics of COVID-19. Patients affected were also facing septic shock and multiple organ failure. Kevin and colleagues find that viral load in COVID-19 patients was peaked during first week but gradually reduced during second week with increased IgG and IgM antibodies (https://doi.org/10.1016/S1473-3099(20)30196-1) followed by increased amount of neutralizing antibodies against spike protein of SARS-CoV-2 leads to viral neutralization inside the body as spike protein plays major role to infect cells. Several studies indicated that viral load inside human body is not associated with the strength of the host immune system but depends on the amount of ACE2 receptor being expressed in the host system. Ling colleagues showed COVID-19 patients show increased NK cell activity and slightly increased amount of IFN-γ-associated T-cell response indicating induction of both humoral and T-cell response (https://www.sciencedirect.com/science/article/pii/S1074761320301813). Combined analysis of patient’s serum showed that levels of neutralizing antibodies are associated with increased T-cell numbers. Xinling Wang and colleagues showed SARS-CoV-2 also infects T-cells through its spike protein found that T- cells are more prone to infection with novel SARS-CoV-2 using CD147 receptor as compared to previous SARS-CoV infection (https://www.nature.com/articles/s41423-020-0424-9). This study suggests a novel route used by SARS-CoV-2 to infect immune cells causing deprived immune response. Macrophages are also involved in the lung damage induced by COVID-19 as activation of pro-inflammatory macrophages induce the release of MCP-1 and IL-8 leading to intense inflammatory damage of lungs. SARS-CoV-2 infection also causes pyroptosis of macrophages. As a greater number of cases continue to appear, so as mutated version of virus with diverse immune response. There is still a long way to go to understand the immunological perspective associated with COVID-19.
Content Writer- Suraj Singh Rawat